Embryology - User contributions [en-gb]

User:Z3289738

2012-10-16T23:45:36Z

Z3289738: /* Lab 9 */

==Lab Attendance==
Lab 1: --[[User:Z3289738|Z3289738]] 11:49, 25 July 2012 (EST)

Lab 2: --[[User:Z3289738|Z3289738]] 10:12, 1 August 2012 (EST)

Lab 3: --[[User:Z3289738|Z3289738]] 10:08, 8 August 2012 (EST)

Lab 4: --[[User:Z3289738|Z3289738]] 10:20, 15 August 2012 (EST)

Lab 5: --[[User:Z3289738|Z3289738]] 10:13, 22 August 2012 (EST)

Lab 6: --[[User:Z3289738|Z3289738]] 10:16, 29 August 2012 (EST)

Lab 7: --[[User:Z3289738|Z3289738]] 10:27, 12 September 2012 (EST)

Lab 8: --[[User:Z3289738|Z3289738]] 10:30, 19 September 2012 (EST)

Lab 9: --[[User:Z3289738|Z3289738]] 10:08, 26 September 2012 (EST)

Lab 10: --[[User:Z3289738|Z3289738]] 11:18, 3 October 2012 (EST)

Lab 12: --[[User:Z3289738|Z3289738]] 10:36, 17 October 2012 (EST)

==Individual Assessments==
===Lab 1 Assessment===

''Q1. Identify the origin of In Vitro Fertilization and the 2010 nobel prize winner associated with this technique and add a correctly formatted link to the Nobel page.''

The idea of In Vitro Fertilization began to formulate in the 1890s, when Walter Heape reported the first known case of embryo transplantation in rabbits. In 1953 John Rock extracted the first intact human fertilized egg. The first successful attempt at IVF was in 1978 by Steptoe and Edward.

Robert G. Edwards, the physiologist who developed the In Vitro Fertilization treatment, was awarded the Nobel Prize in Physiology or Medicine in 2010. [http://www.nobelprize.org/nobel_prizes/medicine/laureates/2010/press.html/# Nobel Prize Page]

''Q2. Identify and add a PubMed reference link to a recent paper on fertilization and describe its key findings (1-2 paragraphs).''

This article looks into the process of embryo implantation. It demonstrates how the activation of the epithelial Na(+) channel triggers prostoglandin E(2) release,phosphorylation of teh transcription factor CREB and upregulation of cyclooxygenase 2, the enzyme required for prostaglandin production and implantation. They detected maximum Epithelial Na(+) channel activation at the time of implantation in mice, and that blocking or knocking down this channel in mice resulted in failure to implant. These results indicate the importance of the Epithelial Na(+) Channel in the process of implantation, and the consequences of defects such as miscarriage and low success rates in IVF.

<pubmed> 22729284</pubmed>

===Lab 2 Assessment===
''Q1. Upload an image from a journal source relating to fertilization or the first 2 weeks of development as demonstrated in the practical class. Including in the image “Summary” window: An image name as a section heading, Any further description of what the image shows, A subsection labeled “Reference” and under this the original image source, appropriate reference and all copyright information and finally a template indicating that this is a student image.

[[File:Z3289738 ANAT Lab 2.jpg|200px|thumb|right|Zygotes showing different distribution of NPB in the 2PN and different PB aligment]]

''Q2. Identify a protein associated with the implantation process, including a brief description of the protein's role (1-2 paragraphs)''

'''Trophinin'''

Trophinin is an membrane adhesive protein expressed on human trophoblastic cells and on uterine endometrium epithelial cells. The protein mediates apical cell adhesion and activate trophectoderm cells for implantation via proliferation and invasion. <ref><pubmed>17487845</pubmed></ref>

===Lab 3 Assessment===

''Q1. Identify the difference between "gestational age" and "post-fertilisation age" and explain why clinically "gestational age" is used in describing human development.''

"Gestational age" is measured from the first day of the woman's last menstrual cycle, whereas "post-fertilisation age" measures the time passed since fertilization of the oocyte. Gestational age is more clinically relevant as it is easier to determine the date of the woman's last menstrual cycle than it is to determine the date of fertilization. Furthermore, gestational age can also be determined before and after birth by measuring the size of the head, thigh bone and abdomen (before birth), and the size of the head and weight after birth. Gestational age is therefore used to determine the infant's medical history and medical plan.

''Q2. Identify using histological descriptions at least 3 different types of tissues formed from somites.''

Somites differentiate to form: (1) '''the axial skeleton (vertebral body & inter-vertebral disk)''', (2) '''dermis''' and (3) '''skeletal muscle'''.

# Cells in the ventromedial half of each somite differentiate into the sclerotome via Sonic hedgehog signalling mechanisms. The Pax 1 transcription factor then converts the sclerotome into chondrocytes (cartilage), which is essential for the functioning of the vertebral column.
# Cells in the dorsolateral portion of the somites differentiate to form the dermomyotone. This is then divided into:
## Dorsal dermatome which later contributes to the formation of the dermis in response to neutropin 3 factors.
## Wnt1 and Wnt3 factors contribute to the formation of the ventral myotome, which is further split into the epaxial myotome (gives rise to erector spinae muscles) and the hypaxial myotome (gives rise to the muscles of the trunk and limbs).

===Lab 4 Assessment===

''Q1. Identify the 2 invasive prenatal diagnostic techniques related to the placenta and 2 abnormalities that can be identified with these techniques.''
# '''Chorionic villus sampling''' (CVS)is an invasive prenatal diagnostic technique that is used to detect genetic abnormalities such as Down syndrome or cystic fibrosis. During the procedure a sample of the placenta is removed via a needle through the abdomen and then examined in a laboratory. It is commonly performed between 10 and 12 weeks of pregnancy/
# '''Amniocentesis''' procedures involve collecting samples of amniotic fluid via a needle through the abdomen to check for genetic abnormalities such as Down syndrome, cystic fibrosis or spina bifida.

''Q2. Identify a paper that uses cord stem cells therapeutically and write a brief (2-3 paragraph) description of the paper's findings.''

F. Ramirez, D. Steenblock, A. Payne and L. Darnall (2006) '''Umbilical Cord Stem Cell Therapy for Cerebral Palsy'''. MED HYPOTHESES RES 3: 679-686 [http://www.journal-mhr.com/PDF_Files/vol_3_2/3_2_PDFs/3_2_2.pdf | Umbilical Cord Stem Cell Therapy for Cerebral Palsy]

This article describes a six month study to evaluate the effectiveness of umbilical cord stem cells in treatment for various brain injuries and disorders, in particular Cerebral Palsy. The study began in 2004, whereby 8 children between the ages of 3-12 who had been diagnosed with Cerebral Palsy underwent transplants with 1.5 million umbilical cord stem cells. The study reported eight of of eight children showed some improvement in mobility and/or cognitive function. Furthermore, one aphasic child started talking again and another who had been blind since birth was able to see after post-treatment.

The results from this preliminary observational pilot study suggests that umbilical cord stem cells may be a safe and promising treatment for children with cerebral palsy.

===Lab 7===
====a) Class exercises====
1. Maturation Hypertrophy - In your groups, design a method to estimate the degree of hypertrophy that occurs during the transition from birth to adulthood. Use the rulers to make rough measurements on the screen and then estimate the degree of hypertrophy as a mean increase in fibre size. Discuss the result as a class. (ie Try estimate the degree of hypertrophy from child to adult cells)

Method: Measured area of the child and adult cells, found an average for each and then worked out the percentage increase.

Answer: 7x increase in area size.

2. The role of satellite cells in muscle hypertrophy - class discussion of data presented in a recent paper - McCarthy et al. 2011. (ie How to we achieve hypertrophy? How do we get proteins into the cells? Degeneration of the myonucleus - Can activate the satellite cells as if the cell is undergoing repair; the nuclei within the cells becomes more active, produces more RNA and the cells get bigger.)

3. Fibre type shift - Discuss an experiment on fiber type shift that has been induced by chronic low frequency stimulation - Martins et al. 2006

====b) Assessment====
''Q1. (a) Provide a one sentence definition of a muscle satellite cell.''

Satellite cells are quiescent stem cells present in adult muscle tissue between the basal lamina of a muscle fiber and are responsible for postnatal hypertrophy and regeneration. <ref><pubmed>16243526</pubmed></ref>

''Q1. (b) In one paragraph, briefly discuss two examples of when satellite cells are activated?''

These cells are normally quiescent in adult muscle, by are activated in response to injury and muscle disease. When activated, the cells begin to proliferate and after aligning they fuse to allow for repair and/or regenration of muscle fibres. Satellite cells assist in the regeneration of muscle tissues in response to muscle injury by either forming multinucleated myotubes or additional quiescent satellite cells. <ref><pubmed>21849021</pubmed></ref>. Furthermore, studies have provided evidence of an increased level of satellite cells in muscular diseases such as Duchenne muscular dystrophy (DMD). <ref><pubmed>16818602</pubmed></ref>

''Q2. In one brief paragraph, describe what happens to skeletal muscle fibre type and size when the innervating motor nerve sustains long term damage such as in spinal cord injury?''

Spinal cord injuries which lead to long term damage to the innervating motor nerve would result in muscle partial or complete paralysis of muscles, leading to muscle atrophy. <ref><pubmed>16940987</pubmed></ref> This results in a significant decrease in cross-sectional area of the immobilized muscle do to lack of use. <ref><pubmed>10483809</pubmed></ref> Another consequence of the decreased muscle mass is an increased level of connective tissues and fat in order to assist the transfer of forces to the tendons.<ref><pubmed>15303112</pubmed></ref> Furthermore, the composition of muscle fibre types are transformed from a mix of type I and type II fibres to predominantly type II (fast twitch) muscle fibres. <ref name="PMID9755066"><pubmed>9755066</pubmed></ref> This is a result of the muscle no longer being used for endurance-type excersises.

=== Lab 8 - Peer Reviews ===

==== Group 1====
Group Assessment Criteria:
# ''The key points relating to the topic that your group was allocated are clearly described'' The introduction explains why the eye is important and lists the anatomical structures, however there is no indication that this project page is about the development of the eye!
# ''The choice of content, headings and sub-headings, diagrams, tables, graphs show a good understanding of the topic area''. The project predominantly focuses on the development of the eye, and goes into detail the development of each individual structure. There are also a lot of student-drawn images and diagrams of developmental stages which shows a good understanding of the topic area.
# ''Content is correctly cited and referenced''. There is no copyright notices for any of the images and they all lack explanations.
# ''The wiki has an element of teaching at a peer level using the student’s own innovative diagrams, tables or figures and/or using interesting examples or explanations''. The text is easy to understand and there are many student-drawn diagrams, which makes the content more interesting to read.
# ''Evidence of significant research relating to basic and applied sciences that goes beyond the formal teaching activities''. I would say the information provided satisfies the aims of the project, however the research does not go ‘beyond the formal teaching activities’ as it lacks additional information such as abnormalities, normal functioning etc.
# ''Relates the topics and content of the Wiki entry to learning aims of embryology.'' The contents and topics are strongly related to the learning aims of embryology.
# ''The content of the wiki should demonstrate to the reader that your group has researched adequately on this topic and covered the key areas necessary to inform your peers in their learning.'' All the content provided is well researched and relevant to the aims of the project. They key areas are well described.

Additional points:
* I feel that this page would benefit from a timeline or ‘weekly development’ table that briefly describes what structures are developed in each week. This would provide a good summary of the content as well as allow reader to be able to understand how the development of each structure relates to each other.
* Good referencing of images throughout project page – relating images to content
* Less paragraphs, more tables, bullet points, emphasize certain important points
* History & research sections look incomplete.

====Group 2====
Group Assessment Criteria:
# ''The key points relating to the topic that your group was allocated are clearly described.'' The introduction outlines the importance of the somatosensory system and provides a good summary of the developmental stages. More emphasis could be made on the key points of the project page.
# ''The choice of content, headings and sub-headings, diagrams, tables, graphs show a good understanding of the topic area.'' The content shows an understanding of the topic area, however the layout makes the text difficult to follow. There is not a clear connection between the ‘Central Somatosensory Differentiation’ and the somatosensory system. There is a lack of diagrams, tables and graphs to explain the written content.
# ''Content is correctly cited and referenced.'' Some sections are correctly referenced whilst others are completely lacking. This area needs working on.
# ''The wiki has an element of teaching at a peer level using the student’s own innovative diagrams, tables or figures and/or using interesting examples or explanations.'' The information is broken down well by headings and subheadings, however there is a lack of relating images to compliment the information. The one student drawn image is very useful.
# ''Evidence of significant research relating to basic and applied sciences that goes beyond the formal teaching activities.'' The information provided is well researched and satisfies the aims of the project in terms of developmental stages, however in order to go ‘beyond the formal teaching activities’ it needs to include sections such as abnormal development and more on the history, current and future research.
# ''Relates the topics and content of the Wiki entry to learning aims of embryology.'' The topics and content relate to the learning aims of embryology by describing the developmental stages if the somatosensory cortex.
# ''The content of the wiki should demonstrate to the reader that your group has researched adequately on this topic and covered the key areas necessary to inform your peers in their learning.'' There has been a fair amount of research into the topic, however a bulk of the information is focused on descriptions of each of the senses. More emphasis should be placed on the development of each of these sense as that is the key topic area.

Additional points:
* The Introduction and Central Somatosensory Differentiation sections were well written and the accompanying diagram was very useful.
* The layout of the page could be improved with the use of tables and diagrams to reduce/replace the amount of text
* The project seems largely incomplete; more research needs to go into the History and research sections and there is a lack of images

==== Group 4 ====
* '''Introduction''': The information is very interesting and provides a good overview of the olfactory system. The only improvement that could be made is clearly stating what content is going to be covered on this project page. Also, “The olfactory system are often '''divide''' into a peripheral mechanism”
* '''History of Discovery''': This sections presents a good summary of each research paper, detailing a background of the researchers and the importance of each discovery. Well done!
* '''Time line of developmental process''': This section shows a good depth of research and provides detailed descriptions of each stage of development. However, the information provided is quite complicated and would not be easily understood by peers. This could be overcome by the use of labeled diagrams or hand drawn images, which I can see is yet to come. Overall this is a well done section, the colors draw the readers attention and I like the use of bolded text to highlight important information.
* '''Anatomy of the Olfactory System & Normal Function''': This provides a good amount of information seeing as the focus of the page is about olfactory development, not the function & final structure. The only improvement could be providing an explanation in the figure provided.
* '''Congenital Abnormalities''': This section is well organized and includes all relevant content. Very interesting to read.
* '''Current Research''': A well researched section and coverage of content. Each paper is summarized and the importance of each discovery is made clear. It would be nice to include a direct link to each article.

====Group 5 ====
*'''Introduction:''' The introduction is quite well written and very detailed. Rather than going straight into details of development, perhaps first make it clear from the exactly what this project page is about and what content you will be covering. There are also some grammatical errors, such as “treatments or cures ‘’’maybe’’’ developed in the future and these conditions can be better managed.” Maybe = may be
* '''Normal eye development:''' This section shows a good depth of research, is strongly related to the aims of the embryology course and shows a good depth of research. Improvements could be made by the use of bullet points, tables or bold text to highlight key points. Also, labeled images or hand-drawn diagrams would go well to compliment the text.
* '''Abnormal Development:''' There is a good depth of research and it is well written. The use of headings, figures and italics makes it easy to follow the flow of information. Improvements could be made by providing more information about the diseases, for example, what is Peters' anomaly (Corneal Opacity) and aniridia (lack of Iris)? Is it curable? What are methods of detection? How will it effect the future baby?
*'''Ocular Manifestations:''' This section seems incomplete; or maybe its just poorly organized? What are the two separate sections? Is this related to the sections that follow?
* '''Research Time line:''' This is a good time line, however only one source has been used. This provides a good summary of significant discoveries, but it has not been explained why these discoveries were important or how it is relevant to the development of the eye.
* '''New Research Development:''' This section is well researched, however the poor structuring and layout of the information makes it difficult to read and follow. For example there are many headings and subheadings however it is unclear what sections of information are grouped together. The images draw the readers attention and there seems to be a good depth of research into the topic.
*'''Group Assessment Criteria:''' The key points relating to the topic that your group was allocated are clearly described in the introduction. The choice of content and depth of research shows a good understanding of the topic area, however the information could be better organized by the use of tables, bullet points and bolded text to highlight key points. The content is correctly cited and referenced. Most sections are well paraphrased for teaching at a peer level, however the use of hand-drawn diagrams and/or labeled images could enhance the information in the text. The information covered is strongly related the the learning aims of embryology.

====Group 6====
Group Assessment Criteria:
# ''The key points relating to the topic that your group was allocated are clearly described.'' The introduction clearly outlines the key points of the project and the content is well described in the text.
# ''The choice of content, headings and sub-headings, diagrams, tables, graphs show a good understanding of the topic area.'' The choice of content and headings shows a good depth of research and understanding of the topic area. The ‘Summary of the inner ear’ table was a good idea and ties in all the information nicely.
# ''Content is correctly cited and referenced.'' There are large paragraphs of texts that have no references. The images provided display the copyright notices and explanations.
# ''The wiki has an element of teaching at a peer level using the student’s own innovative diagrams, tables or figures and/or using interesting examples or explanations.'' The introduction is well written and catches the readers interest and attention. Most of the normal development section is easy to understand, however the abnormalities section is difficult to understand due to the scientific jargon. Some hand-drawn images and tables would be beneficial in order to reduce the large paragraphs of text.
# ''Evidence of significant research relating to basic and applied sciences that goes beyond the formal teaching activities.'' The amount of information provided is evidence of the significant research that went into this project, and the sections such as ‘Technologies to overcome the problems’ shows research that goes ‘beyond the formal teaching activities’.
# ''Relates the topics and content of the Wiki entry to learning aims of embryology.'' The topics and content are well related to the learning aims of embryology
# ''The content of the wiki should demonstrate to the reader that your group has researched adequately on this topic and covered the key areas necessary to inform your peers in their learning.'' All the content is relevant to the key areas of the development of the eye and demonstrates an extensive amount of research into the topic.

Additional points:
* The amount of text is overwhelming. You should make better use of tables, figures and diagrams to breakup/replace the text.
* Adult anatomy and histology: no reference to histology. Would be beneficial to have a brief explanation of the functions of each structure.
* Overall impression: Very well researched topic and I'm sure the use of tables, pictures and diagrams will make it more appealing to read!

=== Lab 9 ===

''Q1. Identify and write a brief description of the findings of a recent research paper on development of one of the endocrine organs covered in today's practical.''

====Development of the Pancreas====

This study aimed to determine the functional role of the SOX9 transcription factor in the process of pancreas development in humans. In mice, the SOX9 has been shown to support endocrine cell differentiation, and it is known that the transition of pancreatic progenitor cells to mature endocrine cells are regulated by the sequential activation and interaction of several transcription factors. The study characterized SOX9 expression during human fetal pancreas development by transfection with SOX9 siRNA or SOX9 expression vectors. The results indicated that SOX9 is important for the expression of NGN3 and molecular markers of endocrine cell differentiation in the human fetal pancreas.

[http://www.sciencedirect.com/science/article/pii/S1357272511002603 SOX9 regulates endocrine cell differentiation during human fetal pancreas development] <ref><pubmed>21983268</pubmed></ref>

''Q2. Identify the embryonic layers and tissues that contribute to the developing teeth.''

# '''Ectoderm''' from the first pharyngeal arch contributes the the '''enamel''' of the tooth. Furthermore, some cells of the oral epithelium differenciate into amnioblasts, which further contribute to the production of enamel.
# '''Neural crest''' gives rise to the '''dental papilla''' of the tooth, as well as various cell types (ondoblasts, cementoblasts, osteoblasts and fibroblasts).
# '''Mesoderm''' contributes to '''cells''' associated with the tooth, including: cementoblasts, osteoblasts and fibroblasts.

[http://www.ncbi.nlm.nih.gov/pubmed/21425080 Contribution of mesoderm to the developing dental papilla.]<ref><pubmed>21425080</pubmed></ref>

==References==

<references/>

User:Z3289738

2012-10-16T23:36:48Z

Z3289738: /* Lab Attendance */

==Lab Attendance==
Lab 1: --[[User:Z3289738|Z3289738]] 11:49, 25 July 2012 (EST)

Lab 2: --[[User:Z3289738|Z3289738]] 10:12, 1 August 2012 (EST)

Lab 3: --[[User:Z3289738|Z3289738]] 10:08, 8 August 2012 (EST)

Lab 4: --[[User:Z3289738|Z3289738]] 10:20, 15 August 2012 (EST)

Lab 5: --[[User:Z3289738|Z3289738]] 10:13, 22 August 2012 (EST)

Lab 6: --[[User:Z3289738|Z3289738]] 10:16, 29 August 2012 (EST)

Lab 7: --[[User:Z3289738|Z3289738]] 10:27, 12 September 2012 (EST)

Lab 8: --[[User:Z3289738|Z3289738]] 10:30, 19 September 2012 (EST)

Lab 9: --[[User:Z3289738|Z3289738]] 10:08, 26 September 2012 (EST)

Lab 10: --[[User:Z3289738|Z3289738]] 11:18, 3 October 2012 (EST)

Lab 12: --[[User:Z3289738|Z3289738]] 10:36, 17 October 2012 (EST)

==Individual Assessments==
===Lab 1 Assessment===

''Q1. Identify the origin of In Vitro Fertilization and the 2010 nobel prize winner associated with this technique and add a correctly formatted link to the Nobel page.''

The idea of In Vitro Fertilization began to formulate in the 1890s, when Walter Heape reported the first known case of embryo transplantation in rabbits. In 1953 John Rock extracted the first intact human fertilized egg. The first successful attempt at IVF was in 1978 by Steptoe and Edward.

Robert G. Edwards, the physiologist who developed the In Vitro Fertilization treatment, was awarded the Nobel Prize in Physiology or Medicine in 2010. [http://www.nobelprize.org/nobel_prizes/medicine/laureates/2010/press.html/# Nobel Prize Page]

''Q2. Identify and add a PubMed reference link to a recent paper on fertilization and describe its key findings (1-2 paragraphs).''

This article looks into the process of embryo implantation. It demonstrates how the activation of the epithelial Na(+) channel triggers prostoglandin E(2) release,phosphorylation of teh transcription factor CREB and upregulation of cyclooxygenase 2, the enzyme required for prostaglandin production and implantation. They detected maximum Epithelial Na(+) channel activation at the time of implantation in mice, and that blocking or knocking down this channel in mice resulted in failure to implant. These results indicate the importance of the Epithelial Na(+) Channel in the process of implantation, and the consequences of defects such as miscarriage and low success rates in IVF.

<pubmed> 22729284</pubmed>

===Lab 2 Assessment===
''Q1. Upload an image from a journal source relating to fertilization or the first 2 weeks of development as demonstrated in the practical class. Including in the image “Summary” window: An image name as a section heading, Any further description of what the image shows, A subsection labeled “Reference” and under this the original image source, appropriate reference and all copyright information and finally a template indicating that this is a student image.

[[File:Z3289738 ANAT Lab 2.jpg|200px|thumb|right|Zygotes showing different distribution of NPB in the 2PN and different PB aligment]]

''Q2. Identify a protein associated with the implantation process, including a brief description of the protein's role (1-2 paragraphs)''

'''Trophinin'''

Trophinin is an membrane adhesive protein expressed on human trophoblastic cells and on uterine endometrium epithelial cells. The protein mediates apical cell adhesion and activate trophectoderm cells for implantation via proliferation and invasion. <ref><pubmed>17487845</pubmed></ref>

===Lab 3 Assessment===

''Q1. Identify the difference between "gestational age" and "post-fertilisation age" and explain why clinically "gestational age" is used in describing human development.''

"Gestational age" is measured from the first day of the woman's last menstrual cycle, whereas "post-fertilisation age" measures the time passed since fertilization of the oocyte. Gestational age is more clinically relevant as it is easier to determine the date of the woman's last menstrual cycle than it is to determine the date of fertilization. Furthermore, gestational age can also be determined before and after birth by measuring the size of the head, thigh bone and abdomen (before birth), and the size of the head and weight after birth. Gestational age is therefore used to determine the infant's medical history and medical plan.

''Q2. Identify using histological descriptions at least 3 different types of tissues formed from somites.''

Somites differentiate to form: (1) '''the axial skeleton (vertebral body & inter-vertebral disk)''', (2) '''dermis''' and (3) '''skeletal muscle'''.

# Cells in the ventromedial half of each somite differentiate into the sclerotome via Sonic hedgehog signalling mechanisms. The Pax 1 transcription factor then converts the sclerotome into chondrocytes (cartilage), which is essential for the functioning of the vertebral column.
# Cells in the dorsolateral portion of the somites differentiate to form the dermomyotone. This is then divided into:
## Dorsal dermatome which later contributes to the formation of the dermis in response to neutropin 3 factors.
## Wnt1 and Wnt3 factors contribute to the formation of the ventral myotome, which is further split into the epaxial myotome (gives rise to erector spinae muscles) and the hypaxial myotome (gives rise to the muscles of the trunk and limbs).

===Lab 4 Assessment===

''Q1. Identify the 2 invasive prenatal diagnostic techniques related to the placenta and 2 abnormalities that can be identified with these techniques.''
# '''Chorionic villus sampling''' (CVS)is an invasive prenatal diagnostic technique that is used to detect genetic abnormalities such as Down syndrome or cystic fibrosis. During the procedure a sample of the placenta is removed via a needle through the abdomen and then examined in a laboratory. It is commonly performed between 10 and 12 weeks of pregnancy/
# '''Amniocentesis''' procedures involve collecting samples of amniotic fluid via a needle through the abdomen to check for genetic abnormalities such as Down syndrome, cystic fibrosis or spina bifida.

''Q2. Identify a paper that uses cord stem cells therapeutically and write a brief (2-3 paragraph) description of the paper's findings.''

F. Ramirez, D. Steenblock, A. Payne and L. Darnall (2006) '''Umbilical Cord Stem Cell Therapy for Cerebral Palsy'''. MED HYPOTHESES RES 3: 679-686 [http://www.journal-mhr.com/PDF_Files/vol_3_2/3_2_PDFs/3_2_2.pdf | Umbilical Cord Stem Cell Therapy for Cerebral Palsy]

This article describes a six month study to evaluate the effectiveness of umbilical cord stem cells in treatment for various brain injuries and disorders, in particular Cerebral Palsy. The study began in 2004, whereby 8 children between the ages of 3-12 who had been diagnosed with Cerebral Palsy underwent transplants with 1.5 million umbilical cord stem cells. The study reported eight of of eight children showed some improvement in mobility and/or cognitive function. Furthermore, one aphasic child started talking again and another who had been blind since birth was able to see after post-treatment.

The results from this preliminary observational pilot study suggests that umbilical cord stem cells may be a safe and promising treatment for children with cerebral palsy.

===Lab 7===
====a) Class exercises====
1. Maturation Hypertrophy - In your groups, design a method to estimate the degree of hypertrophy that occurs during the transition from birth to adulthood. Use the rulers to make rough measurements on the screen and then estimate the degree of hypertrophy as a mean increase in fibre size. Discuss the result as a class. (ie Try estimate the degree of hypertrophy from child to adult cells)

Method: Measured area of the child and adult cells, found an average for each and then worked out the percentage increase.

Answer: 7x increase in area size.

2. The role of satellite cells in muscle hypertrophy - class discussion of data presented in a recent paper - McCarthy et al. 2011. (ie How to we achieve hypertrophy? How do we get proteins into the cells? Degeneration of the myonucleus - Can activate the satellite cells as if the cell is undergoing repair; the nuclei within the cells becomes more active, produces more RNA and the cells get bigger.)

3. Fibre type shift - Discuss an experiment on fiber type shift that has been induced by chronic low frequency stimulation - Martins et al. 2006

====b) Assessment====
''Q1. (a) Provide a one sentence definition of a muscle satellite cell.''

Satellite cells are quiescent stem cells present in adult muscle tissue between the basal lamina of a muscle fiber and are responsible for postnatal hypertrophy and regeneration. <ref><pubmed>16243526</pubmed></ref>

''Q1. (b) In one paragraph, briefly discuss two examples of when satellite cells are activated?''

These cells are normally quiescent in adult muscle, by are activated in response to injury and muscle disease. When activated, the cells begin to proliferate and after aligning they fuse to allow for repair and/or regenration of muscle fibres. Satellite cells assist in the regeneration of muscle tissues in response to muscle injury by either forming multinucleated myotubes or additional quiescent satellite cells. <ref><pubmed>21849021</pubmed></ref>. Furthermore, studies have provided evidence of an increased level of satellite cells in muscular diseases such as Duchenne muscular dystrophy (DMD). <ref><pubmed>16818602</pubmed></ref>

''Q2. In one brief paragraph, describe what happens to skeletal muscle fibre type and size when the innervating motor nerve sustains long term damage such as in spinal cord injury?''

Spinal cord injuries which lead to long term damage to the innervating motor nerve would result in muscle partial or complete paralysis of muscles, leading to muscle atrophy. <ref><pubmed>16940987</pubmed></ref> This results in a significant decrease in cross-sectional area of the immobilized muscle do to lack of use. <ref><pubmed>10483809</pubmed></ref> Another consequence of the decreased muscle mass is an increased level of connective tissues and fat in order to assist the transfer of forces to the tendons.<ref><pubmed>15303112</pubmed></ref> Furthermore, the composition of muscle fibre types are transformed from a mix of type I and type II fibres to predominantly type II (fast twitch) muscle fibres. <ref name="PMID9755066"><pubmed>9755066</pubmed></ref> This is a result of the muscle no longer being used for endurance-type excersises.

=== Lab 8 - Peer Reviews ===

==== Group 1====
Group Assessment Criteria:
# ''The key points relating to the topic that your group was allocated are clearly described'' The introduction explains why the eye is important and lists the anatomical structures, however there is no indication that this project page is about the development of the eye!
# ''The choice of content, headings and sub-headings, diagrams, tables, graphs show a good understanding of the topic area''. The project predominantly focuses on the development of the eye, and goes into detail the development of each individual structure. There are also a lot of student-drawn images and diagrams of developmental stages which shows a good understanding of the topic area.
# ''Content is correctly cited and referenced''. There is no copyright notices for any of the images and they all lack explanations.
# ''The wiki has an element of teaching at a peer level using the student’s own innovative diagrams, tables or figures and/or using interesting examples or explanations''. The text is easy to understand and there are many student-drawn diagrams, which makes the content more interesting to read.
# ''Evidence of significant research relating to basic and applied sciences that goes beyond the formal teaching activities''. I would say the information provided satisfies the aims of the project, however the research does not go ‘beyond the formal teaching activities’ as it lacks additional information such as abnormalities, normal functioning etc.
# ''Relates the topics and content of the Wiki entry to learning aims of embryology.'' The contents and topics are strongly related to the learning aims of embryology.
# ''The content of the wiki should demonstrate to the reader that your group has researched adequately on this topic and covered the key areas necessary to inform your peers in their learning.'' All the content provided is well researched and relevant to the aims of the project. They key areas are well described.

Additional points:
* I feel that this page would benefit from a timeline or ‘weekly development’ table that briefly describes what structures are developed in each week. This would provide a good summary of the content as well as allow reader to be able to understand how the development of each structure relates to each other.
* Good referencing of images throughout project page – relating images to content
* Less paragraphs, more tables, bullet points, emphasize certain important points
* History & research sections look incomplete.

====Group 2====
Group Assessment Criteria:
# ''The key points relating to the topic that your group was allocated are clearly described.'' The introduction outlines the importance of the somatosensory system and provides a good summary of the developmental stages. More emphasis could be made on the key points of the project page.
# ''The choice of content, headings and sub-headings, diagrams, tables, graphs show a good understanding of the topic area.'' The content shows an understanding of the topic area, however the layout makes the text difficult to follow. There is not a clear connection between the ‘Central Somatosensory Differentiation’ and the somatosensory system. There is a lack of diagrams, tables and graphs to explain the written content.
# ''Content is correctly cited and referenced.'' Some sections are correctly referenced whilst others are completely lacking. This area needs working on.
# ''The wiki has an element of teaching at a peer level using the student’s own innovative diagrams, tables or figures and/or using interesting examples or explanations.'' The information is broken down well by headings and subheadings, however there is a lack of relating images to compliment the information. The one student drawn image is very useful.
# ''Evidence of significant research relating to basic and applied sciences that goes beyond the formal teaching activities.'' The information provided is well researched and satisfies the aims of the project in terms of developmental stages, however in order to go ‘beyond the formal teaching activities’ it needs to include sections such as abnormal development and more on the history, current and future research.
# ''Relates the topics and content of the Wiki entry to learning aims of embryology.'' The topics and content relate to the learning aims of embryology by describing the developmental stages if the somatosensory cortex.
# ''The content of the wiki should demonstrate to the reader that your group has researched adequately on this topic and covered the key areas necessary to inform your peers in their learning.'' There has been a fair amount of research into the topic, however a bulk of the information is focused on descriptions of each of the senses. More emphasis should be placed on the development of each of these sense as that is the key topic area.

Additional points:
* The Introduction and Central Somatosensory Differentiation sections were well written and the accompanying diagram was very useful.
* The layout of the page could be improved with the use of tables and diagrams to reduce/replace the amount of text
* The project seems largely incomplete; more research needs to go into the History and research sections and there is a lack of images

==== Group 4 ====
* '''Introduction''': The information is very interesting and provides a good overview of the olfactory system. The only improvement that could be made is clearly stating what content is going to be covered on this project page. Also, “The olfactory system are often '''divide''' into a peripheral mechanism”
* '''History of Discovery''': This sections presents a good summary of each research paper, detailing a background of the researchers and the importance of each discovery. Well done!
* '''Time line of developmental process''': This section shows a good depth of research and provides detailed descriptions of each stage of development. However, the information provided is quite complicated and would not be easily understood by peers. This could be overcome by the use of labeled diagrams or hand drawn images, which I can see is yet to come. Overall this is a well done section, the colors draw the readers attention and I like the use of bolded text to highlight important information.
* '''Anatomy of the Olfactory System & Normal Function''': This provides a good amount of information seeing as the focus of the page is about olfactory development, not the function & final structure. The only improvement could be providing an explanation in the figure provided.
* '''Congenital Abnormalities''': This section is well organized and includes all relevant content. Very interesting to read.
* '''Current Research''': A well researched section and coverage of content. Each paper is summarized and the importance of each discovery is made clear. It would be nice to include a direct link to each article.

====Group 5 ====
*'''Introduction:''' The introduction is quite well written and very detailed. Rather than going straight into details of development, perhaps first make it clear from the exactly what this project page is about and what content you will be covering. There are also some grammatical errors, such as “treatments or cures ‘’’maybe’’’ developed in the future and these conditions can be better managed.” Maybe = may be
* '''Normal eye development:''' This section shows a good depth of research, is strongly related to the aims of the embryology course and shows a good depth of research. Improvements could be made by the use of bullet points, tables or bold text to highlight key points. Also, labeled images or hand-drawn diagrams would go well to compliment the text.
* '''Abnormal Development:''' There is a good depth of research and it is well written. The use of headings, figures and italics makes it easy to follow the flow of information. Improvements could be made by providing more information about the diseases, for example, what is Peters' anomaly (Corneal Opacity) and aniridia (lack of Iris)? Is it curable? What are methods of detection? How will it effect the future baby?
*'''Ocular Manifestations:''' This section seems incomplete; or maybe its just poorly organized? What are the two separate sections? Is this related to the sections that follow?
* '''Research Time line:''' This is a good time line, however only one source has been used. This provides a good summary of significant discoveries, but it has not been explained why these discoveries were important or how it is relevant to the development of the eye.
* '''New Research Development:''' This section is well researched, however the poor structuring and layout of the information makes it difficult to read and follow. For example there are many headings and subheadings however it is unclear what sections of information are grouped together. The images draw the readers attention and there seems to be a good depth of research into the topic.
*'''Group Assessment Criteria:''' The key points relating to the topic that your group was allocated are clearly described in the introduction. The choice of content and depth of research shows a good understanding of the topic area, however the information could be better organized by the use of tables, bullet points and bolded text to highlight key points. The content is correctly cited and referenced. Most sections are well paraphrased for teaching at a peer level, however the use of hand-drawn diagrams and/or labeled images could enhance the information in the text. The information covered is strongly related the the learning aims of embryology.

====Group 6====
Group Assessment Criteria:
# ''The key points relating to the topic that your group was allocated are clearly described.'' The introduction clearly outlines the key points of the project and the content is well described in the text.
# ''The choice of content, headings and sub-headings, diagrams, tables, graphs show a good understanding of the topic area.'' The choice of content and headings shows a good depth of research and understanding of the topic area. The ‘Summary of the inner ear’ table was a good idea and ties in all the information nicely.
# ''Content is correctly cited and referenced.'' There are large paragraphs of texts that have no references. The images provided display the copyright notices and explanations.
# ''The wiki has an element of teaching at a peer level using the student’s own innovative diagrams, tables or figures and/or using interesting examples or explanations.'' The introduction is well written and catches the readers interest and attention. Most of the normal development section is easy to understand, however the abnormalities section is difficult to understand due to the scientific jargon. Some hand-drawn images and tables would be beneficial in order to reduce the large paragraphs of text.
# ''Evidence of significant research relating to basic and applied sciences that goes beyond the formal teaching activities.'' The amount of information provided is evidence of the significant research that went into this project, and the sections such as ‘Technologies to overcome the problems’ shows research that goes ‘beyond the formal teaching activities’.
# ''Relates the topics and content of the Wiki entry to learning aims of embryology.'' The topics and content are well related to the learning aims of embryology
# ''The content of the wiki should demonstrate to the reader that your group has researched adequately on this topic and covered the key areas necessary to inform your peers in their learning.'' All the content is relevant to the key areas of the development of the eye and demonstrates an extensive amount of research into the topic.

Additional points:
* The amount of text is overwhelming. You should make better use of tables, figures and diagrams to breakup/replace the text.
* Adult anatomy and histology: no reference to histology. Would be beneficial to have a brief explanation of the functions of each structure.
* Overall impression: Very well researched topic and I'm sure the use of tables, pictures and diagrams will make it more appealing to read!

=== Lab 9 ===

''Q1. Identify and write a brief description of the findings of a recent research paper on development of one of the endocrine organs covered in today's practical.''

====Development of the Pancreas====

[http://www.sciencedirect.com/science/article/pii/S1357272511002603 SOX9 regulates endocrine cell differentiation during human fetal pancreas development] <ref><pubmed>21983268</pubmed></ref>

''Q2. Identify the embryonic layers and tissues that contribute to the developing teeth.''

# '''Ectoderm''' from the first pharyngeal arch contributes the the '''enamel''' of the tooth. Furthermore, some cells of the oral epithelium differenciate into amnioblasts, which further contribute to the production of enamel.
# '''Neural crest''' gives rise to the '''dental papilla''' of the tooth, as well as various cell types (ondoblasts, cementoblasts, osteoblasts and fibroblasts).
# '''Mesoderm''' contributes to '''cells''' associated with the tooth, including: cementoblasts, osteoblasts and fibroblasts.

[http://www.ncbi.nlm.nih.gov/pubmed/21425080 Contribution of mesoderm to the developing dental papilla.]<ref><pubmed>21425080</pubmed></ref>

==References==

<references/>

User:Z3289738

2012-10-03T01:58:17Z

Z3289738: /* Lab 9 */

==Lab Attendance==
Lab 1: --[[User:Z3289738|Z3289738]] 11:49, 25 July 2012 (EST)

Lab 2: --[[User:Z3289738|Z3289738]] 10:12, 1 August 2012 (EST)

Lab 3: --[[User:Z3289738|Z3289738]] 10:08, 8 August 2012 (EST)

Lab 4: --[[User:Z3289738|Z3289738]] 10:20, 15 August 2012 (EST)

Lab 5: --[[User:Z3289738|Z3289738]] 10:13, 22 August 2012 (EST)

Lab 6: --[[User:Z3289738|Z3289738]] 10:16, 29 August 2012 (EST)

Lab 7: --[[User:Z3289738|Z3289738]] 10:27, 12 September 2012 (EST)

Lab 8: --[[User:Z3289738|Z3289738]] 10:30, 19 September 2012 (EST)

Lab 9: --[[User:Z3289738|Z3289738]] 10:08, 26 September 2012 (EST)

Lab 9: --[[User:Z3289738|Z3289738]] 11:18, 3 October 2012 (EST)

==Individual Assessments==
===Lab 1 Assessment===

''Q1. Identify the origin of In Vitro Fertilization and the 2010 nobel prize winner associated with this technique and add a correctly formatted link to the Nobel page.''

The idea of In Vitro Fertilization began to formulate in the 1890s, when Walter Heape reported the first known case of embryo transplantation in rabbits. In 1953 John Rock extracted the first intact human fertilized egg. The first successful attempt at IVF was in 1978 by Steptoe and Edward.

Robert G. Edwards, the physiologist who developed the In Vitro Fertilization treatment, was awarded the Nobel Prize in Physiology or Medicine in 2010. [http://www.nobelprize.org/nobel_prizes/medicine/laureates/2010/press.html/# Nobel Prize Page]

''Q2. Identify and add a PubMed reference link to a recent paper on fertilization and describe its key findings (1-2 paragraphs).''

This article looks into the process of embryo implantation. It demonstrates how the activation of the epithelial Na(+) channel triggers prostoglandin E(2) release,phosphorylation of teh transcription factor CREB and upregulation of cyclooxygenase 2, the enzyme required for prostaglandin production and implantation. They detected maximum Epithelial Na(+) channel activation at the time of implantation in mice, and that blocking or knocking down this channel in mice resulted in failure to implant. These results indicate the importance of the Epithelial Na(+) Channel in the process of implantation, and the consequences of defects such as miscarriage and low success rates in IVF.

<pubmed> 22729284</pubmed>

===Lab 2 Assessment===
''Q1. Upload an image from a journal source relating to fertilization or the first 2 weeks of development as demonstrated in the practical class. Including in the image “Summary” window: An image name as a section heading, Any further description of what the image shows, A subsection labeled “Reference” and under this the original image source, appropriate reference and all copyright information and finally a template indicating that this is a student image.

[[File:Z3289738 ANAT Lab 2.jpg|200px|thumb|right|Zygotes showing different distribution of NPB in the 2PN and different PB aligment]]

''Q2. Identify a protein associated with the implantation process, including a brief description of the protein's role (1-2 paragraphs)''

'''Trophinin'''

Trophinin is an membrane adhesive protein expressed on human trophoblastic cells and on uterine endometrium epithelial cells. The protein mediates apical cell adhesion and activate trophectoderm cells for implantation via proliferation and invasion. <ref><pubmed>17487845</pubmed></ref>

===Lab 3 Assessment===

''Q1. Identify the difference between "gestational age" and "post-fertilisation age" and explain why clinically "gestational age" is used in describing human development.''

"Gestational age" is measured from the first day of the woman's last menstrual cycle, whereas "post-fertilisation age" measures the time passed since fertilization of the oocyte. Gestational age is more clinically relevant as it is easier to determine the date of the woman's last menstrual cycle than it is to determine the date of fertilization. Furthermore, gestational age can also be determined before and after birth by measuring the size of the head, thigh bone and abdomen (before birth), and the size of the head and weight after birth. Gestational age is therefore used to determine the infant's medical history and medical plan.

''Q2. Identify using histological descriptions at least 3 different types of tissues formed from somites.''

Somites differentiate to form: (1) '''the axial skeleton (vertebral body & inter-vertebral disk)''', (2) '''dermis''' and (3) '''skeletal muscle'''.

# Cells in the ventromedial half of each somite differentiate into the sclerotome via Sonic hedgehog signalling mechanisms. The Pax 1 transcription factor then converts the sclerotome into chondrocytes (cartilage), which is essential for the functioning of the vertebral column.
# Cells in the dorsolateral portion of the somites differentiate to form the dermomyotone. This is then divided into:
## Dorsal dermatome which later contributes to the formation of the dermis in response to neutropin 3 factors.
## Wnt1 and Wnt3 factors contribute to the formation of the ventral myotome, which is further split into the epaxial myotome (gives rise to erector spinae muscles) and the hypaxial myotome (gives rise to the muscles of the trunk and limbs).

===Lab 4 Assessment===

''Q1. Identify the 2 invasive prenatal diagnostic techniques related to the placenta and 2 abnormalities that can be identified with these techniques.''
# '''Chorionic villus sampling''' (CVS)is an invasive prenatal diagnostic technique that is used to detect genetic abnormalities such as Down syndrome or cystic fibrosis. During the procedure a sample of the placenta is removed via a needle through the abdomen and then examined in a laboratory. It is commonly performed between 10 and 12 weeks of pregnancy/
# '''Amniocentesis''' procedures involve collecting samples of amniotic fluid via a needle through the abdomen to check for genetic abnormalities such as Down syndrome, cystic fibrosis or spina bifida.

''Q2. Identify a paper that uses cord stem cells therapeutically and write a brief (2-3 paragraph) description of the paper's findings.''

F. Ramirez, D. Steenblock, A. Payne and L. Darnall (2006) '''Umbilical Cord Stem Cell Therapy for Cerebral Palsy'''. MED HYPOTHESES RES 3: 679-686 [http://www.journal-mhr.com/PDF_Files/vol_3_2/3_2_PDFs/3_2_2.pdf | Umbilical Cord Stem Cell Therapy for Cerebral Palsy]

This article describes a six month study to evaluate the effectiveness of umbilical cord stem cells in treatment for various brain injuries and disorders, in particular Cerebral Palsy. The study began in 2004, whereby 8 children between the ages of 3-12 who had been diagnosed with Cerebral Palsy underwent transplants with 1.5 million umbilical cord stem cells. The study reported eight of of eight children showed some improvement in mobility and/or cognitive function. Furthermore, one aphasic child started talking again and another who had been blind since birth was able to see after post-treatment.

The results from this preliminary observational pilot study suggests that umbilical cord stem cells may be a safe and promising treatment for children with cerebral palsy.

===Lab 7===
====a) Class exercises====
1. Maturation Hypertrophy - In your groups, design a method to estimate the degree of hypertrophy that occurs during the transition from birth to adulthood. Use the rulers to make rough measurements on the screen and then estimate the degree of hypertrophy as a mean increase in fibre size. Discuss the result as a class. (ie Try estimate the degree of hypertrophy from child to adult cells)

Method: Measured area of the child and adult cells, found an average for each and then worked out the percentage increase.

Answer: 7x increase in area size.

2. The role of satellite cells in muscle hypertrophy - class discussion of data presented in a recent paper - McCarthy et al. 2011. (ie How to we achieve hypertrophy? How do we get proteins into the cells? Degeneration of the myonucleus - Can activate the satellite cells as if the cell is undergoing repair; the nuclei within the cells becomes more active, produces more RNA and the cells get bigger.)

3. Fibre type shift - Discuss an experiment on fiber type shift that has been induced by chronic low frequency stimulation - Martins et al. 2006

====b) Assessment====
''Q1. (a) Provide a one sentence definition of a muscle satellite cell.''

Satellite cells are quiescent stem cells present in adult muscle tissue between the basal lamina of a muscle fiber and are responsible for postnatal hypertrophy and regeneration. <ref><pubmed>16243526</pubmed></ref>

''Q1. (b) In one paragraph, briefly discuss two examples of when satellite cells are activated?''

These cells are normally quiescent in adult muscle, by are activated in response to injury and muscle disease. When activated, the cells begin to proliferate and after aligning they fuse to allow for repair and/or regenration of muscle fibres. Satellite cells assist in the regeneration of muscle tissues in response to muscle injury by either forming multinucleated myotubes or additional quiescent satellite cells. <ref><pubmed>21849021</pubmed></ref>. Furthermore, studies have provided evidence of an increased level of satellite cells in muscular diseases such as Duchenne muscular dystrophy (DMD). <ref><pubmed>16818602</pubmed></ref>

''Q2. In one brief paragraph, describe what happens to skeletal muscle fibre type and size when the innervating motor nerve sustains long term damage such as in spinal cord injury?''

Spinal cord injuries which lead to long term damage to the innervating motor nerve would result in muscle partial or complete paralysis of muscles, leading to muscle atrophy. <ref><pubmed>16940987</pubmed></ref> This results in a significant decrease in cross-sectional area of the immobilized muscle do to lack of use. <ref><pubmed>10483809</pubmed></ref> Another consequence of the decreased muscle mass is an increased level of connective tissues and fat in order to assist the transfer of forces to the tendons.<ref><pubmed>15303112</pubmed></ref> Furthermore, the composition of muscle fibre types are transformed from a mix of type I and type II fibres to predominantly type II (fast twitch) muscle fibres. <ref name="PMID9755066"><pubmed>9755066</pubmed></ref> This is a result of the muscle no longer being used for endurance-type excersises.

=== Lab 8 - Peer Reviews ===

==== Group 1====
Group Assessment Criteria:
# ''The key points relating to the topic that your group was allocated are clearly described'' The introduction explains why the eye is important and lists the anatomical structures, however there is no indication that this project page is about the development of the eye!
# ''The choice of content, headings and sub-headings, diagrams, tables, graphs show a good understanding of the topic area''. The project predominantly focuses on the development of the eye, and goes into detail the development of each individual structure. There are also a lot of student-drawn images and diagrams of developmental stages which shows a good understanding of the topic area.
# ''Content is correctly cited and referenced''. There is no copyright notices for any of the images and they all lack explanations.
# ''The wiki has an element of teaching at a peer level using the student’s own innovative diagrams, tables or figures and/or using interesting examples or explanations''. The text is easy to understand and there are many student-drawn diagrams, which makes the content more interesting to read.
# ''Evidence of significant research relating to basic and applied sciences that goes beyond the formal teaching activities''. I would say the information provided satisfies the aims of the project, however the research does not go ‘beyond the formal teaching activities’ as it lacks additional information such as abnormalities, normal functioning etc.
# ''Relates the topics and content of the Wiki entry to learning aims of embryology.'' The contents and topics are strongly related to the learning aims of embryology.
# ''The content of the wiki should demonstrate to the reader that your group has researched adequately on this topic and covered the key areas necessary to inform your peers in their learning.'' All the content provided is well researched and relevant to the aims of the project. They key areas are well described.

Additional points:
* I feel that this page would benefit from a timeline or ‘weekly development’ table that briefly describes what structures are developed in each week. This would provide a good summary of the content as well as allow reader to be able to understand how the development of each structure relates to each other.
* Good referencing of images throughout project page – relating images to content
* Less paragraphs, more tables, bullet points, emphasize certain important points
* History & research sections look incomplete.

====Group 2====
Group Assessment Criteria:
# ''The key points relating to the topic that your group was allocated are clearly described.'' The introduction outlines the importance of the somatosensory system and provides a good summary of the developmental stages. More emphasis could be made on the key points of the project page.
# ''The choice of content, headings and sub-headings, diagrams, tables, graphs show a good understanding of the topic area.'' The content shows an understanding of the topic area, however the layout makes the text difficult to follow. There is not a clear connection between the ‘Central Somatosensory Differentiation’ and the somatosensory system. There is a lack of diagrams, tables and graphs to explain the written content.
# ''Content is correctly cited and referenced.'' Some sections are correctly referenced whilst others are completely lacking. This area needs working on.
# ''The wiki has an element of teaching at a peer level using the student’s own innovative diagrams, tables or figures and/or using interesting examples or explanations.'' The information is broken down well by headings and subheadings, however there is a lack of relating images to compliment the information. The one student drawn image is very useful.
# ''Evidence of significant research relating to basic and applied sciences that goes beyond the formal teaching activities.'' The information provided is well researched and satisfies the aims of the project in terms of developmental stages, however in order to go ‘beyond the formal teaching activities’ it needs to include sections such as abnormal development and more on the history, current and future research.
# ''Relates the topics and content of the Wiki entry to learning aims of embryology.'' The topics and content relate to the learning aims of embryology by describing the developmental stages if the somatosensory cortex.
# ''The content of the wiki should demonstrate to the reader that your group has researched adequately on this topic and covered the key areas necessary to inform your peers in their learning.'' There has been a fair amount of research into the topic, however a bulk of the information is focused on descriptions of each of the senses. More emphasis should be placed on the development of each of these sense as that is the key topic area.

Additional points:
* The Introduction and Central Somatosensory Differentiation sections were well written and the accompanying diagram was very useful.
* The layout of the page could be improved with the use of tables and diagrams to reduce/replace the amount of text
* The project seems largely incomplete; more research needs to go into the History and research sections and there is a lack of images

==== Group 4 ====
* '''Introduction''': The information is very interesting and provides a good overview of the olfactory system. The only improvement that could be made is clearly stating what content is going to be covered on this project page. Also, “The olfactory system are often '''divide''' into a peripheral mechanism”
* '''History of Discovery''': This sections presents a good summary of each research paper, detailing a background of the researchers and the importance of each discovery. Well done!
* '''Time line of developmental process''': This section shows a good depth of research and provides detailed descriptions of each stage of development. However, the information provided is quite complicated and would not be easily understood by peers. This could be overcome by the use of labeled diagrams or hand drawn images, which I can see is yet to come. Overall this is a well done section, the colors draw the readers attention and I like the use of bolded text to highlight important information.
* '''Anatomy of the Olfactory System & Normal Function''': This provides a good amount of information seeing as the focus of the page is about olfactory development, not the function & final structure. The only improvement could be providing an explanation in the figure provided.
* '''Congenital Abnormalities''': This section is well organized and includes all relevant content. Very interesting to read.
* '''Current Research''': A well researched section and coverage of content. Each paper is summarized and the importance of each discovery is made clear. It would be nice to include a direct link to each article.

====Group 5 ====
*'''Introduction:''' The introduction is quite well written and very detailed. Rather than going straight into details of development, perhaps first make it clear from the exactly what this project page is about and what content you will be covering. There are also some grammatical errors, such as “treatments or cures ‘’’maybe’’’ developed in the future and these conditions can be better managed.” Maybe = may be
* '''Normal eye development:''' This section shows a good depth of research, is strongly related to the aims of the embryology course and shows a good depth of research. Improvements could be made by the use of bullet points, tables or bold text to highlight key points. Also, labeled images or hand-drawn diagrams would go well to compliment the text.
* '''Abnormal Development:''' There is a good depth of research and it is well written. The use of headings, figures and italics makes it easy to follow the flow of information. Improvements could be made by providing more information about the diseases, for example, what is Peters' anomaly (Corneal Opacity) and aniridia (lack of Iris)? Is it curable? What are methods of detection? How will it effect the future baby?
*'''Ocular Manifestations:''' This section seems incomplete; or maybe its just poorly organized? What are the two separate sections? Is this related to the sections that follow?
* '''Research Time line:''' This is a good time line, however only one source has been used. This provides a good summary of significant discoveries, but it has not been explained why these discoveries were important or how it is relevant to the development of the eye.
* '''New Research Development:''' This section is well researched, however the poor structuring and layout of the information makes it difficult to read and follow. For example there are many headings and subheadings however it is unclear what sections of information are grouped together. The images draw the readers attention and there seems to be a good depth of research into the topic.
*'''Group Assessment Criteria:''' The key points relating to the topic that your group was allocated are clearly described in the introduction. The choice of content and depth of research shows a good understanding of the topic area, however the information could be better organized by the use of tables, bullet points and bolded text to highlight key points. The content is correctly cited and referenced. Most sections are well paraphrased for teaching at a peer level, however the use of hand-drawn diagrams and/or labeled images could enhance the information in the text. The information covered is strongly related the the learning aims of embryology.

====Group 6====
Group Assessment Criteria:
# ''The key points relating to the topic that your group was allocated are clearly described.'' The introduction clearly outlines the key points of the project and the content is well described in the text.
# ''The choice of content, headings and sub-headings, diagrams, tables, graphs show a good understanding of the topic area.'' The choice of content and headings shows a good depth of research and understanding of the topic area. The ‘Summary of the inner ear’ table was a good idea and ties in all the information nicely.
# ''Content is correctly cited and referenced.'' There are large paragraphs of texts that have no references. The images provided display the copyright notices and explanations.
# ''The wiki has an element of teaching at a peer level using the student’s own innovative diagrams, tables or figures and/or using interesting examples or explanations.'' The introduction is well written and catches the readers interest and attention. Most of the normal development section is easy to understand, however the abnormalities section is difficult to understand due to the scientific jargon. Some hand-drawn images and tables would be beneficial in order to reduce the large paragraphs of text.
# ''Evidence of significant research relating to basic and applied sciences that goes beyond the formal teaching activities.'' The amount of information provided is evidence of the significant research that went into this project, and the sections such as ‘Technologies to overcome the problems’ shows research that goes ‘beyond the formal teaching activities’.
# ''Relates the topics and content of the Wiki entry to learning aims of embryology.'' The topics and content are well related to the learning aims of embryology
# ''The content of the wiki should demonstrate to the reader that your group has researched adequately on this topic and covered the key areas necessary to inform your peers in their learning.'' All the content is relevant to the key areas of the development of the eye and demonstrates an extensive amount of research into the topic.

Additional points:
* The amount of text is overwhelming. You should make better use of tables, figures and diagrams to breakup/replace the text.
* Adult anatomy and histology: no reference to histology. Would be beneficial to have a brief explanation of the functions of each structure.
* Overall impression: Very well researched topic and I'm sure the use of tables, pictures and diagrams will make it more appealing to read!

=== Lab 9 ===

''Q1. Identify and write a brief description of the findings of a recent research paper on development of one of the endocrine organs covered in today's practical.''

====Development of the Pancreas====

[http://www.sciencedirect.com/science/article/pii/S1357272511002603 SOX9 regulates endocrine cell differentiation during human fetal pancreas development] <ref><pubmed>21983268</pubmed></ref>

''Q2. Identify the embryonic layers and tissues that contribute to the developing teeth.''

# '''Ectoderm''' from the first pharyngeal arch contributes the the '''enamel''' of the tooth. Furthermore, some cells of the oral epithelium differenciate into amnioblasts, which further contribute to the production of enamel.
# '''Neural crest''' gives rise to the '''dental papilla''' of the tooth, as well as various cell types (ondoblasts, cementoblasts, osteoblasts and fibroblasts).
# '''Mesoderm''' contributes to '''cells''' associated with the tooth, including: cementoblasts, osteoblasts and fibroblasts.

[http://www.ncbi.nlm.nih.gov/pubmed/21425080 Contribution of mesoderm to the developing dental papilla.]<ref><pubmed>21425080</pubmed></ref>

==References==

<references/>

User:Z3289738

2012-10-03T01:36:24Z

Z3289738: /* Lab 9 */

==Lab Attendance==
Lab 1: --[[User:Z3289738|Z3289738]] 11:49, 25 July 2012 (EST)

Lab 2: --[[User:Z3289738|Z3289738]] 10:12, 1 August 2012 (EST)

Lab 3: --[[User:Z3289738|Z3289738]] 10:08, 8 August 2012 (EST)

Lab 4: --[[User:Z3289738|Z3289738]] 10:20, 15 August 2012 (EST)

Lab 5: --[[User:Z3289738|Z3289738]] 10:13, 22 August 2012 (EST)

Lab 6: --[[User:Z3289738|Z3289738]] 10:16, 29 August 2012 (EST)

Lab 7: --[[User:Z3289738|Z3289738]] 10:27, 12 September 2012 (EST)

Lab 8: --[[User:Z3289738|Z3289738]] 10:30, 19 September 2012 (EST)

Lab 9: --[[User:Z3289738|Z3289738]] 10:08, 26 September 2012 (EST)

Lab 9: --[[User:Z3289738|Z3289738]] 11:18, 3 October 2012 (EST)

==Individual Assessments==
===Lab 1 Assessment===

''Q1. Identify the origin of In Vitro Fertilization and the 2010 nobel prize winner associated with this technique and add a correctly formatted link to the Nobel page.''

The idea of In Vitro Fertilization began to formulate in the 1890s, when Walter Heape reported the first known case of embryo transplantation in rabbits. In 1953 John Rock extracted the first intact human fertilized egg. The first successful attempt at IVF was in 1978 by Steptoe and Edward.

Robert G. Edwards, the physiologist who developed the In Vitro Fertilization treatment, was awarded the Nobel Prize in Physiology or Medicine in 2010. [http://www.nobelprize.org/nobel_prizes/medicine/laureates/2010/press.html/# Nobel Prize Page]

''Q2. Identify and add a PubMed reference link to a recent paper on fertilization and describe its key findings (1-2 paragraphs).''

This article looks into the process of embryo implantation. It demonstrates how the activation of the epithelial Na(+) channel triggers prostoglandin E(2) release,phosphorylation of teh transcription factor CREB and upregulation of cyclooxygenase 2, the enzyme required for prostaglandin production and implantation. They detected maximum Epithelial Na(+) channel activation at the time of implantation in mice, and that blocking or knocking down this channel in mice resulted in failure to implant. These results indicate the importance of the Epithelial Na(+) Channel in the process of implantation, and the consequences of defects such as miscarriage and low success rates in IVF.

<pubmed> 22729284</pubmed>

===Lab 2 Assessment===
''Q1. Upload an image from a journal source relating to fertilization or the first 2 weeks of development as demonstrated in the practical class. Including in the image “Summary” window: An image name as a section heading, Any further description of what the image shows, A subsection labeled “Reference” and under this the original image source, appropriate reference and all copyright information and finally a template indicating that this is a student image.

[[File:Z3289738 ANAT Lab 2.jpg|200px|thumb|right|Zygotes showing different distribution of NPB in the 2PN and different PB aligment]]

''Q2. Identify a protein associated with the implantation process, including a brief description of the protein's role (1-2 paragraphs)''

'''Trophinin'''

Trophinin is an membrane adhesive protein expressed on human trophoblastic cells and on uterine endometrium epithelial cells. The protein mediates apical cell adhesion and activate trophectoderm cells for implantation via proliferation and invasion. <ref><pubmed>17487845</pubmed></ref>

===Lab 3 Assessment===

''Q1. Identify the difference between "gestational age" and "post-fertilisation age" and explain why clinically "gestational age" is used in describing human development.''

"Gestational age" is measured from the first day of the woman's last menstrual cycle, whereas "post-fertilisation age" measures the time passed since fertilization of the oocyte. Gestational age is more clinically relevant as it is easier to determine the date of the woman's last menstrual cycle than it is to determine the date of fertilization. Furthermore, gestational age can also be determined before and after birth by measuring the size of the head, thigh bone and abdomen (before birth), and the size of the head and weight after birth. Gestational age is therefore used to determine the infant's medical history and medical plan.

''Q2. Identify using histological descriptions at least 3 different types of tissues formed from somites.''

Somites differentiate to form: (1) '''the axial skeleton (vertebral body & inter-vertebral disk)''', (2) '''dermis''' and (3) '''skeletal muscle'''.

# Cells in the ventromedial half of each somite differentiate into the sclerotome via Sonic hedgehog signalling mechanisms. The Pax 1 transcription factor then converts the sclerotome into chondrocytes (cartilage), which is essential for the functioning of the vertebral column.
# Cells in the dorsolateral portion of the somites differentiate to form the dermomyotone. This is then divided into:
## Dorsal dermatome which later contributes to the formation of the dermis in response to neutropin 3 factors.
## Wnt1 and Wnt3 factors contribute to the formation of the ventral myotome, which is further split into the epaxial myotome (gives rise to erector spinae muscles) and the hypaxial myotome (gives rise to the muscles of the trunk and limbs).

===Lab 4 Assessment===

''Q1. Identify the 2 invasive prenatal diagnostic techniques related to the placenta and 2 abnormalities that can be identified with these techniques.''
# '''Chorionic villus sampling''' (CVS)is an invasive prenatal diagnostic technique that is used to detect genetic abnormalities such as Down syndrome or cystic fibrosis. During the procedure a sample of the placenta is removed via a needle through the abdomen and then examined in a laboratory. It is commonly performed between 10 and 12 weeks of pregnancy/
# '''Amniocentesis''' procedures involve collecting samples of amniotic fluid via a needle through the abdomen to check for genetic abnormalities such as Down syndrome, cystic fibrosis or spina bifida.

''Q2. Identify a paper that uses cord stem cells therapeutically and write a brief (2-3 paragraph) description of the paper's findings.''

F. Ramirez, D. Steenblock, A. Payne and L. Darnall (2006) '''Umbilical Cord Stem Cell Therapy for Cerebral Palsy'''. MED HYPOTHESES RES 3: 679-686 [http://www.journal-mhr.com/PDF_Files/vol_3_2/3_2_PDFs/3_2_2.pdf | Umbilical Cord Stem Cell Therapy for Cerebral Palsy]

This article describes a six month study to evaluate the effectiveness of umbilical cord stem cells in treatment for various brain injuries and disorders, in particular Cerebral Palsy. The study began in 2004, whereby 8 children between the ages of 3-12 who had been diagnosed with Cerebral Palsy underwent transplants with 1.5 million umbilical cord stem cells. The study reported eight of of eight children showed some improvement in mobility and/or cognitive function. Furthermore, one aphasic child started talking again and another who had been blind since birth was able to see after post-treatment.

The results from this preliminary observational pilot study suggests that umbilical cord stem cells may be a safe and promising treatment for children with cerebral palsy.

===Lab 7===
====a) Class exercises====
1. Maturation Hypertrophy - In your groups, design a method to estimate the degree of hypertrophy that occurs during the transition from birth to adulthood. Use the rulers to make rough measurements on the screen and then estimate the degree of hypertrophy as a mean increase in fibre size. Discuss the result as a class. (ie Try estimate the degree of hypertrophy from child to adult cells)

Method: Measured area of the child and adult cells, found an average for each and then worked out the percentage increase.

Answer: 7x increase in area size.

2. The role of satellite cells in muscle hypertrophy - class discussion of data presented in a recent paper - McCarthy et al. 2011. (ie How to we achieve hypertrophy? How do we get proteins into the cells? Degeneration of the myonucleus - Can activate the satellite cells as if the cell is undergoing repair; the nuclei within the cells becomes more active, produces more RNA and the cells get bigger.)

3. Fibre type shift - Discuss an experiment on fiber type shift that has been induced by chronic low frequency stimulation - Martins et al. 2006

====b) Assessment====
''Q1. (a) Provide a one sentence definition of a muscle satellite cell.''

Satellite cells are quiescent stem cells present in adult muscle tissue between the basal lamina of a muscle fiber and are responsible for postnatal hypertrophy and regeneration. <ref><pubmed>16243526</pubmed></ref>

''Q1. (b) In one paragraph, briefly discuss two examples of when satellite cells are activated?''

These cells are normally quiescent in adult muscle, by are activated in response to injury and muscle disease. When activated, the cells begin to proliferate and after aligning they fuse to allow for repair and/or regenration of muscle fibres. Satellite cells assist in the regeneration of muscle tissues in response to muscle injury by either forming multinucleated myotubes or additional quiescent satellite cells. <ref><pubmed>21849021</pubmed></ref>. Furthermore, studies have provided evidence of an increased level of satellite cells in muscular diseases such as Duchenne muscular dystrophy (DMD). <ref><pubmed>16818602</pubmed></ref>

''Q2. In one brief paragraph, describe what happens to skeletal muscle fibre type and size when the innervating motor nerve sustains long term damage such as in spinal cord injury?''

Spinal cord injuries which lead to long term damage to the innervating motor nerve would result in muscle partial or complete paralysis of muscles, leading to muscle atrophy. <ref><pubmed>16940987</pubmed></ref> This results in a significant decrease in cross-sectional area of the immobilized muscle do to lack of use. <ref><pubmed>10483809</pubmed></ref> Another consequence of the decreased muscle mass is an increased level of connective tissues and fat in order to assist the transfer of forces to the tendons.<ref><pubmed>15303112</pubmed></ref> Furthermore, the composition of muscle fibre types are transformed from a mix of type I and type II fibres to predominantly type II (fast twitch) muscle fibres. <ref name="PMID9755066"><pubmed>9755066</pubmed></ref> This is a result of the muscle no longer being used for endurance-type excersises.

=== Lab 8 - Peer Reviews ===

==== Group 1====
Group Assessment Criteria:
# ''The key points relating to the topic that your group was allocated are clearly described'' The introduction explains why the eye is important and lists the anatomical structures, however there is no indication that this project page is about the development of the eye!
# ''The choice of content, headings and sub-headings, diagrams, tables, graphs show a good understanding of the topic area''. The project predominantly focuses on the development of the eye, and goes into detail the development of each individual structure. There are also a lot of student-drawn images and diagrams of developmental stages which shows a good understanding of the topic area.
# ''Content is correctly cited and referenced''. There is no copyright notices for any of the images and they all lack explanations.
# ''The wiki has an element of teaching at a peer level using the student’s own innovative diagrams, tables or figures and/or using interesting examples or explanations''. The text is easy to understand and there are many student-drawn diagrams, which makes the content more interesting to read.
# ''Evidence of significant research relating to basic and applied sciences that goes beyond the formal teaching activities''. I would say the information provided satisfies the aims of the project, however the research does not go ‘beyond the formal teaching activities’ as it lacks additional information such as abnormalities, normal functioning etc.
# ''Relates the topics and content of the Wiki entry to learning aims of embryology.'' The contents and topics are strongly related to the learning aims of embryology.
# ''The content of the wiki should demonstrate to the reader that your group has researched adequately on this topic and covered the key areas necessary to inform your peers in their learning.'' All the content provided is well researched and relevant to the aims of the project. They key areas are well described.

Additional points:
* I feel that this page would benefit from a timeline or ‘weekly development’ table that briefly describes what structures are developed in each week. This would provide a good summary of the content as well as allow reader to be able to understand how the development of each structure relates to each other.
* Good referencing of images throughout project page – relating images to content
* Less paragraphs, more tables, bullet points, emphasize certain important points
* History & research sections look incomplete.

====Group 2====
Group Assessment Criteria:
# ''The key points relating to the topic that your group was allocated are clearly described.'' The introduction outlines the importance of the somatosensory system and provides a good summary of the developmental stages. More emphasis could be made on the key points of the project page.
# ''The choice of content, headings and sub-headings, diagrams, tables, graphs show a good understanding of the topic area.'' The content shows an understanding of the topic area, however the layout makes the text difficult to follow. There is not a clear connection between the ‘Central Somatosensory Differentiation’ and the somatosensory system. There is a lack of diagrams, tables and graphs to explain the written content.
# ''Content is correctly cited and referenced.'' Some sections are correctly referenced whilst others are completely lacking. This area needs working on.
# ''The wiki has an element of teaching at a peer level using the student’s own innovative diagrams, tables or figures and/or using interesting examples or explanations.'' The information is broken down well by headings and subheadings, however there is a lack of relating images to compliment the information. The one student drawn image is very useful.
# ''Evidence of significant research relating to basic and applied sciences that goes beyond the formal teaching activities.'' The information provided is well researched and satisfies the aims of the project in terms of developmental stages, however in order to go ‘beyond the formal teaching activities’ it needs to include sections such as abnormal development and more on the history, current and future research.
# ''Relates the topics and content of the Wiki entry to learning aims of embryology.'' The topics and content relate to the learning aims of embryology by describing the developmental stages if the somatosensory cortex.
# ''The content of the wiki should demonstrate to the reader that your group has researched adequately on this topic and covered the key areas necessary to inform your peers in their learning.'' There has been a fair amount of research into the topic, however a bulk of the information is focused on descriptions of each of the senses. More emphasis should be placed on the development of each of these sense as that is the key topic area.

Additional points:
* The Introduction and Central Somatosensory Differentiation sections were well written and the accompanying diagram was very useful.
* The layout of the page could be improved with the use of tables and diagrams to reduce/replace the amount of text
* The project seems largely incomplete; more research needs to go into the History and research sections and there is a lack of images

==== Group 4 ====
* '''Introduction''': The information is very interesting and provides a good overview of the olfactory system. The only improvement that could be made is clearly stating what content is going to be covered on this project page. Also, “The olfactory system are often '''divide''' into a peripheral mechanism”
* '''History of Discovery''': This sections presents a good summary of each research paper, detailing a background of the researchers and the importance of each discovery. Well done!
* '''Time line of developmental process''': This section shows a good depth of research and provides detailed descriptions of each stage of development. However, the information provided is quite complicated and would not be easily understood by peers. This could be overcome by the use of labeled diagrams or hand drawn images, which I can see is yet to come. Overall this is a well done section, the colors draw the readers attention and I like the use of bolded text to highlight important information.
* '''Anatomy of the Olfactory System & Normal Function''': This provides a good amount of information seeing as the focus of the page is about olfactory development, not the function & final structure. The only improvement could be providing an explanation in the figure provided.
* '''Congenital Abnormalities''': This section is well organized and includes all relevant content. Very interesting to read.
* '''Current Research''': A well researched section and coverage of content. Each paper is summarized and the importance of each discovery is made clear. It would be nice to include a direct link to each article.

====Group 5 ====
*'''Introduction:''' The introduction is quite well written and very detailed. Rather than going straight into details of development, perhaps first make it clear from the exactly what this project page is about and what content you will be covering. There are also some grammatical errors, such as “treatments or cures ‘’’maybe’’’ developed in the future and these conditions can be better managed.” Maybe = may be
* '''Normal eye development:''' This section shows a good depth of research, is strongly related to the aims of the embryology course and shows a good depth of research. Improvements could be made by the use of bullet points, tables or bold text to highlight key points. Also, labeled images or hand-drawn diagrams would go well to compliment the text.
* '''Abnormal Development:''' There is a good depth of research and it is well written. The use of headings, figures and italics makes it easy to follow the flow of information. Improvements could be made by providing more information about the diseases, for example, what is Peters' anomaly (Corneal Opacity) and aniridia (lack of Iris)? Is it curable? What are methods of detection? How will it effect the future baby?
*'''Ocular Manifestations:''' This section seems incomplete; or maybe its just poorly organized? What are the two separate sections? Is this related to the sections that follow?
* '''Research Time line:''' This is a good time line, however only one source has been used. This provides a good summary of significant discoveries, but it has not been explained why these discoveries were important or how it is relevant to the development of the eye.
* '''New Research Development:''' This section is well researched, however the poor structuring and layout of the information makes it difficult to read and follow. For example there are many headings and subheadings however it is unclear what sections of information are grouped together. The images draw the readers attention and there seems to be a good depth of research into the topic.
*'''Group Assessment Criteria:''' The key points relating to the topic that your group was allocated are clearly described in the introduction. The choice of content and depth of research shows a good understanding of the topic area, however the information could be better organized by the use of tables, bullet points and bolded text to highlight key points. The content is correctly cited and referenced. Most sections are well paraphrased for teaching at a peer level, however the use of hand-drawn diagrams and/or labeled images could enhance the information in the text. The information covered is strongly related the the learning aims of embryology.

====Group 6====
Group Assessment Criteria:
# ''The key points relating to the topic that your group was allocated are clearly described.'' The introduction clearly outlines the key points of the project and the content is well described in the text.
# ''The choice of content, headings and sub-headings, diagrams, tables, graphs show a good understanding of the topic area.'' The choice of content and headings shows a good depth of research and understanding of the topic area. The ‘Summary of the inner ear’ table was a good idea and ties in all the information nicely.
# ''Content is correctly cited and referenced.'' There are large paragraphs of texts that have no references. The images provided display the copyright notices and explanations.
# ''The wiki has an element of teaching at a peer level using the student’s own innovative diagrams, tables or figures and/or using interesting examples or explanations.'' The introduction is well written and catches the readers interest and attention. Most of the normal development section is easy to understand, however the abnormalities section is difficult to understand due to the scientific jargon. Some hand-drawn images and tables would be beneficial in order to reduce the large paragraphs of text.
# ''Evidence of significant research relating to basic and applied sciences that goes beyond the formal teaching activities.'' The amount of information provided is evidence of the significant research that went into this project, and the sections such as ‘Technologies to overcome the problems’ shows research that goes ‘beyond the formal teaching activities’.
# ''Relates the topics and content of the Wiki entry to learning aims of embryology.'' The topics and content are well related to the learning aims of embryology
# ''The content of the wiki should demonstrate to the reader that your group has researched adequately on this topic and covered the key areas necessary to inform your peers in their learning.'' All the content is relevant to the key areas of the development of the eye and demonstrates an extensive amount of research into the topic.

Additional points:
* The amount of text is overwhelming. You should make better use of tables, figures and diagrams to breakup/replace the text.
* Adult anatomy and histology: no reference to histology. Would be beneficial to have a brief explanation of the functions of each structure.
* Overall impression: Very well researched topic and I'm sure the use of tables, pictures and diagrams will make it more appealing to read!

=== Lab 9 ===

''Q1. Identify and write a brief description of the findings of a recent research paper on development of one of the endocrine organs covered in today's practical.''

''Q2. Identify the embryonic layers and tissues that contribute to the developing teeth.''

# '''Ectoderm''' from the first pharyngeal arch contributes the the '''enamel''' of the tooth. Furthermore, some cells of the oral epithelium differenciate into amnioblasts, which further contribute to the production of enamel.
# '''Neural crest''' gives rise to the '''dental papilla''' of the tooth, as well as various cell types (ondoblasts, cementoblasts, osteoblasts and fibroblasts).
# '''Mesoderm''' contributes to '''cells''' associated with the tooth, including: cementoblasts, osteoblasts and fibroblasts.

[http://www.ncbi.nlm.nih.gov/pubmed/21425080 Contribution of mesoderm to the developing dental papilla.]<ref><pubmed>21425080</pubmed></ref>

==References==

<references/>

User:Z3289738

2012-10-03T01:21:07Z

Z3289738:

==Lab Attendance==
Lab 1: --[[User:Z3289738|Z3289738]] 11:49, 25 July 2012 (EST)

Lab 2: --[[User:Z3289738|Z3289738]] 10:12, 1 August 2012 (EST)

Lab 3: --[[User:Z3289738|Z3289738]] 10:08, 8 August 2012 (EST)

Lab 4: --[[User:Z3289738|Z3289738]] 10:20, 15 August 2012 (EST)

Lab 5: --[[User:Z3289738|Z3289738]] 10:13, 22 August 2012 (EST)

Lab 6: --[[User:Z3289738|Z3289738]] 10:16, 29 August 2012 (EST)

Lab 7: --[[User:Z3289738|Z3289738]] 10:27, 12 September 2012 (EST)

Lab 8: --[[User:Z3289738|Z3289738]] 10:30, 19 September 2012 (EST)

Lab 9: --[[User:Z3289738|Z3289738]] 10:08, 26 September 2012 (EST)

Lab 9: --[[User:Z3289738|Z3289738]] 11:18, 3 October 2012 (EST)

==Individual Assessments==
===Lab 1 Assessment===

''Q1. Identify the origin of In Vitro Fertilization and the 2010 nobel prize winner associated with this technique and add a correctly formatted link to the Nobel page.''

The idea of In Vitro Fertilization began to formulate in the 1890s, when Walter Heape reported the first known case of embryo transplantation in rabbits. In 1953 John Rock extracted the first intact human fertilized egg. The first successful attempt at IVF was in 1978 by Steptoe and Edward.

Robert G. Edwards, the physiologist who developed the In Vitro Fertilization treatment, was awarded the Nobel Prize in Physiology or Medicine in 2010. [http://www.nobelprize.org/nobel_prizes/medicine/laureates/2010/press.html/# Nobel Prize Page]

''Q2. Identify and add a PubMed reference link to a recent paper on fertilization and describe its key findings (1-2 paragraphs).''

This article looks into the process of embryo implantation. It demonstrates how the activation of the epithelial Na(+) channel triggers prostoglandin E(2) release,phosphorylation of teh transcription factor CREB and upregulation of cyclooxygenase 2, the enzyme required for prostaglandin production and implantation. They detected maximum Epithelial Na(+) channel activation at the time of implantation in mice, and that blocking or knocking down this channel in mice resulted in failure to implant. These results indicate the importance of the Epithelial Na(+) Channel in the process of implantation, and the consequences of defects such as miscarriage and low success rates in IVF.

<pubmed> 22729284</pubmed>

===Lab 2 Assessment===
''Q1. Upload an image from a journal source relating to fertilization or the first 2 weeks of development as demonstrated in the practical class. Including in the image “Summary” window: An image name as a section heading, Any further description of what the image shows, A subsection labeled “Reference” and under this the original image source, appropriate reference and all copyright information and finally a template indicating that this is a student image.

[[File:Z3289738 ANAT Lab 2.jpg|200px|thumb|right|Zygotes showing different distribution of NPB in the 2PN and different PB aligment]]

''Q2. Identify a protein associated with the implantation process, including a brief description of the protein's role (1-2 paragraphs)''

'''Trophinin'''

Trophinin is an membrane adhesive protein expressed on human trophoblastic cells and on uterine endometrium epithelial cells. The protein mediates apical cell adhesion and activate trophectoderm cells for implantation via proliferation and invasion. <ref><pubmed>17487845</pubmed></ref>

===Lab 3 Assessment===

''Q1. Identify the difference between "gestational age" and "post-fertilisation age" and explain why clinically "gestational age" is used in describing human development.''

"Gestational age" is measured from the first day of the woman's last menstrual cycle, whereas "post-fertilisation age" measures the time passed since fertilization of the oocyte. Gestational age is more clinically relevant as it is easier to determine the date of the woman's last menstrual cycle than it is to determine the date of fertilization. Furthermore, gestational age can also be determined before and after birth by measuring the size of the head, thigh bone and abdomen (before birth), and the size of the head and weight after birth. Gestational age is therefore used to determine the infant's medical history and medical plan.

''Q2. Identify using histological descriptions at least 3 different types of tissues formed from somites.''

Somites differentiate to form: (1) '''the axial skeleton (vertebral body & inter-vertebral disk)''', (2) '''dermis''' and (3) '''skeletal muscle'''.

# Cells in the ventromedial half of each somite differentiate into the sclerotome via Sonic hedgehog signalling mechanisms. The Pax 1 transcription factor then converts the sclerotome into chondrocytes (cartilage), which is essential for the functioning of the vertebral column.
# Cells in the dorsolateral portion of the somites differentiate to form the dermomyotone. This is then divided into:
## Dorsal dermatome which later contributes to the formation of the dermis in response to neutropin 3 factors.
## Wnt1 and Wnt3 factors contribute to the formation of the ventral myotome, which is further split into the epaxial myotome (gives rise to erector spinae muscles) and the hypaxial myotome (gives rise to the muscles of the trunk and limbs).

===Lab 4 Assessment===

''Q1. Identify the 2 invasive prenatal diagnostic techniques related to the placenta and 2 abnormalities that can be identified with these techniques.''
# '''Chorionic villus sampling''' (CVS)is an invasive prenatal diagnostic technique that is used to detect genetic abnormalities such as Down syndrome or cystic fibrosis. During the procedure a sample of the placenta is removed via a needle through the abdomen and then examined in a laboratory. It is commonly performed between 10 and 12 weeks of pregnancy/
# '''Amniocentesis''' procedures involve collecting samples of amniotic fluid via a needle through the abdomen to check for genetic abnormalities such as Down syndrome, cystic fibrosis or spina bifida.

''Q2. Identify a paper that uses cord stem cells therapeutically and write a brief (2-3 paragraph) description of the paper's findings.''

F. Ramirez, D. Steenblock, A. Payne and L. Darnall (2006) '''Umbilical Cord Stem Cell Therapy for Cerebral Palsy'''. MED HYPOTHESES RES 3: 679-686 [http://www.journal-mhr.com/PDF_Files/vol_3_2/3_2_PDFs/3_2_2.pdf | Umbilical Cord Stem Cell Therapy for Cerebral Palsy]

This article describes a six month study to evaluate the effectiveness of umbilical cord stem cells in treatment for various brain injuries and disorders, in particular Cerebral Palsy. The study began in 2004, whereby 8 children between the ages of 3-12 who had been diagnosed with Cerebral Palsy underwent transplants with 1.5 million umbilical cord stem cells. The study reported eight of of eight children showed some improvement in mobility and/or cognitive function. Furthermore, one aphasic child started talking again and another who had been blind since birth was able to see after post-treatment.

The results from this preliminary observational pilot study suggests that umbilical cord stem cells may be a safe and promising treatment for children with cerebral palsy.

===Lab 7===
====a) Class exercises====
1. Maturation Hypertrophy - In your groups, design a method to estimate the degree of hypertrophy that occurs during the transition from birth to adulthood. Use the rulers to make rough measurements on the screen and then estimate the degree of hypertrophy as a mean increase in fibre size. Discuss the result as a class. (ie Try estimate the degree of hypertrophy from child to adult cells)

Method: Measured area of the child and adult cells, found an average for each and then worked out the percentage increase.

Answer: 7x increase in area size.

2. The role of satellite cells in muscle hypertrophy - class discussion of data presented in a recent paper - McCarthy et al. 2011. (ie How to we achieve hypertrophy? How do we get proteins into the cells? Degeneration of the myonucleus - Can activate the satellite cells as if the cell is undergoing repair; the nuclei within the cells becomes more active, produces more RNA and the cells get bigger.)

3. Fibre type shift - Discuss an experiment on fiber type shift that has been induced by chronic low frequency stimulation - Martins et al. 2006

====b) Assessment====
''Q1. (a) Provide a one sentence definition of a muscle satellite cell.''

Satellite cells are quiescent stem cells present in adult muscle tissue between the basal lamina of a muscle fiber and are responsible for postnatal hypertrophy and regeneration. <ref><pubmed>16243526</pubmed></ref>

''Q1. (b) In one paragraph, briefly discuss two examples of when satellite cells are activated?''

These cells are normally quiescent in adult muscle, by are activated in response to injury and muscle disease. When activated, the cells begin to proliferate and after aligning they fuse to allow for repair and/or regenration of muscle fibres. Satellite cells assist in the regeneration of muscle tissues in response to muscle injury by either forming multinucleated myotubes or additional quiescent satellite cells. <ref><pubmed>21849021</pubmed></ref>. Furthermore, studies have provided evidence of an increased level of satellite cells in muscular diseases such as Duchenne muscular dystrophy (DMD). <ref><pubmed>16818602</pubmed></ref>

''Q2. In one brief paragraph, describe what happens to skeletal muscle fibre type and size when the innervating motor nerve sustains long term damage such as in spinal cord injury?''

Spinal cord injuries which lead to long term damage to the innervating motor nerve would result in muscle partial or complete paralysis of muscles, leading to muscle atrophy. <ref><pubmed>16940987</pubmed></ref> This results in a significant decrease in cross-sectional area of the immobilized muscle do to lack of use. <ref><pubmed>10483809</pubmed></ref> Another consequence of the decreased muscle mass is an increased level of connective tissues and fat in order to assist the transfer of forces to the tendons.<ref><pubmed>15303112</pubmed></ref> Furthermore, the composition of muscle fibre types are transformed from a mix of type I and type II fibres to predominantly type II (fast twitch) muscle fibres. <ref name="PMID9755066"><pubmed>9755066</pubmed></ref> This is a result of the muscle no longer being used for endurance-type excersises.

=== Lab 8 - Peer Reviews ===

==== Group 1====
Group Assessment Criteria:
# ''The key points relating to the topic that your group was allocated are clearly described'' The introduction explains why the eye is important and lists the anatomical structures, however there is no indication that this project page is about the development of the eye!
# ''The choice of content, headings and sub-headings, diagrams, tables, graphs show a good understanding of the topic area''. The project predominantly focuses on the development of the eye, and goes into detail the development of each individual structure. There are also a lot of student-drawn images and diagrams of developmental stages which shows a good understanding of the topic area.
# ''Content is correctly cited and referenced''. There is no copyright notices for any of the images and they all lack explanations.
# ''The wiki has an element of teaching at a peer level using the student’s own innovative diagrams, tables or figures and/or using interesting examples or explanations''. The text is easy to understand and there are many student-drawn diagrams, which makes the content more interesting to read.
# ''Evidence of significant research relating to basic and applied sciences that goes beyond the formal teaching activities''. I would say the information provided satisfies the aims of the project, however the research does not go ‘beyond the formal teaching activities’ as it lacks additional information such as abnormalities, normal functioning etc.
# ''Relates the topics and content of the Wiki entry to learning aims of embryology.'' The contents and topics are strongly related to the learning aims of embryology.
# ''The content of the wiki should demonstrate to the reader that your group has researched adequately on this topic and covered the key areas necessary to inform your peers in their learning.'' All the content provided is well researched and relevant to the aims of the project. They key areas are well described.

Additional points:
* I feel that this page would benefit from a timeline or ‘weekly development’ table that briefly describes what structures are developed in each week. This would provide a good summary of the content as well as allow reader to be able to understand how the development of each structure relates to each other.
* Good referencing of images throughout project page – relating images to content
* Less paragraphs, more tables, bullet points, emphasize certain important points
* History & research sections look incomplete.

====Group 2====
Group Assessment Criteria:
# ''The key points relating to the topic that your group was allocated are clearly described.'' The introduction outlines the importance of the somatosensory system and provides a good summary of the developmental stages. More emphasis could be made on the key points of the project page.
# ''The choice of content, headings and sub-headings, diagrams, tables, graphs show a good understanding of the topic area.'' The content shows an understanding of the topic area, however the layout makes the text difficult to follow. There is not a clear connection between the ‘Central Somatosensory Differentiation’ and the somatosensory system. There is a lack of diagrams, tables and graphs to explain the written content.
# ''Content is correctly cited and referenced.'' Some sections are correctly referenced whilst others are completely lacking. This area needs working on.
# ''The wiki has an element of teaching at a peer level using the student’s own innovative diagrams, tables or figures and/or using interesting examples or explanations.'' The information is broken down well by headings and subheadings, however there is a lack of relating images to compliment the information. The one student drawn image is very useful.
# ''Evidence of significant research relating to basic and applied sciences that goes beyond the formal teaching activities.'' The information provided is well researched and satisfies the aims of the project in terms of developmental stages, however in order to go ‘beyond the formal teaching activities’ it needs to include sections such as abnormal development and more on the history, current and future research.
# ''Relates the topics and content of the Wiki entry to learning aims of embryology.'' The topics and content relate to the learning aims of embryology by describing the developmental stages if the somatosensory cortex.
# ''The content of the wiki should demonstrate to the reader that your group has researched adequately on this topic and covered the key areas necessary to inform your peers in their learning.'' There has been a fair amount of research into the topic, however a bulk of the information is focused on descriptions of each of the senses. More emphasis should be placed on the development of each of these sense as that is the key topic area.

Additional points:
* The Introduction and Central Somatosensory Differentiation sections were well written and the accompanying diagram was very useful.
* The layout of the page could be improved with the use of tables and diagrams to reduce/replace the amount of text
* The project seems largely incomplete; more research needs to go into the History and research sections and there is a lack of images

==== Group 4 ====
* '''Introduction''': The information is very interesting and provides a good overview of the olfactory system. The only improvement that could be made is clearly stating what content is going to be covered on this project page. Also, “The olfactory system are often '''divide''' into a peripheral mechanism”
* '''History of Discovery''': This sections presents a good summary of each research paper, detailing a background of the researchers and the importance of each discovery. Well done!
* '''Time line of developmental process''': This section shows a good depth of research and provides detailed descriptions of each stage of development. However, the information provided is quite complicated and would not be easily understood by peers. This could be overcome by the use of labeled diagrams or hand drawn images, which I can see is yet to come. Overall this is a well done section, the colors draw the readers attention and I like the use of bolded text to highlight important information.
* '''Anatomy of the Olfactory System & Normal Function''': This provides a good amount of information seeing as the focus of the page is about olfactory development, not the function & final structure. The only improvement could be providing an explanation in the figure provided.
* '''Congenital Abnormalities''': This section is well organized and includes all relevant content. Very interesting to read.
* '''Current Research''': A well researched section and coverage of content. Each paper is summarized and the importance of each discovery is made clear. It would be nice to include a direct link to each article.

====Group 5 ====
*'''Introduction:''' The introduction is quite well written and very detailed. Rather than going straight into details of development, perhaps first make it clear from the exactly what this project page is about and what content you will be covering. There are also some grammatical errors, such as “treatments or cures ‘’’maybe’’’ developed in the future and these conditions can be better managed.” Maybe = may be
* '''Normal eye development:''' This section shows a good depth of research, is strongly related to the aims of the embryology course and shows a good depth of research. Improvements could be made by the use of bullet points, tables or bold text to highlight key points. Also, labeled images or hand-drawn diagrams would go well to compliment the text.
* '''Abnormal Development:''' There is a good depth of research and it is well written. The use of headings, figures and italics makes it easy to follow the flow of information. Improvements could be made by providing more information about the diseases, for example, what is Peters' anomaly (Corneal Opacity) and aniridia (lack of Iris)? Is it curable? What are methods of detection? How will it effect the future baby?
*'''Ocular Manifestations:''' This section seems incomplete; or maybe its just poorly organized? What are the two separate sections? Is this related to the sections that follow?
* '''Research Time line:''' This is a good time line, however only one source has been used. This provides a good summary of significant discoveries, but it has not been explained why these discoveries were important or how it is relevant to the development of the eye.
* '''New Research Development:''' This section is well researched, however the poor structuring and layout of the information makes it difficult to read and follow. For example there are many headings and subheadings however it is unclear what sections of information are grouped together. The images draw the readers attention and there seems to be a good depth of research into the topic.
*'''Group Assessment Criteria:''' The key points relating to the topic that your group was allocated are clearly described in the introduction. The choice of content and depth of research shows a good understanding of the topic area, however the information could be better organized by the use of tables, bullet points and bolded text to highlight key points. The content is correctly cited and referenced. Most sections are well paraphrased for teaching at a peer level, however the use of hand-drawn diagrams and/or labeled images could enhance the information in the text. The information covered is strongly related the the learning aims of embryology.

====Group 6====
Group Assessment Criteria:
# ''The key points relating to the topic that your group was allocated are clearly described.'' The introduction clearly outlines the key points of the project and the content is well described in the text.
# ''The choice of content, headings and sub-headings, diagrams, tables, graphs show a good understanding of the topic area.'' The choice of content and headings shows a good depth of research and understanding of the topic area. The ‘Summary of the inner ear’ table was a good idea and ties in all the information nicely.
# ''Content is correctly cited and referenced.'' There are large paragraphs of texts that have no references. The images provided display the copyright notices and explanations.
# ''The wiki has an element of teaching at a peer level using the student’s own innovative diagrams, tables or figures and/or using interesting examples or explanations.'' The introduction is well written and catches the readers interest and attention. Most of the normal development section is easy to understand, however the abnormalities section is difficult to understand due to the scientific jargon. Some hand-drawn images and tables would be beneficial in order to reduce the large paragraphs of text.
# ''Evidence of significant research relating to basic and applied sciences that goes beyond the formal teaching activities.'' The amount of information provided is evidence of the significant research that went into this project, and the sections such as ‘Technologies to overcome the problems’ shows research that goes ‘beyond the formal teaching activities’.
# ''Relates the topics and content of the Wiki entry to learning aims of embryology.'' The topics and content are well related to the learning aims of embryology
# ''The content of the wiki should demonstrate to the reader that your group has researched adequately on this topic and covered the key areas necessary to inform your peers in their learning.'' All the content is relevant to the key areas of the development of the eye and demonstrates an extensive amount of research into the topic.

Additional points:
* The amount of text is overwhelming. You should make better use of tables, figures and diagrams to breakup/replace the text.
* Adult anatomy and histology: no reference to histology. Would be beneficial to have a brief explanation of the functions of each structure.
* Overall impression: Very well researched topic and I'm sure the use of tables, pictures and diagrams will make it more appealing to read!

=== Lab 9 ===

''Q1. Identify and write a brief description of the findings of a recent research paper on development of one of the endocrine organs covered in today's practical.''

''Q2. Identify the embryonic layers and tissues that contribute to the developing teeth.''

==References==

<references/>

User:Z3289738

2012-10-03T01:18:50Z

Z3289738: /* Lab Attendance */

==Lab Attendance==
Lab 1: --[[User:Z3289738|Z3289738]] 11:49, 25 July 2012 (EST)

Lab 2: --[[User:Z3289738|Z3289738]] 10:12, 1 August 2012 (EST)

Lab 3: --[[User:Z3289738|Z3289738]] 10:08, 8 August 2012 (EST)

Lab 4: --[[User:Z3289738|Z3289738]] 10:20, 15 August 2012 (EST)

Lab 5: --[[User:Z3289738|Z3289738]] 10:13, 22 August 2012 (EST)

Lab 6: --[[User:Z3289738|Z3289738]] 10:16, 29 August 2012 (EST)

Lab 7: --[[User:Z3289738|Z3289738]] 10:27, 12 September 2012 (EST)

Lab 8: --[[User:Z3289738|Z3289738]] 10:30, 19 September 2012 (EST)

Lab 9: --[[User:Z3289738|Z3289738]] 10:08, 26 September 2012 (EST)

Lab 9: --[[User:Z3289738|Z3289738]] 11:18, 3 October 2012 (EST)

==Individual Assessments==
===Lab 1 Assessment===

''Q1. Identify the origin of In Vitro Fertilization and the 2010 nobel prize winner associated with this technique and add a correctly formatted link to the Nobel page.''

The idea of In Vitro Fertilization began to formulate in the 1890s, when Walter Heape reported the first known case of embryo transplantation in rabbits. In 1953 John Rock extracted the first intact human fertilized egg. The first successful attempt at IVF was in 1978 by Steptoe and Edward.

Robert G. Edwards, the physiologist who developed the In Vitro Fertilization treatment, was awarded the Nobel Prize in Physiology or Medicine in 2010. [http://www.nobelprize.org/nobel_prizes/medicine/laureates/2010/press.html/# Nobel Prize Page]

''Q2. Identify and add a PubMed reference link to a recent paper on fertilization and describe its key findings (1-2 paragraphs).''

This article looks into the process of embryo implantation. It demonstrates how the activation of the epithelial Na(+) channel triggers prostoglandin E(2) release,phosphorylation of teh transcription factor CREB and upregulation of cyclooxygenase 2, the enzyme required for prostaglandin production and implantation. They detected maximum Epithelial Na(+) channel activation at the time of implantation in mice, and that blocking or knocking down this channel in mice resulted in failure to implant. These results indicate the importance of the Epithelial Na(+) Channel in the process of implantation, and the consequences of defects such as miscarriage and low success rates in IVF.

<pubmed> 22729284</pubmed>

===Lab 2 Assessment===
''Q1. Upload an image from a journal source relating to fertilization or the first 2 weeks of development as demonstrated in the practical class. Including in the image “Summary” window: An image name as a section heading, Any further description of what the image shows, A subsection labeled “Reference” and under this the original image source, appropriate reference and all copyright information and finally a template indicating that this is a student image.

[[File:Z3289738 ANAT Lab 2.jpg|200px|thumb|right|Zygotes showing different distribution of NPB in the 2PN and different PB aligment]]

''Q2. Identify a protein associated with the implantation process, including a brief description of the protein's role (1-2 paragraphs)''

'''Trophinin'''

Trophinin is an membrane adhesive protein expressed on human trophoblastic cells and on uterine endometrium epithelial cells. The protein mediates apical cell adhesion and activate trophectoderm cells for implantation via proliferation and invasion. <ref><pubmed>17487845</pubmed></ref>

===Lab 3 Assessment===

''Q1. Identify the difference between "gestational age" and "post-fertilisation age" and explain why clinically "gestational age" is used in describing human development.''

"Gestational age" is measured from the first day of the woman's last menstrual cycle, whereas "post-fertilisation age" measures the time passed since fertilization of the oocyte. Gestational age is more clinically relevant as it is easier to determine the date of the woman's last menstrual cycle than it is to determine the date of fertilization. Furthermore, gestational age can also be determined before and after birth by measuring the size of the head, thigh bone and abdomen (before birth), and the size of the head and weight after birth. Gestational age is therefore used to determine the infant's medical history and medical plan.

''Q2. Identify using histological descriptions at least 3 different types of tissues formed from somites.''

Somites differentiate to form: (1) '''the axial skeleton (vertebral body & inter-vertebral disk)''', (2) '''dermis''' and (3) '''skeletal muscle'''.

# Cells in the ventromedial half of each somite differentiate into the sclerotome via Sonic hedgehog signalling mechanisms. The Pax 1 transcription factor then converts the sclerotome into chondrocytes (cartilage), which is essential for the functioning of the vertebral column.
# Cells in the dorsolateral portion of the somites differentiate to form the dermomyotone. This is then divided into:
## Dorsal dermatome which later contributes to the formation of the dermis in response to neutropin 3 factors.
## Wnt1 and Wnt3 factors contribute to the formation of the ventral myotome, which is further split into the epaxial myotome (gives rise to erector spinae muscles) and the hypaxial myotome (gives rise to the muscles of the trunk and limbs).

===Lab 4 Assessment===

''Q1. Identify the 2 invasive prenatal diagnostic techniques related to the placenta and 2 abnormalities that can be identified with these techniques.''
# '''Chorionic villus sampling''' (CVS)is an invasive prenatal diagnostic technique that is used to detect genetic abnormalities such as Down syndrome or cystic fibrosis. During the procedure a sample of the placenta is removed via a needle through the abdomen and then examined in a laboratory. It is commonly performed between 10 and 12 weeks of pregnancy/
# '''Amniocentesis''' procedures involve collecting samples of amniotic fluid via a needle through the abdomen to check for genetic abnormalities such as Down syndrome, cystic fibrosis or spina bifida.

''Q2. Identify a paper that uses cord stem cells therapeutically and write a brief (2-3 paragraph) description of the paper's findings.''

F. Ramirez, D. Steenblock, A. Payne and L. Darnall (2006) '''Umbilical Cord Stem Cell Therapy for Cerebral Palsy'''. MED HYPOTHESES RES 3: 679-686 [http://www.journal-mhr.com/PDF_Files/vol_3_2/3_2_PDFs/3_2_2.pdf | Umbilical Cord Stem Cell Therapy for Cerebral Palsy]

This article describes a six month study to evaluate the effectiveness of umbilical cord stem cells in treatment for various brain injuries and disorders, in particular Cerebral Palsy. The study began in 2004, whereby 8 children between the ages of 3-12 who had been diagnosed with Cerebral Palsy underwent transplants with 1.5 million umbilical cord stem cells. The study reported eight of of eight children showed some improvement in mobility and/or cognitive function. Furthermore, one aphasic child started talking again and another who had been blind since birth was able to see after post-treatment.

The results from this preliminary observational pilot study suggests that umbilical cord stem cells may be a safe and promising treatment for children with cerebral palsy.

===Lab 7===
====a) Class exercises====
1. Maturation Hypertrophy - In your groups, design a method to estimate the degree of hypertrophy that occurs during the transition from birth to adulthood. Use the rulers to make rough measurements on the screen and then estimate the degree of hypertrophy as a mean increase in fibre size. Discuss the result as a class. (ie Try estimate the degree of hypertrophy from child to adult cells)

Method: Measured area of the child and adult cells, found an average for each and then worked out the percentage increase.

Answer: 7x increase in area size.

2. The role of satellite cells in muscle hypertrophy - class discussion of data presented in a recent paper - McCarthy et al. 2011. (ie How to we achieve hypertrophy? How do we get proteins into the cells? Degeneration of the myonucleus - Can activate the satellite cells as if the cell is undergoing repair; the nuclei within the cells becomes more active, produces more RNA and the cells get bigger.)

3. Fibre type shift - Discuss an experiment on fiber type shift that has been induced by chronic low frequency stimulation - Martins et al. 2006

====b) Assessment====
''Q1. (a) Provide a one sentence definition of a muscle satellite cell.''

Satellite cells are quiescent stem cells present in adult muscle tissue between the basal lamina of a muscle fiber and are responsible for postnatal hypertrophy and regeneration. <ref><pubmed>16243526</pubmed></ref>

''Q1. (b) In one paragraph, briefly discuss two examples of when satellite cells are activated?''

These cells are normally quiescent in adult muscle, by are activated in response to injury and muscle disease. When activated, the cells begin to proliferate and after aligning they fuse to allow for repair and/or regenration of muscle fibres. Satellite cells assist in the regeneration of muscle tissues in response to muscle injury by either forming multinucleated myotubes or additional quiescent satellite cells. <ref><pubmed>21849021</pubmed></ref>. Furthermore, studies have provided evidence of an increased level of satellite cells in muscular diseases such as Duchenne muscular dystrophy (DMD). <ref><pubmed>16818602</pubmed></ref>

''Q2. In one brief paragraph, describe what happens to skeletal muscle fibre type and size when the innervating motor nerve sustains long term damage such as in spinal cord injury?''

Spinal cord injuries which lead to long term damage to the innervating motor nerve would result in muscle partial or complete paralysis of muscles, leading to muscle atrophy. <ref><pubmed>16940987</pubmed></ref> This results in a significant decrease in cross-sectional area of the immobilized muscle do to lack of use. <ref><pubmed>10483809</pubmed></ref> Another consequence of the decreased muscle mass is an increased level of connective tissues and fat in order to assist the transfer of forces to the tendons.<ref><pubmed>15303112</pubmed></ref> Furthermore, the composition of muscle fibre types are transformed from a mix of type I and type II fibres to predominantly type II (fast twitch) muscle fibres. <ref name="PMID9755066"><pubmed>9755066</pubmed></ref> This is a result of the muscle no longer being used for endurance-type excersises.

=== Lab 8 - Peer Reviews ===

==== Group 1====
Group Assessment Criteria:
# ''The key points relating to the topic that your group was allocated are clearly described'' The introduction explains why the eye is important and lists the anatomical structures, however there is no indication that this project page is about the development of the eye!
# ''The choice of content, headings and sub-headings, diagrams, tables, graphs show a good understanding of the topic area''. The project predominantly focuses on the development of the eye, and goes into detail the development of each individual structure. There are also a lot of student-drawn images and diagrams of developmental stages which shows a good understanding of the topic area.
# ''Content is correctly cited and referenced''. There is no copyright notices for any of the images and they all lack explanations.
# ''The wiki has an element of teaching at a peer level using the student’s own innovative diagrams, tables or figures and/or using interesting examples or explanations''. The text is easy to understand and there are many student-drawn diagrams, which makes the content more interesting to read.
# ''Evidence of significant research relating to basic and applied sciences that goes beyond the formal teaching activities''. I would say the information provided satisfies the aims of the project, however the research does not go ‘beyond the formal teaching activities’ as it lacks additional information such as abnormalities, normal functioning etc.
# ''Relates the topics and content of the Wiki entry to learning aims of embryology.'' The contents and topics are strongly related to the learning aims of embryology.
# ''The content of the wiki should demonstrate to the reader that your group has researched adequately on this topic and covered the key areas necessary to inform your peers in their learning.'' All the content provided is well researched and relevant to the aims of the project. They key areas are well described.

Additional points:
* I feel that this page would benefit from a timeline or ‘weekly development’ table that briefly describes what structures are developed in each week. This would provide a good summary of the content as well as allow reader to be able to understand how the development of each structure relates to each other.
* Good referencing of images throughout project page – relating images to content
* Less paragraphs, more tables, bullet points, emphasize certain important points
* History & research sections look incomplete.

====Group 2====
Group Assessment Criteria:
# ''The key points relating to the topic that your group was allocated are clearly described.'' The introduction outlines the importance of the somatosensory system and provides a good summary of the developmental stages. More emphasis could be made on the key points of the project page.
# ''The choice of content, headings and sub-headings, diagrams, tables, graphs show a good understanding of the topic area.'' The content shows an understanding of the topic area, however the layout makes the text difficult to follow. There is not a clear connection between the ‘Central Somatosensory Differentiation’ and the somatosensory system. There is a lack of diagrams, tables and graphs to explain the written content.
# ''Content is correctly cited and referenced.'' Some sections are correctly referenced whilst others are completely lacking. This area needs working on.
# ''The wiki has an element of teaching at a peer level using the student’s own innovative diagrams, tables or figures and/or using interesting examples or explanations.'' The information is broken down well by headings and subheadings, however there is a lack of relating images to compliment the information. The one student drawn image is very useful.
# ''Evidence of significant research relating to basic and applied sciences that goes beyond the formal teaching activities.'' The information provided is well researched and satisfies the aims of the project in terms of developmental stages, however in order to go ‘beyond the formal teaching activities’ it needs to include sections such as abnormal development and more on the history, current and future research.
# ''Relates the topics and content of the Wiki entry to learning aims of embryology.'' The topics and content relate to the learning aims of embryology by describing the developmental stages if the somatosensory cortex.
# ''The content of the wiki should demonstrate to the reader that your group has researched adequately on this topic and covered the key areas necessary to inform your peers in their learning.'' There has been a fair amount of research into the topic, however a bulk of the information is focused on descriptions of each of the senses. More emphasis should be placed on the development of each of these sense as that is the key topic area.

Additional points:
* The Introduction and Central Somatosensory Differentiation sections were well written and the accompanying diagram was very useful.
* The layout of the page could be improved with the use of tables and diagrams to reduce/replace the amount of text
* The project seems largely incomplete; more research needs to go into the History and research sections and there is a lack of images

==== Group 4 ====
* '''Introduction''': The information is very interesting and provides a good overview of the olfactory system. The only improvement that could be made is clearly stating what content is going to be covered on this project page. Also, “The olfactory system are often '''divide''' into a peripheral mechanism”
* '''History of Discovery''': This sections presents a good summary of each research paper, detailing a background of the researchers and the importance of each discovery. Well done!
* '''Time line of developmental process''': This section shows a good depth of research and provides detailed descriptions of each stage of development. However, the information provided is quite complicated and would not be easily understood by peers. This could be overcome by the use of labeled diagrams or hand drawn images, which I can see is yet to come. Overall this is a well done section, the colors draw the readers attention and I like the use of bolded text to highlight important information.
* '''Anatomy of the Olfactory System & Normal Function''': This provides a good amount of information seeing as the focus of the page is about olfactory development, not the function & final structure. The only improvement could be providing an explanation in the figure provided.
* '''Congenital Abnormalities''': This section is well organized and includes all relevant content. Very interesting to read.
* '''Current Research''': A well researched section and coverage of content. Each paper is summarized and the importance of each discovery is made clear. It would be nice to include a direct link to each article.

====Group 5 ====
*'''Introduction:''' The introduction is quite well written and very detailed. Rather than going straight into details of development, perhaps first make it clear from the exactly what this project page is about and what content you will be covering. There are also some grammatical errors, such as “treatments or cures ‘’’maybe’’’ developed in the future and these conditions can be better managed.” Maybe = may be
* '''Normal eye development:''' This section shows a good depth of research, is strongly related to the aims of the embryology course and shows a good depth of research. Improvements could be made by the use of bullet points, tables or bold text to highlight key points. Also, labeled images or hand-drawn diagrams would go well to compliment the text.
* '''Abnormal Development:''' There is a good depth of research and it is well written. The use of headings, figures and italics makes it easy to follow the flow of information. Improvements could be made by providing more information about the diseases, for example, what is Peters' anomaly (Corneal Opacity) and aniridia (lack of Iris)? Is it curable? What are methods of detection? How will it effect the future baby?
*'''Ocular Manifestations:''' This section seems incomplete; or maybe its just poorly organized? What are the two separate sections? Is this related to the sections that follow?
* '''Research Time line:''' This is a good time line, however only one source has been used. This provides a good summary of significant discoveries, but it has not been explained why these discoveries were important or how it is relevant to the development of the eye.
* '''New Research Development:''' This section is well researched, however the poor structuring and layout of the information makes it difficult to read and follow. For example there are many headings and subheadings however it is unclear what sections of information are grouped together. The images draw the readers attention and there seems to be a good depth of research into the topic.
*'''Group Assessment Criteria:''' The key points relating to the topic that your group was allocated are clearly described in the introduction. The choice of content and depth of research shows a good understanding of the topic area, however the information could be better organized by the use of tables, bullet points and bolded text to highlight key points. The content is correctly cited and referenced. Most sections are well paraphrased for teaching at a peer level, however the use of hand-drawn diagrams and/or labeled images could enhance the information in the text. The information covered is strongly related the the learning aims of embryology.

====Group 6====
Group Assessment Criteria:
# ''The key points relating to the topic that your group was allocated are clearly described.'' The introduction clearly outlines the key points of the project and the content is well described in the text.
# ''The choice of content, headings and sub-headings, diagrams, tables, graphs show a good understanding of the topic area.'' The choice of content and headings shows a good depth of research and understanding of the topic area. The ‘Summary of the inner ear’ table was a good idea and ties in all the information nicely.
# ''Content is correctly cited and referenced.'' There are large paragraphs of texts that have no references. The images provided display the copyright notices and explanations.
# ''The wiki has an element of teaching at a peer level using the student’s own innovative diagrams, tables or figures and/or using interesting examples or explanations.'' The introduction is well written and catches the readers interest and attention. Most of the normal development section is easy to understand, however the abnormalities section is difficult to understand due to the scientific jargon. Some hand-drawn images and tables would be beneficial in order to reduce the large paragraphs of text.
# ''Evidence of significant research relating to basic and applied sciences that goes beyond the formal teaching activities.'' The amount of information provided is evidence of the significant research that went into this project, and the sections such as ‘Technologies to overcome the problems’ shows research that goes ‘beyond the formal teaching activities’.
# ''Relates the topics and content of the Wiki entry to learning aims of embryology.'' The topics and content are well related to the learning aims of embryology
# ''The content of the wiki should demonstrate to the reader that your group has researched adequately on this topic and covered the key areas necessary to inform your peers in their learning.'' All the content is relevant to the key areas of the development of the eye and demonstrates an extensive amount of research into the topic.

Additional points:
* The amount of text is overwhelming. You should make better use of tables, figures and diagrams to breakup/replace the text.
* Adult anatomy and histology: no reference to histology. Would be beneficial to have a brief explanation of the functions of each structure.
* Overall impression: Very well researched topic and I'm sure the use of tables, pictures and diagrams will make it more appealing to read!

==References==

<references/>

Talk:2012 Group Project 3

2012-10-01T12:23:05Z

Z3289738: /* Discussion of Contributions via Email */

{{2012GroupDiscussion}}

--[[User:Z8600021|Mark Hill]] 09:54, 18 September 2012 (EST) This is a recent review on taste. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2922655 http://jcb.rupress.org/content/190/3/285 JCB content allows reuse.

==Group evaluation==

The introduction section is very informative and I like the picture included discussing the 5 basic tastes which is interesting to read. I really enjoy your descriptions of bitter and sweet and find it interesting to read. I like the research you included in this section but I believe this needs to be referenced. Currently in the introduction you have only 1 references, so I would suggest that you find more to further validate your information (note that there are no references in the first paragraph). I like in your picture that you included a description. The cell biology section I would probably put in its own section with = = to break up the contend displayed. In this section it is clear that this has been researched however there have been no references listed at all here.

The taste map section has clearly been well researched yet poorly referenced. It would be interesting to look at if possible a progression of the understanding of the taste map. In the picture of the tongue, I would suggest that it has a better description on the enlarged image. However, some of this text is rather hard to read, such as the descriptions of the first and second order neurons. As you have included terms in there which would be foreign to most people, I would try to include either a picture to show exactly where these parts are such as the NTS which can give the reader a better understanding of what you’re saying. Note that you say things like “copious scientific conjecture surrounds…” however there is no references here! This section is well researched which is great, but I would really consider putting it into slightly easier terms to better comprehension.

In the cortical areas section, a similar approach applies: when describing locations of things such as the I/fO, you should really include a clear diagram as to where all of these are. I can see you included the section of the brain however don’t see it as too informative so a better description there would be appropriate. I would also note that you are repeating your references again, and it would be advisable that you find alternative information to include as well.

The timeline section is very informative and really stands out. I’m assuming you will be including the photos later this week. This is well written and gives a truly informative description of the embryological changes that occur. It will look much better and be better to understand once the photos have been included. Note that you have used the same references pretty well the whole time in this section. Although that paper may have a lot of information about what you are needing to talk about, I would also encourage you to research more papers in order to compliment the information you have listed.

The history of discoveries section is well set out and clear and concise. In some areas I would suggest a brief descripton of what you have written such as “PKD2L”, and also make sure you include the appropriate references as all I can see currently it numbers.

In the adult tongue and taste bud section, is this also what the tongue looks like from week 15? If not what changes occurs for it to form into what you have described as the adult tongue and what enhances these changes? This section is informative however it is really lacking references. The taste bud picture you have is quite good, but is that also what the taste bud looks like at 15 weeks?

The abnormalities section is really interesting and is rather enjoyable to read. Are they the only abnormalities that can happen to the tongue? How about environmental? Does alcohol, smoking or drugs affects its development of either the tongue or the taste buds? Additonally, your current research is very thorough and interesting. In regards to the photos you have there, I would make sure that they are set out appropriately, with the information that this is a student project.

Finally, the glossary needs to be highlighted to make it stand out and more words need to be included. Note that in your references, reference 5 can not be accessible, so make sure you fix that up. Overall, it was interesting to read and I enjoyed the display of photos that were also included!

--------

The overall set up of the page I think is very good. In the introduction there is a balance between pictures and text which makes it a bit easier to read. Also its easy to follow, the text itself isn’t confusing and is understandable.

There is a good overview of the different types of receptors and their function, also there is a brief section on the adult tongue which is good, however there needs to be more focus on the embryological development rather than just a simple table on that. There also needs to be some images added to that component as well to make it more understandable.

The sections on abnormalities and current research need to be organised a bit better because they are a little hard to follow, especially with the placing of the images. The glossary is simple and understandable, however there needs to be more work done on the reference list.

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The layout and balance between text and figures, tables, and diagrams is extremely well accomplished. All the information of the page is really intriguing and easy to follow on the majority.
I would suggest placing the history of discoveries immediately after the introduction so that readers may appreciate all the research that would have had to take place in order to put all the information on this page. As well, this would help in having a separation between the two tables used.

When it comes to images, make sure that everything in the image is relevant to the accompanying text and important to the reader. One image where you might fall short of this criteria, is the very first image on the page about the five basic tastes, the names of the protein structures is more distracting and confusing than enlightening and overall would not aid in informing the reader.

I believe the introduction is very important in assisting the reader in gaining an overall understanding of the page and it’s aims. Hence I believe it is important to include a more succinct introduction with such aims. In this case, the introduction to the gustatory system begins defining structures and functions which are better off used elsewhere. Instead try giving an overview of the system and maybe give the reader a reason to read on.

The images used in the abnormality section are scattered and make it hard for the reader to determine which image corresponds to which idea, I would suggest ensuring that each image is detrimental to aiding the reader’s thoughts. This was an extremely interesting section.

Current research is clear, concise and easy to follow with a pleasant arrangement of ideas, text, and images. It was interesting to read. Additionally, the references and glossary are extensive and well done. I would suggest having a link to the glossary from within the text.

Well done on your project so far, and good luck with the rest.

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The introduction seemed to go into a lot of detail. for example, the information on Type II receptors should be placed in the same section as neural pathways, not the introduction. Can you also include in your introduction, an overview of what you are going to talk about in your project? That would give your project more structure.

With the neural pathway section, can you draw or find a diagram for that section? I find it hard to understand without one. The taste map section goes into a lot of detail which I think is unnecessary because this is a development project.

Current research section is very interesting. I don't think you need to add any more content on that section - that section to me looks complete, besides a few formatting and referencing issues with the images.

Overall, I felt there wasn't enough written on the development of taste, either the receptors (taste buds) or the neural pathways. Your project seem to focus on the anatomy and physiology or function of the taste system. This is alright to keep but the focus should be on development. You do have a Time-line of taste development that summarizes the development of the Gustatory system which is great to see. I think use that as a starting point and expand on each stage in text form, below the table. In week 12 development in this time-line, you mention 'epithelial types I and II', what are they? Are they similar to skin cells?

Overall, the balance between images and text is great. The colourful images work wonders in breaking up the text. Having said that, Many of your images did not have the correct PMID referencing. These images include:
* images of taste being revoked by visualizing ATP release
* CVP of WT and DKO mouse with H & E and SEM
* histology - can you give a more relevant title for this image? We know it's histology; we can see that. What is this image about?
* Abnormal of Tongue - it should say abnormality of tongue

The history section is excellent because it spans over such a long time - 350BC to 2010. The layout of a coloured table for history is beautiful, clear and concise.

--[[User:Z3332863|Z3332863]] 16:35, 23 September 2012 (EST)

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- The introduction of taste is very descriptive and encapsulates the anatomy, physiology and cell biology. Although it is very detailed it doesn’t indicate that the project is about development.

- There is a lot of detail about the taste neural pathway and cortical areas which I’m not sure is relevant to olfactory development unless you mention how they develop as well.

- Figure 2 and 3 do not have any copyright information associated so remember to add those.

- The development section is very nicely put together and hopefully you will add images further down the line. I’ve noticed that in week 8 of development you have the same ref after each line…I’m sure you can just put it at the end of the paragraph as it is same for each line. Same goes for week 14 and 15. Also since you have 2 references for the entire section --- you might want to look at other articles as well.

- Some things that I missed in the section were patterning molecules and genes. Also any signalling mechanisms that control differentiation.

- The history section is exceptionally done with the use of tables, description and references.

- I thoroughly enjoyed your abnormality section. The images are nicely done as well. Although you have described many genes and molecules which are not specified in the normal development portion so the reader don’t understand their roles. Maybe address this in your normal development section.

- The current development section is also very nicely put together but again things like Shh and WNT should be in development section.

Overall very nicely put together and great balance of pictures and text. Although this is a development topic so the major emphasis should be on development of the organ --- Normal development is good but there is too much content in that section that can be left out.

--[[User:Z3333794|Z3333794]] 10:52, 23 September 2012 (EST)

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Abundant information, including a nice coloured in table, which is a cool idea. Unfinished though, the images to go with it would make it great. The page seems to be segmented into sections with a large amount of text, and sections with many pictures. Try for a more even distribution, if possible. Pictures seem to be relevant, with good explanations, referencing and certificates. Helpful and interesting abnormalities and current research sections

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Your introduction is quite good and gives us a brief overview of the different tastes. I also like it that you touch on the fact that it is important we recognise (via taste) food which would be dangerous to our health. In my opinion, after you mention the research (ending the sentence with …’may exist.’) you should tell the reader what you will be discussing on your page. The few lines on fatty acids does not seem to fit in, and should be part of your history section and possibly current/future research. Some specific information seems to have been researched, such as what umami codes for; however, references have not been provided. Also make sure that the image has the correct information – title, description, references, copyright, student template.

It would be more logical to put the history section next. Following this by the timeline and then go back to the cell biology, receptors and taste map etc.

The history section is good with many significant dates and clear descriptions incorporated in a table. I do see lots of numbers, which I think relate to references. I cannot find these references anywhere, so please edit this and make sure it is included in your list of references. There are also a few references listed in full in the table, so please put these down as proper references. Also, there is no good description for the year 2007 (it is mainly a reference).

The developmental timeline is expansive and very interesting! It really relates to the different developmental stages and tells us what happens over time. I hope you can include images with appropriate labels and information to this table, as it will greatly complement your text. Please do check your spelling, eg. ‘epithelium’ in week 6. Also references in this section are appropriate and are not doubled-up in the reference list. Do check reference 5 as it comes up with a cite error.

The section on cell biology and type 2 receptors is clear and easy to read. I cannot see any references though! Please be careful cause this might indicate plagiarism. The taste map is interesting and I am glad you mentioned research has indicated that the different receptors are in fact located all over the tongue – not just in particular sections. If possible, look for the original paper(s) that made this discovery.

The section on neural pathways is a little more difficult to read and I did not understand some of it. Particular terms are used in sentences which suggest little effort has been put in to explain everything in your own words. This is further indicated by the lack of references in the ‘first order neuron’ section and the majority of the ‘second order neuron’ section. I might be wrong, but then do add all your jargon to the glossary. If possible, also try to find other papers which present the same information to strengthen your points mentioned. Images for both the taste map and the cortex need referencing, copyright info, etc.

Adult tongue and taste buds. It is good you include some anatomy and physiology into your section. Do keep in mind the majority of your project should focus on embryonic development. You included the appropriate names, eg. sulcus terminalis, and I am glad to see that has also been put in the glossary. Some more terms do need to be added, eg. circumvallate. The text is good, clear and easy to read. Images are appropriate and relate to the text but need proper descriptions, citations, etc. A major let down of this section is the lack of references – please include this.

Personally, I found the abnormalities section very interesting! However, you are suddenly talking about all these genes and factors which you have not mentioned anywhere else. It might be good to provide a brief description of these in the development section or incorporate them into your developmental timeline. Images all have copyright information, but other information is missing, such as the student template and/or reference. Please check and add this.

Current research includes a lot of information. All different sections have their references which are displayed in the reference list. If you can, provide links to the website of the research groups working on current projects. Be careful not to just put your reference at the end, as you may also have to reference within the paragraph. Both pictures used will need the student template. The double tongue image will need a reference in its description too.

As mentioned before, add and edit the glossary and reference list. You should also add to the useful links (make this external links) and the image gallery, or delete these subheadings, as there is nothing there now.

Hope this helps!
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"In regards to the information presented (outcomes 1 and 9), the timeline for the development is good and written with clarity. However, I noticed the section on structure only referred to the adult state rather than focusing on the embryonic origin of each structure (ectoderm, endoderm and mesoderm). I would suggest that you elaborate on the developmental stages introduced in the timeline in order to build on the information you have already provided. This is important in regards to outcome 6 so that you can relate your research to embryology – the development of taste should be your focus. The history timeline was great to read as it was very concise and clear.

The page shows a good level of peer teaching with clear language and a good balance between images and text (outcome 4) with technical terms explained in the glossary. An improvement could be to make a link between any technical language and the glossary to avoid scrolling up and down to the page. Your Current Research section (outcome 5) was very interesting to read and showed you went beyond the scope of basic research on taste – good work!

In terms of layout (outcome 2), whilst the images are interesting and relevant to the text, some are not appropriately referenced nor described; make sure to reference appropriately and at least write one or two sentences to make the images relevant to the reader. Additionally, the introduction should not be under another subheading (Gustatory system) as it creates some confusion; I would suggest making the introduction its own heading in order to make the page flow. Similarly, the history timeline would best be placed towards the beginning of the page, under the introduction.

I noticed some areas (such as the section on Structure) were not appropriately or consistently referenced. Make sure to include a citation anytime you introduce a researched idea or information to avoid being accused of plagiarism. I noticed the history timeline had good consistent referencing; however the numbers just need to be formatted so they come under the reference list. If you click on the Tutorial: References page linked from the student page, it tells you how to do this. Hope the feedback helps and all the best for your project!"

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The introduction is very detailed but did not mention anything about the development of the taste. But I thought the mechanisms behind sweet and salty tastes are very interesting. Maybe do the same for the other 3 tastes? The image of the basic 5 tastes is a bit small, maybe upload a bigger version of the image. Also, the image is lacking some reference, copyright information and a student image template.

The type II receptor section is pretty good and descriptive but it does not really relate to the development of the taste. The taste map is a very eye-catchy image and it would be really useful if it had all the needed information such as the copyright notice. The timeline of the gustatory system is very well-presented and easy to read. I understand the project is not completed yet, therefore more images are still to be put in. Only 2 references have been used in the timeline section, maybe try to research more and use different resources. There are some citing error but it should be quite easy to fix.

Histories of discoveries section is very detailed and easy to read but the referencing needs to be fixed. The adult tongue and taste bud section is very clear and precise and contain a lot of useful information but it does not really relate to the research topic, should beware of going off-track. The hand-drawn diagram of the taste bud is impressive and easy to understand but again lacking in some referencing information such as who drew it. The abnormalities section is good and well-researched and it is interesting to know about which gene or receptors will effect the development of taste and sensation. Maybe the abnormalities section can be included into the current research section because abnormalities are repeated in the current research section below. There are detailed definitions of terms in the glossary which is good because it really helps the reader to understand more about the research topic.

Overall, the page is looking good. The main thing that needs to be fixed will be the images that are already on the page, they need the correct and essential information with them when uploaded on the page or else, they will get deleted and there will be no images on the page and the nice balance of images and text now will be gone. There seem to be a lot of anatomy and biology of the taste system but not a lot of information about their development. Although there is a timeline of development but i think more information is needed. Referencing is pretty good with only one or two minor citing error but it should be easy to fix. Structure of the page is clear and simple with headings and sub-headings being consistent, making the page easy to read and follow. Hope this helps :)

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The introduction is good, explaining the function and mechanisms behind.

The taste map text and picture are useful however lack referencing information.

The cortical areas section is very interesting and well referenced.

The table timeline is a very good way to summarise the development of taste. It is succinct and well referenced, even though one paper was referred to for most of the information.

The history table is similarly good, very succinct and straightforward, however lacks some references, and the references that were included could be improved by using the wiki referencing system.

The structure and function section is useful but doesn't add much to the text in terms of embryological development. Also make sure the images are properly referenced with the "student template" included.

The abnormalities section is very good and well researched, although maybe try and avoid referring to the articles that have been researched in the text and rather just refer to them using the wiki referencing system. The images are good as well but don't forget the "student template" here also.

The current research section is interesting and well researched, the use of succinct subheadings to summarise the paper's findings was good.

The useful links and image sections need to be added to, and the glossary section can be improved by putting the key terms in bold, but that is otherwise good.

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Initially the page seems to have a good balance between text and diagrams/photographs. However the figures included are not properly labelled once you click on the file and some of them don't appear to have any copyright information included. Some of the pictures could do with being a bit smaller as they take up a large proportion of the page. The student drawn image of the tongue is particularly impressive but does still need to have the student template included. The references seem limited in comparison to other groups perhaps suggesting a lack of depth or variety of research. There also appears to be a coding problem relating to reference number 5. The general layout and use of subheadings is great. It may be useful to link the words in the glossary to their occurrence in the text.

The introductory paragraphs are very well written. They are easy to understand and interesting and give a good overview of how taste functions. Similarly the section on taste map is well written clearly explaining the neurological factors associated with taste. However the presence of the picture in isolation is confusing as it is representing an the old method of taste association. Perhaps this would be resolved if a diagram of the newer taste map was also included. Also you say that the old taste map has been disproved by recent research but that research is not referenced. In fact it appears that very little of that section is referenced. The section on cortical areas is well done.

The timeline of developmental processes is good, the table an easy visual format and the information concise and effective. The only point of contention would be the direct quote in Wk8-9 which seems out of place in comparison to the remainder of the entries which are nicely paraphrased. The history section is similarly well done being extensive and comprehensive. That is excepting some Pub Med references which are just placed in the text rather than in the reference list at the bottom. While interesting and well written the part detailing the Adult Tongue and Taste Buds seems out of place in a embryology course.

The sections on the effect of gene expression on the formation of taste abnormalities and current research are good. However it may be useful to put the information regarding each picture as a caption rather than plain text.

It will be interesting to see what is put in the section "Image Gallery"

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The information provided is both informative and well organised. The use of tables and figures make the text easy to follow and the diagrams make the information easier to understand. When it comes to images however, they seem to be somewhat irrelevant next to some of the information in some cases. Try to move them around and make sure they accompany relevant text.

The introduction does not give the reader the overview of the topic, but rather explores structures and function which makes it difficult to order. Simplifying the introduction, and moving some of the more detailed information such as the information about the type 2 receptors to the relevant section would improve the page.

Other information that is difficult to understand is the text which involves certain genes and molecules without explaining their function or role. Explaining these aspects of the genes and molecules would make the information flow better.
The section on current research is very informative and seems to be complete. However, I did note some errors with the citation of the image used, working on the references is very important for the other images as well as not all have the copyright information.

I also noticed that many of the references are repeated numerous times. Week 8 of development for example have the same reference after a number of sentences. A variety of sources will improve the accuracy of the information rather than derive all the information from a single source.

There is a great focus on the anatomy and physiology of taste, however, it is important to remember that the focus of this project is about development, and therefore including a timeline or a table which covers this information is very important. The page seems to be very organised and the inclusion of tables and diagrams along with the extensive glossary make this page stand out. Well done.

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The page that you have created is very extensive and was well formatted in relation to the ratio of images to text on the page.
Found that the colours and use of table for the breakdown of information in relation to ‘Timeline of developmental process’ and ‘history of discoveries’ condensed the material and made it easily understandable. This made me want to keep reading.

With majority of the images that are uploaded onto the page there needs to be the correct information and referencing provided for the summary box. From where the image was sourced (ideally of reliable and scientific literature in origin), identifying that it has been uploaded for a student assignment and copyright information-permission to use uploaded image and any other information that is pertaining to the topic and why the image was used/relevant.
Further, those of you within your group that have drawn an uploaded image, have to ensure that you have stated in the summary box that it was student drawn prior to final assessment/evaluation.

The glossary is able to be expanded upon and potentially ensuring that the words that are being explained/elaborated are bolded. As a reader, I would find it easier to read and distinguish if they were bolded.
The reference list that has been developed appears to demonstrate that as a group you have are well read and researched, however, the citation errors will have to be addressed and resolved prior to final marking of the project. I really appreciated the layout (headings, summary and images) of the page.

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The introduction is well written and very informative. You should add the history timeline directly below the introduction, because where it currently is feels like it is floating. With it after the introduction it will create a flow to your page and separate the two tables.
In your development table I noted a column called images, the adding of images to show the development stage you are describing will give this section some more flair. If you are not adding images don’t forget to delete the column.

Your section on adult taste and tongue is very interesting but maybe if there is a difference, i.e. newborns tongues are more sensitive to a taste than adults, a comparison would be interesting here.

In abnormalities you mention p2x receptors, maybe you could add this to the glossary and give a brief explanation about what they are and do. This would be a good idea for any other receptor or genes/proteins mention above that you don’t want to explain in detail in the main section.
--[[User:Z3220343|Z3220343]] 21:31, 25 September 2012 (EST)

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Your introductory paragraph is sufficiently detailed. However, there is only one reference. You need to show more research by adding more references to support your text. It is good that you have added an image to support the text, but you need to write that it is a student uploaded image.
Cell biology and type 2 receptors sections don’t have any references cited at all. You need to add appropriate references.

There was an image of the tongue showing the tastes in different sections of the tongue. The image didn’t have the source referenced.

The taste map section needs more referencing and citations.

Cortical area is sufficiently detailed and has appropriate numbers of references, along with a supportive image. However, you should add more description of what the image is about.
“Timeline of Developmental Processes of the Gustatory System” looks nice so far, with appropriate citations. But you may need to add some more information, and it needs to add images to support the text.

History of discoveries section looks nice, but needs a bit more texts explaining each of the discoveries. It also needs some more references, and perhaps adding some images to support the text would make it easier to visualise the discoveries.

“Adult Tongue and Taste Buds – Structure and Function” is overall lacking in text and needs more research and references. You need to explain more of the structures and functions of the tongue. The image of the ‘drawing of the tongue’ needs a bit more description in the caption. Perhaps explain what each of the labels mean. The papillae image should say that it is a student uploaded image.

Current research section is done reasonably well so far. The reference needs appropriate formatting. Perhaps reduce the size of the image showing the double tongue; it is rather graphic and somewhat disturbing.

You do not have any useful links listed. You need to add links.

Glossary section is good so far. Perhaps add some more words, and make the text bold to make it easier to spot the different words.

Image gallery does not have images under the heading.

References section: number 5 needs to be fixed.

There are not external links listed under the heading, you need to add external links with appropriate formatting.

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Group 3- Taste

Overall this is an excellent project. Well written, great informative photos, good use of tables, and comprehensive information that's well explained.

A few of the photos don't have the appropriate copyright information and some sections of text haven't been referenced, but in general this ticks all of the boxes

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Taste

The introduction is very detailed, with descriptions of the varies components of taste. Although informative, there needs to be more about the development of the different aspects of taste. I feel that the type 2 receptor part doesn't belong here as this section is here to introduce the topic (maybe put it in a separate heading or in the neural pathway section?). There also needs to be a diagram if you are to include this as if is hard to follow. The balance between text and images is good, though some of the images are not labelled or properly referenced. Histories of discoveries section is very detailed and the table was very easy to read. The section the development of the taste is very informative and shows a of effort is placed into the of research of the topic (as it is often hard when the topic is not well understood). The section on the Structure and Function of the adult tongue gives the anatomy of the tongue, and should come before the part on neural pathways. The current research provided descriptions of the research and their goal and is done well.

==Questions for group==
--[[User:Z3330986|Z3330986]] 14:29, 18 September 2012 (EST)--[[User:Z3330986|Z3330986]] 14:29, 18 September 2012 (EST)
Hey guys,

Did I see someone write about or have articles about Sprouty (''spry'') genes?

I can't find it, but I'm sure I saw it. Let me know :)

--[[User:Z3332337|Z3332337]] 11:10, 18 September 2012 (EST)

--

Also, I've just been going over the main page and I wonder if a picture of the overall tongue, not only sections or histological drawings (which were really good btw) would be good to point out the anatomical features?? Like the sulcus terminalis which was pointed out.
I'd be happy to draw it. This would be for the Basic structure section.

Let me know ASAP so I can do it tonight :)

--[[User:Z3332337|Z3332337]] 11:30, 18 September 2012 (EST)

--

Yep, i think that would be a good idea. Go for it :)

--[[User:Z3330986|Z3330986]] 14:29, 18 September 2012 (EST)

Roger that (y). I'll have it done by around 10'ish tonight to be realistic.

--[[User:Z3332337|Z3332337]] 17:10, 18 September 2012 (EST)

--

Guys!!! I'm following image upload instructions to the letter and it keeps giving me database error. :( I need to upload figures 1 and 6 from this article. Let me know, k?

--[[User:Z3332337|Z3332337]] 17:58, 18 September 2012 (EST)

--
I had the same problem during the Lab assignments so i used a different image instead. I'm not sure if its related to the image itself? Maybe just email mark?

Maybe everyone could add some words from their relevant sections and hopefully we can come up with a pretty comprehensive glossary
--[[User:Z3330986|Z3330986]] 20:40, 18 September 2012 (EST)

== Discussion of Contributions via Email ==

Hey guys,
I know its getting late but I'm quite worried that we missed the central theme of 'embryonic development' and focused too much on adult structure and function of taste...

Please look at this article and see if there is anything relevant to your section that you can add -
[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1995452/ | Factors that regulate embryonic gustatory development]

--[[User:Z3289738|Z3289738]] 22:22, 1 October 2012 (EST)

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Hey,
It would be nice to have pictures but they're all SEM and TEM images so they're difficult to recreate by hand. What I did instead was indicated to the reader which figure to refer to. Have a look at my section, if you think you can draw a few then that would be great!

--[[User:Z3289738|Z3289738]] 20:17, 1 October 2012 (EST)

--

Hey guys,
I changed the order of the content on our page coz I thought it would make more sense for this topic to have the embryology stuff first and then move on to details of the adult features. Let me know what you think!

Also if you can each send me a brief sentence outlining each of your sections I'll put together an intro.

Thanks,
--[[User:Z3289738|Z3289738]] 09:14, 1 October 2012 (EST)

--

Jared: hi guys,

just confirming our meeting tome tomorrow after the first lecture [after mid sem break]

Thanks :-0.

Nat:
Yup, meet outside the lecture room?

--[[User:Z3332337|Z3332337]] 11:07, 11 September 2012 (EST)

--

Hey Guys,

Jared :
becuase we are on holidays as of now, make sure we are communicating about any contributions and copy and past any email discusions onto this page.

--

Hey guys,
So here's our plan for the next few weeks. If you want you can start writing up a particular section before next week!

* Wed 5/09: Have heading finalized; divide work.
* Wed 12/09: Sections finished. Discuss in class of any areas of improvement.
* Wed 19/09: Peer Assessment!

Have a good break :)

--[[User:Z3289738|Z3289738]] 11:58, 29 August 2012 (EST)

--

Hey guys,
I thought of a few headings, please let me know if you have anything to add or change!

* Intro
* History of discoveries
* Gustatory system - this is really important!!
* Tongue and taste buds - structure and function
* Taste map
* Weekly development
* Abnormalities
* Current Research
* Future research

Not including the intro we can each choose 2 areas. I'll get started on History of discoveries and Weekly development.

If you're having problems with your section, or feel that it is irrelevant, or find something else along the way just email the group and we can make changes!

Have a great week :)

Nat

--[[User:Z3289738|Z3289738]] 10:58, 5 September 2012 (EST)

--

That sounds good, maybe we should try and meet before next wednesday to make final changes?

--

Sure, how about somewhere between the two Embryology lectures (12-3pm) on Tuesday?

Which sections do you want to do? I just put them up on our wiki page.

Nat --[[User:Z3289738|Z3289738]] 11:35, 5 September 2012 (EST)

--

well i have been already doing current research and structure + development, but im happy to do more work :) and yes perhaps straight after our fist lecture 11-12pm?

--

Jordan --[[User:Z3330986|Z3330986]] 11:50, 5 September 2012 (EST)

Hi everyone i'll be happy to "Gustatory system" and "taste map." I think it would make it a bit easier as i have covered the neural pathways of taste in some detail in Neuroanatomy.

--

Okay awesome guys

So the division of work so far is:
* Introduction to the Gustatory System - '''Jordan'''
* Timeline of Developmental Processes of the Gustatory System - '''Nat'''
* History of Discoveries - '''Nat'''
* Adult Tongue and Taste Buds – Structure and Function - '''Jared'''
* Taste Map - '''Jordan'''
* Abnormalities - '''Liz?'''
* Current Research - '''Jared'''
* Future Research - '''Liz?'''

Liz are you happy with those sections?

And Jared be careful with the 'Taste Maps' section, I just read that it may be a misconception! If thats the case then maybe just how the brain interprets the 5 different types of taste.

Nat
--[[User:Z3289738|Z3289738]] 11:56, 5 September 2012 (EST)

Hi guys,
Yes I'm happy with these sections and am on it.

Liz
--[[User:Z3332337|Z3332337]] 13:46, 6 September 2012 (EST)

--
Hi,

Can someone help me with image uploading?

The website say okay to use for commercial etc...

this is the link, is that enough information to get around copyright ????
http://embryology.med.unsw.edu.au/embryology/index.php?title=File:Structure_of_Tongue.gif

Thank you, Jared

hi guys,

just confirming our meeting tome tomorrow after the first lecture.

Thanks :-0.

== Useful articles ==

Hi there,

I'm going to links to the articles I find here so you guys can see them and I don't lose them.

===Future Research===

1) A Test for Measuring Gustatory Function
[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2823587/?tool=pmcentrez]

This is pretty good for future methods of detecting defects in taste, but requires communication about reception of the tastant. Could be used when the children grow up. Great for adults.

2) The gustatory cortex and multisensory integration
[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2726647/?tool=pmcentrez]

3) REWIRING THE GUSTATORY SYSTEM: SPECIFICITY BETWEEN NERVE AND TASTE BUD FIELD IS CRITICAL FOR NORMAL SALT DISCRIMINATION
[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2812680/?tool=pmcentrez]
(Not sure where I would put this, I'm going to put it in future research]

===Abnormalities===

1) Gustatory Imagery Reveals Functional Connectivity from the Prefrontal to Insular Cortices Traced with Magnetoencephalography
[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3132751/?tool=pmcentrez]

This article essentially highlights that taste imagery is a learned response in the Insular Cortices (IC), imaged by fMRI and PET scans, and that disruption in this learning process changes the way we perceive taste. Again, I don't know how relevant this would be in the developing embryo unless there would be damage in the pre-frontal IC.

Any ideas guys??

2) Defects in the Peripheral Taste Structure and Function in the MRL/lpr Mouse Model of Autoimmune Disease
[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3334929/?tool=pmcentrez]

3) Knocking out P2X receptors reduces transmitter secretion in taste buds
[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3188419/?tool=pmcentrez]
<pubmed>21940456</pubmed>

This was a GREAT article. Basically spoke about how using double knockout (DKO) mice for taste receptors P2X2 and P2X3 were knocked out and how it didn't release the neurotransmitter ATP when a tastant was administered, whereas the WT (wild type) mice did release ATP.

--

4) Taste Function in Mice with a Targeted Mutation of the Pkd1l3 Gene
[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2924428/?tool=pmcentrez]

<pubmed>20605874</pubmed>

5) FGF Signaling Regulates the Number of Posterior Taste Papillae by Controlling Progenitor Field Size
[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3107195/?tool=pmcentrez]

<pubmed>21655085</pubmed>

6) Taste receptor cells arise from local epithelium, not neurogenic ectoderm.
[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2924428/?tool=pmcentrez]

<pubmed>7892199</pubmed>

7) Downregulation of Dlx5 and Dlx6 expression by Hand2 is essential for initiation of tongue morphogenesis
[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3091495/?tool=pmcentrez]

--[[User:Z3332337|Z3332337]] 15:30, 16 September 2012 (EST)

===Other??===

1) Olfactory and Gustatory Sensory Changes to Tobacco Smoke in Pregnant Smokers
[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3375030/?tool=pmcentrez]

This article is unrequired for this specific project (I realised this AFTER i read most of it) because it talks about how pregnancy affects the 'want' to smoke. So it's more behavioral rather than research into developmental problems that smoking may cause.

2) CODING IN THE MAMMALIAN GUSTATORY SYSTEM
[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2902637/?tool=pmcentrez]

Liz
--[[User:Z3332337|Z3332337]] 14:09, 6 September 2012 (EST)

----

Hi guys, just putting a subheading of interesting articles found:

'''1.''' <pubmed>21978088</pubmed>

'''2.''' [http://embryology.med.unsw.edu.au/notes/tongue.htm#17108952 UNSW Embryology Development of Taste]

This website provides a really great overview of taste developmental timing & overview, tastebuds, receptors, pathways, genes and provides great references for further research - and its a UNSW site!

'''3.''' [http://www.sciencedaily.com/releases/2006/12/061205214617.htm Researchers Discover Initial Steps In Development Of Taste]

A Science News story that looks at the role of Wnt pathway in the development of taste. "In the present study, the researchers found that in mice in which the actions of Wnt proteins were blocked, taste papilla buds completely failed to develop. Conversely, in mice in which Wnt signaling was over activated, their tongues were covered with many and large papillae and taste buds." It also briefly discusses neural pathways of taste and abnormalities.

'''4.''' Purves D, Augustine GJ, Fitzpatrick D, et al., editors. Neuroscience. 2nd edition. Sunderland (MA): Sinauer Associates; 2001. '''Taste Receptors and the Transduction of Taste Signals'''. Available from: http://www.ncbi.nlm.nih.gov/books/NBK11148/

This book chapter covers a variety of transduction mechanisms for taste cells. It is quite detailed, however has some great diagrams to explain the content. The concluding paragraph provides a good summary: "The overall picture that emerges from these admittedly complicated details is that taste cells have a variety of transduction mechanisms. In general, individual taste cells respond to several types of chemical stimuli. Nevertheless, taste cells also exhibit gustatory selectivity. Like olfactory cells, the lower the threshold concentration for detecting a single tastant, the greater the selectivity of the relevant taste cell. Finally, taste receptor mechanisms also adapt to the ongoing presence of a stimulus, although the mechanisms are not understood. If a chemical is left on the tongue for a sufficient time, it ceases to be perceived (consider saliva, for example). Thus, to obtain the full taste of foods, one must either frequently change the types of foods placed in the mouth or wait a sufficient time between helpings, facts that have long been appreciated by restauranteurs and gourmets."

'''5.''' <pubmed>17108952</pubmed>
This article describes the receptors and cells involved in the different types of taste (sweet, sour, bitter, salty and umami).

'''6.''' <pubmed>17287575</pubmed>
This review focuses on the development of fungiform papillae in rodents.

'''7.''' <pubmed>15581865</pubmed>
This article focuses on the role of Sonic hedgehog on tongue and taste papilla development.

'''8'''
Liu HX, Komatsu Y, Mishina Y, Mistretta CM.
http://www.ncbi.nlm.nih.gov/pubmed/22659543
This is an article about neural crest contributions to taste development

--[[User:Z3289738|Z3289738]] 10:44, 22 August 2012 (EST)

----
Remember: textbooks are a good foundation, but articles are best to gain info from.

--[[User:Z3332337|Z3332337]] 11:32, 29 August 2012 (EST)

Hey, Just need somewhere to put this:
*[http://embryology.med.unsw.edu.au/embryology/index.php?title=Sensory_-_Taste_Development Sensory Taste Development; UNSW Embryology]
*[http://www.ncbi.nlm.nih.gov/pubmed/8955790 Embryonic and early fetal development of human taste buds: a transmission electron microscopical study] <ref name=PMID8955790><pubmed>8955790</pubmed></ref> - Can't access full article!
*[http://www.ncbi.nlm.nih.gov/pubmed/9455607 Scanning electron microscopical studies of developing gustatory papillae in humans.] <ref><pubmed>9455607</pubmed></ref>
*[http://www.ncbi.nlm.nih.gov/pubmed/9541477 Innervation of developing human taste buds. An immunohistochemical study] <ref><pubmed>9541477</pubmed></ref>
*[http://www.ncbi.nlm.nih.gov/pubmed/8241557 Evidence for stimulus access to taste cells and nerves during development: an electron microscopic study.] <ref><pubmed>8241557</pubmed></ref>

--[[User:Z3289738|Z3289738]] 11:24, 19 September 2012 (EST)

== Headings==
* Introduction
* History of Major Discoveries (early researchers)
* Time line of Developmental processes
- this is the major focus of the project (ie: developmental processes)

- week by week
** Tongue
** Taste
* Final Structure and Function of the Tongue
* Abnormal structure and function
^ these 2 can be minor sections.
* Technologies to detect abnormalities during pregnancy?
* Current research (recent findings)
* Glossary and Abbreviations
* References

--[[User:Z3332337|Z3332337]] 11:30, 29 August 2012 (EST)

Notes from Mark Hill:
* Origins of sensory
* Central pathway for taste
* Neural crest contributions
* Overview diagram of sensory diagram (can be hand drawn)
* Journal of Cell biology - Taste [http://jcb.rupress.org/content/190/3/285.full JCB]
* Links between taste and smell
* Tongue has muscular and sensory functions - segregate the two

==Division of Work==

Natalie - Normal function & abnormal function

Liz - tongue & taste development

Jordan - time line of discoveries

Jared - structure & function; recent findings

==Topic Choice==

Hey guys,
Unfortunately a lot of other groups seem to want to do hearing & vision as well, so I thought maybe we should choose to do '''taste'''. Let me know what you think!

I also brainstormed a few topic headings... feel free to add to it or change the order around

Headings:
* Introduction (what is the project about?)
* Time line of major discoveries / History (early researchers)
* Structure & Function
* Tongue development (brief)
* Taste development - time line and detailed
* Normal function
* Abnormal function
* Current research (recent findings)
* Glossary and Abbreviations
* References

--[[User:Z3289738|Z3289738]] 11:42, 15 August 2012 (EST)

----

==Lets do: Sensory - Hearing==

From a bit of research this afternoon, I couldn't find much on skin development in terms of "sense organ"/"sense development". I suggest if we do Sensory we do hearing as there was alot of information (inner, middle, outer). And also there are specific screening procedures involved during pregancy.

Couple of link below with basic surface information that we could use as a starting point.

[http://cwx.prenhall.com/bookbind/pubbooks/martini10/chapter18/custom3/deluxe-content.html]

[http://www.spuc.org.uk/education/abortion/human-development]

----

Hi guys

Organ = liver

Sensory = vision / skin / hearing

--[[User:Z3289738|Z3289738]] 12:02, 8 August 2012 (EST)

really usefull website including information on phisiology etc
[http://www.cf.ac.uk/biosi/staffinfo/jacob/teaching/sensory/taste.html]

== Stucture & Function ==

'''Structure/ Parts'''
general including tissue type muslces + mucosa etc

- anterior 2/3 and posterior 1/3 (sculus terminulis)- we are manily concerned with 2/3 of tounge as it responsible for papillae + soft palate and epiglottis containing
- papillae, contain chemo-recpetors

'''Function'''
- direct vs indriect
- parts of tounge detecting differnt tastes/ flavours

'''Pathway'''
chmeorecpetors (translation/ transduction)
process of chemical to elecectrical

Talk:2012 Group Project 3

2012-10-01T12:22:11Z

Z3289738: /* Discussion of Contributions via Email */

{{2012GroupDiscussion}}

--[[User:Z8600021|Mark Hill]] 09:54, 18 September 2012 (EST) This is a recent review on taste. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2922655 http://jcb.rupress.org/content/190/3/285 JCB content allows reuse.

==Group evaluation==

The introduction section is very informative and I like the picture included discussing the 5 basic tastes which is interesting to read. I really enjoy your descriptions of bitter and sweet and find it interesting to read. I like the research you included in this section but I believe this needs to be referenced. Currently in the introduction you have only 1 references, so I would suggest that you find more to further validate your information (note that there are no references in the first paragraph). I like in your picture that you included a description. The cell biology section I would probably put in its own section with = = to break up the contend displayed. In this section it is clear that this has been researched however there have been no references listed at all here.

The taste map section has clearly been well researched yet poorly referenced. It would be interesting to look at if possible a progression of the understanding of the taste map. In the picture of the tongue, I would suggest that it has a better description on the enlarged image. However, some of this text is rather hard to read, such as the descriptions of the first and second order neurons. As you have included terms in there which would be foreign to most people, I would try to include either a picture to show exactly where these parts are such as the NTS which can give the reader a better understanding of what you’re saying. Note that you say things like “copious scientific conjecture surrounds…” however there is no references here! This section is well researched which is great, but I would really consider putting it into slightly easier terms to better comprehension.

In the cortical areas section, a similar approach applies: when describing locations of things such as the I/fO, you should really include a clear diagram as to where all of these are. I can see you included the section of the brain however don’t see it as too informative so a better description there would be appropriate. I would also note that you are repeating your references again, and it would be advisable that you find alternative information to include as well.

The timeline section is very informative and really stands out. I’m assuming you will be including the photos later this week. This is well written and gives a truly informative description of the embryological changes that occur. It will look much better and be better to understand once the photos have been included. Note that you have used the same references pretty well the whole time in this section. Although that paper may have a lot of information about what you are needing to talk about, I would also encourage you to research more papers in order to compliment the information you have listed.

The history of discoveries section is well set out and clear and concise. In some areas I would suggest a brief descripton of what you have written such as “PKD2L”, and also make sure you include the appropriate references as all I can see currently it numbers.

In the adult tongue and taste bud section, is this also what the tongue looks like from week 15? If not what changes occurs for it to form into what you have described as the adult tongue and what enhances these changes? This section is informative however it is really lacking references. The taste bud picture you have is quite good, but is that also what the taste bud looks like at 15 weeks?

The abnormalities section is really interesting and is rather enjoyable to read. Are they the only abnormalities that can happen to the tongue? How about environmental? Does alcohol, smoking or drugs affects its development of either the tongue or the taste buds? Additonally, your current research is very thorough and interesting. In regards to the photos you have there, I would make sure that they are set out appropriately, with the information that this is a student project.

Finally, the glossary needs to be highlighted to make it stand out and more words need to be included. Note that in your references, reference 5 can not be accessible, so make sure you fix that up. Overall, it was interesting to read and I enjoyed the display of photos that were also included!

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The overall set up of the page I think is very good. In the introduction there is a balance between pictures and text which makes it a bit easier to read. Also its easy to follow, the text itself isn’t confusing and is understandable.

There is a good overview of the different types of receptors and their function, also there is a brief section on the adult tongue which is good, however there needs to be more focus on the embryological development rather than just a simple table on that. There also needs to be some images added to that component as well to make it more understandable.

The sections on abnormalities and current research need to be organised a bit better because they are a little hard to follow, especially with the placing of the images. The glossary is simple and understandable, however there needs to be more work done on the reference list.

--------

The layout and balance between text and figures, tables, and diagrams is extremely well accomplished. All the information of the page is really intriguing and easy to follow on the majority.
I would suggest placing the history of discoveries immediately after the introduction so that readers may appreciate all the research that would have had to take place in order to put all the information on this page. As well, this would help in having a separation between the two tables used.

When it comes to images, make sure that everything in the image is relevant to the accompanying text and important to the reader. One image where you might fall short of this criteria, is the very first image on the page about the five basic tastes, the names of the protein structures is more distracting and confusing than enlightening and overall would not aid in informing the reader.

I believe the introduction is very important in assisting the reader in gaining an overall understanding of the page and it’s aims. Hence I believe it is important to include a more succinct introduction with such aims. In this case, the introduction to the gustatory system begins defining structures and functions which are better off used elsewhere. Instead try giving an overview of the system and maybe give the reader a reason to read on.

The images used in the abnormality section are scattered and make it hard for the reader to determine which image corresponds to which idea, I would suggest ensuring that each image is detrimental to aiding the reader’s thoughts. This was an extremely interesting section.

Current research is clear, concise and easy to follow with a pleasant arrangement of ideas, text, and images. It was interesting to read. Additionally, the references and glossary are extensive and well done. I would suggest having a link to the glossary from within the text.

Well done on your project so far, and good luck with the rest.

--------

The introduction seemed to go into a lot of detail. for example, the information on Type II receptors should be placed in the same section as neural pathways, not the introduction. Can you also include in your introduction, an overview of what you are going to talk about in your project? That would give your project more structure.

With the neural pathway section, can you draw or find a diagram for that section? I find it hard to understand without one. The taste map section goes into a lot of detail which I think is unnecessary because this is a development project.

Current research section is very interesting. I don't think you need to add any more content on that section - that section to me looks complete, besides a few formatting and referencing issues with the images.

Overall, I felt there wasn't enough written on the development of taste, either the receptors (taste buds) or the neural pathways. Your project seem to focus on the anatomy and physiology or function of the taste system. This is alright to keep but the focus should be on development. You do have a Time-line of taste development that summarizes the development of the Gustatory system which is great to see. I think use that as a starting point and expand on each stage in text form, below the table. In week 12 development in this time-line, you mention 'epithelial types I and II', what are they? Are they similar to skin cells?

Overall, the balance between images and text is great. The colourful images work wonders in breaking up the text. Having said that, Many of your images did not have the correct PMID referencing. These images include:
* images of taste being revoked by visualizing ATP release
* CVP of WT and DKO mouse with H & E and SEM
* histology - can you give a more relevant title for this image? We know it's histology; we can see that. What is this image about?
* Abnormal of Tongue - it should say abnormality of tongue

The history section is excellent because it spans over such a long time - 350BC to 2010. The layout of a coloured table for history is beautiful, clear and concise.

--[[User:Z3332863|Z3332863]] 16:35, 23 September 2012 (EST)

----

- The introduction of taste is very descriptive and encapsulates the anatomy, physiology and cell biology. Although it is very detailed it doesn’t indicate that the project is about development.

- There is a lot of detail about the taste neural pathway and cortical areas which I’m not sure is relevant to olfactory development unless you mention how they develop as well.

- Figure 2 and 3 do not have any copyright information associated so remember to add those.

- The development section is very nicely put together and hopefully you will add images further down the line. I’ve noticed that in week 8 of development you have the same ref after each line…I’m sure you can just put it at the end of the paragraph as it is same for each line. Same goes for week 14 and 15. Also since you have 2 references for the entire section --- you might want to look at other articles as well.

- Some things that I missed in the section were patterning molecules and genes. Also any signalling mechanisms that control differentiation.

- The history section is exceptionally done with the use of tables, description and references.

- I thoroughly enjoyed your abnormality section. The images are nicely done as well. Although you have described many genes and molecules which are not specified in the normal development portion so the reader don’t understand their roles. Maybe address this in your normal development section.

- The current development section is also very nicely put together but again things like Shh and WNT should be in development section.

Overall very nicely put together and great balance of pictures and text. Although this is a development topic so the major emphasis should be on development of the organ --- Normal development is good but there is too much content in that section that can be left out.

--[[User:Z3333794|Z3333794]] 10:52, 23 September 2012 (EST)

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Abundant information, including a nice coloured in table, which is a cool idea. Unfinished though, the images to go with it would make it great. The page seems to be segmented into sections with a large amount of text, and sections with many pictures. Try for a more even distribution, if possible. Pictures seem to be relevant, with good explanations, referencing and certificates. Helpful and interesting abnormalities and current research sections

--------

Your introduction is quite good and gives us a brief overview of the different tastes. I also like it that you touch on the fact that it is important we recognise (via taste) food which would be dangerous to our health. In my opinion, after you mention the research (ending the sentence with …’may exist.’) you should tell the reader what you will be discussing on your page. The few lines on fatty acids does not seem to fit in, and should be part of your history section and possibly current/future research. Some specific information seems to have been researched, such as what umami codes for; however, references have not been provided. Also make sure that the image has the correct information – title, description, references, copyright, student template.

It would be more logical to put the history section next. Following this by the timeline and then go back to the cell biology, receptors and taste map etc.

The history section is good with many significant dates and clear descriptions incorporated in a table. I do see lots of numbers, which I think relate to references. I cannot find these references anywhere, so please edit this and make sure it is included in your list of references. There are also a few references listed in full in the table, so please put these down as proper references. Also, there is no good description for the year 2007 (it is mainly a reference).

The developmental timeline is expansive and very interesting! It really relates to the different developmental stages and tells us what happens over time. I hope you can include images with appropriate labels and information to this table, as it will greatly complement your text. Please do check your spelling, eg. ‘epithelium’ in week 6. Also references in this section are appropriate and are not doubled-up in the reference list. Do check reference 5 as it comes up with a cite error.

The section on cell biology and type 2 receptors is clear and easy to read. I cannot see any references though! Please be careful cause this might indicate plagiarism. The taste map is interesting and I am glad you mentioned research has indicated that the different receptors are in fact located all over the tongue – not just in particular sections. If possible, look for the original paper(s) that made this discovery.

The section on neural pathways is a little more difficult to read and I did not understand some of it. Particular terms are used in sentences which suggest little effort has been put in to explain everything in your own words. This is further indicated by the lack of references in the ‘first order neuron’ section and the majority of the ‘second order neuron’ section. I might be wrong, but then do add all your jargon to the glossary. If possible, also try to find other papers which present the same information to strengthen your points mentioned. Images for both the taste map and the cortex need referencing, copyright info, etc.

Adult tongue and taste buds. It is good you include some anatomy and physiology into your section. Do keep in mind the majority of your project should focus on embryonic development. You included the appropriate names, eg. sulcus terminalis, and I am glad to see that has also been put in the glossary. Some more terms do need to be added, eg. circumvallate. The text is good, clear and easy to read. Images are appropriate and relate to the text but need proper descriptions, citations, etc. A major let down of this section is the lack of references – please include this.

Personally, I found the abnormalities section very interesting! However, you are suddenly talking about all these genes and factors which you have not mentioned anywhere else. It might be good to provide a brief description of these in the development section or incorporate them into your developmental timeline. Images all have copyright information, but other information is missing, such as the student template and/or reference. Please check and add this.

Current research includes a lot of information. All different sections have their references which are displayed in the reference list. If you can, provide links to the website of the research groups working on current projects. Be careful not to just put your reference at the end, as you may also have to reference within the paragraph. Both pictures used will need the student template. The double tongue image will need a reference in its description too.

As mentioned before, add and edit the glossary and reference list. You should also add to the useful links (make this external links) and the image gallery, or delete these subheadings, as there is nothing there now.

Hope this helps!
------
"In regards to the information presented (outcomes 1 and 9), the timeline for the development is good and written with clarity. However, I noticed the section on structure only referred to the adult state rather than focusing on the embryonic origin of each structure (ectoderm, endoderm and mesoderm). I would suggest that you elaborate on the developmental stages introduced in the timeline in order to build on the information you have already provided. This is important in regards to outcome 6 so that you can relate your research to embryology – the development of taste should be your focus. The history timeline was great to read as it was very concise and clear.

The page shows a good level of peer teaching with clear language and a good balance between images and text (outcome 4) with technical terms explained in the glossary. An improvement could be to make a link between any technical language and the glossary to avoid scrolling up and down to the page. Your Current Research section (outcome 5) was very interesting to read and showed you went beyond the scope of basic research on taste – good work!

In terms of layout (outcome 2), whilst the images are interesting and relevant to the text, some are not appropriately referenced nor described; make sure to reference appropriately and at least write one or two sentences to make the images relevant to the reader. Additionally, the introduction should not be under another subheading (Gustatory system) as it creates some confusion; I would suggest making the introduction its own heading in order to make the page flow. Similarly, the history timeline would best be placed towards the beginning of the page, under the introduction.

I noticed some areas (such as the section on Structure) were not appropriately or consistently referenced. Make sure to include a citation anytime you introduce a researched idea or information to avoid being accused of plagiarism. I noticed the history timeline had good consistent referencing; however the numbers just need to be formatted so they come under the reference list. If you click on the Tutorial: References page linked from the student page, it tells you how to do this. Hope the feedback helps and all the best for your project!"

------

The introduction is very detailed but did not mention anything about the development of the taste. But I thought the mechanisms behind sweet and salty tastes are very interesting. Maybe do the same for the other 3 tastes? The image of the basic 5 tastes is a bit small, maybe upload a bigger version of the image. Also, the image is lacking some reference, copyright information and a student image template.

The type II receptor section is pretty good and descriptive but it does not really relate to the development of the taste. The taste map is a very eye-catchy image and it would be really useful if it had all the needed information such as the copyright notice. The timeline of the gustatory system is very well-presented and easy to read. I understand the project is not completed yet, therefore more images are still to be put in. Only 2 references have been used in the timeline section, maybe try to research more and use different resources. There are some citing error but it should be quite easy to fix.

Histories of discoveries section is very detailed and easy to read but the referencing needs to be fixed. The adult tongue and taste bud section is very clear and precise and contain a lot of useful information but it does not really relate to the research topic, should beware of going off-track. The hand-drawn diagram of the taste bud is impressive and easy to understand but again lacking in some referencing information such as who drew it. The abnormalities section is good and well-researched and it is interesting to know about which gene or receptors will effect the development of taste and sensation. Maybe the abnormalities section can be included into the current research section because abnormalities are repeated in the current research section below. There are detailed definitions of terms in the glossary which is good because it really helps the reader to understand more about the research topic.

Overall, the page is looking good. The main thing that needs to be fixed will be the images that are already on the page, they need the correct and essential information with them when uploaded on the page or else, they will get deleted and there will be no images on the page and the nice balance of images and text now will be gone. There seem to be a lot of anatomy and biology of the taste system but not a lot of information about their development. Although there is a timeline of development but i think more information is needed. Referencing is pretty good with only one or two minor citing error but it should be easy to fix. Structure of the page is clear and simple with headings and sub-headings being consistent, making the page easy to read and follow. Hope this helps :)

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The introduction is good, explaining the function and mechanisms behind.

The taste map text and picture are useful however lack referencing information.

The cortical areas section is very interesting and well referenced.

The table timeline is a very good way to summarise the development of taste. It is succinct and well referenced, even though one paper was referred to for most of the information.

The history table is similarly good, very succinct and straightforward, however lacks some references, and the references that were included could be improved by using the wiki referencing system.

The structure and function section is useful but doesn't add much to the text in terms of embryological development. Also make sure the images are properly referenced with the "student template" included.

The abnormalities section is very good and well researched, although maybe try and avoid referring to the articles that have been researched in the text and rather just refer to them using the wiki referencing system. The images are good as well but don't forget the "student template" here also.

The current research section is interesting and well researched, the use of succinct subheadings to summarise the paper's findings was good.

The useful links and image sections need to be added to, and the glossary section can be improved by putting the key terms in bold, but that is otherwise good.

--------
Initially the page seems to have a good balance between text and diagrams/photographs. However the figures included are not properly labelled once you click on the file and some of them don't appear to have any copyright information included. Some of the pictures could do with being a bit smaller as they take up a large proportion of the page. The student drawn image of the tongue is particularly impressive but does still need to have the student template included. The references seem limited in comparison to other groups perhaps suggesting a lack of depth or variety of research. There also appears to be a coding problem relating to reference number 5. The general layout and use of subheadings is great. It may be useful to link the words in the glossary to their occurrence in the text.

The introductory paragraphs are very well written. They are easy to understand and interesting and give a good overview of how taste functions. Similarly the section on taste map is well written clearly explaining the neurological factors associated with taste. However the presence of the picture in isolation is confusing as it is representing an the old method of taste association. Perhaps this would be resolved if a diagram of the newer taste map was also included. Also you say that the old taste map has been disproved by recent research but that research is not referenced. In fact it appears that very little of that section is referenced. The section on cortical areas is well done.

The timeline of developmental processes is good, the table an easy visual format and the information concise and effective. The only point of contention would be the direct quote in Wk8-9 which seems out of place in comparison to the remainder of the entries which are nicely paraphrased. The history section is similarly well done being extensive and comprehensive. That is excepting some Pub Med references which are just placed in the text rather than in the reference list at the bottom. While interesting and well written the part detailing the Adult Tongue and Taste Buds seems out of place in a embryology course.

The sections on the effect of gene expression on the formation of taste abnormalities and current research are good. However it may be useful to put the information regarding each picture as a caption rather than plain text.

It will be interesting to see what is put in the section "Image Gallery"

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The information provided is both informative and well organised. The use of tables and figures make the text easy to follow and the diagrams make the information easier to understand. When it comes to images however, they seem to be somewhat irrelevant next to some of the information in some cases. Try to move them around and make sure they accompany relevant text.

The introduction does not give the reader the overview of the topic, but rather explores structures and function which makes it difficult to order. Simplifying the introduction, and moving some of the more detailed information such as the information about the type 2 receptors to the relevant section would improve the page.

Other information that is difficult to understand is the text which involves certain genes and molecules without explaining their function or role. Explaining these aspects of the genes and molecules would make the information flow better.
The section on current research is very informative and seems to be complete. However, I did note some errors with the citation of the image used, working on the references is very important for the other images as well as not all have the copyright information.

I also noticed that many of the references are repeated numerous times. Week 8 of development for example have the same reference after a number of sentences. A variety of sources will improve the accuracy of the information rather than derive all the information from a single source.

There is a great focus on the anatomy and physiology of taste, however, it is important to remember that the focus of this project is about development, and therefore including a timeline or a table which covers this information is very important. The page seems to be very organised and the inclusion of tables and diagrams along with the extensive glossary make this page stand out. Well done.

----
The page that you have created is very extensive and was well formatted in relation to the ratio of images to text on the page.
Found that the colours and use of table for the breakdown of information in relation to ‘Timeline of developmental process’ and ‘history of discoveries’ condensed the material and made it easily understandable. This made me want to keep reading.

With majority of the images that are uploaded onto the page there needs to be the correct information and referencing provided for the summary box. From where the image was sourced (ideally of reliable and scientific literature in origin), identifying that it has been uploaded for a student assignment and copyright information-permission to use uploaded image and any other information that is pertaining to the topic and why the image was used/relevant.
Further, those of you within your group that have drawn an uploaded image, have to ensure that you have stated in the summary box that it was student drawn prior to final assessment/evaluation.

The glossary is able to be expanded upon and potentially ensuring that the words that are being explained/elaborated are bolded. As a reader, I would find it easier to read and distinguish if they were bolded.
The reference list that has been developed appears to demonstrate that as a group you have are well read and researched, however, the citation errors will have to be addressed and resolved prior to final marking of the project. I really appreciated the layout (headings, summary and images) of the page.

----
The introduction is well written and very informative. You should add the history timeline directly below the introduction, because where it currently is feels like it is floating. With it after the introduction it will create a flow to your page and separate the two tables.
In your development table I noted a column called images, the adding of images to show the development stage you are describing will give this section some more flair. If you are not adding images don’t forget to delete the column.

Your section on adult taste and tongue is very interesting but maybe if there is a difference, i.e. newborns tongues are more sensitive to a taste than adults, a comparison would be interesting here.

In abnormalities you mention p2x receptors, maybe you could add this to the glossary and give a brief explanation about what they are and do. This would be a good idea for any other receptor or genes/proteins mention above that you don’t want to explain in detail in the main section.
--[[User:Z3220343|Z3220343]] 21:31, 25 September 2012 (EST)

---

Your introductory paragraph is sufficiently detailed. However, there is only one reference. You need to show more research by adding more references to support your text. It is good that you have added an image to support the text, but you need to write that it is a student uploaded image.
Cell biology and type 2 receptors sections don’t have any references cited at all. You need to add appropriate references.

There was an image of the tongue showing the tastes in different sections of the tongue. The image didn’t have the source referenced.

The taste map section needs more referencing and citations.

Cortical area is sufficiently detailed and has appropriate numbers of references, along with a supportive image. However, you should add more description of what the image is about.
“Timeline of Developmental Processes of the Gustatory System” looks nice so far, with appropriate citations. But you may need to add some more information, and it needs to add images to support the text.

History of discoveries section looks nice, but needs a bit more texts explaining each of the discoveries. It also needs some more references, and perhaps adding some images to support the text would make it easier to visualise the discoveries.

“Adult Tongue and Taste Buds – Structure and Function” is overall lacking in text and needs more research and references. You need to explain more of the structures and functions of the tongue. The image of the ‘drawing of the tongue’ needs a bit more description in the caption. Perhaps explain what each of the labels mean. The papillae image should say that it is a student uploaded image.

Current research section is done reasonably well so far. The reference needs appropriate formatting. Perhaps reduce the size of the image showing the double tongue; it is rather graphic and somewhat disturbing.

You do not have any useful links listed. You need to add links.

Glossary section is good so far. Perhaps add some more words, and make the text bold to make it easier to spot the different words.

Image gallery does not have images under the heading.

References section: number 5 needs to be fixed.

There are not external links listed under the heading, you need to add external links with appropriate formatting.

----

Group 3- Taste

Overall this is an excellent project. Well written, great informative photos, good use of tables, and comprehensive information that's well explained.

A few of the photos don't have the appropriate copyright information and some sections of text haven't been referenced, but in general this ticks all of the boxes

----

Taste

The introduction is very detailed, with descriptions of the varies components of taste. Although informative, there needs to be more about the development of the different aspects of taste. I feel that the type 2 receptor part doesn't belong here as this section is here to introduce the topic (maybe put it in a separate heading or in the neural pathway section?). There also needs to be a diagram if you are to include this as if is hard to follow. The balance between text and images is good, though some of the images are not labelled or properly referenced. Histories of discoveries section is very detailed and the table was very easy to read. The section the development of the taste is very informative and shows a of effort is placed into the of research of the topic (as it is often hard when the topic is not well understood). The section on the Structure and Function of the adult tongue gives the anatomy of the tongue, and should come before the part on neural pathways. The current research provided descriptions of the research and their goal and is done well.

==Questions for group==
--[[User:Z3330986|Z3330986]] 14:29, 18 September 2012 (EST)--[[User:Z3330986|Z3330986]] 14:29, 18 September 2012 (EST)
Hey guys,

Did I see someone write about or have articles about Sprouty (''spry'') genes?

I can't find it, but I'm sure I saw it. Let me know :)

--[[User:Z3332337|Z3332337]] 11:10, 18 September 2012 (EST)

--

Also, I've just been going over the main page and I wonder if a picture of the overall tongue, not only sections or histological drawings (which were really good btw) would be good to point out the anatomical features?? Like the sulcus terminalis which was pointed out.
I'd be happy to draw it. This would be for the Basic structure section.

Let me know ASAP so I can do it tonight :)

--[[User:Z3332337|Z3332337]] 11:30, 18 September 2012 (EST)

--

Yep, i think that would be a good idea. Go for it :)

--[[User:Z3330986|Z3330986]] 14:29, 18 September 2012 (EST)

Roger that (y). I'll have it done by around 10'ish tonight to be realistic.

--[[User:Z3332337|Z3332337]] 17:10, 18 September 2012 (EST)

--

Guys!!! I'm following image upload instructions to the letter and it keeps giving me database error. :( I need to upload figures 1 and 6 from this article. Let me know, k?

--[[User:Z3332337|Z3332337]] 17:58, 18 September 2012 (EST)

--
I had the same problem during the Lab assignments so i used a different image instead. I'm not sure if its related to the image itself? Maybe just email mark?

Maybe everyone could add some words from their relevant sections and hopefully we can come up with a pretty comprehensive glossary
--[[User:Z3330986|Z3330986]] 20:40, 18 September 2012 (EST)

== Discussion of Contributions via Email ==

Hey guys,
I know its getting late but I'm quite worried that we missed the central theme of 'embryonic development' and focused too much on adult structure and function of taste...

Please look at this article and see if there is anything relevant to your section that you can add
[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1995452/]

--[[User:Z3289738|Z3289738]] 22:22, 1 October 2012 (EST)

--

Hey,
It would be nice to have pictures but they're all SEM and TEM images so they're difficult to recreate by hand. What I did instead was indicated to the reader which figure to refer to. Have a look at my section, if you think you can draw a few then that would be great!

--[[User:Z3289738|Z3289738]] 20:17, 1 October 2012 (EST)

--

Hey guys,
I changed the order of the content on our page coz I thought it would make more sense for this topic to have the embryology stuff first and then move on to details of the adult features. Let me know what you think!

Also if you can each send me a brief sentence outlining each of your sections I'll put together an intro.

Thanks,
--[[User:Z3289738|Z3289738]] 09:14, 1 October 2012 (EST)

--

Jared: hi guys,

just confirming our meeting tome tomorrow after the first lecture [after mid sem break]

Thanks :-0.

Nat:
Yup, meet outside the lecture room?

--[[User:Z3332337|Z3332337]] 11:07, 11 September 2012 (EST)

--

Hey Guys,

Jared :
becuase we are on holidays as of now, make sure we are communicating about any contributions and copy and past any email discusions onto this page.

--

Hey guys,
So here's our plan for the next few weeks. If you want you can start writing up a particular section before next week!

* Wed 5/09: Have heading finalized; divide work.
* Wed 12/09: Sections finished. Discuss in class of any areas of improvement.
* Wed 19/09: Peer Assessment!

Have a good break :)

--[[User:Z3289738|Z3289738]] 11:58, 29 August 2012 (EST)

--

Hey guys,
I thought of a few headings, please let me know if you have anything to add or change!

* Intro
* History of discoveries
* Gustatory system - this is really important!!
* Tongue and taste buds - structure and function
* Taste map
* Weekly development
* Abnormalities
* Current Research
* Future research

Not including the intro we can each choose 2 areas. I'll get started on History of discoveries and Weekly development.

If you're having problems with your section, or feel that it is irrelevant, or find something else along the way just email the group and we can make changes!

Have a great week :)

Nat

--[[User:Z3289738|Z3289738]] 10:58, 5 September 2012 (EST)

--

That sounds good, maybe we should try and meet before next wednesday to make final changes?

--

Sure, how about somewhere between the two Embryology lectures (12-3pm) on Tuesday?

Which sections do you want to do? I just put them up on our wiki page.

Nat --[[User:Z3289738|Z3289738]] 11:35, 5 September 2012 (EST)

--

well i have been already doing current research and structure + development, but im happy to do more work :) and yes perhaps straight after our fist lecture 11-12pm?

--

Jordan --[[User:Z3330986|Z3330986]] 11:50, 5 September 2012 (EST)

Hi everyone i'll be happy to "Gustatory system" and "taste map." I think it would make it a bit easier as i have covered the neural pathways of taste in some detail in Neuroanatomy.

--

Okay awesome guys

So the division of work so far is:
* Introduction to the Gustatory System - '''Jordan'''
* Timeline of Developmental Processes of the Gustatory System - '''Nat'''
* History of Discoveries - '''Nat'''
* Adult Tongue and Taste Buds – Structure and Function - '''Jared'''
* Taste Map - '''Jordan'''
* Abnormalities - '''Liz?'''
* Current Research - '''Jared'''
* Future Research - '''Liz?'''

Liz are you happy with those sections?

And Jared be careful with the 'Taste Maps' section, I just read that it may be a misconception! If thats the case then maybe just how the brain interprets the 5 different types of taste.

Nat
--[[User:Z3289738|Z3289738]] 11:56, 5 September 2012 (EST)

Hi guys,
Yes I'm happy with these sections and am on it.

Liz
--[[User:Z3332337|Z3332337]] 13:46, 6 September 2012 (EST)

--
Hi,

Can someone help me with image uploading?

The website say okay to use for commercial etc...

this is the link, is that enough information to get around copyright ????
http://embryology.med.unsw.edu.au/embryology/index.php?title=File:Structure_of_Tongue.gif

Thank you, Jared

hi guys,

just confirming our meeting tome tomorrow after the first lecture.

Thanks :-0.

== Useful articles ==

Hi there,

I'm going to links to the articles I find here so you guys can see them and I don't lose them.

===Future Research===

1) A Test for Measuring Gustatory Function
[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2823587/?tool=pmcentrez]

This is pretty good for future methods of detecting defects in taste, but requires communication about reception of the tastant. Could be used when the children grow up. Great for adults.

2) The gustatory cortex and multisensory integration
[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2726647/?tool=pmcentrez]

3) REWIRING THE GUSTATORY SYSTEM: SPECIFICITY BETWEEN NERVE AND TASTE BUD FIELD IS CRITICAL FOR NORMAL SALT DISCRIMINATION
[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2812680/?tool=pmcentrez]
(Not sure where I would put this, I'm going to put it in future research]

===Abnormalities===

1) Gustatory Imagery Reveals Functional Connectivity from the Prefrontal to Insular Cortices Traced with Magnetoencephalography
[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3132751/?tool=pmcentrez]

This article essentially highlights that taste imagery is a learned response in the Insular Cortices (IC), imaged by fMRI and PET scans, and that disruption in this learning process changes the way we perceive taste. Again, I don't know how relevant this would be in the developing embryo unless there would be damage in the pre-frontal IC.

Any ideas guys??

2) Defects in the Peripheral Taste Structure and Function in the MRL/lpr Mouse Model of Autoimmune Disease
[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3334929/?tool=pmcentrez]

3) Knocking out P2X receptors reduces transmitter secretion in taste buds
[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3188419/?tool=pmcentrez]
<pubmed>21940456</pubmed>

This was a GREAT article. Basically spoke about how using double knockout (DKO) mice for taste receptors P2X2 and P2X3 were knocked out and how it didn't release the neurotransmitter ATP when a tastant was administered, whereas the WT (wild type) mice did release ATP.

--

4) Taste Function in Mice with a Targeted Mutation of the Pkd1l3 Gene
[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2924428/?tool=pmcentrez]

<pubmed>20605874</pubmed>

5) FGF Signaling Regulates the Number of Posterior Taste Papillae by Controlling Progenitor Field Size
[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3107195/?tool=pmcentrez]

<pubmed>21655085</pubmed>

6) Taste receptor cells arise from local epithelium, not neurogenic ectoderm.
[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2924428/?tool=pmcentrez]

<pubmed>7892199</pubmed>

7) Downregulation of Dlx5 and Dlx6 expression by Hand2 is essential for initiation of tongue morphogenesis
[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3091495/?tool=pmcentrez]

--[[User:Z3332337|Z3332337]] 15:30, 16 September 2012 (EST)

===Other??===

1) Olfactory and Gustatory Sensory Changes to Tobacco Smoke in Pregnant Smokers
[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3375030/?tool=pmcentrez]

This article is unrequired for this specific project (I realised this AFTER i read most of it) because it talks about how pregnancy affects the 'want' to smoke. So it's more behavioral rather than research into developmental problems that smoking may cause.

2) CODING IN THE MAMMALIAN GUSTATORY SYSTEM
[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2902637/?tool=pmcentrez]

Liz
--[[User:Z3332337|Z3332337]] 14:09, 6 September 2012 (EST)

----

Hi guys, just putting a subheading of interesting articles found:

'''1.''' <pubmed>21978088</pubmed>

'''2.''' [http://embryology.med.unsw.edu.au/notes/tongue.htm#17108952 UNSW Embryology Development of Taste]

This website provides a really great overview of taste developmental timing & overview, tastebuds, receptors, pathways, genes and provides great references for further research - and its a UNSW site!

'''3.''' [http://www.sciencedaily.com/releases/2006/12/061205214617.htm Researchers Discover Initial Steps In Development Of Taste]

A Science News story that looks at the role of Wnt pathway in the development of taste. "In the present study, the researchers found that in mice in which the actions of Wnt proteins were blocked, taste papilla buds completely failed to develop. Conversely, in mice in which Wnt signaling was over activated, their tongues were covered with many and large papillae and taste buds." It also briefly discusses neural pathways of taste and abnormalities.

'''4.''' Purves D, Augustine GJ, Fitzpatrick D, et al., editors. Neuroscience. 2nd edition. Sunderland (MA): Sinauer Associates; 2001. '''Taste Receptors and the Transduction of Taste Signals'''. Available from: http://www.ncbi.nlm.nih.gov/books/NBK11148/

This book chapter covers a variety of transduction mechanisms for taste cells. It is quite detailed, however has some great diagrams to explain the content. The concluding paragraph provides a good summary: "The overall picture that emerges from these admittedly complicated details is that taste cells have a variety of transduction mechanisms. In general, individual taste cells respond to several types of chemical stimuli. Nevertheless, taste cells also exhibit gustatory selectivity. Like olfactory cells, the lower the threshold concentration for detecting a single tastant, the greater the selectivity of the relevant taste cell. Finally, taste receptor mechanisms also adapt to the ongoing presence of a stimulus, although the mechanisms are not understood. If a chemical is left on the tongue for a sufficient time, it ceases to be perceived (consider saliva, for example). Thus, to obtain the full taste of foods, one must either frequently change the types of foods placed in the mouth or wait a sufficient time between helpings, facts that have long been appreciated by restauranteurs and gourmets."

'''5.''' <pubmed>17108952</pubmed>
This article describes the receptors and cells involved in the different types of taste (sweet, sour, bitter, salty and umami).

'''6.''' <pubmed>17287575</pubmed>
This review focuses on the development of fungiform papillae in rodents.

'''7.''' <pubmed>15581865</pubmed>
This article focuses on the role of Sonic hedgehog on tongue and taste papilla development.

'''8'''
Liu HX, Komatsu Y, Mishina Y, Mistretta CM.
http://www.ncbi.nlm.nih.gov/pubmed/22659543
This is an article about neural crest contributions to taste development

--[[User:Z3289738|Z3289738]] 10:44, 22 August 2012 (EST)

----
Remember: textbooks are a good foundation, but articles are best to gain info from.

--[[User:Z3332337|Z3332337]] 11:32, 29 August 2012 (EST)

Hey, Just need somewhere to put this:
*[http://embryology.med.unsw.edu.au/embryology/index.php?title=Sensory_-_Taste_Development Sensory Taste Development; UNSW Embryology]
*[http://www.ncbi.nlm.nih.gov/pubmed/8955790 Embryonic and early fetal development of human taste buds: a transmission electron microscopical study] <ref name=PMID8955790><pubmed>8955790</pubmed></ref> - Can't access full article!
*[http://www.ncbi.nlm.nih.gov/pubmed/9455607 Scanning electron microscopical studies of developing gustatory papillae in humans.] <ref><pubmed>9455607</pubmed></ref>
*[http://www.ncbi.nlm.nih.gov/pubmed/9541477 Innervation of developing human taste buds. An immunohistochemical study] <ref><pubmed>9541477</pubmed></ref>
*[http://www.ncbi.nlm.nih.gov/pubmed/8241557 Evidence for stimulus access to taste cells and nerves during development: an electron microscopic study.] <ref><pubmed>8241557</pubmed></ref>

--[[User:Z3289738|Z3289738]] 11:24, 19 September 2012 (EST)

== Headings==
* Introduction
* History of Major Discoveries (early researchers)
* Time line of Developmental processes
- this is the major focus of the project (ie: developmental processes)

- week by week
** Tongue
** Taste
* Final Structure and Function of the Tongue
* Abnormal structure and function
^ these 2 can be minor sections.
* Technologies to detect abnormalities during pregnancy?
* Current research (recent findings)
* Glossary and Abbreviations
* References

--[[User:Z3332337|Z3332337]] 11:30, 29 August 2012 (EST)

Notes from Mark Hill:
* Origins of sensory
* Central pathway for taste
* Neural crest contributions
* Overview diagram of sensory diagram (can be hand drawn)
* Journal of Cell biology - Taste [http://jcb.rupress.org/content/190/3/285.full JCB]
* Links between taste and smell
* Tongue has muscular and sensory functions - segregate the two

==Division of Work==

Natalie - Normal function & abnormal function

Liz - tongue & taste development

Jordan - time line of discoveries

Jared - structure & function; recent findings

==Topic Choice==

Hey guys,
Unfortunately a lot of other groups seem to want to do hearing & vision as well, so I thought maybe we should choose to do '''taste'''. Let me know what you think!

I also brainstormed a few topic headings... feel free to add to it or change the order around

Headings:
* Introduction (what is the project about?)
* Time line of major discoveries / History (early researchers)
* Structure & Function
* Tongue development (brief)
* Taste development - time line and detailed
* Normal function
* Abnormal function
* Current research (recent findings)
* Glossary and Abbreviations
* References

--[[User:Z3289738|Z3289738]] 11:42, 15 August 2012 (EST)

----

==Lets do: Sensory - Hearing==

From a bit of research this afternoon, I couldn't find much on skin development in terms of "sense organ"/"sense development". I suggest if we do Sensory we do hearing as there was alot of information (inner, middle, outer). And also there are specific screening procedures involved during pregancy.

Couple of link below with basic surface information that we could use as a starting point.

[http://cwx.prenhall.com/bookbind/pubbooks/martini10/chapter18/custom3/deluxe-content.html]

[http://www.spuc.org.uk/education/abortion/human-development]

----

Hi guys

Organ = liver

Sensory = vision / skin / hearing

--[[User:Z3289738|Z3289738]] 12:02, 8 August 2012 (EST)

really usefull website including information on phisiology etc
[http://www.cf.ac.uk/biosi/staffinfo/jacob/teaching/sensory/taste.html]

== Stucture & Function ==

'''Structure/ Parts'''
general including tissue type muslces + mucosa etc

- anterior 2/3 and posterior 1/3 (sculus terminulis)- we are manily concerned with 2/3 of tounge as it responsible for papillae + soft palate and epiglottis containing
- papillae, contain chemo-recpetors

'''Function'''
- direct vs indriect
- parts of tounge detecting differnt tastes/ flavours

'''Pathway'''
chmeorecpetors (translation/ transduction)
process of chemical to elecectrical

Talk:2012 Group Project 3

2012-10-01T10:17:08Z

Z3289738: /* Discussion of Contributions via Email */

{{2012GroupDiscussion}}

--[[User:Z8600021|Mark Hill]] 09:54, 18 September 2012 (EST) This is a recent review on taste. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2922655 http://jcb.rupress.org/content/190/3/285 JCB content allows reuse.

==Group evaluation==

The introduction section is very informative and I like the picture included discussing the 5 basic tastes which is interesting to read. I really enjoy your descriptions of bitter and sweet and find it interesting to read. I like the research you included in this section but I believe this needs to be referenced. Currently in the introduction you have only 1 references, so I would suggest that you find more to further validate your information (note that there are no references in the first paragraph). I like in your picture that you included a description. The cell biology section I would probably put in its own section with = = to break up the contend displayed. In this section it is clear that this has been researched however there have been no references listed at all here.

The taste map section has clearly been well researched yet poorly referenced. It would be interesting to look at if possible a progression of the understanding of the taste map. In the picture of the tongue, I would suggest that it has a better description on the enlarged image. However, some of this text is rather hard to read, such as the descriptions of the first and second order neurons. As you have included terms in there which would be foreign to most people, I would try to include either a picture to show exactly where these parts are such as the NTS which can give the reader a better understanding of what you’re saying. Note that you say things like “copious scientific conjecture surrounds…” however there is no references here! This section is well researched which is great, but I would really consider putting it into slightly easier terms to better comprehension.

In the cortical areas section, a similar approach applies: when describing locations of things such as the I/fO, you should really include a clear diagram as to where all of these are. I can see you included the section of the brain however don’t see it as too informative so a better description there would be appropriate. I would also note that you are repeating your references again, and it would be advisable that you find alternative information to include as well.

The timeline section is very informative and really stands out. I’m assuming you will be including the photos later this week. This is well written and gives a truly informative description of the embryological changes that occur. It will look much better and be better to understand once the photos have been included. Note that you have used the same references pretty well the whole time in this section. Although that paper may have a lot of information about what you are needing to talk about, I would also encourage you to research more papers in order to compliment the information you have listed.

The history of discoveries section is well set out and clear and concise. In some areas I would suggest a brief descripton of what you have written such as “PKD2L”, and also make sure you include the appropriate references as all I can see currently it numbers.

In the adult tongue and taste bud section, is this also what the tongue looks like from week 15? If not what changes occurs for it to form into what you have described as the adult tongue and what enhances these changes? This section is informative however it is really lacking references. The taste bud picture you have is quite good, but is that also what the taste bud looks like at 15 weeks?

The abnormalities section is really interesting and is rather enjoyable to read. Are they the only abnormalities that can happen to the tongue? How about environmental? Does alcohol, smoking or drugs affects its development of either the tongue or the taste buds? Additonally, your current research is very thorough and interesting. In regards to the photos you have there, I would make sure that they are set out appropriately, with the information that this is a student project.

Finally, the glossary needs to be highlighted to make it stand out and more words need to be included. Note that in your references, reference 5 can not be accessible, so make sure you fix that up. Overall, it was interesting to read and I enjoyed the display of photos that were also included!

--------

The overall set up of the page I think is very good. In the introduction there is a balance between pictures and text which makes it a bit easier to read. Also its easy to follow, the text itself isn’t confusing and is understandable.

There is a good overview of the different types of receptors and their function, also there is a brief section on the adult tongue which is good, however there needs to be more focus on the embryological development rather than just a simple table on that. There also needs to be some images added to that component as well to make it more understandable.

The sections on abnormalities and current research need to be organised a bit better because they are a little hard to follow, especially with the placing of the images. The glossary is simple and understandable, however there needs to be more work done on the reference list.

--------

The layout and balance between text and figures, tables, and diagrams is extremely well accomplished. All the information of the page is really intriguing and easy to follow on the majority.
I would suggest placing the history of discoveries immediately after the introduction so that readers may appreciate all the research that would have had to take place in order to put all the information on this page. As well, this would help in having a separation between the two tables used.

When it comes to images, make sure that everything in the image is relevant to the accompanying text and important to the reader. One image where you might fall short of this criteria, is the very first image on the page about the five basic tastes, the names of the protein structures is more distracting and confusing than enlightening and overall would not aid in informing the reader.

I believe the introduction is very important in assisting the reader in gaining an overall understanding of the page and it’s aims. Hence I believe it is important to include a more succinct introduction with such aims. In this case, the introduction to the gustatory system begins defining structures and functions which are better off used elsewhere. Instead try giving an overview of the system and maybe give the reader a reason to read on.

The images used in the abnormality section are scattered and make it hard for the reader to determine which image corresponds to which idea, I would suggest ensuring that each image is detrimental to aiding the reader’s thoughts. This was an extremely interesting section.

Current research is clear, concise and easy to follow with a pleasant arrangement of ideas, text, and images. It was interesting to read. Additionally, the references and glossary are extensive and well done. I would suggest having a link to the glossary from within the text.

Well done on your project so far, and good luck with the rest.

--------

The introduction seemed to go into a lot of detail. for example, the information on Type II receptors should be placed in the same section as neural pathways, not the introduction. Can you also include in your introduction, an overview of what you are going to talk about in your project? That would give your project more structure.

With the neural pathway section, can you draw or find a diagram for that section? I find it hard to understand without one. The taste map section goes into a lot of detail which I think is unnecessary because this is a development project.

Current research section is very interesting. I don't think you need to add any more content on that section - that section to me looks complete, besides a few formatting and referencing issues with the images.

Overall, I felt there wasn't enough written on the development of taste, either the receptors (taste buds) or the neural pathways. Your project seem to focus on the anatomy and physiology or function of the taste system. This is alright to keep but the focus should be on development. You do have a Time-line of taste development that summarizes the development of the Gustatory system which is great to see. I think use that as a starting point and expand on each stage in text form, below the table. In week 12 development in this time-line, you mention 'epithelial types I and II', what are they? Are they similar to skin cells?

Overall, the balance between images and text is great. The colourful images work wonders in breaking up the text. Having said that, Many of your images did not have the correct PMID referencing. These images include:
* images of taste being revoked by visualizing ATP release
* CVP of WT and DKO mouse with H & E and SEM
* histology - can you give a more relevant title for this image? We know it's histology; we can see that. What is this image about?
* Abnormal of Tongue - it should say abnormality of tongue

The history section is excellent because it spans over such a long time - 350BC to 2010. The layout of a coloured table for history is beautiful, clear and concise.

--[[User:Z3332863|Z3332863]] 16:35, 23 September 2012 (EST)

----

- The introduction of taste is very descriptive and encapsulates the anatomy, physiology and cell biology. Although it is very detailed it doesn’t indicate that the project is about development.

- There is a lot of detail about the taste neural pathway and cortical areas which I’m not sure is relevant to olfactory development unless you mention how they develop as well.

- Figure 2 and 3 do not have any copyright information associated so remember to add those.

- The development section is very nicely put together and hopefully you will add images further down the line. I’ve noticed that in week 8 of development you have the same ref after each line…I’m sure you can just put it at the end of the paragraph as it is same for each line. Same goes for week 14 and 15. Also since you have 2 references for the entire section --- you might want to look at other articles as well.

- Some things that I missed in the section were patterning molecules and genes. Also any signalling mechanisms that control differentiation.

- The history section is exceptionally done with the use of tables, description and references.

- I thoroughly enjoyed your abnormality section. The images are nicely done as well. Although you have described many genes and molecules which are not specified in the normal development portion so the reader don’t understand their roles. Maybe address this in your normal development section.

- The current development section is also very nicely put together but again things like Shh and WNT should be in development section.

Overall very nicely put together and great balance of pictures and text. Although this is a development topic so the major emphasis should be on development of the organ --- Normal development is good but there is too much content in that section that can be left out.

--[[User:Z3333794|Z3333794]] 10:52, 23 September 2012 (EST)

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Abundant information, including a nice coloured in table, which is a cool idea. Unfinished though, the images to go with it would make it great. The page seems to be segmented into sections with a large amount of text, and sections with many pictures. Try for a more even distribution, if possible. Pictures seem to be relevant, with good explanations, referencing and certificates. Helpful and interesting abnormalities and current research sections

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Your introduction is quite good and gives us a brief overview of the different tastes. I also like it that you touch on the fact that it is important we recognise (via taste) food which would be dangerous to our health. In my opinion, after you mention the research (ending the sentence with …’may exist.’) you should tell the reader what you will be discussing on your page. The few lines on fatty acids does not seem to fit in, and should be part of your history section and possibly current/future research. Some specific information seems to have been researched, such as what umami codes for; however, references have not been provided. Also make sure that the image has the correct information – title, description, references, copyright, student template.

It would be more logical to put the history section next. Following this by the timeline and then go back to the cell biology, receptors and taste map etc.

The history section is good with many significant dates and clear descriptions incorporated in a table. I do see lots of numbers, which I think relate to references. I cannot find these references anywhere, so please edit this and make sure it is included in your list of references. There are also a few references listed in full in the table, so please put these down as proper references. Also, there is no good description for the year 2007 (it is mainly a reference).

The developmental timeline is expansive and very interesting! It really relates to the different developmental stages and tells us what happens over time. I hope you can include images with appropriate labels and information to this table, as it will greatly complement your text. Please do check your spelling, eg. ‘epithelium’ in week 6. Also references in this section are appropriate and are not doubled-up in the reference list. Do check reference 5 as it comes up with a cite error.

The section on cell biology and type 2 receptors is clear and easy to read. I cannot see any references though! Please be careful cause this might indicate plagiarism. The taste map is interesting and I am glad you mentioned research has indicated that the different receptors are in fact located all over the tongue – not just in particular sections. If possible, look for the original paper(s) that made this discovery.

The section on neural pathways is a little more difficult to read and I did not understand some of it. Particular terms are used in sentences which suggest little effort has been put in to explain everything in your own words. This is further indicated by the lack of references in the ‘first order neuron’ section and the majority of the ‘second order neuron’ section. I might be wrong, but then do add all your jargon to the glossary. If possible, also try to find other papers which present the same information to strengthen your points mentioned. Images for both the taste map and the cortex need referencing, copyright info, etc.

Adult tongue and taste buds. It is good you include some anatomy and physiology into your section. Do keep in mind the majority of your project should focus on embryonic development. You included the appropriate names, eg. sulcus terminalis, and I am glad to see that has also been put in the glossary. Some more terms do need to be added, eg. circumvallate. The text is good, clear and easy to read. Images are appropriate and relate to the text but need proper descriptions, citations, etc. A major let down of this section is the lack of references – please include this.

Personally, I found the abnormalities section very interesting! However, you are suddenly talking about all these genes and factors which you have not mentioned anywhere else. It might be good to provide a brief description of these in the development section or incorporate them into your developmental timeline. Images all have copyright information, but other information is missing, such as the student template and/or reference. Please check and add this.

Current research includes a lot of information. All different sections have their references which are displayed in the reference list. If you can, provide links to the website of the research groups working on current projects. Be careful not to just put your reference at the end, as you may also have to reference within the paragraph. Both pictures used will need the student template. The double tongue image will need a reference in its description too.

As mentioned before, add and edit the glossary and reference list. You should also add to the useful links (make this external links) and the image gallery, or delete these subheadings, as there is nothing there now.

Hope this helps!
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"In regards to the information presented (outcomes 1 and 9), the timeline for the development is good and written with clarity. However, I noticed the section on structure only referred to the adult state rather than focusing on the embryonic origin of each structure (ectoderm, endoderm and mesoderm). I would suggest that you elaborate on the developmental stages introduced in the timeline in order to build on the information you have already provided. This is important in regards to outcome 6 so that you can relate your research to embryology – the development of taste should be your focus. The history timeline was great to read as it was very concise and clear.

The page shows a good level of peer teaching with clear language and a good balance between images and text (outcome 4) with technical terms explained in the glossary. An improvement could be to make a link between any technical language and the glossary to avoid scrolling up and down to the page. Your Current Research section (outcome 5) was very interesting to read and showed you went beyond the scope of basic research on taste – good work!

In terms of layout (outcome 2), whilst the images are interesting and relevant to the text, some are not appropriately referenced nor described; make sure to reference appropriately and at least write one or two sentences to make the images relevant to the reader. Additionally, the introduction should not be under another subheading (Gustatory system) as it creates some confusion; I would suggest making the introduction its own heading in order to make the page flow. Similarly, the history timeline would best be placed towards the beginning of the page, under the introduction.

I noticed some areas (such as the section on Structure) were not appropriately or consistently referenced. Make sure to include a citation anytime you introduce a researched idea or information to avoid being accused of plagiarism. I noticed the history timeline had good consistent referencing; however the numbers just need to be formatted so they come under the reference list. If you click on the Tutorial: References page linked from the student page, it tells you how to do this. Hope the feedback helps and all the best for your project!"

------

The introduction is very detailed but did not mention anything about the development of the taste. But I thought the mechanisms behind sweet and salty tastes are very interesting. Maybe do the same for the other 3 tastes? The image of the basic 5 tastes is a bit small, maybe upload a bigger version of the image. Also, the image is lacking some reference, copyright information and a student image template.

The type II receptor section is pretty good and descriptive but it does not really relate to the development of the taste. The taste map is a very eye-catchy image and it would be really useful if it had all the needed information such as the copyright notice. The timeline of the gustatory system is very well-presented and easy to read. I understand the project is not completed yet, therefore more images are still to be put in. Only 2 references have been used in the timeline section, maybe try to research more and use different resources. There are some citing error but it should be quite easy to fix.

Histories of discoveries section is very detailed and easy to read but the referencing needs to be fixed. The adult tongue and taste bud section is very clear and precise and contain a lot of useful information but it does not really relate to the research topic, should beware of going off-track. The hand-drawn diagram of the taste bud is impressive and easy to understand but again lacking in some referencing information such as who drew it. The abnormalities section is good and well-researched and it is interesting to know about which gene or receptors will effect the development of taste and sensation. Maybe the abnormalities section can be included into the current research section because abnormalities are repeated in the current research section below. There are detailed definitions of terms in the glossary which is good because it really helps the reader to understand more about the research topic.

Overall, the page is looking good. The main thing that needs to be fixed will be the images that are already on the page, they need the correct and essential information with them when uploaded on the page or else, they will get deleted and there will be no images on the page and the nice balance of images and text now will be gone. There seem to be a lot of anatomy and biology of the taste system but not a lot of information about their development. Although there is a timeline of development but i think more information is needed. Referencing is pretty good with only one or two minor citing error but it should be easy to fix. Structure of the page is clear and simple with headings and sub-headings being consistent, making the page easy to read and follow. Hope this helps :)

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The introduction is good, explaining the function and mechanisms behind.

The taste map text and picture are useful however lack referencing information.

The cortical areas section is very interesting and well referenced.

The table timeline is a very good way to summarise the development of taste. It is succinct and well referenced, even though one paper was referred to for most of the information.

The history table is similarly good, very succinct and straightforward, however lacks some references, and the references that were included could be improved by using the wiki referencing system.

The structure and function section is useful but doesn't add much to the text in terms of embryological development. Also make sure the images are properly referenced with the "student template" included.

The abnormalities section is very good and well researched, although maybe try and avoid referring to the articles that have been researched in the text and rather just refer to them using the wiki referencing system. The images are good as well but don't forget the "student template" here also.

The current research section is interesting and well researched, the use of succinct subheadings to summarise the paper's findings was good.

The useful links and image sections need to be added to, and the glossary section can be improved by putting the key terms in bold, but that is otherwise good.

--------
Initially the page seems to have a good balance between text and diagrams/photographs. However the figures included are not properly labelled once you click on the file and some of them don't appear to have any copyright information included. Some of the pictures could do with being a bit smaller as they take up a large proportion of the page. The student drawn image of the tongue is particularly impressive but does still need to have the student template included. The references seem limited in comparison to other groups perhaps suggesting a lack of depth or variety of research. There also appears to be a coding problem relating to reference number 5. The general layout and use of subheadings is great. It may be useful to link the words in the glossary to their occurrence in the text.

The introductory paragraphs are very well written. They are easy to understand and interesting and give a good overview of how taste functions. Similarly the section on taste map is well written clearly explaining the neurological factors associated with taste. However the presence of the picture in isolation is confusing as it is representing an the old method of taste association. Perhaps this would be resolved if a diagram of the newer taste map was also included. Also you say that the old taste map has been disproved by recent research but that research is not referenced. In fact it appears that very little of that section is referenced. The section on cortical areas is well done.

The timeline of developmental processes is good, the table an easy visual format and the information concise and effective. The only point of contention would be the direct quote in Wk8-9 which seems out of place in comparison to the remainder of the entries which are nicely paraphrased. The history section is similarly well done being extensive and comprehensive. That is excepting some Pub Med references which are just placed in the text rather than in the reference list at the bottom. While interesting and well written the part detailing the Adult Tongue and Taste Buds seems out of place in a embryology course.

The sections on the effect of gene expression on the formation of taste abnormalities and current research are good. However it may be useful to put the information regarding each picture as a caption rather than plain text.

It will be interesting to see what is put in the section "Image Gallery"

---------
The information provided is both informative and well organised. The use of tables and figures make the text easy to follow and the diagrams make the information easier to understand. When it comes to images however, they seem to be somewhat irrelevant next to some of the information in some cases. Try to move them around and make sure they accompany relevant text.

The introduction does not give the reader the overview of the topic, but rather explores structures and function which makes it difficult to order. Simplifying the introduction, and moving some of the more detailed information such as the information about the type 2 receptors to the relevant section would improve the page.

Other information that is difficult to understand is the text which involves certain genes and molecules without explaining their function or role. Explaining these aspects of the genes and molecules would make the information flow better.
The section on current research is very informative and seems to be complete. However, I did note some errors with the citation of the image used, working on the references is very important for the other images as well as not all have the copyright information.

I also noticed that many of the references are repeated numerous times. Week 8 of development for example have the same reference after a number of sentences. A variety of sources will improve the accuracy of the information rather than derive all the information from a single source.

There is a great focus on the anatomy and physiology of taste, however, it is important to remember that the focus of this project is about development, and therefore including a timeline or a table which covers this information is very important. The page seems to be very organised and the inclusion of tables and diagrams along with the extensive glossary make this page stand out. Well done.

----
The page that you have created is very extensive and was well formatted in relation to the ratio of images to text on the page.
Found that the colours and use of table for the breakdown of information in relation to ‘Timeline of developmental process’ and ‘history of discoveries’ condensed the material and made it easily understandable. This made me want to keep reading.

With majority of the images that are uploaded onto the page there needs to be the correct information and referencing provided for the summary box. From where the image was sourced (ideally of reliable and scientific literature in origin), identifying that it has been uploaded for a student assignment and copyright information-permission to use uploaded image and any other information that is pertaining to the topic and why the image was used/relevant.
Further, those of you within your group that have drawn an uploaded image, have to ensure that you have stated in the summary box that it was student drawn prior to final assessment/evaluation.

The glossary is able to be expanded upon and potentially ensuring that the words that are being explained/elaborated are bolded. As a reader, I would find it easier to read and distinguish if they were bolded.
The reference list that has been developed appears to demonstrate that as a group you have are well read and researched, however, the citation errors will have to be addressed and resolved prior to final marking of the project. I really appreciated the layout (headings, summary and images) of the page.

----
The introduction is well written and very informative. You should add the history timeline directly below the introduction, because where it currently is feels like it is floating. With it after the introduction it will create a flow to your page and separate the two tables.
In your development table I noted a column called images, the adding of images to show the development stage you are describing will give this section some more flair. If you are not adding images don’t forget to delete the column.

Your section on adult taste and tongue is very interesting but maybe if there is a difference, i.e. newborns tongues are more sensitive to a taste than adults, a comparison would be interesting here.

In abnormalities you mention p2x receptors, maybe you could add this to the glossary and give a brief explanation about what they are and do. This would be a good idea for any other receptor or genes/proteins mention above that you don’t want to explain in detail in the main section.
--[[User:Z3220343|Z3220343]] 21:31, 25 September 2012 (EST)

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Your introductory paragraph is sufficiently detailed. However, there is only one reference. You need to show more research by adding more references to support your text. It is good that you have added an image to support the text, but you need to write that it is a student uploaded image.
Cell biology and type 2 receptors sections don’t have any references cited at all. You need to add appropriate references.

There was an image of the tongue showing the tastes in different sections of the tongue. The image didn’t have the source referenced.

The taste map section needs more referencing and citations.

Cortical area is sufficiently detailed and has appropriate numbers of references, along with a supportive image. However, you should add more description of what the image is about.
“Timeline of Developmental Processes of the Gustatory System” looks nice so far, with appropriate citations. But you may need to add some more information, and it needs to add images to support the text.

History of discoveries section looks nice, but needs a bit more texts explaining each of the discoveries. It also needs some more references, and perhaps adding some images to support the text would make it easier to visualise the discoveries.

“Adult Tongue and Taste Buds – Structure and Function” is overall lacking in text and needs more research and references. You need to explain more of the structures and functions of the tongue. The image of the ‘drawing of the tongue’ needs a bit more description in the caption. Perhaps explain what each of the labels mean. The papillae image should say that it is a student uploaded image.

Current research section is done reasonably well so far. The reference needs appropriate formatting. Perhaps reduce the size of the image showing the double tongue; it is rather graphic and somewhat disturbing.

You do not have any useful links listed. You need to add links.

Glossary section is good so far. Perhaps add some more words, and make the text bold to make it easier to spot the different words.

Image gallery does not have images under the heading.

References section: number 5 needs to be fixed.

There are not external links listed under the heading, you need to add external links with appropriate formatting.

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Group 3- Taste

Overall this is an excellent project. Well written, great informative photos, good use of tables, and comprehensive information that's well explained.

A few of the photos don't have the appropriate copyright information and some sections of text haven't been referenced, but in general this ticks all of the boxes

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Taste

The introduction is very detailed, with descriptions of the varies components of taste. Although informative, there needs to be more about the development of the different aspects of taste. I feel that the type 2 receptor part doesn't belong here as this section is here to introduce the topic (maybe put it in a separate heading or in the neural pathway section?). There also needs to be a diagram if you are to include this as if is hard to follow. The balance between text and images is good, though some of the images are not labelled or properly referenced. Histories of discoveries section is very detailed and the table was very easy to read. The section the development of the taste is very informative and shows a of effort is placed into the of research of the topic (as it is often hard when the topic is not well understood). The section on the Structure and Function of the adult tongue gives the anatomy of the tongue, and should come before the part on neural pathways. The current research provided descriptions of the research and their goal and is done well.

==Questions for group==
--[[User:Z3330986|Z3330986]] 14:29, 18 September 2012 (EST)--[[User:Z3330986|Z3330986]] 14:29, 18 September 2012 (EST)
Hey guys,

Did I see someone write about or have articles about Sprouty (''spry'') genes?

I can't find it, but I'm sure I saw it. Let me know :)

--[[User:Z3332337|Z3332337]] 11:10, 18 September 2012 (EST)

--

Also, I've just been going over the main page and I wonder if a picture of the overall tongue, not only sections or histological drawings (which were really good btw) would be good to point out the anatomical features?? Like the sulcus terminalis which was pointed out.
I'd be happy to draw it. This would be for the Basic structure section.

Let me know ASAP so I can do it tonight :)

--[[User:Z3332337|Z3332337]] 11:30, 18 September 2012 (EST)

--

Yep, i think that would be a good idea. Go for it :)

--[[User:Z3330986|Z3330986]] 14:29, 18 September 2012 (EST)

Roger that (y). I'll have it done by around 10'ish tonight to be realistic.

--[[User:Z3332337|Z3332337]] 17:10, 18 September 2012 (EST)

--

Guys!!! I'm following image upload instructions to the letter and it keeps giving me database error. :( I need to upload figures 1 and 6 from this article. Let me know, k?

--[[User:Z3332337|Z3332337]] 17:58, 18 September 2012 (EST)

--
I had the same problem during the Lab assignments so i used a different image instead. I'm not sure if its related to the image itself? Maybe just email mark?

Maybe everyone could add some words from their relevant sections and hopefully we can come up with a pretty comprehensive glossary
--[[User:Z3330986|Z3330986]] 20:40, 18 September 2012 (EST)

== Discussion of Contributions via Email ==

Hey,
It would be nice to have pictures but they're all SEM and TEM images so they're difficult to recreate by hand. What I did instead was indicated to the reader which figure to refer to. Have a look at my section, if you think you can draw a few then that would be great!

--[[User:Z3289738|Z3289738]] 20:17, 1 October 2012 (EST)

--

Hey guys,
I changed the order of the content on our page coz I thought it would make more sense for this topic to have the embryology stuff first and then move on to details of the adult features. Let me know what you think!

Also if you can each send me a brief sentence outlining each of your sections I'll put together an intro.

Thanks,
--[[User:Z3289738|Z3289738]] 09:14, 1 October 2012 (EST)

--

Jared: hi guys,

just confirming our meeting tome tomorrow after the first lecture [after mid sem break]

Thanks :-0.

Nat:
Yup, meet outside the lecture room?

--[[User:Z3332337|Z3332337]] 11:07, 11 September 2012 (EST)

--

Hey Guys,

Jared :
becuase we are on holidays as of now, make sure we are communicating about any contributions and copy and past any email discusions onto this page.

--

Hey guys,
So here's our plan for the next few weeks. If you want you can start writing up a particular section before next week!

* Wed 5/09: Have heading finalized; divide work.
* Wed 12/09: Sections finished. Discuss in class of any areas of improvement.
* Wed 19/09: Peer Assessment!

Have a good break :)

--[[User:Z3289738|Z3289738]] 11:58, 29 August 2012 (EST)

--

Hey guys,
I thought of a few headings, please let me know if you have anything to add or change!

* Intro
* History of discoveries
* Gustatory system - this is really important!!
* Tongue and taste buds - structure and function
* Taste map
* Weekly development
* Abnormalities
* Current Research
* Future research

Not including the intro we can each choose 2 areas. I'll get started on History of discoveries and Weekly development.

If you're having problems with your section, or feel that it is irrelevant, or find something else along the way just email the group and we can make changes!

Have a great week :)

Nat

--[[User:Z3289738|Z3289738]] 10:58, 5 September 2012 (EST)

--

That sounds good, maybe we should try and meet before next wednesday to make final changes?

--

Sure, how about somewhere between the two Embryology lectures (12-3pm) on Tuesday?

Which sections do you want to do? I just put them up on our wiki page.

Nat --[[User:Z3289738|Z3289738]] 11:35, 5 September 2012 (EST)

--

well i have been already doing current research and structure + development, but im happy to do more work :) and yes perhaps straight after our fist lecture 11-12pm?

--

Jordan --[[User:Z3330986|Z3330986]] 11:50, 5 September 2012 (EST)

Hi everyone i'll be happy to "Gustatory system" and "taste map." I think it would make it a bit easier as i have covered the neural pathways of taste in some detail in Neuroanatomy.

--

Okay awesome guys

So the division of work so far is:
* Introduction to the Gustatory System - '''Jordan'''
* Timeline of Developmental Processes of the Gustatory System - '''Nat'''
* History of Discoveries - '''Nat'''
* Adult Tongue and Taste Buds – Structure and Function - '''Jared'''
* Taste Map - '''Jordan'''
* Abnormalities - '''Liz?'''
* Current Research - '''Jared'''
* Future Research - '''Liz?'''

Liz are you happy with those sections?

And Jared be careful with the 'Taste Maps' section, I just read that it may be a misconception! If thats the case then maybe just how the brain interprets the 5 different types of taste.

Nat
--[[User:Z3289738|Z3289738]] 11:56, 5 September 2012 (EST)

Hi guys,
Yes I'm happy with these sections and am on it.

Liz
--[[User:Z3332337|Z3332337]] 13:46, 6 September 2012 (EST)

--
Hi,

Can someone help me with image uploading?

The website say okay to use for commercial etc...

this is the link, is that enough information to get around copyright ????
http://embryology.med.unsw.edu.au/embryology/index.php?title=File:Structure_of_Tongue.gif

Thank you, Jared

hi guys,

just confirming our meeting tome tomorrow after the first lecture.

Thanks :-0.

== Useful articles ==

Hi there,

I'm going to links to the articles I find here so you guys can see them and I don't lose them.

===Future Research===

1) A Test for Measuring Gustatory Function
[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2823587/?tool=pmcentrez]

This is pretty good for future methods of detecting defects in taste, but requires communication about reception of the tastant. Could be used when the children grow up. Great for adults.

2) The gustatory cortex and multisensory integration
[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2726647/?tool=pmcentrez]

3) REWIRING THE GUSTATORY SYSTEM: SPECIFICITY BETWEEN NERVE AND TASTE BUD FIELD IS CRITICAL FOR NORMAL SALT DISCRIMINATION
[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2812680/?tool=pmcentrez]
(Not sure where I would put this, I'm going to put it in future research]

===Abnormalities===

1) Gustatory Imagery Reveals Functional Connectivity from the Prefrontal to Insular Cortices Traced with Magnetoencephalography
[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3132751/?tool=pmcentrez]

This article essentially highlights that taste imagery is a learned response in the Insular Cortices (IC), imaged by fMRI and PET scans, and that disruption in this learning process changes the way we perceive taste. Again, I don't know how relevant this would be in the developing embryo unless there would be damage in the pre-frontal IC.

Any ideas guys??

2) Defects in the Peripheral Taste Structure and Function in the MRL/lpr Mouse Model of Autoimmune Disease
[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3334929/?tool=pmcentrez]

3) Knocking out P2X receptors reduces transmitter secretion in taste buds
[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3188419/?tool=pmcentrez]
<pubmed>21940456</pubmed>

This was a GREAT article. Basically spoke about how using double knockout (DKO) mice for taste receptors P2X2 and P2X3 were knocked out and how it didn't release the neurotransmitter ATP when a tastant was administered, whereas the WT (wild type) mice did release ATP.

--

4) Taste Function in Mice with a Targeted Mutation of the Pkd1l3 Gene
[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2924428/?tool=pmcentrez]

<pubmed>20605874</pubmed>

5) FGF Signaling Regulates the Number of Posterior Taste Papillae by Controlling Progenitor Field Size
[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3107195/?tool=pmcentrez]

<pubmed>21655085</pubmed>

6) Taste receptor cells arise from local epithelium, not neurogenic ectoderm.
[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2924428/?tool=pmcentrez]

<pubmed>7892199</pubmed>

7) Downregulation of Dlx5 and Dlx6 expression by Hand2 is essential for initiation of tongue morphogenesis
[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3091495/?tool=pmcentrez]

--[[User:Z3332337|Z3332337]] 15:30, 16 September 2012 (EST)

===Other??===

1) Olfactory and Gustatory Sensory Changes to Tobacco Smoke in Pregnant Smokers
[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3375030/?tool=pmcentrez]

This article is unrequired for this specific project (I realised this AFTER i read most of it) because it talks about how pregnancy affects the 'want' to smoke. So it's more behavioral rather than research into developmental problems that smoking may cause.

2) CODING IN THE MAMMALIAN GUSTATORY SYSTEM
[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2902637/?tool=pmcentrez]

Liz
--[[User:Z3332337|Z3332337]] 14:09, 6 September 2012 (EST)

----

Hi guys, just putting a subheading of interesting articles found:

'''1.''' <pubmed>21978088</pubmed>

'''2.''' [http://embryology.med.unsw.edu.au/notes/tongue.htm#17108952 UNSW Embryology Development of Taste]

This website provides a really great overview of taste developmental timing & overview, tastebuds, receptors, pathways, genes and provides great references for further research - and its a UNSW site!

'''3.''' [http://www.sciencedaily.com/releases/2006/12/061205214617.htm Researchers Discover Initial Steps In Development Of Taste]

A Science News story that looks at the role of Wnt pathway in the development of taste. "In the present study, the researchers found that in mice in which the actions of Wnt proteins were blocked, taste papilla buds completely failed to develop. Conversely, in mice in which Wnt signaling was over activated, their tongues were covered with many and large papillae and taste buds." It also briefly discusses neural pathways of taste and abnormalities.

'''4.''' Purves D, Augustine GJ, Fitzpatrick D, et al., editors. Neuroscience. 2nd edition. Sunderland (MA): Sinauer Associates; 2001. '''Taste Receptors and the Transduction of Taste Signals'''. Available from: http://www.ncbi.nlm.nih.gov/books/NBK11148/

This book chapter covers a variety of transduction mechanisms for taste cells. It is quite detailed, however has some great diagrams to explain the content. The concluding paragraph provides a good summary: "The overall picture that emerges from these admittedly complicated details is that taste cells have a variety of transduction mechanisms. In general, individual taste cells respond to several types of chemical stimuli. Nevertheless, taste cells also exhibit gustatory selectivity. Like olfactory cells, the lower the threshold concentration for detecting a single tastant, the greater the selectivity of the relevant taste cell. Finally, taste receptor mechanisms also adapt to the ongoing presence of a stimulus, although the mechanisms are not understood. If a chemical is left on the tongue for a sufficient time, it ceases to be perceived (consider saliva, for example). Thus, to obtain the full taste of foods, one must either frequently change the types of foods placed in the mouth or wait a sufficient time between helpings, facts that have long been appreciated by restauranteurs and gourmets."

'''5.''' <pubmed>17108952</pubmed>
This article describes the receptors and cells involved in the different types of taste (sweet, sour, bitter, salty and umami).

'''6.''' <pubmed>17287575</pubmed>
This review focuses on the development of fungiform papillae in rodents.

'''7.''' <pubmed>15581865</pubmed>
This article focuses on the role of Sonic hedgehog on tongue and taste papilla development.

'''8'''
Liu HX, Komatsu Y, Mishina Y, Mistretta CM.
http://www.ncbi.nlm.nih.gov/pubmed/22659543
This is an article about neural crest contributions to taste development

--[[User:Z3289738|Z3289738]] 10:44, 22 August 2012 (EST)

----
Remember: textbooks are a good foundation, but articles are best to gain info from.

--[[User:Z3332337|Z3332337]] 11:32, 29 August 2012 (EST)

Hey, Just need somewhere to put this:
*[http://embryology.med.unsw.edu.au/embryology/index.php?title=Sensory_-_Taste_Development Sensory Taste Development; UNSW Embryology]
*[http://www.ncbi.nlm.nih.gov/pubmed/8955790 Embryonic and early fetal development of human taste buds: a transmission electron microscopical study] <ref name=PMID8955790><pubmed>8955790</pubmed></ref> - Can't access full article!
*[http://www.ncbi.nlm.nih.gov/pubmed/9455607 Scanning electron microscopical studies of developing gustatory papillae in humans.] <ref><pubmed>9455607</pubmed></ref>
*[http://www.ncbi.nlm.nih.gov/pubmed/9541477 Innervation of developing human taste buds. An immunohistochemical study] <ref><pubmed>9541477</pubmed></ref>
*[http://www.ncbi.nlm.nih.gov/pubmed/8241557 Evidence for stimulus access to taste cells and nerves during development: an electron microscopic study.] <ref><pubmed>8241557</pubmed></ref>

--[[User:Z3289738|Z3289738]] 11:24, 19 September 2012 (EST)

== Headings==
* Introduction
* History of Major Discoveries (early researchers)
* Time line of Developmental processes
- this is the major focus of the project (ie: developmental processes)

- week by week
** Tongue
** Taste
* Final Structure and Function of the Tongue
* Abnormal structure and function
^ these 2 can be minor sections.
* Technologies to detect abnormalities during pregnancy?
* Current research (recent findings)
* Glossary and Abbreviations
* References

--[[User:Z3332337|Z3332337]] 11:30, 29 August 2012 (EST)

Notes from Mark Hill:
* Origins of sensory
* Central pathway for taste
* Neural crest contributions
* Overview diagram of sensory diagram (can be hand drawn)
* Journal of Cell biology - Taste [http://jcb.rupress.org/content/190/3/285.full JCB]
* Links between taste and smell
* Tongue has muscular and sensory functions - segregate the two

==Division of Work==

Natalie - Normal function & abnormal function

Liz - tongue & taste development

Jordan - time line of discoveries

Jared - structure & function; recent findings

==Topic Choice==

Hey guys,
Unfortunately a lot of other groups seem to want to do hearing & vision as well, so I thought maybe we should choose to do '''taste'''. Let me know what you think!

I also brainstormed a few topic headings... feel free to add to it or change the order around

Headings:
* Introduction (what is the project about?)
* Time line of major discoveries / History (early researchers)
* Structure & Function
* Tongue development (brief)
* Taste development - time line and detailed
* Normal function
* Abnormal function
* Current research (recent findings)
* Glossary and Abbreviations
* References

--[[User:Z3289738|Z3289738]] 11:42, 15 August 2012 (EST)

----

==Lets do: Sensory - Hearing==

From a bit of research this afternoon, I couldn't find much on skin development in terms of "sense organ"/"sense development". I suggest if we do Sensory we do hearing as there was alot of information (inner, middle, outer). And also there are specific screening procedures involved during pregancy.

Couple of link below with basic surface information that we could use as a starting point.

[http://cwx.prenhall.com/bookbind/pubbooks/martini10/chapter18/custom3/deluxe-content.html]

[http://www.spuc.org.uk/education/abortion/human-development]

----

Hi guys

Organ = liver

Sensory = vision / skin / hearing

--[[User:Z3289738|Z3289738]] 12:02, 8 August 2012 (EST)

really usefull website including information on phisiology etc
[http://www.cf.ac.uk/biosi/staffinfo/jacob/teaching/sensory/taste.html]

== Stucture & Function ==

'''Structure/ Parts'''
general including tissue type muslces + mucosa etc

- anterior 2/3 and posterior 1/3 (sculus terminulis)- we are manily concerned with 2/3 of tounge as it responsible for papillae + soft palate and epiglottis containing
- papillae, contain chemo-recpetors

'''Function'''
- direct vs indriect
- parts of tounge detecting differnt tastes/ flavours

'''Pathway'''
chmeorecpetors (translation/ transduction)
process of chemical to elecectrical

2012 Group Project 3

2012-09-30T23:44:26Z

Z3289738: /* Glossary */

=Taste Development=

== Introduction ==
**NEED TO ADD**

==Adult Tongue and Taste Buds – Structure and Function==

'''Structure'''

The tongue is located on the floor of the oral cavity, It is a muscular structure with sensory units crowning. The tongue is divided into an anterior two thirds and a posterior one third. These regions are divided by a V-shaped groove at the back of the tongue (sulcus terminalis). The anterior two thirds of the tongue is covered by stratified squamous epithelium, It contains a roughened surface and has projections called papillae that vary in shape and number.

''''The image below is a simplistic diagram of the surface of the tongue showing the locations of the different papillae and other important features'''

{|
| [[Image:Drawing of Tongue.png|500px]]

'''Papillae'''
[[File:Papillae.jpg|Left|thumb|200px|Close up of Human Tongue Papillae]]

There are 4 types of papillae on the tongue.
The most numerous papillae are the filiform papillae, which function to provide a surface that aids in holding food on the tongue during chewing but do not contain taste buds. The larger, less numerous fungiform papillae which contain taste buds, as do foliate papillae. Circumvallate papillae form a wide V at the sulcus terminalis also containing taste bus. There are no papillae or taste buds located on the posterior third of the tongue, having mucosal folds and the lingual tonsils instead.

'''Function'''

The tongue is for tasting, swallowing, and speech.
The functional unit of the taste bud is a taste cell, there are between 50 and 100 taste cells in each taste bud these taste cells represent all 5 different tastes. Historically is was believed that different areas of the tongue were responsible for different taste sensations although this has since been disregarded.[http://users.rcn.com/jkimball.ma.ultranet/BiologyPages/W/Welcome.html] The papillae contain taste buds which are connected to the oral cavity via a taste pore, the function of the taste bud is to transmit a chemical signal from the oral cavity to a taste cell, this chemical signal is the converted into an electrical impulse and delivered to the brain via nerve fibres for interpretation.

'''The image below is a simplistic hand-drawn cross section of a taste bud unit (not to scale)'''

[[File:Taste_bud_1.jpg|x400px|alt=Cross section of a taste bud unit|Cross section of a taste bud unit]]

==History of Discoveries==

{| cellpadding=5 style="border:1px solid #BBB"
|- bgcolor="#faecc8"
|''' Date'''|| '''Significant Discovery'''

|- bgcolor="#faf6ed"
|'''350BC'''
|| Aristotle writes about the basic tastes, sweet and bitter. He also notes that it can be modified by salty and acidic. <ref name="PMID22717400"><pubmed>22717400</pubmed></ref>

|- bgcolor="#faecc8"
|'''1901'''
|| D. Hanig publishes a paper describing taste sensitivity in different regions of the tongue.
''Interesting fact:'' The modern concept of a 'tongue map' is a misinterpretation of this study. <ref name="PMID22717400"/>

|- bgcolor="#faf6ed"
|style=white-space:nowrap|'''1908'''
|Kikunae Ikeda, a professor of the Tokyo Imperial University, discovered and identified the fifth basic taste: umami (savouriness), made palatable by glutamate. <ref><pubmed>12438213</pubmed></ref>
[http://chemse.oxfordjournals.org/content/27/9/847.long New Seasonings]

|- bgcolor="#faecc8"
|style=white-space:nowrap|'''1931-32'''
| A chemist named Arthur Fox and his college noted that they had different sensitivities to the bitter tasting Phenylthiocarbamide (PTC).<ref>Blakeslee AF, Fox AL. Our different taste worlds. J Hered. 1932;23:97–107.</ref> Geneticists later confirm these findings, and discover that non-tasting is a recessive genetic trait. <ref><pubmed>17782493</pubmed></ref>
[http://www.ncbi.nlm.nih.gov/pubmed/17782493 Inherited taste deficiency]

|- bgcolor="#faf6ed"
|style=white-space:nowrap|'''1965'''
|Farbman's study of the developing taste but in rat fungiform papilla was significant in increasing our understanding of taste bud development. <ref><pubmed>14300090</pubmed></ref>
[http://www.sciencedirect.com/science/article/pii/0012160665900400 Electron microscope study of the developing taste bud in rat fungiform papilla.]

|- bgcolor="#faecc8"
|style=white-space:nowrap|'''1992'''
|McLaughlin SK et al. discovery a taste cell-specific G-protein within the taste buds called Gustucon. This protein is later used to mark bitter, umami and sweet cells. <ref><pubmed>1608467 </pubmed></ref>
[http://www.nature.com/nature/journal/v357/n6379/abs/357563a0.html Gustducin is a taste-cell-specific G protein closely related to the transducins]

|- bgcolor="#faf6ed"
|style=white-space:nowrap|'''1995'''
|Barlow et al. experimented with Axolotl salamanders and concluded that taste buds from this species arise exclusively from epithelial tissue, "oropharyngeal [[#Glossary |'''epithelium''']]". <ref name="PMID17826760"><pubmed>17826760</pubmed></ref>
[http://www.ncbi.nlm.nih.gov/pubmed/17826760 Embryonic origin of gustatory cranial sensory neurons]

|- bgcolor="#faecc8"
|style=white-space:nowrap|'''1996'''
| Witt M and Reutter K of the Technical University Dresden in Germany, carried out a transmission electron microscopy study to investigate the embryonic and fetal development of Human taste buds. Their results suggest an "at least dual function of embryonic/fetal taste buds", including non-gustatory, paracrine functions prior to the 14th week and gustatory after the 14th week. <ref name="PMID8955790"><pubmed>8955790</pubmed></ref>
[http://www.ncbi.nlm.nih.gov/pubmed/8955790 Embryonic and early fetal development of human taste buds: a transmission electron microscopical study]

|- bgcolor="#faf6ed"
|style=white-space:nowrap|'''2000'''
|Chandrashekar, J. et al. discover the first taste sonsors, the T2R bitter taste receptors. <ref><pubmed>10761935</pubmed></ref>
[http://www.sciencedirect.com/science/article/pii/S0092867400807060 T2Rs Function as Bitter Taste Receptors]

|- bgcolor="#faecc8"
|style=white-space:nowrap|'''2001'''
|Nelson, G. et al. discover the sweet receptor: a combination of T1R2 and T1R3. <ref><pubmed>11509186</pubmed></ref>
[http://www.ncbi.nlm.nih.gov/pubmed/11509186?dopt=Abstract&holding=npg Mammalian sweet taste receptors.]

|- bgcolor="#faf6ed"
|style=white-space:nowrap|'''2002'''
|Nelson G. et al. discover the amino acid (umami) taste receptor: a combination of T1R1 and T1R3 identified. <ref><pubmed>11894099</pubmed></ref>
[http://www.ncbi.nlm.nih.gov/pubmed/11894099?dopt=Abstract&holding=npg An amino-acid taste receptor]

|- bgcolor="#faecc8"
|style=white-space:nowrap|'''2005'''
|Dyer, J. et al. discover sweet taste receptors in the GI tract. <ref><pubmed>17855558</pubmed></ref>
[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1986582/ Sweet taste signaling in the gut]

|- bgcolor="#faf6ed"
|style=white-space:nowrap|'''2006'''
|Huang, A. L et al. discover cells for sour taste, identified by PKD2L1 (a polycystic kidney disease-like ion channel). <ref><pubmed>16929298</pubmed></ref>
[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1571047/ The Cells and Logic for Mammalian Sour Taste detection]

|- bgcolor="#faecc8"
|style=white-space:nowrap|'''2007'''
|Harlow DE, Barlow LA of the University of Colorado Denver Health Sciences Center provide evidence of the "embryonic origin of gustatory cranial sensory neurons". <ref name="PMID17826760"/>
[http://www.ncbi.nlm.nih.gov/pubmed/17826760 Embryonic origin of gustatory cranial sensory neurons.]

|- bgcolor="#faf6ed"
|style=white-space:nowrap|'''2009'''
|A study by Hevezi P et al, presents "the first comprehensive characterization of gene expression in primate taste buds", as opposed to previous studies which focused on rodents. <ref><pubmed>19636377</pubmed></ref>
[http://www.ncbi.nlm.nih.gov/pubmed/19636377 Genome-wide analysis of gene expression in primate taste buds reveals links to diverse processes]

|- bgcolor="#faecc8"
|style=white-space:nowrap|'''2010'''
|Chandrashekar, J. et al. identify epithelial sodium channel (ENaC) as the sodium-salt taste receptor. <ref><pubmed>20107438</pubmed></ref>
[http://www.ncbi.nlm.nih.gov/pubmed/20107438?dopt=Abstract&holding=npg The cells and peripheral representation of sodium taste in mice]
|}

== Human Weekly Development - Two Prominent Studies ==
Martin Witt and Klaus Reutter of the University of Tubingen in Germany published two prominent studies regarding developing taste buds in humans. Their first study in 1996 was a transmission electron microscopical (TEM) study of the taste bud primordium and its morphological changes during the 8th-15th postovulatory week. Their next study in 1997 built on their previous findings by using Scanning Electron Microscopy (SEM) to observe the development of gustatory [[#Glossary |'''papillae''']] during postovulatory weeks 6-15.

The findings of these two studies are summarized in the table below. The figures provided relate to the images on their respective research papers.

# [http://onlinelibrary.wiley.com/doi/10.1002/(SICI)1097-0185(199612)246:4%3C507::AID-AR10%3E3.0.CO;2-S/pdf Embryonic and early fetal development of human taste buds: a transmission electron microscopical study, 1996]
# [http://chemse.oxfordjournals.org/content/22/6/601.long Scanning electron microscopical studies of developing gustatory papillae in humans, 1997]

===Timeline of Developmental Processes of Human Taste Buds===
{| cellpadding=5 style="border:1px solid #BBB"
|- bgcolor="#89CFF0"
|'''Postovulatory Week'''||'''Description'''

|- bgcolor="#BCD4E6"
|'''Week 6''' ||
The surface of the developing tongue is covered by nearly flat epithelium (1997, Figure 1). The first gustatory papillae of the tongue appear in the caudal mid-line near the foramen caecum and the first circumvallate papilla develops on the dorsal mid-line. <ref name="PMID9455607"><pubmed>9455607</pubmed></ref>

|- bgcolor="#89CFF0"
| '''Weeks 6 to 7'''||
Nerve fibers approach the basal lamina of lingual epithelium. At this stage the lingual epithelium consists of two to three cell layers and there is not yet any sign of cell specializations indicating early taste bud formation. <ref name=PMID8955790/>

|- bgcolor="#BCD4E6"
| '''Week 7 '''||
A series of irregular epithelial swellings in the anterior part and marginal parts of the tongue indicate early forming fungiform papillae. Furthermore, a V-like lane is observed anterior to the [[#Glossary |'''sulcus terminalis''']], which represents a smooth surface for developing circumvallate papillae (1997, Figure 2). Witt M et al observe that these circumvallate papillae are larger than the developing fungiform papillae of the same age, later noting that the fungiform papillae tend to increase in size over the 8-15th weeks of gestation, whilst the size of vallate papillae tend to remain constant during this period. <ref name=PMID9455607/>

|- bgcolor="#89CFF0"
| ''' Week 8 ''' ||
* The taste bud primordium are still differentiated, elongated epithelial cells, resting on a slightly developed core of young dermal papilla.
* The lingual epithelium shows first signs of taste bud development as nerve fibers coming from the dermal papilla penetrate the epithelial basal lamina and form synapses with taste bud progenitor cells (1996, Figure 1). These synapses demonstrate the neuronal connection between the taste bud primordium and the central nervous system, reaching a maximum around the 12th to 13th week. However, it is important to note that at this time these cells are still poorly differentiated, elongated epithelial cells.
* Ciliated cells also appear around the 8th week, however the significance of these cells which are scattered randomly across the lingual surface remains unclear. <ref name=PMID8955790/>

|- bgcolor="#BCD4E6"
|''' Week 9''' ||
By this stage, although a taste pore is not present, the surface of circumvallate papillae usually contains a taste pit partly filled with microvillus-like processes from the underlying taste bud cells (1997, Figure 10). <ref name=PMID9455607/>

|- bgcolor="#89CFF0"
|''' Weeks 10-11''' ||
At this stage, the lingual epithelium compromises of about four cell layers, and the first shallow grooves above the taste bud primordium are developed. Fungiform papillae appear on the lateral margins and the tip of the tongue, containing taste bud primordial that display the first signs of a primitive pore formation (1996, Figure 6). <ref name=PMID8955790/>

|- bgcolor="#BCD4E6"
|''' Week 12 ''' ||
Taste bud cells are more clearly differentiated into epithelial cell types II and III. <ref name=PMID8955790/>

|- bgcolor="#89CFF0"
|''' Weeks 12-13 ''' ||
At this stage the taste bud primordial are all located on the top of dermal papillae. There is also maximum synapses between cells and afferent nerve fibers, which intermingle with each other to form a plexus-like structure (1996, Figure 6a). <ref name=PMID8955790/>

|- bgcolor="#BCD4E6"
|''' Weeks 14 -15 ''' ||
The shape and size of the taste buds primordial begins to resemble those of adult taste buds (1996, Figure 9). By the 14th week the taste pores develop as the taste pits are filled by microvilli, and bubble like vesicles indicate the secretory activity of these cells (1996, Figure 10). However, the taste buds only achieve a fully developed function in week 15 of gestation with the development of type I cells to produce the mucous material in the taste pit. <ref name=PMID8955790/>
|}

==Abnormalities==

===Knocking out P2X Receptors===

[[File:Image of taste being evoked by visualising ATP release.jpeg|Left|thumb|200px|Evoking taste - ATP release in tongue]]

Gustatory abnormalities has not been widely researched and what has been researched has been through animal testing, most commonly we have found on mice.

In Huang, 2008 this team used the release of the [[#Glossary |'''ectoderm''']], ATP (adenosine triphosphate) as a quantitative measurement of gustatory sensation and taste. This was done by using a comparison of wild type (WT) and double knockout (DKO) mice. P2X receptors, P2X2 and P2X3 were knocked out in the DKO mice. The premise of this article was that knocking out P2X receptors reduces transmitter secretion of ATP in taste buds, therefore they cannot taste.

It should be noted that the taste buds in DKO are functional, but are not stimulated by the administration of tastants.

The transmission of release of ATP is secretion through gap junction hemichannels (pannexin 1 gap junction).

When both P2X2 and P2X3 are knocked out, no taste is elicited. However they found that if either P2X2 OR P2X3 was knocked out there was a taste response. So the inference made from this is that if one of the two receptors from the P2X family was knocked out there still can have taste response. The WT mice showed significant stimulation by tastants whereas DKO had little to no stimulation of ATP release.<ref><pubmed>21940456</pubmed></ref>

===FGF signalling and genes===

Sprouty, or ''Srpy'', genes have been related to regulating the development of circumvallate papillae (CVP). The CVP are large dome shaped papillae, which form a 'V' just in front of the terminal sulcus.

By knocking out ''Spry'' genes using mice which had ''Spry1'' and ''Spry2'' knocked out showed that the number of CVP doubled. However, when Fibroblast [[#Glossary |'''Growth Factor''']] gene ("Fgf10") was absent, the number of CVP was significantly reduced, if not completely absent. The correlation between ''Spry1/2'' and ''Fgf10'' is that ''Spry1/2'' antagonizes "Fgf10" to limit the size of the CVP progenitor placode. Exclusive expression of ''Fgf10'' in the [[#Glossary |'''mesenchyme''']] is necessary for the formation of CVP.

'''This image shows the CVP stained with H&E and scanned by Scanning Electron Microscope (SEM)'''
[[File:CVP of WT(top) and DKO(bottom) mice with H&E and SEM.png]]

'''This image shows the location of the CVP and the increased number in DKO mice by SEM'''
[[File:Mouse circumvallate papilla 01.jpg|300px]]

Taste buds develop from the mesenchyme but require local signalling to properly differentiate. Some signalling factors for proper development of taste buds besides FGF are: [[#Glossary |'''Sonic Hedgehog''']] (SHH), Bone Morphogenetic Proteins (BMPs), Epidermal Growth Factor (EGF).

Additionally, this proves that the anterior and posterior developments of the tongue are derived from embryonic tissues, where the anterior tongue is derived from the [[#Glossary |'''ectoderm''']] and the posterior tongue is derived from the [[#Glossary |'''endoderm''']]. Taste buds develop from the mesenchyme but require local signalling to properly differentiate. Some signalling factors for proper development of taste buds besides FGF are: Sonic Hedgehog (SHH), Bone Morphogenetic Proteins (BMPs), Epidermal Growth Factor (EGF).

As mentioned above, this article shows that the anterior and posterior developments of the tongue are derived from embryonic tissues, where the anterior tongue is derived front the ectoderm and the posterior tongue is derived from the endoderm. Secondly, FGF is required to regulate the growth of taste buds, while ''Spry'' genes limit the number of CVP. ''Fgf10''& ''Spry 1&2''work antagonistically through receptor tyrosine kinase (RTK)signalling.

However, the deletion of ''Spry2''led to the increase of CVPs it should be noted that they found that a significant decrease in number of fungiform papillae. In contrast, the absence of ''Fgf10'', while leading to the absence of CVPs lead to an increase in number and size of fungiform papillae. Therefore these genes have different effects on the anterior and posterior developing tongue and taste buds.<ref><pubmed>21655085</pubmed></ref>

==Gustatory System==

[[Image:Taste qualities.gif|thumb|The five basic tastes]]

Taste or more appropriately gustation, is a fundamental survival tool in animals as it directs the consumption of essential nutrients. The five tastes that exist within the human gustatory system: salty, sweet, sour, bitter and umami, all signify basic physiological requirements. Salty tastes denote the presence of Na+, an important ion involved in the transportation and retention of water across cell membranes. Sweetness is the recognition of carbohydrates, essential for maintaining optimal brain function and providing the basis for energy production in muscle tissue via ATP [[#Glossary |'''hydrolysis''']]. Similarly umami codes for the presence of L-amino acids, especially L-glutamate which is an integral component of protein synthesis.

These different modalities not only function to maintain the proper intake of nutrients within the body but also, by way of aversion, prohibit the consumption of undesired or poisonous materials. The bitter modality for example is generally regarded as displeasing to the human palate. It represents a high acid content which may be a result of foods which have become rotten or are inherently poisonous to the body.<ref name=PMID20696704><pubmed>20696704</pubmed></ref>

Research has historically limited itself to investigating the mechanisms of these five taste qualities though it must be noted many other modalities may exist. Of particular conjecture is the existence of fatty acid recognition. In the past the detection of fat in food has been attributed to somatosensory inputs <ref name=PMID20696704/> from the tongue, that is, the oily feel and texture of fat rather than its actual ‘taste’ allows the brain to encode for its presence. Further research is therefore required to elicit the precise mechanisms of fat detection.

===Cell Biology===

The five taste qualities are not all detected by the same type of receptor cell located within the taste bud. Like rods and cones in the eye which detect different wavelengths of light, there are specific types of receptors for different tastes. For example, sweet, umami and bitter are recognized by Type II G-protein coupled receptors, whereas sour is related to Type III presynaptic cells. The cell type involved in salty taste transduction is unknown however it is known that sodium ions can enter the receptor cell membrane via ion channel permeation.

====Type II receptors====

When a bitter, sweet or umami ligand binds to a type II G-coupled receptor, a cascade of chemical reactions causes the release of Ca2+ which in turn mediates [[#Glossary |'''exocystosis''']] of ATP. The function of this ATP is threefold:

# Stimulates gustatory nerve afferents which project to gustatory nuclei in the spinal cord
# Excites Type III presynaptic nerve fibers to release serotonin.
# Has a positive feedback effect on type II receptor cells, increasing the level of ATP production.

The role of serotonin is believed to be in the form of lateral inhibition i.e. when a bitter quality is recognized, adjacent receptors for sweetness are deactivated and thus the two tastes may be clearly differentiated. It also has a negative feedback effect on receptor cells, inhibiting umami, bitter and sweet taste transduction.

==Taste Map==
[[Image:Taste map.png|thumb|left|250px|Obsolete idea of the tongue map]]
The idea of a tongue map has disseminated through society for many years. This concept purports that different areas of the tongue are specialized to detect either sweet, salty, sour and bitter tastes. Recent research however has completely nullified such claims and suggests instead that different forms of taste are recognized all over the tongue as well as via the palate. Thus the term ''taste map'' has come to take on a new meaning and that is, the precise areas of taste modalities processing in areas of cortex and its subsequent neural inputs.

===Neural Pathways===

'''First order [[#Glossary |'''neuron''']]''' - From the receptors located in the taste buds, gustatory nerve afferents project to the ipsilateral rostral 1/3 of the nucleus tractus solitarius (NTS), located in the medulla. This rostral 1/3 is commonly referred to as the ''gustatory nucleus''.

The ''gustatory nucleus'' receives input from cranial nerves VII (''Facial n.''), IX (''Hypglossal n.''), and X (''Vagus n.'') via special visceral afferent (SVA) nerve fibers. A summary of their functions is as follows:

* ''Facial nerve n''. - carries taste information from the anterior 2/3 of the tongue.
* ''Hypoglossal n.'' - carries taste information from the posterior 1/3 of the tongue.
* ''Vagus n''. - carries taste information from the palate

'''Second order neurons''' - From the NTS second order neurons carry taste information to the Ventral posteromedial (VPM) nucleus in the thalamus.<ref name=PMID21885776/>

Copious scientific conjecture surrounds how each taste modality is transmitted to the brain. The ‘labelled-line’ hypothesis suggests that there are taste specific neurons which exclusively carry that taste modality to cortical areas. In analogous terms it can be viewed like the pipelines leading toward a house. Each pipeline carries its own utility, there is one for gas, another for water and finally for electricity with each terminating in slightly different areas of the house. In the same way, on the tongues there are different receptors for each taste which concurrently have individual nerve tracts leading to the primary gustatory cortex.

Contrapuntally there is electrophysiological evidence that single nerve afferents carry multiple modalities. These studies show one nerve afferent may have both a strong and a weak activation in response to a multiple taste stimuli.

===Cortical Areas===

[[Image:Primary gustatory cortex.png|thumb|Primary gustatory cortex]]

The location of the taste perception centers has been observed via functional magnetic resonance imaging (fMRI) studies. The primary taste cortex has been identified as being located in the anterior insula/frontal operculum (I/fO)<ref name=PMID22245354><pubmed>22245354</pubmed></ref>, with the secondary taste cortex in the caudolateral orbitofrontal cortex.<ref name=PMID21305668><pubmed>21305668</pubmed></ref> Within the insula there are further subdivisions related to each taste modality. Two photon calcium imaging research has outlined certain ’hot-spots’ of activation which are clearly delineated in relation to each taste. For example, the bitter modality is represented on the insula cortex approximately 1mm posterior to the middle cerebral artery whereas the sweet modality is represented 2.5mm rostrodorsal to the bitter field with no apparent overlap.<ref name=PMID21885776><pubmed>21885776</pubmed></ref> These findings lend weight to the idea that there is only one receptor for each taste quality.

It is interesting to note the relationship between taste and the reward centers of the brain. There is evidence of neural input to the ventral tegmental area (the origin of the mesolimbic dopaminergic reward pathway) and nucleus accumbens (involved in the conversion of motivation into physical action).<ref name=PMID21885776/> Neural connections such as this provide the foundations in explaining concepts such as flavour learning and preference. It may also give some insight into chronic problems such as food addiction and craving. As of yet however the gustatory neural network is not well understood and more research is required to elucidate the relationship between pleasure and taste sensation

==Current Research==
We have an evolving understanding of Embryonic Taste development, through the use of state-of-the-art technology and research techniques we are able to make brilliant discoveries that continue to connect the dots of this amazing natural process of human development.
The majority of research in taste development is involving mice, these mammals show similar embryonic pathways to humans and research is performed in ethical and humane methods.

[[File:Histology.jpg|Left|thumb|200px|Image shows histological stains of a mice tongue showing dysplasia]]

'''Synergistic relationships of Six Genes '''

In an animal study using mice by Suzuki Y, Ikeda K, Kawakami K.(2011) Firstly nominating "[[#Glossary |'''Six Genes''']]" as a major component in [[#Glossary |'''gustatory ''']] development, stating that deficiencies in certain Six genes (specifically Six1 & Six4) leads to poor development. Their research also highlights evidence of cooperative relationships between Six genes for normal advance. This experiment involved breeding mice containing exclusively Six1 and Six4 genes and examining the expression of these genes in papillae under high powered microscope observation. Understanding the role of certain genes along with the intrinsic relationships they hold is crucial for the ability to identify possible causes and correction of any abnormalities <ref><pubmed>21978088</pubmed></ref>

'''Neural Crest responsibilities '''

Another Animal Study involving mice explores a new idea of [[#Glossary |'''Neural crest''']] (NC) contribution in taste development, specifically the development of papillae and taste buds. Liu HX, Komatsu Y, Mishina Y, Mistretta CM. (2012) suggest that Neural crest cells travel to the location of the tongue in early embryonic stages, gain epithelium phenotypes, multiply and then differentiate to eventually form taste papillae. The experiment involved the comparison of 2 different types of Cre line mice, which both express Cre gene in neural crest protocol, the different distribution patterns where observed in specific regions that NC is responsible for.<ref><pubmed>22659543</pubmed></ref>

'''Augmentation of Endoderm'''

In an animal study conducted by Rothova M, Thompson H, Lickert H, Tucker AS.(2012) exploring the historically debated issue of endoderm contribution to tongue development showed promising evidence that position of taste buds are patterned by the border of ectoderm and endoderm derivative epithelium. This study was accomplished via microscopic examination of previously stained specimens. Concluding endoderm has direct influence on gustatory development <ref><pubmed>22581563</pubmed></ref>

'''Changes in Taste Cells over time'''

Research by
Ozdener H, Spielman AI, Rawson NE.(2012) developing a culture which allows taste cells to survive for up to 12 months, empowers researchers to study the processes of proliferation, differentiation and function. This experiment will provide a precedent for future study of taste cells, as these cells are able to operate and grow normally. <ref><pubmed>22643728</pubmed></ref>

'''Shh key component of taste bud proginators'''

A [[#Glossary |'''tamoxifen''']] treatment which suppresses Sonic hedgehog (Shh) secretion in mice proving to reduce the number of cells visible within papillae, in contrast mice not treated with tamoxifen showed a mark increase of cells within papillae, these cells are assumed to become taste cells in later development.
Specific mice were bred to trace the destination of taste placode cells, the study concluded that Shh expressing placodes are taste bud proginators which in turn become taste cells within taste buds although do not have any precursors relationship with papillae. The results were obtain by examination of mice embryos using Bright-field or multichannel fluorescent images through the use of an "Axiocam CCD camera and Axioplan fluorescence microscope with Axiovision software" a study by Harlow, Yang, Williams, Barlow (2011)<ref><pubmed>PMC2674259</pubmed></ref>

'''WNT family exhibit various roles''' [[File:Abnormal of tongue.jpg|thumb|200px|Image shows an example of tongue abnormalities, this is called "double tongue" each side has independent movement!]]

The WNT gene family has a function of signally proteins for various reason such as development, In 2010 Liu, Staubach Grosse, Walton, Saims, Gumucio, Mistretta explored recent findings on the role of WNT's in tongue and papillae development, Concluding that WNT/β-catenin is essential for fungiform papillae differing to WNT5a which proved to be principle in tongue development. Intrinsic chemical mediators were considered by manipulating a tissue culture and then thoroughly examined by scanning photomicrograph. <ref><pubmed>PMC2768563</pubmed></ref>

[http://www.surgicalneurologyint.com/article.asp?issn=2152-7806;year=2012;volume=3;issue=1;spage=23;epage=23;aulast=Manjila]

==Glossary==

* '''Ectoderm'''- outer germ layer of embryo

* '''Endoderm''' - inner germ layer of embryo

* '''Epithelium''' - basic animal tissue that is composed of tightly packed cells, usually covering the outer portion of organs

* '''Exocystosis''' - movement of contents out of cell

* '''Ganglia''' - the accumulation of a nerve cell body

* '''Growth factor''' - a substance that stimulates the growth of cells

* '''Gustatory''' - anything that relates to the taste sense

* '''Hydrolysis''' - breakdown of a chemical when it reacts with water

* '''Mesoderm''' - middle germ layer of embryo

* '''Mesenchyme''' - multipotential cells

* '''Neural crest''' - a part of the ectoderm found on both sides of the neural tube

* '''Neuron''' - most simplistic unit of the nervous system

* '''Neurotransmitter''' - chemicals which allow the passing of signals from neuron to neuron via connecting part (synapse)

* '''Papillae''' - small rough surface projection

* '''Six genes''' - a family of genes

* '''Sonic hedgehog (Shh)''' - signalling protein involved in normal development

* '''Sulcus terminalis''' - describes a physical transition point separating the anterior 2/3 of the tongue from the posterior 1/3

* '''Tamoxifen''' - hormonal altering drug

* '''Type I taste cells''' - The most abundant cells in taste buds; involved in terminating synaptic transmissions (similar to the role of glial cells in the CNS).

* '''Type II taste cells''' - Receptor cells acting as primary detectors of sweet, bitter or umami taste.

* '''Type III taste cells''' - Presynaptic cells that respond to sweet, salty, sour, bitter and umami compounds.

== References ==
<references/>

==External Links==
{{External Links}}

http://www.webmd.com/oral-health/picture-of-the-tongue

http://www.tutorvista.com/content/biology/biology-iv/nervous-coordination/tongue-structure.php#parts-of-tongue

http://www.cf.ac.uk/biosi/staffinfo/jacob/teaching/sensory/taste.html

--[[User:Z8600021|Mark Hill]] 12:22, 15 August 2012 (EST) Please leave the content listed below the line at the bottom of your project page.

----

{{2012Projects}}

2012 Group Project 3

2012-09-30T23:43:59Z

Z3289738: /* Glossary */

=Taste Development=

== Introduction ==
**NEED TO ADD**

==Adult Tongue and Taste Buds – Structure and Function==

'''Structure'''

The tongue is located on the floor of the oral cavity, It is a muscular structure with sensory units crowning. The tongue is divided into an anterior two thirds and a posterior one third. These regions are divided by a V-shaped groove at the back of the tongue (sulcus terminalis). The anterior two thirds of the tongue is covered by stratified squamous epithelium, It contains a roughened surface and has projections called papillae that vary in shape and number.

''''The image below is a simplistic diagram of the surface of the tongue showing the locations of the different papillae and other important features'''

{|
| [[Image:Drawing of Tongue.png|500px]]

'''Papillae'''
[[File:Papillae.jpg|Left|thumb|200px|Close up of Human Tongue Papillae]]

There are 4 types of papillae on the tongue.
The most numerous papillae are the filiform papillae, which function to provide a surface that aids in holding food on the tongue during chewing but do not contain taste buds. The larger, less numerous fungiform papillae which contain taste buds, as do foliate papillae. Circumvallate papillae form a wide V at the sulcus terminalis also containing taste bus. There are no papillae or taste buds located on the posterior third of the tongue, having mucosal folds and the lingual tonsils instead.

'''Function'''

The tongue is for tasting, swallowing, and speech.
The functional unit of the taste bud is a taste cell, there are between 50 and 100 taste cells in each taste bud these taste cells represent all 5 different tastes. Historically is was believed that different areas of the tongue were responsible for different taste sensations although this has since been disregarded.[http://users.rcn.com/jkimball.ma.ultranet/BiologyPages/W/Welcome.html] The papillae contain taste buds which are connected to the oral cavity via a taste pore, the function of the taste bud is to transmit a chemical signal from the oral cavity to a taste cell, this chemical signal is the converted into an electrical impulse and delivered to the brain via nerve fibres for interpretation.

'''The image below is a simplistic hand-drawn cross section of a taste bud unit (not to scale)'''

[[File:Taste_bud_1.jpg|x400px|alt=Cross section of a taste bud unit|Cross section of a taste bud unit]]

==History of Discoveries==

{| cellpadding=5 style="border:1px solid #BBB"
|- bgcolor="#faecc8"
|''' Date'''|| '''Significant Discovery'''

|- bgcolor="#faf6ed"
|'''350BC'''
|| Aristotle writes about the basic tastes, sweet and bitter. He also notes that it can be modified by salty and acidic. <ref name="PMID22717400"><pubmed>22717400</pubmed></ref>

|- bgcolor="#faecc8"
|'''1901'''
|| D. Hanig publishes a paper describing taste sensitivity in different regions of the tongue.
''Interesting fact:'' The modern concept of a 'tongue map' is a misinterpretation of this study. <ref name="PMID22717400"/>

|- bgcolor="#faf6ed"
|style=white-space:nowrap|'''1908'''
|Kikunae Ikeda, a professor of the Tokyo Imperial University, discovered and identified the fifth basic taste: umami (savouriness), made palatable by glutamate. <ref><pubmed>12438213</pubmed></ref>
[http://chemse.oxfordjournals.org/content/27/9/847.long New Seasonings]

|- bgcolor="#faecc8"
|style=white-space:nowrap|'''1931-32'''
| A chemist named Arthur Fox and his college noted that they had different sensitivities to the bitter tasting Phenylthiocarbamide (PTC).<ref>Blakeslee AF, Fox AL. Our different taste worlds. J Hered. 1932;23:97–107.</ref> Geneticists later confirm these findings, and discover that non-tasting is a recessive genetic trait. <ref><pubmed>17782493</pubmed></ref>
[http://www.ncbi.nlm.nih.gov/pubmed/17782493 Inherited taste deficiency]

|- bgcolor="#faf6ed"
|style=white-space:nowrap|'''1965'''
|Farbman's study of the developing taste but in rat fungiform papilla was significant in increasing our understanding of taste bud development. <ref><pubmed>14300090</pubmed></ref>
[http://www.sciencedirect.com/science/article/pii/0012160665900400 Electron microscope study of the developing taste bud in rat fungiform papilla.]

|- bgcolor="#faecc8"
|style=white-space:nowrap|'''1992'''
|McLaughlin SK et al. discovery a taste cell-specific G-protein within the taste buds called Gustucon. This protein is later used to mark bitter, umami and sweet cells. <ref><pubmed>1608467 </pubmed></ref>
[http://www.nature.com/nature/journal/v357/n6379/abs/357563a0.html Gustducin is a taste-cell-specific G protein closely related to the transducins]

|- bgcolor="#faf6ed"
|style=white-space:nowrap|'''1995'''
|Barlow et al. experimented with Axolotl salamanders and concluded that taste buds from this species arise exclusively from epithelial tissue, "oropharyngeal [[#Glossary |'''epithelium''']]". <ref name="PMID17826760"><pubmed>17826760</pubmed></ref>
[http://www.ncbi.nlm.nih.gov/pubmed/17826760 Embryonic origin of gustatory cranial sensory neurons]

|- bgcolor="#faecc8"
|style=white-space:nowrap|'''1996'''
| Witt M and Reutter K of the Technical University Dresden in Germany, carried out a transmission electron microscopy study to investigate the embryonic and fetal development of Human taste buds. Their results suggest an "at least dual function of embryonic/fetal taste buds", including non-gustatory, paracrine functions prior to the 14th week and gustatory after the 14th week. <ref name="PMID8955790"><pubmed>8955790</pubmed></ref>
[http://www.ncbi.nlm.nih.gov/pubmed/8955790 Embryonic and early fetal development of human taste buds: a transmission electron microscopical study]

|- bgcolor="#faf6ed"
|style=white-space:nowrap|'''2000'''
|Chandrashekar, J. et al. discover the first taste sonsors, the T2R bitter taste receptors. <ref><pubmed>10761935</pubmed></ref>
[http://www.sciencedirect.com/science/article/pii/S0092867400807060 T2Rs Function as Bitter Taste Receptors]

|- bgcolor="#faecc8"
|style=white-space:nowrap|'''2001'''
|Nelson, G. et al. discover the sweet receptor: a combination of T1R2 and T1R3. <ref><pubmed>11509186</pubmed></ref>
[http://www.ncbi.nlm.nih.gov/pubmed/11509186?dopt=Abstract&holding=npg Mammalian sweet taste receptors.]

|- bgcolor="#faf6ed"
|style=white-space:nowrap|'''2002'''
|Nelson G. et al. discover the amino acid (umami) taste receptor: a combination of T1R1 and T1R3 identified. <ref><pubmed>11894099</pubmed></ref>
[http://www.ncbi.nlm.nih.gov/pubmed/11894099?dopt=Abstract&holding=npg An amino-acid taste receptor]

|- bgcolor="#faecc8"
|style=white-space:nowrap|'''2005'''
|Dyer, J. et al. discover sweet taste receptors in the GI tract. <ref><pubmed>17855558</pubmed></ref>
[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1986582/ Sweet taste signaling in the gut]

|- bgcolor="#faf6ed"
|style=white-space:nowrap|'''2006'''
|Huang, A. L et al. discover cells for sour taste, identified by PKD2L1 (a polycystic kidney disease-like ion channel). <ref><pubmed>16929298</pubmed></ref>
[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1571047/ The Cells and Logic for Mammalian Sour Taste detection]

|- bgcolor="#faecc8"
|style=white-space:nowrap|'''2007'''
|Harlow DE, Barlow LA of the University of Colorado Denver Health Sciences Center provide evidence of the "embryonic origin of gustatory cranial sensory neurons". <ref name="PMID17826760"/>
[http://www.ncbi.nlm.nih.gov/pubmed/17826760 Embryonic origin of gustatory cranial sensory neurons.]

|- bgcolor="#faf6ed"
|style=white-space:nowrap|'''2009'''
|A study by Hevezi P et al, presents "the first comprehensive characterization of gene expression in primate taste buds", as opposed to previous studies which focused on rodents. <ref><pubmed>19636377</pubmed></ref>
[http://www.ncbi.nlm.nih.gov/pubmed/19636377 Genome-wide analysis of gene expression in primate taste buds reveals links to diverse processes]

|- bgcolor="#faecc8"
|style=white-space:nowrap|'''2010'''
|Chandrashekar, J. et al. identify epithelial sodium channel (ENaC) as the sodium-salt taste receptor. <ref><pubmed>20107438</pubmed></ref>
[http://www.ncbi.nlm.nih.gov/pubmed/20107438?dopt=Abstract&holding=npg The cells and peripheral representation of sodium taste in mice]
|}

== Human Weekly Development - Two Prominent Studies ==
Martin Witt and Klaus Reutter of the University of Tubingen in Germany published two prominent studies regarding developing taste buds in humans. Their first study in 1996 was a transmission electron microscopical (TEM) study of the taste bud primordium and its morphological changes during the 8th-15th postovulatory week. Their next study in 1997 built on their previous findings by using Scanning Electron Microscopy (SEM) to observe the development of gustatory [[#Glossary |'''papillae''']] during postovulatory weeks 6-15.

The findings of these two studies are summarized in the table below. The figures provided relate to the images on their respective research papers.

# [http://onlinelibrary.wiley.com/doi/10.1002/(SICI)1097-0185(199612)246:4%3C507::AID-AR10%3E3.0.CO;2-S/pdf Embryonic and early fetal development of human taste buds: a transmission electron microscopical study, 1996]
# [http://chemse.oxfordjournals.org/content/22/6/601.long Scanning electron microscopical studies of developing gustatory papillae in humans, 1997]

===Timeline of Developmental Processes of Human Taste Buds===
{| cellpadding=5 style="border:1px solid #BBB"
|- bgcolor="#89CFF0"
|'''Postovulatory Week'''||'''Description'''

|- bgcolor="#BCD4E6"
|'''Week 6''' ||
The surface of the developing tongue is covered by nearly flat epithelium (1997, Figure 1). The first gustatory papillae of the tongue appear in the caudal mid-line near the foramen caecum and the first circumvallate papilla develops on the dorsal mid-line. <ref name="PMID9455607"><pubmed>9455607</pubmed></ref>

|- bgcolor="#89CFF0"
| '''Weeks 6 to 7'''||
Nerve fibers approach the basal lamina of lingual epithelium. At this stage the lingual epithelium consists of two to three cell layers and there is not yet any sign of cell specializations indicating early taste bud formation. <ref name=PMID8955790/>

|- bgcolor="#BCD4E6"
| '''Week 7 '''||
A series of irregular epithelial swellings in the anterior part and marginal parts of the tongue indicate early forming fungiform papillae. Furthermore, a V-like lane is observed anterior to the [[#Glossary |'''sulcus terminalis''']], which represents a smooth surface for developing circumvallate papillae (1997, Figure 2). Witt M et al observe that these circumvallate papillae are larger than the developing fungiform papillae of the same age, later noting that the fungiform papillae tend to increase in size over the 8-15th weeks of gestation, whilst the size of vallate papillae tend to remain constant during this period. <ref name=PMID9455607/>

|- bgcolor="#89CFF0"
| ''' Week 8 ''' ||
* The taste bud primordium are still differentiated, elongated epithelial cells, resting on a slightly developed core of young dermal papilla.
* The lingual epithelium shows first signs of taste bud development as nerve fibers coming from the dermal papilla penetrate the epithelial basal lamina and form synapses with taste bud progenitor cells (1996, Figure 1). These synapses demonstrate the neuronal connection between the taste bud primordium and the central nervous system, reaching a maximum around the 12th to 13th week. However, it is important to note that at this time these cells are still poorly differentiated, elongated epithelial cells.
* Ciliated cells also appear around the 8th week, however the significance of these cells which are scattered randomly across the lingual surface remains unclear. <ref name=PMID8955790/>

|- bgcolor="#BCD4E6"
|''' Week 9''' ||
By this stage, although a taste pore is not present, the surface of circumvallate papillae usually contains a taste pit partly filled with microvillus-like processes from the underlying taste bud cells (1997, Figure 10). <ref name=PMID9455607/>

|- bgcolor="#89CFF0"
|''' Weeks 10-11''' ||
At this stage, the lingual epithelium compromises of about four cell layers, and the first shallow grooves above the taste bud primordium are developed. Fungiform papillae appear on the lateral margins and the tip of the tongue, containing taste bud primordial that display the first signs of a primitive pore formation (1996, Figure 6). <ref name=PMID8955790/>

|- bgcolor="#BCD4E6"
|''' Week 12 ''' ||
Taste bud cells are more clearly differentiated into epithelial cell types II and III. <ref name=PMID8955790/>

|- bgcolor="#89CFF0"
|''' Weeks 12-13 ''' ||
At this stage the taste bud primordial are all located on the top of dermal papillae. There is also maximum synapses between cells and afferent nerve fibers, which intermingle with each other to form a plexus-like structure (1996, Figure 6a). <ref name=PMID8955790/>

|- bgcolor="#BCD4E6"
|''' Weeks 14 -15 ''' ||
The shape and size of the taste buds primordial begins to resemble those of adult taste buds (1996, Figure 9). By the 14th week the taste pores develop as the taste pits are filled by microvilli, and bubble like vesicles indicate the secretory activity of these cells (1996, Figure 10). However, the taste buds only achieve a fully developed function in week 15 of gestation with the development of type I cells to produce the mucous material in the taste pit. <ref name=PMID8955790/>
|}

==Abnormalities==

===Knocking out P2X Receptors===

[[File:Image of taste being evoked by visualising ATP release.jpeg|Left|thumb|200px|Evoking taste - ATP release in tongue]]

Gustatory abnormalities has not been widely researched and what has been researched has been through animal testing, most commonly we have found on mice.

In Huang, 2008 this team used the release of the [[#Glossary |'''ectoderm''']], ATP (adenosine triphosphate) as a quantitative measurement of gustatory sensation and taste. This was done by using a comparison of wild type (WT) and double knockout (DKO) mice. P2X receptors, P2X2 and P2X3 were knocked out in the DKO mice. The premise of this article was that knocking out P2X receptors reduces transmitter secretion of ATP in taste buds, therefore they cannot taste.

It should be noted that the taste buds in DKO are functional, but are not stimulated by the administration of tastants.

The transmission of release of ATP is secretion through gap junction hemichannels (pannexin 1 gap junction).

When both P2X2 and P2X3 are knocked out, no taste is elicited. However they found that if either P2X2 OR P2X3 was knocked out there was a taste response. So the inference made from this is that if one of the two receptors from the P2X family was knocked out there still can have taste response. The WT mice showed significant stimulation by tastants whereas DKO had little to no stimulation of ATP release.<ref><pubmed>21940456</pubmed></ref>

===FGF signalling and genes===

Sprouty, or ''Srpy'', genes have been related to regulating the development of circumvallate papillae (CVP). The CVP are large dome shaped papillae, which form a 'V' just in front of the terminal sulcus.

By knocking out ''Spry'' genes using mice which had ''Spry1'' and ''Spry2'' knocked out showed that the number of CVP doubled. However, when Fibroblast [[#Glossary |'''Growth Factor''']] gene ("Fgf10") was absent, the number of CVP was significantly reduced, if not completely absent. The correlation between ''Spry1/2'' and ''Fgf10'' is that ''Spry1/2'' antagonizes "Fgf10" to limit the size of the CVP progenitor placode. Exclusive expression of ''Fgf10'' in the [[#Glossary |'''mesenchyme''']] is necessary for the formation of CVP.

'''This image shows the CVP stained with H&E and scanned by Scanning Electron Microscope (SEM)'''
[[File:CVP of WT(top) and DKO(bottom) mice with H&E and SEM.png]]

'''This image shows the location of the CVP and the increased number in DKO mice by SEM'''
[[File:Mouse circumvallate papilla 01.jpg|300px]]

Taste buds develop from the mesenchyme but require local signalling to properly differentiate. Some signalling factors for proper development of taste buds besides FGF are: [[#Glossary |'''Sonic Hedgehog''']] (SHH), Bone Morphogenetic Proteins (BMPs), Epidermal Growth Factor (EGF).

Additionally, this proves that the anterior and posterior developments of the tongue are derived from embryonic tissues, where the anterior tongue is derived from the [[#Glossary |'''ectoderm''']] and the posterior tongue is derived from the [[#Glossary |'''endoderm''']]. Taste buds develop from the mesenchyme but require local signalling to properly differentiate. Some signalling factors for proper development of taste buds besides FGF are: Sonic Hedgehog (SHH), Bone Morphogenetic Proteins (BMPs), Epidermal Growth Factor (EGF).

As mentioned above, this article shows that the anterior and posterior developments of the tongue are derived from embryonic tissues, where the anterior tongue is derived front the ectoderm and the posterior tongue is derived from the endoderm. Secondly, FGF is required to regulate the growth of taste buds, while ''Spry'' genes limit the number of CVP. ''Fgf10''& ''Spry 1&2''work antagonistically through receptor tyrosine kinase (RTK)signalling.

However, the deletion of ''Spry2''led to the increase of CVPs it should be noted that they found that a significant decrease in number of fungiform papillae. In contrast, the absence of ''Fgf10'', while leading to the absence of CVPs lead to an increase in number and size of fungiform papillae. Therefore these genes have different effects on the anterior and posterior developing tongue and taste buds.<ref><pubmed>21655085</pubmed></ref>

==Gustatory System==

[[Image:Taste qualities.gif|thumb|The five basic tastes]]

Taste or more appropriately gustation, is a fundamental survival tool in animals as it directs the consumption of essential nutrients. The five tastes that exist within the human gustatory system: salty, sweet, sour, bitter and umami, all signify basic physiological requirements. Salty tastes denote the presence of Na+, an important ion involved in the transportation and retention of water across cell membranes. Sweetness is the recognition of carbohydrates, essential for maintaining optimal brain function and providing the basis for energy production in muscle tissue via ATP [[#Glossary |'''hydrolysis''']]. Similarly umami codes for the presence of L-amino acids, especially L-glutamate which is an integral component of protein synthesis.

These different modalities not only function to maintain the proper intake of nutrients within the body but also, by way of aversion, prohibit the consumption of undesired or poisonous materials. The bitter modality for example is generally regarded as displeasing to the human palate. It represents a high acid content which may be a result of foods which have become rotten or are inherently poisonous to the body.<ref name=PMID20696704><pubmed>20696704</pubmed></ref>

Research has historically limited itself to investigating the mechanisms of these five taste qualities though it must be noted many other modalities may exist. Of particular conjecture is the existence of fatty acid recognition. In the past the detection of fat in food has been attributed to somatosensory inputs <ref name=PMID20696704/> from the tongue, that is, the oily feel and texture of fat rather than its actual ‘taste’ allows the brain to encode for its presence. Further research is therefore required to elicit the precise mechanisms of fat detection.

===Cell Biology===

The five taste qualities are not all detected by the same type of receptor cell located within the taste bud. Like rods and cones in the eye which detect different wavelengths of light, there are specific types of receptors for different tastes. For example, sweet, umami and bitter are recognized by Type II G-protein coupled receptors, whereas sour is related to Type III presynaptic cells. The cell type involved in salty taste transduction is unknown however it is known that sodium ions can enter the receptor cell membrane via ion channel permeation.

====Type II receptors====

When a bitter, sweet or umami ligand binds to a type II G-coupled receptor, a cascade of chemical reactions causes the release of Ca2+ which in turn mediates [[#Glossary |'''exocystosis''']] of ATP. The function of this ATP is threefold:

# Stimulates gustatory nerve afferents which project to gustatory nuclei in the spinal cord
# Excites Type III presynaptic nerve fibers to release serotonin.
# Has a positive feedback effect on type II receptor cells, increasing the level of ATP production.

The role of serotonin is believed to be in the form of lateral inhibition i.e. when a bitter quality is recognized, adjacent receptors for sweetness are deactivated and thus the two tastes may be clearly differentiated. It also has a negative feedback effect on receptor cells, inhibiting umami, bitter and sweet taste transduction.

==Taste Map==
[[Image:Taste map.png|thumb|left|250px|Obsolete idea of the tongue map]]
The idea of a tongue map has disseminated through society for many years. This concept purports that different areas of the tongue are specialized to detect either sweet, salty, sour and bitter tastes. Recent research however has completely nullified such claims and suggests instead that different forms of taste are recognized all over the tongue as well as via the palate. Thus the term ''taste map'' has come to take on a new meaning and that is, the precise areas of taste modalities processing in areas of cortex and its subsequent neural inputs.

===Neural Pathways===

'''First order [[#Glossary |'''neuron''']]''' - From the receptors located in the taste buds, gustatory nerve afferents project to the ipsilateral rostral 1/3 of the nucleus tractus solitarius (NTS), located in the medulla. This rostral 1/3 is commonly referred to as the ''gustatory nucleus''.

The ''gustatory nucleus'' receives input from cranial nerves VII (''Facial n.''), IX (''Hypglossal n.''), and X (''Vagus n.'') via special visceral afferent (SVA) nerve fibers. A summary of their functions is as follows:

* ''Facial nerve n''. - carries taste information from the anterior 2/3 of the tongue.
* ''Hypoglossal n.'' - carries taste information from the posterior 1/3 of the tongue.
* ''Vagus n''. - carries taste information from the palate

'''Second order neurons''' - From the NTS second order neurons carry taste information to the Ventral posteromedial (VPM) nucleus in the thalamus.<ref name=PMID21885776/>

Copious scientific conjecture surrounds how each taste modality is transmitted to the brain. The ‘labelled-line’ hypothesis suggests that there are taste specific neurons which exclusively carry that taste modality to cortical areas. In analogous terms it can be viewed like the pipelines leading toward a house. Each pipeline carries its own utility, there is one for gas, another for water and finally for electricity with each terminating in slightly different areas of the house. In the same way, on the tongues there are different receptors for each taste which concurrently have individual nerve tracts leading to the primary gustatory cortex.

Contrapuntally there is electrophysiological evidence that single nerve afferents carry multiple modalities. These studies show one nerve afferent may have both a strong and a weak activation in response to a multiple taste stimuli.

===Cortical Areas===

[[Image:Primary gustatory cortex.png|thumb|Primary gustatory cortex]]

The location of the taste perception centers has been observed via functional magnetic resonance imaging (fMRI) studies. The primary taste cortex has been identified as being located in the anterior insula/frontal operculum (I/fO)<ref name=PMID22245354><pubmed>22245354</pubmed></ref>, with the secondary taste cortex in the caudolateral orbitofrontal cortex.<ref name=PMID21305668><pubmed>21305668</pubmed></ref> Within the insula there are further subdivisions related to each taste modality. Two photon calcium imaging research has outlined certain ’hot-spots’ of activation which are clearly delineated in relation to each taste. For example, the bitter modality is represented on the insula cortex approximately 1mm posterior to the middle cerebral artery whereas the sweet modality is represented 2.5mm rostrodorsal to the bitter field with no apparent overlap.<ref name=PMID21885776><pubmed>21885776</pubmed></ref> These findings lend weight to the idea that there is only one receptor for each taste quality.

It is interesting to note the relationship between taste and the reward centers of the brain. There is evidence of neural input to the ventral tegmental area (the origin of the mesolimbic dopaminergic reward pathway) and nucleus accumbens (involved in the conversion of motivation into physical action).<ref name=PMID21885776/> Neural connections such as this provide the foundations in explaining concepts such as flavour learning and preference. It may also give some insight into chronic problems such as food addiction and craving. As of yet however the gustatory neural network is not well understood and more research is required to elucidate the relationship between pleasure and taste sensation

==Current Research==
We have an evolving understanding of Embryonic Taste development, through the use of state-of-the-art technology and research techniques we are able to make brilliant discoveries that continue to connect the dots of this amazing natural process of human development.
The majority of research in taste development is involving mice, these mammals show similar embryonic pathways to humans and research is performed in ethical and humane methods.

[[File:Histology.jpg|Left|thumb|200px|Image shows histological stains of a mice tongue showing dysplasia]]

'''Synergistic relationships of Six Genes '''

In an animal study using mice by Suzuki Y, Ikeda K, Kawakami K.(2011) Firstly nominating "[[#Glossary |'''Six Genes''']]" as a major component in [[#Glossary |'''gustatory ''']] development, stating that deficiencies in certain Six genes (specifically Six1 & Six4) leads to poor development. Their research also highlights evidence of cooperative relationships between Six genes for normal advance. This experiment involved breeding mice containing exclusively Six1 and Six4 genes and examining the expression of these genes in papillae under high powered microscope observation. Understanding the role of certain genes along with the intrinsic relationships they hold is crucial for the ability to identify possible causes and correction of any abnormalities <ref><pubmed>21978088</pubmed></ref>

'''Neural Crest responsibilities '''

Another Animal Study involving mice explores a new idea of [[#Glossary |'''Neural crest''']] (NC) contribution in taste development, specifically the development of papillae and taste buds. Liu HX, Komatsu Y, Mishina Y, Mistretta CM. (2012) suggest that Neural crest cells travel to the location of the tongue in early embryonic stages, gain epithelium phenotypes, multiply and then differentiate to eventually form taste papillae. The experiment involved the comparison of 2 different types of Cre line mice, which both express Cre gene in neural crest protocol, the different distribution patterns where observed in specific regions that NC is responsible for.<ref><pubmed>22659543</pubmed></ref>

'''Augmentation of Endoderm'''

In an animal study conducted by Rothova M, Thompson H, Lickert H, Tucker AS.(2012) exploring the historically debated issue of endoderm contribution to tongue development showed promising evidence that position of taste buds are patterned by the border of ectoderm and endoderm derivative epithelium. This study was accomplished via microscopic examination of previously stained specimens. Concluding endoderm has direct influence on gustatory development <ref><pubmed>22581563</pubmed></ref>

'''Changes in Taste Cells over time'''

Research by
Ozdener H, Spielman AI, Rawson NE.(2012) developing a culture which allows taste cells to survive for up to 12 months, empowers researchers to study the processes of proliferation, differentiation and function. This experiment will provide a precedent for future study of taste cells, as these cells are able to operate and grow normally. <ref><pubmed>22643728</pubmed></ref>

'''Shh key component of taste bud proginators'''

A [[#Glossary |'''tamoxifen''']] treatment which suppresses Sonic hedgehog (Shh) secretion in mice proving to reduce the number of cells visible within papillae, in contrast mice not treated with tamoxifen showed a mark increase of cells within papillae, these cells are assumed to become taste cells in later development.
Specific mice were bred to trace the destination of taste placode cells, the study concluded that Shh expressing placodes are taste bud proginators which in turn become taste cells within taste buds although do not have any precursors relationship with papillae. The results were obtain by examination of mice embryos using Bright-field or multichannel fluorescent images through the use of an "Axiocam CCD camera and Axioplan fluorescence microscope with Axiovision software" a study by Harlow, Yang, Williams, Barlow (2011)<ref><pubmed>PMC2674259</pubmed></ref>

'''WNT family exhibit various roles''' [[File:Abnormal of tongue.jpg|thumb|200px|Image shows an example of tongue abnormalities, this is called "double tongue" each side has independent movement!]]

The WNT gene family has a function of signally proteins for various reason such as development, In 2010 Liu, Staubach Grosse, Walton, Saims, Gumucio, Mistretta explored recent findings on the role of WNT's in tongue and papillae development, Concluding that WNT/β-catenin is essential for fungiform papillae differing to WNT5a which proved to be principle in tongue development. Intrinsic chemical mediators were considered by manipulating a tissue culture and then thoroughly examined by scanning photomicrograph. <ref><pubmed>PMC2768563</pubmed></ref>

[http://www.surgicalneurologyint.com/article.asp?issn=2152-7806;year=2012;volume=3;issue=1;spage=23;epage=23;aulast=Manjila]

==Glossary==

* '''Ectoderm'''- outer germ layer of embryo

* '''Endoderm''' - inner germ layer of embryo

* '''Epithelium''' - basic animal tissue that is composed of tightly packed cells, usually covering the outer portion of organs

* '''Exocystosis''' - movement of contents out of cell

* '''Ganglia''' - the accumulation of a nerve cell body

* '''Growth factor''' - a substance that stimulates the growth of cells

* '''Gustatory''' - anything that relates to the taste sense

* '''Hydrolysis''' - breakdown of a chemical when it reacts with water

* '''Mesoderm''' - middle germ layer of embryo

* '''Mesenchyme''' - multipotential cells

* '''Neural crest''' - a part of the ectoderm found on both sides of the neural tube

* '''Neuron''' - most simplistic unit of the nervous system

* '''Neurotransmitter''' - chemicals which allow the passing of signals from neuron to neuron via connecting part (synapse)

* '''Papillae''' - small rough surface projection

* '''Six genes''' - a family of genes

* '''Sonic hedgehog (Shh)''' - signalling protein involved in normal development

* '''Sulcus terminalis''' - describes a physical transition point separating the anterior 2/3 of the tongue from the posterior 1/3

* '''Tamoxifen''' - hormonal altering drug

* '''Type I taste cell''' - The most abundant cells in taste buds; involved in terminating synaptic transmissions (similar to the role of glial cells in the CNS).

* '''Type II taste cells''' - Receptor cells acting as primary detectors of sweet, bitter or umami taste.

* '''Type III taste cells''' - Presynaptic cells that respond to sweet, salty, sour, bitter and umami compounds.

== References ==
<references/>

==External Links==
{{External Links}}

http://www.webmd.com/oral-health/picture-of-the-tongue

http://www.tutorvista.com/content/biology/biology-iv/nervous-coordination/tongue-structure.php#parts-of-tongue

http://www.cf.ac.uk/biosi/staffinfo/jacob/teaching/sensory/taste.html

--[[User:Z8600021|Mark Hill]] 12:22, 15 August 2012 (EST) Please leave the content listed below the line at the bottom of your project page.

----

{{2012Projects}}

2012 Group Project 3

2012-09-30T23:31:48Z

Z3289738: /* Knocking out P2X Receptors */

=Taste Development=

== Introduction ==
**NEED TO ADD**

==Adult Tongue and Taste Buds – Structure and Function==

'''Structure'''

The tongue is located on the floor of the oral cavity, It is a muscular structure with sensory units crowning. The tongue is divided into an anterior two thirds and a posterior one third. These regions are divided by a V-shaped groove at the back of the tongue (sulcus terminalis). The anterior two thirds of the tongue is covered by stratified squamous epithelium, It contains a roughened surface and has projections called papillae that vary in shape and number.

''''The image below is a simplistic diagram of the surface of the tongue showing the locations of the different papillae and other important features'''

{|
| [[Image:Drawing of Tongue.png|500px]]

'''Papillae'''
[[File:Papillae.jpg|Left|thumb|200px|Close up of Human Tongue Papillae]]

There are 4 types of papillae on the tongue.
The most numerous papillae are the filiform papillae, which function to provide a surface that aids in holding food on the tongue during chewing but do not contain taste buds. The larger, less numerous fungiform papillae which contain taste buds, as do foliate papillae. Circumvallate papillae form a wide V at the sulcus terminalis also containing taste bus. There are no papillae or taste buds located on the posterior third of the tongue, having mucosal folds and the lingual tonsils instead.

'''Function'''

The tongue is for tasting, swallowing, and speech.
The functional unit of the taste bud is a taste cell, there are between 50 and 100 taste cells in each taste bud these taste cells represent all 5 different tastes. Historically is was believed that different areas of the tongue were responsible for different taste sensations although this has since been disregarded.[http://users.rcn.com/jkimball.ma.ultranet/BiologyPages/W/Welcome.html] The papillae contain taste buds which are connected to the oral cavity via a taste pore, the function of the taste bud is to transmit a chemical signal from the oral cavity to a taste cell, this chemical signal is the converted into an electrical impulse and delivered to the brain via nerve fibres for interpretation.

'''The image below is a simplistic hand-drawn cross section of a taste bud unit (not to scale)'''

[[File:Taste_bud_1.jpg|x400px|alt=Cross section of a taste bud unit|Cross section of a taste bud unit]]

==History of Discoveries==

{| cellpadding=5 style="border:1px solid #BBB"
|- bgcolor="#faecc8"
|''' Date'''|| '''Significant Discovery'''

|- bgcolor="#faf6ed"
|'''350BC'''
|| Aristotle writes about the basic tastes, sweet and bitter. He also notes that it can be modified by salty and acidic. <ref name="PMID22717400"><pubmed>22717400</pubmed></ref>

|- bgcolor="#faecc8"
|'''1901'''
|| D. Hanig publishes a paper describing taste sensitivity in different regions of the tongue.
''Interesting fact:'' The modern concept of a 'tongue map' is a misinterpretation of this study. <ref name="PMID22717400"/>

|- bgcolor="#faf6ed"
|style=white-space:nowrap|'''1908'''
|Kikunae Ikeda, a professor of the Tokyo Imperial University, discovered and identified the fifth basic taste: umami (savouriness), made palatable by glutamate. <ref><pubmed>12438213</pubmed></ref>
[http://chemse.oxfordjournals.org/content/27/9/847.long New Seasonings]

|- bgcolor="#faecc8"
|style=white-space:nowrap|'''1931-32'''
| A chemist named Arthur Fox and his college noted that they had different sensitivities to the bitter tasting Phenylthiocarbamide (PTC).<ref>Blakeslee AF, Fox AL. Our different taste worlds. J Hered. 1932;23:97–107.</ref> Geneticists later confirm these findings, and discover that non-tasting is a recessive genetic trait. <ref><pubmed>17782493</pubmed></ref>
[http://www.ncbi.nlm.nih.gov/pubmed/17782493 Inherited taste deficiency]

|- bgcolor="#faf6ed"
|style=white-space:nowrap|'''1965'''
|Farbman's study of the developing taste but in rat fungiform papilla was significant in increasing our understanding of taste bud development. <ref><pubmed>14300090</pubmed></ref>
[http://www.sciencedirect.com/science/article/pii/0012160665900400 Electron microscope study of the developing taste bud in rat fungiform papilla.]

|- bgcolor="#faecc8"
|style=white-space:nowrap|'''1992'''
|McLaughlin SK et al. discovery a taste cell-specific G-protein within the taste buds called Gustucon. This protein is later used to mark bitter, umami and sweet cells. <ref><pubmed>1608467 </pubmed></ref>
[http://www.nature.com/nature/journal/v357/n6379/abs/357563a0.html Gustducin is a taste-cell-specific G protein closely related to the transducins]

|- bgcolor="#faf6ed"
|style=white-space:nowrap|'''1995'''
|Barlow et al. experimented with Axolotl salamanders and concluded that taste buds from this species arise exclusively from epithelial tissue, "oropharyngeal [[#Glossary |'''epithelium''']]". <ref name="PMID17826760"><pubmed>17826760</pubmed></ref>
[http://www.ncbi.nlm.nih.gov/pubmed/17826760 Embryonic origin of gustatory cranial sensory neurons]

|- bgcolor="#faecc8"
|style=white-space:nowrap|'''1996'''
| Witt M and Reutter K of the Technical University Dresden in Germany, carried out a transmission electron microscopy study to investigate the embryonic and fetal development of Human taste buds. Their results suggest an "at least dual function of embryonic/fetal taste buds", including non-gustatory, paracrine functions prior to the 14th week and gustatory after the 14th week. <ref name="PMID8955790"><pubmed>8955790</pubmed></ref>
[http://www.ncbi.nlm.nih.gov/pubmed/8955790 Embryonic and early fetal development of human taste buds: a transmission electron microscopical study]

|- bgcolor="#faf6ed"
|style=white-space:nowrap|'''2000'''
|Chandrashekar, J. et al. discover the first taste sonsors, the T2R bitter taste receptors. <ref><pubmed>10761935</pubmed></ref>
[http://www.sciencedirect.com/science/article/pii/S0092867400807060 T2Rs Function as Bitter Taste Receptors]

|- bgcolor="#faecc8"
|style=white-space:nowrap|'''2001'''
|Nelson, G. et al. discover the sweet receptor: a combination of T1R2 and T1R3. <ref><pubmed>11509186</pubmed></ref>
[http://www.ncbi.nlm.nih.gov/pubmed/11509186?dopt=Abstract&holding=npg Mammalian sweet taste receptors.]

|- bgcolor="#faf6ed"
|style=white-space:nowrap|'''2002'''
|Nelson G. et al. discover the amino acid (umami) taste receptor: a combination of T1R1 and T1R3 identified. <ref><pubmed>11894099</pubmed></ref>
[http://www.ncbi.nlm.nih.gov/pubmed/11894099?dopt=Abstract&holding=npg An amino-acid taste receptor]

|- bgcolor="#faecc8"
|style=white-space:nowrap|'''2005'''
|Dyer, J. et al. discover sweet taste receptors in the GI tract. <ref><pubmed>17855558</pubmed></ref>
[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1986582/ Sweet taste signaling in the gut]

|- bgcolor="#faf6ed"
|style=white-space:nowrap|'''2006'''
|Huang, A. L et al. discover cells for sour taste, identified by PKD2L1 (a polycystic kidney disease-like ion channel). <ref><pubmed>16929298</pubmed></ref>
[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1571047/ The Cells and Logic for Mammalian Sour Taste detection]

|- bgcolor="#faecc8"
|style=white-space:nowrap|'''2007'''
|Harlow DE, Barlow LA of the University of Colorado Denver Health Sciences Center provide evidence of the "embryonic origin of gustatory cranial sensory neurons". <ref name="PMID17826760"/>
[http://www.ncbi.nlm.nih.gov/pubmed/17826760 Embryonic origin of gustatory cranial sensory neurons.]

|- bgcolor="#faf6ed"
|style=white-space:nowrap|'''2009'''
|A study by Hevezi P et al, presents "the first comprehensive characterization of gene expression in primate taste buds", as opposed to previous studies which focused on rodents. <ref><pubmed>19636377</pubmed></ref>
[http://www.ncbi.nlm.nih.gov/pubmed/19636377 Genome-wide analysis of gene expression in primate taste buds reveals links to diverse processes]

|- bgcolor="#faecc8"
|style=white-space:nowrap|'''2010'''
|Chandrashekar, J. et al. identify epithelial sodium channel (ENaC) as the sodium-salt taste receptor. <ref><pubmed>20107438</pubmed></ref>
[http://www.ncbi.nlm.nih.gov/pubmed/20107438?dopt=Abstract&holding=npg The cells and peripheral representation of sodium taste in mice]
|}

== Human Weekly Development - Two Prominent Studies ==
Martin Witt and Klaus Reutter of the University of Tubingen in Germany published two prominent studies regarding developing taste buds in humans. Their first study in 1996 was a transmission electron microscopical (TEM) study of the taste bud primordium and its morphological changes during the 8th-15th postovulatory week. Their next study in 1997 built on their previous findings by using Scanning Electron Microscopy (SEM) to observe the development of gustatory [[#Glossary |'''papillae''']] during postovulatory weeks 6-15.

The findings of these two studies are summarized in the table below. The figures provided relate to the images on their respective research papers.

# [http://onlinelibrary.wiley.com/doi/10.1002/(SICI)1097-0185(199612)246:4%3C507::AID-AR10%3E3.0.CO;2-S/pdf Embryonic and early fetal development of human taste buds: a transmission electron microscopical study, 1996]
# [http://chemse.oxfordjournals.org/content/22/6/601.long Scanning electron microscopical studies of developing gustatory papillae in humans, 1997]

===Timeline of Developmental Processes of Human Taste Buds===
{| cellpadding=5 style="border:1px solid #BBB"
|- bgcolor="#89CFF0"
|'''Postovulatory Week'''||'''Description'''

|- bgcolor="#BCD4E6"
|'''Week 6''' ||
The surface of the developing tongue is covered by nearly flat epithelium (1997, Figure 1). The first gustatory papillae of the tongue appear in the caudal mid-line near the foramen caecum and the first circumvallate papilla develops on the dorsal mid-line. <ref name="PMID9455607"><pubmed>9455607</pubmed></ref>

|- bgcolor="#89CFF0"
| '''Weeks 6 to 7'''||
Nerve fibers approach the basal lamina of lingual epithelium. At this stage the lingual epithelium consists of two to three cell layers and there is not yet any sign of cell specializations indicating early taste bud formation. <ref name=PMID8955790/>

|- bgcolor="#BCD4E6"
| '''Week 7 '''||
A series of irregular epithelial swellings in the anterior part and marginal parts of the tongue indicate early forming fungiform papillae. Furthermore, a V-like lane is observed anterior to the [[#Glossary |'''sulcus terminalis''']], which represents a smooth surface for developing circumvallate papillae (1997, Figure 2). Witt M et al observe that these circumvallate papillae are larger than the developing fungiform papillae of the same age, later noting that the fungiform papillae tend to increase in size over the 8-15th weeks of gestation, whilst the size of vallate papillae tend to remain constant during this period. <ref name=PMID9455607/>

|- bgcolor="#89CFF0"
| ''' Week 8 ''' ||
* The taste bud primordium are still differentiated, elongated epithelial cells, resting on a slightly developed core of young dermal papilla.
* The lingual epithelium shows first signs of taste bud development as nerve fibers coming from the dermal papilla penetrate the epithelial basal lamina and form synapses with taste bud progenitor cells (1996, Figure 1). These synapses demonstrate the neuronal connection between the taste bud primordium and the central nervous system, reaching a maximum around the 12th to 13th week. However, it is important to note that at this time these cells are still poorly differentiated, elongated epithelial cells.
* Ciliated cells also appear around the 8th week, however the significance of these cells which are scattered randomly across the lingual surface remains unclear. <ref name=PMID8955790/>

|- bgcolor="#BCD4E6"
|''' Week 9''' ||
By this stage, although a taste pore is not present, the surface of circumvallate papillae usually contains a taste pit partly filled with microvillus-like processes from the underlying taste bud cells (1997, Figure 10). <ref name=PMID9455607/>

|- bgcolor="#89CFF0"
|''' Weeks 10-11''' ||
At this stage, the lingual epithelium compromises of about four cell layers, and the first shallow grooves above the taste bud primordium are developed. Fungiform papillae appear on the lateral margins and the tip of the tongue, containing taste bud primordial that display the first signs of a primitive pore formation (1996, Figure 6). <ref name=PMID8955790/>

|- bgcolor="#BCD4E6"
|''' Week 12 ''' ||
Taste bud cells are more clearly differentiated into epithelial cell types II and III. <ref name=PMID8955790/>

|- bgcolor="#89CFF0"
|''' Weeks 12-13 ''' ||
At this stage the taste bud primordial are all located on the top of dermal papillae. There is also maximum synapses between cells and afferent nerve fibers, which intermingle with each other to form a plexus-like structure (1996, Figure 6a). <ref name=PMID8955790/>

|- bgcolor="#BCD4E6"
|''' Weeks 14 -15 ''' ||
The shape and size of the taste buds primordial begins to resemble those of adult taste buds (1996, Figure 9). By the 14th week the taste pores develop as the taste pits are filled by microvilli, and bubble like vesicles indicate the secretory activity of these cells (1996, Figure 10). However, the taste buds only achieve a fully developed function in week 15 of gestation with the development of type I cells to produce the mucous material in the taste pit. <ref name=PMID8955790/>
|}

==Abnormalities==

===Knocking out P2X Receptors===

[[File:Image of taste being evoked by visualising ATP release.jpeg|Left|thumb|200px|Evoking taste - ATP release in tongue]]

Gustatory abnormalities has not been widely researched and what has been researched has been through animal testing, most commonly we have found on mice.

In Huang, 2008 this team used the release of the [[#Glossary |'''ectoderm''']], ATP (adenosine triphosphate) as a quantitative measurement of gustatory sensation and taste. This was done by using a comparison of wild type (WT) and double knockout (DKO) mice. P2X receptors, P2X2 and P2X3 were knocked out in the DKO mice. The premise of this article was that knocking out P2X receptors reduces transmitter secretion of ATP in taste buds, therefore they cannot taste.

It should be noted that the taste buds in DKO are functional, but are not stimulated by the administration of tastants.

The transmission of release of ATP is secretion through gap junction hemichannels (pannexin 1 gap junction).

When both P2X2 and P2X3 are knocked out, no taste is elicited. However they found that if either P2X2 OR P2X3 was knocked out there was a taste response. So the inference made from this is that if one of the two receptors from the P2X family was knocked out there still can have taste response. The WT mice showed significant stimulation by tastants whereas DKO had little to no stimulation of ATP release.<ref><pubmed>21940456</pubmed></ref>

===FGF signalling and genes===

Sprouty, or ''Srpy'', genes have been related to regulating the development of circumvallate papillae (CVP). The CVP are large dome shaped papillae, which form a 'V' just in front of the terminal sulcus.

By knocking out ''Spry'' genes using mice which had ''Spry1'' and ''Spry2'' knocked out showed that the number of CVP doubled. However, when Fibroblast [[#Glossary |'''Growth Factor''']] gene ("Fgf10") was absent, the number of CVP was significantly reduced, if not completely absent. The correlation between ''Spry1/2'' and ''Fgf10'' is that ''Spry1/2'' antagonizes "Fgf10" to limit the size of the CVP progenitor placode. Exclusive expression of ''Fgf10'' in the [[#Glossary |'''mesenchyme''']] is necessary for the formation of CVP.

'''This image shows the CVP stained with H&E and scanned by Scanning Electron Microscope (SEM)'''
[[File:CVP of WT(top) and DKO(bottom) mice with H&E and SEM.png]]

'''This image shows the location of the CVP and the increased number in DKO mice by SEM'''
[[File:Mouse circumvallate papilla 01.jpg|300px]]

Taste buds develop from the mesenchyme but require local signalling to properly differentiate. Some signalling factors for proper development of taste buds besides FGF are: [[#Glossary |'''Sonic Hedgehog''']] (SHH), Bone Morphogenetic Proteins (BMPs), Epidermal Growth Factor (EGF).

Additionally, this proves that the anterior and posterior developments of the tongue are derived from embryonic tissues, where the anterior tongue is derived from the [[#Glossary |'''ectoderm''']] and the posterior tongue is derived from the [[#Glossary |'''endoderm''']]. Taste buds develop from the mesenchyme but require local signalling to properly differentiate. Some signalling factors for proper development of taste buds besides FGF are: Sonic Hedgehog (SHH), Bone Morphogenetic Proteins (BMPs), Epidermal Growth Factor (EGF).

As mentioned above, this article shows that the anterior and posterior developments of the tongue are derived from embryonic tissues, where the anterior tongue is derived front the ectoderm and the posterior tongue is derived from the endoderm. Secondly, FGF is required to regulate the growth of taste buds, while ''Spry'' genes limit the number of CVP. ''Fgf10''& ''Spry 1&2''work antagonistically through receptor tyrosine kinase (RTK)signalling.

However, the deletion of ''Spry2''led to the increase of CVPs it should be noted that they found that a significant decrease in number of fungiform papillae. In contrast, the absence of ''Fgf10'', while leading to the absence of CVPs lead to an increase in number and size of fungiform papillae. Therefore these genes have different effects on the anterior and posterior developing tongue and taste buds.<ref><pubmed>21655085</pubmed></ref>

==Gustatory System==

[[Image:Taste qualities.gif|thumb|The five basic tastes]]

Taste or more appropriately gustation, is a fundamental survival tool in animals as it directs the consumption of essential nutrients. The five tastes that exist within the human gustatory system: salty, sweet, sour, bitter and umami, all signify basic physiological requirements. Salty tastes denote the presence of Na+, an important ion involved in the transportation and retention of water across cell membranes. Sweetness is the recognition of carbohydrates, essential for maintaining optimal brain function and providing the basis for energy production in muscle tissue via ATP [[#Glossary |'''hydrolysis''']]. Similarly umami codes for the presence of L-amino acids, especially L-glutamate which is an integral component of protein synthesis.

These different modalities not only function to maintain the proper intake of nutrients within the body but also, by way of aversion, prohibit the consumption of undesired or poisonous materials. The bitter modality for example is generally regarded as displeasing to the human palate. It represents a high acid content which may be a result of foods which have become rotten or are inherently poisonous to the body.<ref name=PMID20696704><pubmed>20696704</pubmed></ref>

Research has historically limited itself to investigating the mechanisms of these five taste qualities though it must be noted many other modalities may exist. Of particular conjecture is the existence of fatty acid recognition. In the past the detection of fat in food has been attributed to somatosensory inputs <ref name=PMID20696704/> from the tongue, that is, the oily feel and texture of fat rather than its actual ‘taste’ allows the brain to encode for its presence. Further research is therefore required to elicit the precise mechanisms of fat detection.

===Cell Biology===

The five taste qualities are not all detected by the same type of receptor cell located within the taste bud. Like rods and cones in the eye which detect different wavelengths of light, there are specific types of receptors for different tastes. For example, sweet, umami and bitter are recognized by Type II G-protein coupled receptors, whereas sour is related to Type III presynaptic cells. The cell type involved in salty taste transduction is unknown however it is known that sodium ions can enter the receptor cell membrane via ion channel permeation.

====Type II receptors====

When a bitter, sweet or umami ligand binds to a type II G-coupled receptor, a cascade of chemical reactions causes the release of Ca2+ which in turn mediates [[#Glossary |'''exocystosis''']] of ATP. The function of this ATP is threefold:

# Stimulates gustatory nerve afferents which project to gustatory nuclei in the spinal cord
# Excites Type III presynaptic nerve fibers to release serotonin.
# Has a positive feedback effect on type II receptor cells, increasing the level of ATP production.

The role of serotonin is believed to be in the form of lateral inhibition i.e. when a bitter quality is recognized, adjacent receptors for sweetness are deactivated and thus the two tastes may be clearly differentiated. It also has a negative feedback effect on receptor cells, inhibiting umami, bitter and sweet taste transduction.

==Taste Map==
[[Image:Taste map.png|thumb|left|250px|Obsolete idea of the tongue map]]
The idea of a tongue map has disseminated through society for many years. This concept purports that different areas of the tongue are specialized to detect either sweet, salty, sour and bitter tastes. Recent research however has completely nullified such claims and suggests instead that different forms of taste are recognized all over the tongue as well as via the palate. Thus the term ''taste map'' has come to take on a new meaning and that is, the precise areas of taste modalities processing in areas of cortex and its subsequent neural inputs.

===Neural Pathways===

'''First order [[#Glossary |'''neuron''']]''' - From the receptors located in the taste buds, gustatory nerve afferents project to the ipsilateral rostral 1/3 of the nucleus tractus solitarius (NTS), located in the medulla. This rostral 1/3 is commonly referred to as the ''gustatory nucleus''.

The ''gustatory nucleus'' receives input from cranial nerves VII (''Facial n.''), IX (''Hypglossal n.''), and X (''Vagus n.'') via special visceral afferent (SVA) nerve fibers. A summary of their functions is as follows:

* ''Facial nerve n''. - carries taste information from the anterior 2/3 of the tongue.
* ''Hypoglossal n.'' - carries taste information from the posterior 1/3 of the tongue.
* ''Vagus n''. - carries taste information from the palate

'''Second order neurons''' - From the NTS second order neurons carry taste information to the Ventral posteromedial (VPM) nucleus in the thalamus.<ref name=PMID21885776/>

Copious scientific conjecture surrounds how each taste modality is transmitted to the brain. The ‘labelled-line’ hypothesis suggests that there are taste specific neurons which exclusively carry that taste modality to cortical areas. In analogous terms it can be viewed like the pipelines leading toward a house. Each pipeline carries its own utility, there is one for gas, another for water and finally for electricity with each terminating in slightly different areas of the house. In the same way, on the tongues there are different receptors for each taste which concurrently have individual nerve tracts leading to the primary gustatory cortex.

Contrapuntally there is electrophysiological evidence that single nerve afferents carry multiple modalities. These studies show one nerve afferent may have both a strong and a weak activation in response to a multiple taste stimuli.

===Cortical Areas===

[[Image:Primary gustatory cortex.png|thumb|Primary gustatory cortex]]

The location of the taste perception centers has been observed via functional magnetic resonance imaging (fMRI) studies. The primary taste cortex has been identified as being located in the anterior insula/frontal operculum (I/fO)<ref name=PMID22245354><pubmed>22245354</pubmed></ref>, with the secondary taste cortex in the caudolateral orbitofrontal cortex.<ref name=PMID21305668><pubmed>21305668</pubmed></ref> Within the insula there are further subdivisions related to each taste modality. Two photon calcium imaging research has outlined certain ’hot-spots’ of activation which are clearly delineated in relation to each taste. For example, the bitter modality is represented on the insula cortex approximately 1mm posterior to the middle cerebral artery whereas the sweet modality is represented 2.5mm rostrodorsal to the bitter field with no apparent overlap.<ref name=PMID21885776><pubmed>21885776</pubmed></ref> These findings lend weight to the idea that there is only one receptor for each taste quality.

It is interesting to note the relationship between taste and the reward centers of the brain. There is evidence of neural input to the ventral tegmental area (the origin of the mesolimbic dopaminergic reward pathway) and nucleus accumbens (involved in the conversion of motivation into physical action).<ref name=PMID21885776/> Neural connections such as this provide the foundations in explaining concepts such as flavour learning and preference. It may also give some insight into chronic problems such as food addiction and craving. As of yet however the gustatory neural network is not well understood and more research is required to elucidate the relationship between pleasure and taste sensation

==Current Research==
We have an evolving understanding of Embryonic Taste development, through the use of state-of-the-art technology and research techniques we are able to make brilliant discoveries that continue to connect the dots of this amazing natural process of human development.
The majority of research in taste development is involving mice, these mammals show similar embryonic pathways to humans and research is performed in ethical and humane methods.

[[File:Histology.jpg|Left|thumb|200px|Image shows histological stains of a mice tongue showing dysplasia]]

'''Synergistic relationships of Six Genes '''

In an animal study using mice by Suzuki Y, Ikeda K, Kawakami K.(2011) Firstly nominating "[[#Glossary |'''Six Genes''']]" as a major component in [[#Glossary |'''gustatory ''']] development, stating that deficiencies in certain Six genes (specifically Six1 & Six4) leads to poor development. Their research also highlights evidence of cooperative relationships between Six genes for normal advance. This experiment involved breeding mice containing exclusively Six1 and Six4 genes and examining the expression of these genes in papillae under high powered microscope observation. Understanding the role of certain genes along with the intrinsic relationships they hold is crucial for the ability to identify possible causes and correction of any abnormalities <ref><pubmed>21978088</pubmed></ref>

'''Neural Crest responsibilities '''

Another Animal Study involving mice explores a new idea of [[#Glossary |'''Neural crest''']] (NC) contribution in taste development, specifically the development of papillae and taste buds. Liu HX, Komatsu Y, Mishina Y, Mistretta CM. (2012) suggest that Neural crest cells travel to the location of the tongue in early embryonic stages, gain epithelium phenotypes, multiply and then differentiate to eventually form taste papillae. The experiment involved the comparison of 2 different types of Cre line mice, which both express Cre gene in neural crest protocol, the different distribution patterns where observed in specific regions that NC is responsible for.<ref><pubmed>22659543</pubmed></ref>

'''Augmentation of Endoderm'''

In an animal study conducted by Rothova M, Thompson H, Lickert H, Tucker AS.(2012) exploring the historically debated issue of endoderm contribution to tongue development showed promising evidence that position of taste buds are patterned by the border of ectoderm and endoderm derivative epithelium. This study was accomplished via microscopic examination of previously stained specimens. Concluding endoderm has direct influence on gustatory development <ref><pubmed>22581563</pubmed></ref>

'''Changes in Taste Cells over time'''

Research by
Ozdener H, Spielman AI, Rawson NE.(2012) developing a culture which allows taste cells to survive for up to 12 months, empowers researchers to study the processes of proliferation, differentiation and function. This experiment will provide a precedent for future study of taste cells, as these cells are able to operate and grow normally. <ref><pubmed>22643728</pubmed></ref>

'''Shh key component of taste bud proginators'''

A [[#Glossary |'''tamoxifen''']] treatment which suppresses Sonic hedgehog (Shh) secretion in mice proving to reduce the number of cells visible within papillae, in contrast mice not treated with tamoxifen showed a mark increase of cells within papillae, these cells are assumed to become taste cells in later development.
Specific mice were bred to trace the destination of taste placode cells, the study concluded that Shh expressing placodes are taste bud proginators which in turn become taste cells within taste buds although do not have any precursors relationship with papillae. The results were obtain by examination of mice embryos using Bright-field or multichannel fluorescent images through the use of an "Axiocam CCD camera and Axioplan fluorescence microscope with Axiovision software" a study by Harlow, Yang, Williams, Barlow (2011)<ref><pubmed>PMC2674259</pubmed></ref>

'''WNT family exhibit various roles''' [[File:Abnormal of tongue.jpg|thumb|200px|Image shows an example of tongue abnormalities, this is called "double tongue" each side has independent movement!]]

The WNT gene family has a function of signally proteins for various reason such as development, In 2010 Liu, Staubach Grosse, Walton, Saims, Gumucio, Mistretta explored recent findings on the role of WNT's in tongue and papillae development, Concluding that WNT/β-catenin is essential for fungiform papillae differing to WNT5a which proved to be principle in tongue development. Intrinsic chemical mediators were considered by manipulating a tissue culture and then thoroughly examined by scanning photomicrograph. <ref><pubmed>PMC2768563</pubmed></ref>

[http://www.surgicalneurologyint.com/article.asp?issn=2152-7806;year=2012;volume=3;issue=1;spage=23;epage=23;aulast=Manjila]

==Glossary==

* '''Ectoderm'''- outer germ layer of embryo

* '''Endoderm''' - inner germ layer of embryo

* '''Epithelium''' - basic animal tissue that is composed of tightly packed cells, usually covering the outer portion of organs

* '''Exocystosis''' - movement of contents out of cell

* '''Ganglia''' - the accumulation of a nerve cell body

* '''Growth factor''' - a substance that stimulates the growth of cells

* '''Gustatory''' - anything that relates to the taste sense

* '''Hydrolysis''' - breakdown of a chemical when it reacts with water

* '''Mesoderm''' - middle germ layer of embryo

* '''Mesenchyme''' - multipotential cells

* '''Neural crest''' - a part of the ectoderm found on both sides of the neural tube

* '''Neuron''' - most simplistic unit of the nervous system

* '''Neurotransmitter''' - chemicals which allow the passing of signals from neuron to neuron via connecting part (synapse)

* '''Papillae''' - small rough surface projection

* '''Six genes''' - a family of genes

* '''Sonic hedgehog (Shh)''' - signalling protein involved in normal development

* '''Sulcus terminalis''' - describes a physical transition point separating the anterior 2/3 of the tongue from the posterior 1/3

* '''Tamoxifen''' - hormonal altering drug

== References ==
<references/>

==External Links==
{{External Links}}

http://www.webmd.com/oral-health/picture-of-the-tongue

http://www.tutorvista.com/content/biology/biology-iv/nervous-coordination/tongue-structure.php#parts-of-tongue

http://www.cf.ac.uk/biosi/staffinfo/jacob/teaching/sensory/taste.html

--[[User:Z8600021|Mark Hill]] 12:22, 15 August 2012 (EST) Please leave the content listed below the line at the bottom of your project page.

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{{2012Projects}}

Talk:2012 Group Project 3

2012-09-30T23:15:03Z

Z3289738: /* Discussion of Contributions via Email */

{{2012GroupDiscussion}}

--[[User:Z8600021|Mark Hill]] 09:54, 18 September 2012 (EST) This is a recent review on taste. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2922655 http://jcb.rupress.org/content/190/3/285 JCB content allows reuse.

==Group evaluation==

The introduction section is very informative and I like the picture included discussing the 5 basic tastes which is interesting to read. I really enjoy your descriptions of bitter and sweet and find it interesting to read. I like the research you included in this section but I believe this needs to be referenced. Currently in the introduction you have only 1 references, so I would suggest that you find more to further validate your information (note that there are no references in the first paragraph). I like in your picture that you included a description. The cell biology section I would probably put in its own section with = = to break up the contend displayed. In this section it is clear that this has been researched however there have been no references listed at all here.

The taste map section has clearly been well researched yet poorly referenced. It would be interesting to look at if possible a progression of the understanding of the taste map. In the picture of the tongue, I would suggest that it has a better description on the enlarged image. However, some of this text is rather hard to read, such as the descriptions of the first and second order neurons. As you have included terms in there which would be foreign to most people, I would try to include either a picture to show exactly where these parts are such as the NTS which can give the reader a better understanding of what you’re saying. Note that you say things like “copious scientific conjecture surrounds…” however there is no references here! This section is well researched which is great, but I would really consider putting it into slightly easier terms to better comprehension.

In the cortical areas section, a similar approach applies: when describing locations of things such as the I/fO, you should really include a clear diagram as to where all of these are. I can see you included the section of the brain however don’t see it as too informative so a better description there would be appropriate. I would also note that you are repeating your references again, and it would be advisable that you find alternative information to include as well.

The timeline section is very informative and really stands out. I’m assuming you will be including the photos later this week. This is well written and gives a truly informative description of the embryological changes that occur. It will look much better and be better to understand once the photos have been included. Note that you have used the same references pretty well the whole time in this section. Although that paper may have a lot of information about what you are needing to talk about, I would also encourage you to research more papers in order to compliment the information you have listed.

The history of discoveries section is well set out and clear and concise. In some areas I would suggest a brief descripton of what you have written such as “PKD2L”, and also make sure you include the appropriate references as all I can see currently it numbers.

In the adult tongue and taste bud section, is this also what the tongue looks like from week 15? If not what changes occurs for it to form into what you have described as the adult tongue and what enhances these changes? This section is informative however it is really lacking references. The taste bud picture you have is quite good, but is that also what the taste bud looks like at 15 weeks?

The abnormalities section is really interesting and is rather enjoyable to read. Are they the only abnormalities that can happen to the tongue? How about environmental? Does alcohol, smoking or drugs affects its development of either the tongue or the taste buds? Additonally, your current research is very thorough and interesting. In regards to the photos you have there, I would make sure that they are set out appropriately, with the information that this is a student project.

Finally, the glossary needs to be highlighted to make it stand out and more words need to be included. Note that in your references, reference 5 can not be accessible, so make sure you fix that up. Overall, it was interesting to read and I enjoyed the display of photos that were also included!

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The overall set up of the page I think is very good. In the introduction there is a balance between pictures and text which makes it a bit easier to read. Also its easy to follow, the text itself isn’t confusing and is understandable.

There is a good overview of the different types of receptors and their function, also there is a brief section on the adult tongue which is good, however there needs to be more focus on the embryological development rather than just a simple table on that. There also needs to be some images added to that component as well to make it more understandable.

The sections on abnormalities and current research need to be organised a bit better because they are a little hard to follow, especially with the placing of the images. The glossary is simple and understandable, however there needs to be more work done on the reference list.

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The layout and balance between text and figures, tables, and diagrams is extremely well accomplished. All the information of the page is really intriguing and easy to follow on the majority.
I would suggest placing the history of discoveries immediately after the introduction so that readers may appreciate all the research that would have had to take place in order to put all the information on this page. As well, this would help in having a separation between the two tables used.

When it comes to images, make sure that everything in the image is relevant to the accompanying text and important to the reader. One image where you might fall short of this criteria, is the very first image on the page about the five basic tastes, the names of the protein structures is more distracting and confusing than enlightening and overall would not aid in informing the reader.

I believe the introduction is very important in assisting the reader in gaining an overall understanding of the page and it’s aims. Hence I believe it is important to include a more succinct introduction with such aims. In this case, the introduction to the gustatory system begins defining structures and functions which are better off used elsewhere. Instead try giving an overview of the system and maybe give the reader a reason to read on.

The images used in the abnormality section are scattered and make it hard for the reader to determine which image corresponds to which idea, I would suggest ensuring that each image is detrimental to aiding the reader’s thoughts. This was an extremely interesting section.

Current research is clear, concise and easy to follow with a pleasant arrangement of ideas, text, and images. It was interesting to read. Additionally, the references and glossary are extensive and well done. I would suggest having a link to the glossary from within the text.

Well done on your project so far, and good luck with the rest.

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The introduction seemed to go into a lot of detail. for example, the information on Type II receptors should be placed in the same section as neural pathways, not the introduction. Can you also include in your introduction, an overview of what you are going to talk about in your project? That would give your project more structure.

With the neural pathway section, can you draw or find a diagram for that section? I find it hard to understand without one. The taste map section goes into a lot of detail which I think is unnecessary because this is a development project.

Current research section is very interesting. I don't think you need to add any more content on that section - that section to me looks complete, besides a few formatting and referencing issues with the images.

Overall, I felt there wasn't enough written on the development of taste, either the receptors (taste buds) or the neural pathways. Your project seem to focus on the anatomy and physiology or function of the taste system. This is alright to keep but the focus should be on development. You do have a Time-line of taste development that summarizes the development of the Gustatory system which is great to see. I think use that as a starting point and expand on each stage in text form, below the table. In week 12 development in this time-line, you mention 'epithelial types I and II', what are they? Are they similar to skin cells?

Overall, the balance between images and text is great. The colourful images work wonders in breaking up the text. Having said that, Many of your images did not have the correct PMID referencing. These images include:
* images of taste being revoked by visualizing ATP release
* CVP of WT and DKO mouse with H & E and SEM
* histology - can you give a more relevant title for this image? We know it's histology; we can see that. What is this image about?
* Abnormal of Tongue - it should say abnormality of tongue

The history section is excellent because it spans over such a long time - 350BC to 2010. The layout of a coloured table for history is beautiful, clear and concise.

--[[User:Z3332863|Z3332863]] 16:35, 23 September 2012 (EST)

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- The introduction of taste is very descriptive and encapsulates the anatomy, physiology and cell biology. Although it is very detailed it doesn’t indicate that the project is about development.

- There is a lot of detail about the taste neural pathway and cortical areas which I’m not sure is relevant to olfactory development unless you mention how they develop as well.

- Figure 2 and 3 do not have any copyright information associated so remember to add those.

- The development section is very nicely put together and hopefully you will add images further down the line. I’ve noticed that in week 8 of development you have the same ref after each line…I’m sure you can just put it at the end of the paragraph as it is same for each line. Same goes for week 14 and 15. Also since you have 2 references for the entire section --- you might want to look at other articles as well.

- Some things that I missed in the section were patterning molecules and genes. Also any signalling mechanisms that control differentiation.

- The history section is exceptionally done with the use of tables, description and references.

- I thoroughly enjoyed your abnormality section. The images are nicely done as well. Although you have described many genes and molecules which are not specified in the normal development portion so the reader don’t understand their roles. Maybe address this in your normal development section.

- The current development section is also very nicely put together but again things like Shh and WNT should be in development section.

Overall very nicely put together and great balance of pictures and text. Although this is a development topic so the major emphasis should be on development of the organ --- Normal development is good but there is too much content in that section that can be left out.

--[[User:Z3333794|Z3333794]] 10:52, 23 September 2012 (EST)

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Abundant information, including a nice coloured in table, which is a cool idea. Unfinished though, the images to go with it would make it great. The page seems to be segmented into sections with a large amount of text, and sections with many pictures. Try for a more even distribution, if possible. Pictures seem to be relevant, with good explanations, referencing and certificates. Helpful and interesting abnormalities and current research sections

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Your introduction is quite good and gives us a brief overview of the different tastes. I also like it that you touch on the fact that it is important we recognise (via taste) food which would be dangerous to our health. In my opinion, after you mention the research (ending the sentence with …’may exist.’) you should tell the reader what you will be discussing on your page. The few lines on fatty acids does not seem to fit in, and should be part of your history section and possibly current/future research. Some specific information seems to have been researched, such as what umami codes for; however, references have not been provided. Also make sure that the image has the correct information – title, description, references, copyright, student template.

It would be more logical to put the history section next. Following this by the timeline and then go back to the cell biology, receptors and taste map etc.

The history section is good with many significant dates and clear descriptions incorporated in a table. I do see lots of numbers, which I think relate to references. I cannot find these references anywhere, so please edit this and make sure it is included in your list of references. There are also a few references listed in full in the table, so please put these down as proper references. Also, there is no good description for the year 2007 (it is mainly a reference).

The developmental timeline is expansive and very interesting! It really relates to the different developmental stages and tells us what happens over time. I hope you can include images with appropriate labels and information to this table, as it will greatly complement your text. Please do check your spelling, eg. ‘epithelium’ in week 6. Also references in this section are appropriate and are not doubled-up in the reference list. Do check reference 5 as it comes up with a cite error.

The section on cell biology and type 2 receptors is clear and easy to read. I cannot see any references though! Please be careful cause this might indicate plagiarism. The taste map is interesting and I am glad you mentioned research has indicated that the different receptors are in fact located all over the tongue – not just in particular sections. If possible, look for the original paper(s) that made this discovery.

The section on neural pathways is a little more difficult to read and I did not understand some of it. Particular terms are used in sentences which suggest little effort has been put in to explain everything in your own words. This is further indicated by the lack of references in the ‘first order neuron’ section and the majority of the ‘second order neuron’ section. I might be wrong, but then do add all your jargon to the glossary. If possible, also try to find other papers which present the same information to strengthen your points mentioned. Images for both the taste map and the cortex need referencing, copyright info, etc.

Adult tongue and taste buds. It is good you include some anatomy and physiology into your section. Do keep in mind the majority of your project should focus on embryonic development. You included the appropriate names, eg. sulcus terminalis, and I am glad to see that has also been put in the glossary. Some more terms do need to be added, eg. circumvallate. The text is good, clear and easy to read. Images are appropriate and relate to the text but need proper descriptions, citations, etc. A major let down of this section is the lack of references – please include this.

Personally, I found the abnormalities section very interesting! However, you are suddenly talking about all these genes and factors which you have not mentioned anywhere else. It might be good to provide a brief description of these in the development section or incorporate them into your developmental timeline. Images all have copyright information, but other information is missing, such as the student template and/or reference. Please check and add this.

Current research includes a lot of information. All different sections have their references which are displayed in the reference list. If you can, provide links to the website of the research groups working on current projects. Be careful not to just put your reference at the end, as you may also have to reference within the paragraph. Both pictures used will need the student template. The double tongue image will need a reference in its description too.

As mentioned before, add and edit the glossary and reference list. You should also add to the useful links (make this external links) and the image gallery, or delete these subheadings, as there is nothing there now.

Hope this helps!
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"In regards to the information presented (outcomes 1 and 9), the timeline for the development is good and written with clarity. However, I noticed the section on structure only referred to the adult state rather than focusing on the embryonic origin of each structure (ectoderm, endoderm and mesoderm). I would suggest that you elaborate on the developmental stages introduced in the timeline in order to build on the information you have already provided. This is important in regards to outcome 6 so that you can relate your research to embryology – the development of taste should be your focus. The history timeline was great to read as it was very concise and clear.

The page shows a good level of peer teaching with clear language and a good balance between images and text (outcome 4) with technical terms explained in the glossary. An improvement could be to make a link between any technical language and the glossary to avoid scrolling up and down to the page. Your Current Research section (outcome 5) was very interesting to read and showed you went beyond the scope of basic research on taste – good work!

In terms of layout (outcome 2), whilst the images are interesting and relevant to the text, some are not appropriately referenced nor described; make sure to reference appropriately and at least write one or two sentences to make the images relevant to the reader. Additionally, the introduction should not be under another subheading (Gustatory system) as it creates some confusion; I would suggest making the introduction its own heading in order to make the page flow. Similarly, the history timeline would best be placed towards the beginning of the page, under the introduction.

I noticed some areas (such as the section on Structure) were not appropriately or consistently referenced. Make sure to include a citation anytime you introduce a researched idea or information to avoid being accused of plagiarism. I noticed the history timeline had good consistent referencing; however the numbers just need to be formatted so they come under the reference list. If you click on the Tutorial: References page linked from the student page, it tells you how to do this. Hope the feedback helps and all the best for your project!"

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The introduction is very detailed but did not mention anything about the development of the taste. But I thought the mechanisms behind sweet and salty tastes are very interesting. Maybe do the same for the other 3 tastes? The image of the basic 5 tastes is a bit small, maybe upload a bigger version of the image. Also, the image is lacking some reference, copyright information and a student image template.

The type II receptor section is pretty good and descriptive but it does not really relate to the development of the taste. The taste map is a very eye-catchy image and it would be really useful if it had all the needed information such as the copyright notice. The timeline of the gustatory system is very well-presented and easy to read. I understand the project is not completed yet, therefore more images are still to be put in. Only 2 references have been used in the timeline section, maybe try to research more and use different resources. There are some citing error but it should be quite easy to fix.

Histories of discoveries section is very detailed and easy to read but the referencing needs to be fixed. The adult tongue and taste bud section is very clear and precise and contain a lot of useful information but it does not really relate to the research topic, should beware of going off-track. The hand-drawn diagram of the taste bud is impressive and easy to understand but again lacking in some referencing information such as who drew it. The abnormalities section is good and well-researched and it is interesting to know about which gene or receptors will effect the development of taste and sensation. Maybe the abnormalities section can be included into the current research section because abnormalities are repeated in the current research section below. There are detailed definitions of terms in the glossary which is good because it really helps the reader to understand more about the research topic.

Overall, the page is looking good. The main thing that needs to be fixed will be the images that are already on the page, they need the correct and essential information with them when uploaded on the page or else, they will get deleted and there will be no images on the page and the nice balance of images and text now will be gone. There seem to be a lot of anatomy and biology of the taste system but not a lot of information about their development. Although there is a timeline of development but i think more information is needed. Referencing is pretty good with only one or two minor citing error but it should be easy to fix. Structure of the page is clear and simple with headings and sub-headings being consistent, making the page easy to read and follow. Hope this helps :)

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The introduction is good, explaining the function and mechanisms behind.

The taste map text and picture are useful however lack referencing information.

The cortical areas section is very interesting and well referenced.

The table timeline is a very good way to summarise the development of taste. It is succinct and well referenced, even though one paper was referred to for most of the information.

The history table is similarly good, very succinct and straightforward, however lacks some references, and the references that were included could be improved by using the wiki referencing system.

The structure and function section is useful but doesn't add much to the text in terms of embryological development. Also make sure the images are properly referenced with the "student template" included.

The abnormalities section is very good and well researched, although maybe try and avoid referring to the articles that have been researched in the text and rather just refer to them using the wiki referencing system. The images are good as well but don't forget the "student template" here also.

The current research section is interesting and well researched, the use of succinct subheadings to summarise the paper's findings was good.

The useful links and image sections need to be added to, and the glossary section can be improved by putting the key terms in bold, but that is otherwise good.

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Initially the page seems to have a good balance between text and diagrams/photographs. However the figures included are not properly labelled once you click on the file and some of them don't appear to have any copyright information included. Some of the pictures could do with being a bit smaller as they take up a large proportion of the page. The student drawn image of the tongue is particularly impressive but does still need to have the student template included. The references seem limited in comparison to other groups perhaps suggesting a lack of depth or variety of research. There also appears to be a coding problem relating to reference number 5. The general layout and use of subheadings is great. It may be useful to link the words in the glossary to their occurrence in the text.

The introductory paragraphs are very well written. They are easy to understand and interesting and give a good overview of how taste functions. Similarly the section on taste map is well written clearly explaining the neurological factors associated with taste. However the presence of the picture in isolation is confusing as it is representing an the old method of taste association. Perhaps this would be resolved if a diagram of the newer taste map was also included. Also you say that the old taste map has been disproved by recent research but that research is not referenced. In fact it appears that very little of that section is referenced. The section on cortical areas is well done.

The timeline of developmental processes is good, the table an easy visual format and the information concise and effective. The only point of contention would be the direct quote in Wk8-9 which seems out of place in comparison to the remainder of the entries which are nicely paraphrased. The history section is similarly well done being extensive and comprehensive. That is excepting some Pub Med references which are just placed in the text rather than in the reference list at the bottom. While interesting and well written the part detailing the Adult Tongue and Taste Buds seems out of place in a embryology course.

The sections on the effect of gene expression on the formation of taste abnormalities and current research are good. However it may be useful to put the information regarding each picture as a caption rather than plain text.

It will be interesting to see what is put in the section "Image Gallery"

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The information provided is both informative and well organised. The use of tables and figures make the text easy to follow and the diagrams make the information easier to understand. When it comes to images however, they seem to be somewhat irrelevant next to some of the information in some cases. Try to move them around and make sure they accompany relevant text.

The introduction does not give the reader the overview of the topic, but rather explores structures and function which makes it difficult to order. Simplifying the introduction, and moving some of the more detailed information such as the information about the type 2 receptors to the relevant section would improve the page.

Other information that is difficult to understand is the text which involves certain genes and molecules without explaining their function or role. Explaining these aspects of the genes and molecules would make the information flow better.
The section on current research is very informative and seems to be complete. However, I did note some errors with the citation of the image used, working on the references is very important for the other images as well as not all have the copyright information.

I also noticed that many of the references are repeated numerous times. Week 8 of development for example have the same reference after a number of sentences. A variety of sources will improve the accuracy of the information rather than derive all the information from a single source.

There is a great focus on the anatomy and physiology of taste, however, it is important to remember that the focus of this project is about development, and therefore including a timeline or a table which covers this information is very important. The page seems to be very organised and the inclusion of tables and diagrams along with the extensive glossary make this page stand out. Well done.

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The page that you have created is very extensive and was well formatted in relation to the ratio of images to text on the page.
Found that the colours and use of table for the breakdown of information in relation to ‘Timeline of developmental process’ and ‘history of discoveries’ condensed the material and made it easily understandable. This made me want to keep reading.

With majority of the images that are uploaded onto the page there needs to be the correct information and referencing provided for the summary box. From where the image was sourced (ideally of reliable and scientific literature in origin), identifying that it has been uploaded for a student assignment and copyright information-permission to use uploaded image and any other information that is pertaining to the topic and why the image was used/relevant.
Further, those of you within your group that have drawn an uploaded image, have to ensure that you have stated in the summary box that it was student drawn prior to final assessment/evaluation.

The glossary is able to be expanded upon and potentially ensuring that the words that are being explained/elaborated are bolded. As a reader, I would find it easier to read and distinguish if they were bolded.
The reference list that has been developed appears to demonstrate that as a group you have are well read and researched, however, the citation errors will have to be addressed and resolved prior to final marking of the project. I really appreciated the layout (headings, summary and images) of the page.

----
The introduction is well written and very informative. You should add the history timeline directly below the introduction, because where it currently is feels like it is floating. With it after the introduction it will create a flow to your page and separate the two tables.
In your development table I noted a column called images, the adding of images to show the development stage you are describing will give this section some more flair. If you are not adding images don’t forget to delete the column.

Your section on adult taste and tongue is very interesting but maybe if there is a difference, i.e. newborns tongues are more sensitive to a taste than adults, a comparison would be interesting here.

In abnormalities you mention p2x receptors, maybe you could add this to the glossary and give a brief explanation about what they are and do. This would be a good idea for any other receptor or genes/proteins mention above that you don’t want to explain in detail in the main section.
--[[User:Z3220343|Z3220343]] 21:31, 25 September 2012 (EST)

---

Your introductory paragraph is sufficiently detailed. However, there is only one reference. You need to show more research by adding more references to support your text. It is good that you have added an image to support the text, but you need to write that it is a student uploaded image.
Cell biology and type 2 receptors sections don’t have any references cited at all. You need to add appropriate references.

There was an image of the tongue showing the tastes in different sections of the tongue. The image didn’t have the source referenced.

The taste map section needs more referencing and citations.

Cortical area is sufficiently detailed and has appropriate numbers of references, along with a supportive image. However, you should add more description of what the image is about.
“Timeline of Developmental Processes of the Gustatory System” looks nice so far, with appropriate citations. But you may need to add some more information, and it needs to add images to support the text.

History of discoveries section looks nice, but needs a bit more texts explaining each of the discoveries. It also needs some more references, and perhaps adding some images to support the text would make it easier to visualise the discoveries.

“Adult Tongue and Taste Buds – Structure and Function” is overall lacking in text and needs more research and references. You need to explain more of the structures and functions of the tongue. The image of the ‘drawing of the tongue’ needs a bit more description in the caption. Perhaps explain what each of the labels mean. The papillae image should say that it is a student uploaded image.

Current research section is done reasonably well so far. The reference needs appropriate formatting. Perhaps reduce the size of the image showing the double tongue; it is rather graphic and somewhat disturbing.

You do not have any useful links listed. You need to add links.

Glossary section is good so far. Perhaps add some more words, and make the text bold to make it easier to spot the different words.

Image gallery does not have images under the heading.

References section: number 5 needs to be fixed.

There are not external links listed under the heading, you need to add external links with appropriate formatting.

----

Group 3- Taste

Overall this is an excellent project. Well written, great informative photos, good use of tables, and comprehensive information that's well explained.

A few of the photos don't have the appropriate copyright information and some sections of text haven't been referenced, but in general this ticks all of the boxes

----

Taste

The introduction is very detailed, with descriptions of the varies components of taste. Although informative, there needs to be more about the development of the different aspects of taste. I feel that the type 2 receptor part doesn't belong here as this section is here to introduce the topic (maybe put it in a separate heading or in the neural pathway section?). There also needs to be a diagram if you are to include this as if is hard to follow. The balance between text and images is good, though some of the images are not labelled or properly referenced. Histories of discoveries section is very detailed and the table was very easy to read. The section the development of the taste is very informative and shows a of effort is placed into the of research of the topic (as it is often hard when the topic is not well understood). The section on the Structure and Function of the adult tongue gives the anatomy of the tongue, and should come before the part on neural pathways. The current research provided descriptions of the research and their goal and is done well.

==Questions for group==
--[[User:Z3330986|Z3330986]] 14:29, 18 September 2012 (EST)--[[User:Z3330986|Z3330986]] 14:29, 18 September 2012 (EST)
Hey guys,

Did I see someone write about or have articles about Sprouty (''spry'') genes?

I can't find it, but I'm sure I saw it. Let me know :)

--[[User:Z3332337|Z3332337]] 11:10, 18 September 2012 (EST)

--

Also, I've just been going over the main page and I wonder if a picture of the overall tongue, not only sections or histological drawings (which were really good btw) would be good to point out the anatomical features?? Like the sulcus terminalis which was pointed out.
I'd be happy to draw it. This would be for the Basic structure section.

Let me know ASAP so I can do it tonight :)

--[[User:Z3332337|Z3332337]] 11:30, 18 September 2012 (EST)

--

Yep, i think that would be a good idea. Go for it :)

--[[User:Z3330986|Z3330986]] 14:29, 18 September 2012 (EST)

Roger that (y). I'll have it done by around 10'ish tonight to be realistic.

--[[User:Z3332337|Z3332337]] 17:10, 18 September 2012 (EST)

--

Guys!!! I'm following image upload instructions to the letter and it keeps giving me database error. :( I need to upload figures 1 and 6 from this article. Let me know, k?

--[[User:Z3332337|Z3332337]] 17:58, 18 September 2012 (EST)

--
I had the same problem during the Lab assignments so i used a different image instead. I'm not sure if its related to the image itself? Maybe just email mark?

Maybe everyone could add some words from their relevant sections and hopefully we can come up with a pretty comprehensive glossary
--[[User:Z3330986|Z3330986]] 20:40, 18 September 2012 (EST)

== Discussion of Contributions via Email ==

Hey guys,
I changed the order of the content on our page coz I thought it would make more sense for this topic to have the embryology stuff first and then move on to details of the adult features. Let me know what you think!

Also if you can each send me a brief sentence outlining each of your sections I'll put together an intro.

Thanks,
--[[User:Z3289738|Z3289738]] 09:14, 1 October 2012 (EST)

--

Jared: hi guys,

just confirming our meeting tome tomorrow after the first lecture [after mid sem break]

Thanks :-0.

Nat:
Yup, meet outside the lecture room?

--[[User:Z3332337|Z3332337]] 11:07, 11 September 2012 (EST)

--

Hey Guys,

Jared :
becuase we are on holidays as of now, make sure we are communicating about any contributions and copy and past any email discusions onto this page.

--

Hey guys,
So here's our plan for the next few weeks. If you want you can start writing up a particular section before next week!

* Wed 5/09: Have heading finalized; divide work.
* Wed 12/09: Sections finished. Discuss in class of any areas of improvement.
* Wed 19/09: Peer Assessment!

Have a good break :)

--[[User:Z3289738|Z3289738]] 11:58, 29 August 2012 (EST)

--

Hey guys,
I thought of a few headings, please let me know if you have anything to add or change!

* Intro
* History of discoveries
* Gustatory system - this is really important!!
* Tongue and taste buds - structure and function
* Taste map
* Weekly development
* Abnormalities
* Current Research
* Future research

Not including the intro we can each choose 2 areas. I'll get started on History of discoveries and Weekly development.

If you're having problems with your section, or feel that it is irrelevant, or find something else along the way just email the group and we can make changes!

Have a great week :)

Nat

--[[User:Z3289738|Z3289738]] 10:58, 5 September 2012 (EST)

--

That sounds good, maybe we should try and meet before next wednesday to make final changes?

--

Sure, how about somewhere between the two Embryology lectures (12-3pm) on Tuesday?

Which sections do you want to do? I just put them up on our wiki page.

Nat --[[User:Z3289738|Z3289738]] 11:35, 5 September 2012 (EST)

--

well i have been already doing current research and structure + development, but im happy to do more work :) and yes perhaps straight after our fist lecture 11-12pm?

--

Jordan --[[User:Z3330986|Z3330986]] 11:50, 5 September 2012 (EST)

Hi everyone i'll be happy to "Gustatory system" and "taste map." I think it would make it a bit easier as i have covered the neural pathways of taste in some detail in Neuroanatomy.

--

Okay awesome guys

So the division of work so far is:
* Introduction to the Gustatory System - '''Jordan'''
* Timeline of Developmental Processes of the Gustatory System - '''Nat'''
* History of Discoveries - '''Nat'''
* Adult Tongue and Taste Buds – Structure and Function - '''Jared'''
* Taste Map - '''Jordan'''
* Abnormalities - '''Liz?'''
* Current Research - '''Jared'''
* Future Research - '''Liz?'''

Liz are you happy with those sections?

And Jared be careful with the 'Taste Maps' section, I just read that it may be a misconception! If thats the case then maybe just how the brain interprets the 5 different types of taste.

Nat
--[[User:Z3289738|Z3289738]] 11:56, 5 September 2012 (EST)

Hi guys,
Yes I'm happy with these sections and am on it.

Liz
--[[User:Z3332337|Z3332337]] 13:46, 6 September 2012 (EST)

--
Hi,

Can someone help me with image uploading?

The website say okay to use for commercial etc...

this is the link, is that enough information to get around copyright ????
http://embryology.med.unsw.edu.au/embryology/index.php?title=File:Structure_of_Tongue.gif

Thank you, Jared

hi guys,

just confirming our meeting tome tomorrow after the first lecture.

Thanks :-0.

== Useful articles ==

Hi there,

I'm going to links to the articles I find here so you guys can see them and I don't lose them.

===Future Research===

1) A Test for Measuring Gustatory Function
[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2823587/?tool=pmcentrez]

This is pretty good for future methods of detecting defects in taste, but requires communication about reception of the tastant. Could be used when the children grow up. Great for adults.

2) The gustatory cortex and multisensory integration
[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2726647/?tool=pmcentrez]

3) REWIRING THE GUSTATORY SYSTEM: SPECIFICITY BETWEEN NERVE AND TASTE BUD FIELD IS CRITICAL FOR NORMAL SALT DISCRIMINATION
[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2812680/?tool=pmcentrez]
(Not sure where I would put this, I'm going to put it in future research]

===Abnormalities===

1) Gustatory Imagery Reveals Functional Connectivity from the Prefrontal to Insular Cortices Traced with Magnetoencephalography
[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3132751/?tool=pmcentrez]

This article essentially highlights that taste imagery is a learned response in the Insular Cortices (IC), imaged by fMRI and PET scans, and that disruption in this learning process changes the way we perceive taste. Again, I don't know how relevant this would be in the developing embryo unless there would be damage in the pre-frontal IC.

Any ideas guys??

2) Defects in the Peripheral Taste Structure and Function in the MRL/lpr Mouse Model of Autoimmune Disease
[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3334929/?tool=pmcentrez]

3) Knocking out P2X receptors reduces transmitter secretion in taste buds
[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3188419/?tool=pmcentrez]
<pubmed>21940456</pubmed>

This was a GREAT article. Basically spoke about how using double knockout (DKO) mice for taste receptors P2X2 and P2X3 were knocked out and how it didn't release the neurotransmitter ATP when a tastant was administered, whereas the WT (wild type) mice did release ATP.

--

4) Taste Function in Mice with a Targeted Mutation of the Pkd1l3 Gene
[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2924428/?tool=pmcentrez]

<pubmed>20605874</pubmed>

5) FGF Signaling Regulates the Number of Posterior Taste Papillae by Controlling Progenitor Field Size
[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3107195/?tool=pmcentrez]

<pubmed>21655085</pubmed>

6) Taste receptor cells arise from local epithelium, not neurogenic ectoderm.
[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2924428/?tool=pmcentrez]

<pubmed>7892199</pubmed>

7) Downregulation of Dlx5 and Dlx6 expression by Hand2 is essential for initiation of tongue morphogenesis
[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3091495/?tool=pmcentrez]

--[[User:Z3332337|Z3332337]] 15:30, 16 September 2012 (EST)

===Other??===

1) Olfactory and Gustatory Sensory Changes to Tobacco Smoke in Pregnant Smokers
[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3375030/?tool=pmcentrez]

This article is unrequired for this specific project (I realised this AFTER i read most of it) because it talks about how pregnancy affects the 'want' to smoke. So it's more behavioral rather than research into developmental problems that smoking may cause.

2) CODING IN THE MAMMALIAN GUSTATORY SYSTEM
[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2902637/?tool=pmcentrez]

Liz
--[[User:Z3332337|Z3332337]] 14:09, 6 September 2012 (EST)

----

Hi guys, just putting a subheading of interesting articles found:

'''1.''' <pubmed>21978088</pubmed>

'''2.''' [http://embryology.med.unsw.edu.au/notes/tongue.htm#17108952 UNSW Embryology Development of Taste]

This website provides a really great overview of taste developmental timing & overview, tastebuds, receptors, pathways, genes and provides great references for further research - and its a UNSW site!

'''3.''' [http://www.sciencedaily.com/releases/2006/12/061205214617.htm Researchers Discover Initial Steps In Development Of Taste]

A Science News story that looks at the role of Wnt pathway in the development of taste. "In the present study, the researchers found that in mice in which the actions of Wnt proteins were blocked, taste papilla buds completely failed to develop. Conversely, in mice in which Wnt signaling was over activated, their tongues were covered with many and large papillae and taste buds." It also briefly discusses neural pathways of taste and abnormalities.

'''4.''' Purves D, Augustine GJ, Fitzpatrick D, et al., editors. Neuroscience. 2nd edition. Sunderland (MA): Sinauer Associates; 2001. '''Taste Receptors and the Transduction of Taste Signals'''. Available from: http://www.ncbi.nlm.nih.gov/books/NBK11148/

This book chapter covers a variety of transduction mechanisms for taste cells. It is quite detailed, however has some great diagrams to explain the content. The concluding paragraph provides a good summary: "The overall picture that emerges from these admittedly complicated details is that taste cells have a variety of transduction mechanisms. In general, individual taste cells respond to several types of chemical stimuli. Nevertheless, taste cells also exhibit gustatory selectivity. Like olfactory cells, the lower the threshold concentration for detecting a single tastant, the greater the selectivity of the relevant taste cell. Finally, taste receptor mechanisms also adapt to the ongoing presence of a stimulus, although the mechanisms are not understood. If a chemical is left on the tongue for a sufficient time, it ceases to be perceived (consider saliva, for example). Thus, to obtain the full taste of foods, one must either frequently change the types of foods placed in the mouth or wait a sufficient time between helpings, facts that have long been appreciated by restauranteurs and gourmets."

'''5.''' <pubmed>17108952</pubmed>
This article describes the receptors and cells involved in the different types of taste (sweet, sour, bitter, salty and umami).

'''6.''' <pubmed>17287575</pubmed>
This review focuses on the development of fungiform papillae in rodents.

'''7.''' <pubmed>15581865</pubmed>
This article focuses on the role of Sonic hedgehog on tongue and taste papilla development.

'''8'''
Liu HX, Komatsu Y, Mishina Y, Mistretta CM.
http://www.ncbi.nlm.nih.gov/pubmed/22659543
This is an article about neural crest contributions to taste development

--[[User:Z3289738|Z3289738]] 10:44, 22 August 2012 (EST)

----
Remember: textbooks are a good foundation, but articles are best to gain info from.

--[[User:Z3332337|Z3332337]] 11:32, 29 August 2012 (EST)

Hey, Just need somewhere to put this:
*[http://embryology.med.unsw.edu.au/embryology/index.php?title=Sensory_-_Taste_Development Sensory Taste Development; UNSW Embryology]
*[http://www.ncbi.nlm.nih.gov/pubmed/8955790 Embryonic and early fetal development of human taste buds: a transmission electron microscopical study] <ref name=PMID8955790><pubmed>8955790</pubmed></ref> - Can't access full article!
*[http://www.ncbi.nlm.nih.gov/pubmed/9455607 Scanning electron microscopical studies of developing gustatory papillae in humans.] <ref><pubmed>9455607</pubmed></ref>
*[http://www.ncbi.nlm.nih.gov/pubmed/9541477 Innervation of developing human taste buds. An immunohistochemical study] <ref><pubmed>9541477</pubmed></ref>
*[http://www.ncbi.nlm.nih.gov/pubmed/8241557 Evidence for stimulus access to taste cells and nerves during development: an electron microscopic study.] <ref><pubmed>8241557</pubmed></ref>

--[[User:Z3289738|Z3289738]] 11:24, 19 September 2012 (EST)

== Headings==
* Introduction
* History of Major Discoveries (early researchers)
* Time line of Developmental processes
- this is the major focus of the project (ie: developmental processes)

- week by week
** Tongue
** Taste
* Final Structure and Function of the Tongue
* Abnormal structure and function
^ these 2 can be minor sections.
* Technologies to detect abnormalities during pregnancy?
* Current research (recent findings)
* Glossary and Abbreviations
* References

--[[User:Z3332337|Z3332337]] 11:30, 29 August 2012 (EST)

Notes from Mark Hill:
* Origins of sensory
* Central pathway for taste
* Neural crest contributions
* Overview diagram of sensory diagram (can be hand drawn)
* Journal of Cell biology - Taste [http://jcb.rupress.org/content/190/3/285.full JCB]
* Links between taste and smell
* Tongue has muscular and sensory functions - segregate the two

==Division of Work==

Natalie - Normal function & abnormal function

Liz - tongue & taste development

Jordan - time line of discoveries

Jared - structure & function; recent findings

==Topic Choice==

Hey guys,
Unfortunately a lot of other groups seem to want to do hearing & vision as well, so I thought maybe we should choose to do '''taste'''. Let me know what you think!

I also brainstormed a few topic headings... feel free to add to it or change the order around

Headings:
* Introduction (what is the project about?)
* Time line of major discoveries / History (early researchers)
* Structure & Function
* Tongue development (brief)
* Taste development - time line and detailed
* Normal function
* Abnormal function
* Current research (recent findings)
* Glossary and Abbreviations
* References

--[[User:Z3289738|Z3289738]] 11:42, 15 August 2012 (EST)

----

==Lets do: Sensory - Hearing==

From a bit of research this afternoon, I couldn't find much on skin development in terms of "sense organ"/"sense development". I suggest if we do Sensory we do hearing as there was alot of information (inner, middle, outer). And also there are specific screening procedures involved during pregancy.

Couple of link below with basic surface information that we could use as a starting point.

[http://cwx.prenhall.com/bookbind/pubbooks/martini10/chapter18/custom3/deluxe-content.html]

[http://www.spuc.org.uk/education/abortion/human-development]

----

Hi guys

Organ = liver

Sensory = vision / skin / hearing

--[[User:Z3289738|Z3289738]] 12:02, 8 August 2012 (EST)

really usefull website including information on phisiology etc
[http://www.cf.ac.uk/biosi/staffinfo/jacob/teaching/sensory/taste.html]

== Stucture & Function ==

'''Structure/ Parts'''
general including tissue type muslces + mucosa etc

- anterior 2/3 and posterior 1/3 (sculus terminulis)- we are manily concerned with 2/3 of tounge as it responsible for papillae + soft palate and epiglottis containing
- papillae, contain chemo-recpetors

'''Function'''
- direct vs indriect
- parts of tounge detecting differnt tastes/ flavours

'''Pathway'''
chmeorecpetors (translation/ transduction)
process of chemical to elecectrical

Talk:2012 Group Project 3

2012-09-30T23:14:39Z

Z3289738: /* Discussion of Contributions via Email */

{{2012GroupDiscussion}}

--[[User:Z8600021|Mark Hill]] 09:54, 18 September 2012 (EST) This is a recent review on taste. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2922655 http://jcb.rupress.org/content/190/3/285 JCB content allows reuse.

==Group evaluation==

The introduction section is very informative and I like the picture included discussing the 5 basic tastes which is interesting to read. I really enjoy your descriptions of bitter and sweet and find it interesting to read. I like the research you included in this section but I believe this needs to be referenced. Currently in the introduction you have only 1 references, so I would suggest that you find more to further validate your information (note that there are no references in the first paragraph). I like in your picture that you included a description. The cell biology section I would probably put in its own section with = = to break up the contend displayed. In this section it is clear that this has been researched however there have been no references listed at all here.

The taste map section has clearly been well researched yet poorly referenced. It would be interesting to look at if possible a progression of the understanding of the taste map. In the picture of the tongue, I would suggest that it has a better description on the enlarged image. However, some of this text is rather hard to read, such as the descriptions of the first and second order neurons. As you have included terms in there which would be foreign to most people, I would try to include either a picture to show exactly where these parts are such as the NTS which can give the reader a better understanding of what you’re saying. Note that you say things like “copious scientific conjecture surrounds…” however there is no references here! This section is well researched which is great, but I would really consider putting it into slightly easier terms to better comprehension.

In the cortical areas section, a similar approach applies: when describing locations of things such as the I/fO, you should really include a clear diagram as to where all of these are. I can see you included the section of the brain however don’t see it as too informative so a better description there would be appropriate. I would also note that you are repeating your references again, and it would be advisable that you find alternative information to include as well.

The timeline section is very informative and really stands out. I’m assuming you will be including the photos later this week. This is well written and gives a truly informative description of the embryological changes that occur. It will look much better and be better to understand once the photos have been included. Note that you have used the same references pretty well the whole time in this section. Although that paper may have a lot of information about what you are needing to talk about, I would also encourage you to research more papers in order to compliment the information you have listed.

The history of discoveries section is well set out and clear and concise. In some areas I would suggest a brief descripton of what you have written such as “PKD2L”, and also make sure you include the appropriate references as all I can see currently it numbers.

In the adult tongue and taste bud section, is this also what the tongue looks like from week 15? If not what changes occurs for it to form into what you have described as the adult tongue and what enhances these changes? This section is informative however it is really lacking references. The taste bud picture you have is quite good, but is that also what the taste bud looks like at 15 weeks?

The abnormalities section is really interesting and is rather enjoyable to read. Are they the only abnormalities that can happen to the tongue? How about environmental? Does alcohol, smoking or drugs affects its development of either the tongue or the taste buds? Additonally, your current research is very thorough and interesting. In regards to the photos you have there, I would make sure that they are set out appropriately, with the information that this is a student project.

Finally, the glossary needs to be highlighted to make it stand out and more words need to be included. Note that in your references, reference 5 can not be accessible, so make sure you fix that up. Overall, it was interesting to read and I enjoyed the display of photos that were also included!

--------

The overall set up of the page I think is very good. In the introduction there is a balance between pictures and text which makes it a bit easier to read. Also its easy to follow, the text itself isn’t confusing and is understandable.

There is a good overview of the different types of receptors and their function, also there is a brief section on the adult tongue which is good, however there needs to be more focus on the embryological development rather than just a simple table on that. There also needs to be some images added to that component as well to make it more understandable.

The sections on abnormalities and current research need to be organised a bit better because they are a little hard to follow, especially with the placing of the images. The glossary is simple and understandable, however there needs to be more work done on the reference list.

--------

The layout and balance between text and figures, tables, and diagrams is extremely well accomplished. All the information of the page is really intriguing and easy to follow on the majority.
I would suggest placing the history of discoveries immediately after the introduction so that readers may appreciate all the research that would have had to take place in order to put all the information on this page. As well, this would help in having a separation between the two tables used.

When it comes to images, make sure that everything in the image is relevant to the accompanying text and important to the reader. One image where you might fall short of this criteria, is the very first image on the page about the five basic tastes, the names of the protein structures is more distracting and confusing than enlightening and overall would not aid in informing the reader.

I believe the introduction is very important in assisting the reader in gaining an overall understanding of the page and it’s aims. Hence I believe it is important to include a more succinct introduction with such aims. In this case, the introduction to the gustatory system begins defining structures and functions which are better off used elsewhere. Instead try giving an overview of the system and maybe give the reader a reason to read on.

The images used in the abnormality section are scattered and make it hard for the reader to determine which image corresponds to which idea, I would suggest ensuring that each image is detrimental to aiding the reader’s thoughts. This was an extremely interesting section.

Current research is clear, concise and easy to follow with a pleasant arrangement of ideas, text, and images. It was interesting to read. Additionally, the references and glossary are extensive and well done. I would suggest having a link to the glossary from within the text.

Well done on your project so far, and good luck with the rest.

--------

The introduction seemed to go into a lot of detail. for example, the information on Type II receptors should be placed in the same section as neural pathways, not the introduction. Can you also include in your introduction, an overview of what you are going to talk about in your project? That would give your project more structure.

With the neural pathway section, can you draw or find a diagram for that section? I find it hard to understand without one. The taste map section goes into a lot of detail which I think is unnecessary because this is a development project.

Current research section is very interesting. I don't think you need to add any more content on that section - that section to me looks complete, besides a few formatting and referencing issues with the images.

Overall, I felt there wasn't enough written on the development of taste, either the receptors (taste buds) or the neural pathways. Your project seem to focus on the anatomy and physiology or function of the taste system. This is alright to keep but the focus should be on development. You do have a Time-line of taste development that summarizes the development of the Gustatory system which is great to see. I think use that as a starting point and expand on each stage in text form, below the table. In week 12 development in this time-line, you mention 'epithelial types I and II', what are they? Are they similar to skin cells?

Overall, the balance between images and text is great. The colourful images work wonders in breaking up the text. Having said that, Many of your images did not have the correct PMID referencing. These images include:
* images of taste being revoked by visualizing ATP release
* CVP of WT and DKO mouse with H & E and SEM
* histology - can you give a more relevant title for this image? We know it's histology; we can see that. What is this image about?
* Abnormal of Tongue - it should say abnormality of tongue

The history section is excellent because it spans over such a long time - 350BC to 2010. The layout of a coloured table for history is beautiful, clear and concise.

--[[User:Z3332863|Z3332863]] 16:35, 23 September 2012 (EST)

----

- The introduction of taste is very descriptive and encapsulates the anatomy, physiology and cell biology. Although it is very detailed it doesn’t indicate that the project is about development.

- There is a lot of detail about the taste neural pathway and cortical areas which I’m not sure is relevant to olfactory development unless you mention how they develop as well.

- Figure 2 and 3 do not have any copyright information associated so remember to add those.

- The development section is very nicely put together and hopefully you will add images further down the line. I’ve noticed that in week 8 of development you have the same ref after each line…I’m sure you can just put it at the end of the paragraph as it is same for each line. Same goes for week 14 and 15. Also since you have 2 references for the entire section --- you might want to look at other articles as well.

- Some things that I missed in the section were patterning molecules and genes. Also any signalling mechanisms that control differentiation.

- The history section is exceptionally done with the use of tables, description and references.

- I thoroughly enjoyed your abnormality section. The images are nicely done as well. Although you have described many genes and molecules which are not specified in the normal development portion so the reader don’t understand their roles. Maybe address this in your normal development section.

- The current development section is also very nicely put together but again things like Shh and WNT should be in development section.

Overall very nicely put together and great balance of pictures and text. Although this is a development topic so the major emphasis should be on development of the organ --- Normal development is good but there is too much content in that section that can be left out.

--[[User:Z3333794|Z3333794]] 10:52, 23 September 2012 (EST)

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Abundant information, including a nice coloured in table, which is a cool idea. Unfinished though, the images to go with it would make it great. The page seems to be segmented into sections with a large amount of text, and sections with many pictures. Try for a more even distribution, if possible. Pictures seem to be relevant, with good explanations, referencing and certificates. Helpful and interesting abnormalities and current research sections

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Your introduction is quite good and gives us a brief overview of the different tastes. I also like it that you touch on the fact that it is important we recognise (via taste) food which would be dangerous to our health. In my opinion, after you mention the research (ending the sentence with …’may exist.’) you should tell the reader what you will be discussing on your page. The few lines on fatty acids does not seem to fit in, and should be part of your history section and possibly current/future research. Some specific information seems to have been researched, such as what umami codes for; however, references have not been provided. Also make sure that the image has the correct information – title, description, references, copyright, student template.

It would be more logical to put the history section next. Following this by the timeline and then go back to the cell biology, receptors and taste map etc.

The history section is good with many significant dates and clear descriptions incorporated in a table. I do see lots of numbers, which I think relate to references. I cannot find these references anywhere, so please edit this and make sure it is included in your list of references. There are also a few references listed in full in the table, so please put these down as proper references. Also, there is no good description for the year 2007 (it is mainly a reference).

The developmental timeline is expansive and very interesting! It really relates to the different developmental stages and tells us what happens over time. I hope you can include images with appropriate labels and information to this table, as it will greatly complement your text. Please do check your spelling, eg. ‘epithelium’ in week 6. Also references in this section are appropriate and are not doubled-up in the reference list. Do check reference 5 as it comes up with a cite error.

The section on cell biology and type 2 receptors is clear and easy to read. I cannot see any references though! Please be careful cause this might indicate plagiarism. The taste map is interesting and I am glad you mentioned research has indicated that the different receptors are in fact located all over the tongue – not just in particular sections. If possible, look for the original paper(s) that made this discovery.

The section on neural pathways is a little more difficult to read and I did not understand some of it. Particular terms are used in sentences which suggest little effort has been put in to explain everything in your own words. This is further indicated by the lack of references in the ‘first order neuron’ section and the majority of the ‘second order neuron’ section. I might be wrong, but then do add all your jargon to the glossary. If possible, also try to find other papers which present the same information to strengthen your points mentioned. Images for both the taste map and the cortex need referencing, copyright info, etc.

Adult tongue and taste buds. It is good you include some anatomy and physiology into your section. Do keep in mind the majority of your project should focus on embryonic development. You included the appropriate names, eg. sulcus terminalis, and I am glad to see that has also been put in the glossary. Some more terms do need to be added, eg. circumvallate. The text is good, clear and easy to read. Images are appropriate and relate to the text but need proper descriptions, citations, etc. A major let down of this section is the lack of references – please include this.

Personally, I found the abnormalities section very interesting! However, you are suddenly talking about all these genes and factors which you have not mentioned anywhere else. It might be good to provide a brief description of these in the development section or incorporate them into your developmental timeline. Images all have copyright information, but other information is missing, such as the student template and/or reference. Please check and add this.

Current research includes a lot of information. All different sections have their references which are displayed in the reference list. If you can, provide links to the website of the research groups working on current projects. Be careful not to just put your reference at the end, as you may also have to reference within the paragraph. Both pictures used will need the student template. The double tongue image will need a reference in its description too.

As mentioned before, add and edit the glossary and reference list. You should also add to the useful links (make this external links) and the image gallery, or delete these subheadings, as there is nothing there now.

Hope this helps!
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"In regards to the information presented (outcomes 1 and 9), the timeline for the development is good and written with clarity. However, I noticed the section on structure only referred to the adult state rather than focusing on the embryonic origin of each structure (ectoderm, endoderm and mesoderm). I would suggest that you elaborate on the developmental stages introduced in the timeline in order to build on the information you have already provided. This is important in regards to outcome 6 so that you can relate your research to embryology – the development of taste should be your focus. The history timeline was great to read as it was very concise and clear.

The page shows a good level of peer teaching with clear language and a good balance between images and text (outcome 4) with technical terms explained in the glossary. An improvement could be to make a link between any technical language and the glossary to avoid scrolling up and down to the page. Your Current Research section (outcome 5) was very interesting to read and showed you went beyond the scope of basic research on taste – good work!

In terms of layout (outcome 2), whilst the images are interesting and relevant to the text, some are not appropriately referenced nor described; make sure to reference appropriately and at least write one or two sentences to make the images relevant to the reader. Additionally, the introduction should not be under another subheading (Gustatory system) as it creates some confusion; I would suggest making the introduction its own heading in order to make the page flow. Similarly, the history timeline would best be placed towards the beginning of the page, under the introduction.

I noticed some areas (such as the section on Structure) were not appropriately or consistently referenced. Make sure to include a citation anytime you introduce a researched idea or information to avoid being accused of plagiarism. I noticed the history timeline had good consistent referencing; however the numbers just need to be formatted so they come under the reference list. If you click on the Tutorial: References page linked from the student page, it tells you how to do this. Hope the feedback helps and all the best for your project!"

------

The introduction is very detailed but did not mention anything about the development of the taste. But I thought the mechanisms behind sweet and salty tastes are very interesting. Maybe do the same for the other 3 tastes? The image of the basic 5 tastes is a bit small, maybe upload a bigger version of the image. Also, the image is lacking some reference, copyright information and a student image template.

The type II receptor section is pretty good and descriptive but it does not really relate to the development of the taste. The taste map is a very eye-catchy image and it would be really useful if it had all the needed information such as the copyright notice. The timeline of the gustatory system is very well-presented and easy to read. I understand the project is not completed yet, therefore more images are still to be put in. Only 2 references have been used in the timeline section, maybe try to research more and use different resources. There are some citing error but it should be quite easy to fix.

Histories of discoveries section is very detailed and easy to read but the referencing needs to be fixed. The adult tongue and taste bud section is very clear and precise and contain a lot of useful information but it does not really relate to the research topic, should beware of going off-track. The hand-drawn diagram of the taste bud is impressive and easy to understand but again lacking in some referencing information such as who drew it. The abnormalities section is good and well-researched and it is interesting to know about which gene or receptors will effect the development of taste and sensation. Maybe the abnormalities section can be included into the current research section because abnormalities are repeated in the current research section below. There are detailed definitions of terms in the glossary which is good because it really helps the reader to understand more about the research topic.

Overall, the page is looking good. The main thing that needs to be fixed will be the images that are already on the page, they need the correct and essential information with them when uploaded on the page or else, they will get deleted and there will be no images on the page and the nice balance of images and text now will be gone. There seem to be a lot of anatomy and biology of the taste system but not a lot of information about their development. Although there is a timeline of development but i think more information is needed. Referencing is pretty good with only one or two minor citing error but it should be easy to fix. Structure of the page is clear and simple with headings and sub-headings being consistent, making the page easy to read and follow. Hope this helps :)

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The introduction is good, explaining the function and mechanisms behind.

The taste map text and picture are useful however lack referencing information.

The cortical areas section is very interesting and well referenced.

The table timeline is a very good way to summarise the development of taste. It is succinct and well referenced, even though one paper was referred to for most of the information.

The history table is similarly good, very succinct and straightforward, however lacks some references, and the references that were included could be improved by using the wiki referencing system.

The structure and function section is useful but doesn't add much to the text in terms of embryological development. Also make sure the images are properly referenced with the "student template" included.

The abnormalities section is very good and well researched, although maybe try and avoid referring to the articles that have been researched in the text and rather just refer to them using the wiki referencing system. The images are good as well but don't forget the "student template" here also.

The current research section is interesting and well researched, the use of succinct subheadings to summarise the paper's findings was good.

The useful links and image sections need to be added to, and the glossary section can be improved by putting the key terms in bold, but that is otherwise good.

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Initially the page seems to have a good balance between text and diagrams/photographs. However the figures included are not properly labelled once you click on the file and some of them don't appear to have any copyright information included. Some of the pictures could do with being a bit smaller as they take up a large proportion of the page. The student drawn image of the tongue is particularly impressive but does still need to have the student template included. The references seem limited in comparison to other groups perhaps suggesting a lack of depth or variety of research. There also appears to be a coding problem relating to reference number 5. The general layout and use of subheadings is great. It may be useful to link the words in the glossary to their occurrence in the text.

The introductory paragraphs are very well written. They are easy to understand and interesting and give a good overview of how taste functions. Similarly the section on taste map is well written clearly explaining the neurological factors associated with taste. However the presence of the picture in isolation is confusing as it is representing an the old method of taste association. Perhaps this would be resolved if a diagram of the newer taste map was also included. Also you say that the old taste map has been disproved by recent research but that research is not referenced. In fact it appears that very little of that section is referenced. The section on cortical areas is well done.

The timeline of developmental processes is good, the table an easy visual format and the information concise and effective. The only point of contention would be the direct quote in Wk8-9 which seems out of place in comparison to the remainder of the entries which are nicely paraphrased. The history section is similarly well done being extensive and comprehensive. That is excepting some Pub Med references which are just placed in the text rather than in the reference list at the bottom. While interesting and well written the part detailing the Adult Tongue and Taste Buds seems out of place in a embryology course.

The sections on the effect of gene expression on the formation of taste abnormalities and current research are good. However it may be useful to put the information regarding each picture as a caption rather than plain text.

It will be interesting to see what is put in the section "Image Gallery"

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The information provided is both informative and well organised. The use of tables and figures make the text easy to follow and the diagrams make the information easier to understand. When it comes to images however, they seem to be somewhat irrelevant next to some of the information in some cases. Try to move them around and make sure they accompany relevant text.

The introduction does not give the reader the overview of the topic, but rather explores structures and function which makes it difficult to order. Simplifying the introduction, and moving some of the more detailed information such as the information about the type 2 receptors to the relevant section would improve the page.

Other information that is difficult to understand is the text which involves certain genes and molecules without explaining their function or role. Explaining these aspects of the genes and molecules would make the information flow better.
The section on current research is very informative and seems to be complete. However, I did note some errors with the citation of the image used, working on the references is very important for the other images as well as not all have the copyright information.

I also noticed that many of the references are repeated numerous times. Week 8 of development for example have the same reference after a number of sentences. A variety of sources will improve the accuracy of the information rather than derive all the information from a single source.

There is a great focus on the anatomy and physiology of taste, however, it is important to remember that the focus of this project is about development, and therefore including a timeline or a table which covers this information is very important. The page seems to be very organised and the inclusion of tables and diagrams along with the extensive glossary make this page stand out. Well done.

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The page that you have created is very extensive and was well formatted in relation to the ratio of images to text on the page.
Found that the colours and use of table for the breakdown of information in relation to ‘Timeline of developmental process’ and ‘history of discoveries’ condensed the material and made it easily understandable. This made me want to keep reading.

With majority of the images that are uploaded onto the page there needs to be the correct information and referencing provided for the summary box. From where the image was sourced (ideally of reliable and scientific literature in origin), identifying that it has been uploaded for a student assignment and copyright information-permission to use uploaded image and any other information that is pertaining to the topic and why the image was used/relevant.
Further, those of you within your group that have drawn an uploaded image, have to ensure that you have stated in the summary box that it was student drawn prior to final assessment/evaluation.

The glossary is able to be expanded upon and potentially ensuring that the words that are being explained/elaborated are bolded. As a reader, I would find it easier to read and distinguish if they were bolded.
The reference list that has been developed appears to demonstrate that as a group you have are well read and researched, however, the citation errors will have to be addressed and resolved prior to final marking of the project. I really appreciated the layout (headings, summary and images) of the page.

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The introduction is well written and very informative. You should add the history timeline directly below the introduction, because where it currently is feels like it is floating. With it after the introduction it will create a flow to your page and separate the two tables.
In your development table I noted a column called images, the adding of images to show the development stage you are describing will give this section some more flair. If you are not adding images don’t forget to delete the column.

Your section on adult taste and tongue is very interesting but maybe if there is a difference, i.e. newborns tongues are more sensitive to a taste than adults, a comparison would be interesting here.

In abnormalities you mention p2x receptors, maybe you could add this to the glossary and give a brief explanation about what they are and do. This would be a good idea for any other receptor or genes/proteins mention above that you don’t want to explain in detail in the main section.
--[[User:Z3220343|Z3220343]] 21:31, 25 September 2012 (EST)

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Your introductory paragraph is sufficiently detailed. However, there is only one reference. You need to show more research by adding more references to support your text. It is good that you have added an image to support the text, but you need to write that it is a student uploaded image.
Cell biology and type 2 receptors sections don’t have any references cited at all. You need to add appropriate references.

There was an image of the tongue showing the tastes in different sections of the tongue. The image didn’t have the source referenced.

The taste map section needs more referencing and citations.

Cortical area is sufficiently detailed and has appropriate numbers of references, along with a supportive image. However, you should add more description of what the image is about.
“Timeline of Developmental Processes of the Gustatory System” looks nice so far, with appropriate citations. But you may need to add some more information, and it needs to add images to support the text.

History of discoveries section looks nice, but needs a bit more texts explaining each of the discoveries. It also needs some more references, and perhaps adding some images to support the text would make it easier to visualise the discoveries.

“Adult Tongue and Taste Buds – Structure and Function” is overall lacking in text and needs more research and references. You need to explain more of the structures and functions of the tongue. The image of the ‘drawing of the tongue’ needs a bit more description in the caption. Perhaps explain what each of the labels mean. The papillae image should say that it is a student uploaded image.

Current research section is done reasonably well so far. The reference needs appropriate formatting. Perhaps reduce the size of the image showing the double tongue; it is rather graphic and somewhat disturbing.

You do not have any useful links listed. You need to add links.

Glossary section is good so far. Perhaps add some more words, and make the text bold to make it easier to spot the different words.

Image gallery does not have images under the heading.

References section: number 5 needs to be fixed.

There are not external links listed under the heading, you need to add external links with appropriate formatting.

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Group 3- Taste

Overall this is an excellent project. Well written, great informative photos, good use of tables, and comprehensive information that's well explained.

A few of the photos don't have the appropriate copyright information and some sections of text haven't been referenced, but in general this ticks all of the boxes

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Taste

The introduction is very detailed, with descriptions of the varies components of taste. Although informative, there needs to be more about the development of the different aspects of taste. I feel that the type 2 receptor part doesn't belong here as this section is here to introduce the topic (maybe put it in a separate heading or in the neural pathway section?). There also needs to be a diagram if you are to include this as if is hard to follow. The balance between text and images is good, though some of the images are not labelled or properly referenced. Histories of discoveries section is very detailed and the table was very easy to read. The section the development of the taste is very informative and shows a of effort is placed into the of research of the topic (as it is often hard when the topic is not well understood). The section on the Structure and Function of the adult tongue gives the anatomy of the tongue, and should come before the part on neural pathways. The current research provided descriptions of the research and their goal and is done well.

==Questions for group==
--[[User:Z3330986|Z3330986]] 14:29, 18 September 2012 (EST)--[[User:Z3330986|Z3330986]] 14:29, 18 September 2012 (EST)
Hey guys,

Did I see someone write about or have articles about Sprouty (''spry'') genes?

I can't find it, but I'm sure I saw it. Let me know :)

--[[User:Z3332337|Z3332337]] 11:10, 18 September 2012 (EST)

--

Also, I've just been going over the main page and I wonder if a picture of the overall tongue, not only sections or histological drawings (which were really good btw) would be good to point out the anatomical features?? Like the sulcus terminalis which was pointed out.
I'd be happy to draw it. This would be for the Basic structure section.

Let me know ASAP so I can do it tonight :)

--[[User:Z3332337|Z3332337]] 11:30, 18 September 2012 (EST)

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Yep, i think that would be a good idea. Go for it :)

--[[User:Z3330986|Z3330986]] 14:29, 18 September 2012 (EST)

Roger that (y). I'll have it done by around 10'ish tonight to be realistic.

--[[User:Z3332337|Z3332337]] 17:10, 18 September 2012 (EST)

--

Guys!!! I'm following image upload instructions to the letter and it keeps giving me database error. :( I need to upload figures 1 and 6 from this article. Let me know, k?

--[[User:Z3332337|Z3332337]] 17:58, 18 September 2012 (EST)

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I had the same problem during the Lab assignments so i used a different image instead. I'm not sure if its related to the image itself? Maybe just email mark?

Maybe everyone could add some words from their relevant sections and hopefully we can come up with a pretty comprehensive glossary
--[[User:Z3330986|Z3330986]] 20:40, 18 September 2012 (EST)

== Discussion of Contributions via Email ==

Hey guys,
I changed the order of the content on our page coz I thought it would make more sense for this topic to have the embryology stuff first and then move on to details of the adult features. Let me know what you think!

Also if you can each send me a brief sentence outlining each of your sections I'll put together an intro.

Thanks,
--[[User:Z3289738|Z3289738]] 09:14, 1 October 2012 (EST)

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Jared: hi guys,

just confirming our meeting tome tomorrow after the first lecture [after mid sem break]

Thanks :-0.

Nat:
Yup, meet outside the lecture room?

--[[User:Z3332337|Z3332337]] 11:07, 11 September 2012 (EST)

--

Hey Guys,

Jared :
becuase we are on holidays as of now, make sure we are communicating about any contributions and copy and past any email discusions onto this page.

--

Hey guys,
So here's our plan for the next few weeks. If you want you can start writing up a particular section before next week!

* Wed 5/09: Have heading finalized; divide work.
* Wed 12/09: Sections finished. Discuss in class of any areas of improvement.
* Wed 19/09: Peer Assessment!

Have a good break :)

--[[User:Z3289738|Z3289738]] 11:58, 29 August 2012 (EST)

--

Hey guys,
I thought of a few headings, please let me know if you have anything to add or change!

* Intro
* History of discoveries
* Gustatory system - this is really important!!
* Tongue and taste buds - structure and function
* Taste map
* Weekly development
* Abnormalities
* Current Research
* Future research

Not including the intro we can each choose 2 areas. I'll get started on History of discoveries and Weekly development.

If you're having problems with your section, or feel that it is irrelevant, or find something else along the way just email the group and we can make changes!

Have a great week :)

Nat

--[[User:Z3289738|Z3289738]] 10:58, 5 September 2012 (EST)

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That sounds good, maybe we should try and meet before next wednesday to make final changes?

--

Sure, how about somewhere between the two Embryology lectures (12-3pm) on Tuesday?

Which sections do you want to do? I just put them up on our wiki page.

Nat --[[User:Z3289738|Z3289738]] 11:35, 5 September 2012 (EST)

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well i have been already doing current research and structure + development, but im happy to do more work :) and yes perhaps straight after our fist lecture 11-12pm?

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Jordan --[[User:Z3330986|Z3330986]] 11:50, 5 September 2012 (EST)

Hi everyone i'll be happy to "Gustatory system" and "taste map." I think it would make it a bit easier as i have covered the neural pathways of taste in some detail in Neuroanatomy.

--

Okay awesome guys

So the division of work so far is:
* Introduction to the Gustatory System - '''Jordan'''
* Timeline of Developmental Processes of the Gustatory System - '''Nat'''
* History of Discoveries - '''Nat'''
* Adult Tongue and Taste Buds – Structure and Function - '''Jared'''
* Taste Map - '''Jordan'''
* Abnormalities - '''Liz?'''
* Current Research - '''Jared'''
* Future Research - '''Liz?'''

Liz are you happy with those sections?

And Jared be careful with the 'Taste Maps' section, I just read that it may be a misconception! If thats the case then maybe just how the brain interprets the 5 different types of taste.

Nat
--[[User:Z3289738|Z3289738]] 11:56, 5 September 2012 (EST)

Hi guys,
Yes I'm happy with these sections and am on it.

Liz
--[[User:Z3332337|Z3332337]] 13:46, 6 September 2012 (EST)

--
Hi,

Can someone help me with image uploading?

The website say okay to use for commercial etc...

this is the link, is that enough information to get around copyright ????
http://embryology.med.unsw.edu.au/embryology/index.php?title=File:Structure_of_Tongue.gif

Thank you, Jared

hi guys,

just confirming our meeting tome tomorrow after the first lecture.

Thanks :-0.

== Useful articles ==

Hi there,

I'm going to links to the articles I find here so you guys can see them and I don't lose them.

===Future Research===

1) A Test for Measuring Gustatory Function
[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2823587/?tool=pmcentrez]

This is pretty good for future methods of detecting defects in taste, but requires communication about reception of the tastant. Could be used when the children grow up. Great for adults.

2) The gustatory cortex and multisensory integration
[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2726647/?tool=pmcentrez]

3) REWIRING THE GUSTATORY SYSTEM: SPECIFICITY BETWEEN NERVE AND TASTE BUD FIELD IS CRITICAL FOR NORMAL SALT DISCRIMINATION
[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2812680/?tool=pmcentrez]
(Not sure where I would put this, I'm going to put it in future research]

===Abnormalities===

1) Gustatory Imagery Reveals Functional Connectivity from the Prefrontal to Insular Cortices Traced with Magnetoencephalography
[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3132751/?tool=pmcentrez]

This article essentially highlights that taste imagery is a learned response in the Insular Cortices (IC), imaged by fMRI and PET scans, and that disruption in this learning process changes the way we perceive taste. Again, I don't know how relevant this would be in the developing embryo unless there would be damage in the pre-frontal IC.

Any ideas guys??

2) Defects in the Peripheral Taste Structure and Function in the MRL/lpr Mouse Model of Autoimmune Disease
[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3334929/?tool=pmcentrez]

3) Knocking out P2X receptors reduces transmitter secretion in taste buds
[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3188419/?tool=pmcentrez]
<pubmed>21940456</pubmed>

This was a GREAT article. Basically spoke about how using double knockout (DKO) mice for taste receptors P2X2 and P2X3 were knocked out and how it didn't release the neurotransmitter ATP when a tastant was administered, whereas the WT (wild type) mice did release ATP.

--

4) Taste Function in Mice with a Targeted Mutation of the Pkd1l3 Gene
[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2924428/?tool=pmcentrez]

<pubmed>20605874</pubmed>

5) FGF Signaling Regulates the Number of Posterior Taste Papillae by Controlling Progenitor Field Size
[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3107195/?tool=pmcentrez]

<pubmed>21655085</pubmed>

6) Taste receptor cells arise from local epithelium, not neurogenic ectoderm.
[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2924428/?tool=pmcentrez]

<pubmed>7892199</pubmed>

7) Downregulation of Dlx5 and Dlx6 expression by Hand2 is essential for initiation of tongue morphogenesis
[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3091495/?tool=pmcentrez]

--[[User:Z3332337|Z3332337]] 15:30, 16 September 2012 (EST)

===Other??===

1) Olfactory and Gustatory Sensory Changes to Tobacco Smoke in Pregnant Smokers
[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3375030/?tool=pmcentrez]

This article is unrequired for this specific project (I realised this AFTER i read most of it) because it talks about how pregnancy affects the 'want' to smoke. So it's more behavioral rather than research into developmental problems that smoking may cause.

2) CODING IN THE MAMMALIAN GUSTATORY SYSTEM
[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2902637/?tool=pmcentrez]

Liz
--[[User:Z3332337|Z3332337]] 14:09, 6 September 2012 (EST)

----

Hi guys, just putting a subheading of interesting articles found:

'''1.''' <pubmed>21978088</pubmed>

'''2.''' [http://embryology.med.unsw.edu.au/notes/tongue.htm#17108952 UNSW Embryology Development of Taste]

This website provides a really great overview of taste developmental timing & overview, tastebuds, receptors, pathways, genes and provides great references for further research - and its a UNSW site!

'''3.''' [http://www.sciencedaily.com/releases/2006/12/061205214617.htm Researchers Discover Initial Steps In Development Of Taste]

A Science News story that looks at the role of Wnt pathway in the development of taste. "In the present study, the researchers found that in mice in which the actions of Wnt proteins were blocked, taste papilla buds completely failed to develop. Conversely, in mice in which Wnt signaling was over activated, their tongues were covered with many and large papillae and taste buds." It also briefly discusses neural pathways of taste and abnormalities.

'''4.''' Purves D, Augustine GJ, Fitzpatrick D, et al., editors. Neuroscience. 2nd edition. Sunderland (MA): Sinauer Associates; 2001. '''Taste Receptors and the Transduction of Taste Signals'''. Available from: http://www.ncbi.nlm.nih.gov/books/NBK11148/

This book chapter covers a variety of transduction mechanisms for taste cells. It is quite detailed, however has some great diagrams to explain the content. The concluding paragraph provides a good summary: "The overall picture that emerges from these admittedly complicated details is that taste cells have a variety of transduction mechanisms. In general, individual taste cells respond to several types of chemical stimuli. Nevertheless, taste cells also exhibit gustatory selectivity. Like olfactory cells, the lower the threshold concentration for detecting a single tastant, the greater the selectivity of the relevant taste cell. Finally, taste receptor mechanisms also adapt to the ongoing presence of a stimulus, although the mechanisms are not understood. If a chemical is left on the tongue for a sufficient time, it ceases to be perceived (consider saliva, for example). Thus, to obtain the full taste of foods, one must either frequently change the types of foods placed in the mouth or wait a sufficient time between helpings, facts that have long been appreciated by restauranteurs and gourmets."

'''5.''' <pubmed>17108952</pubmed>
This article describes the receptors and cells involved in the different types of taste (sweet, sour, bitter, salty and umami).

'''6.''' <pubmed>17287575</pubmed>
This review focuses on the development of fungiform papillae in rodents.

'''7.''' <pubmed>15581865</pubmed>
This article focuses on the role of Sonic hedgehog on tongue and taste papilla development.

'''8'''
Liu HX, Komatsu Y, Mishina Y, Mistretta CM.
http://www.ncbi.nlm.nih.gov/pubmed/22659543
This is an article about neural crest contributions to taste development

--[[User:Z3289738|Z3289738]] 10:44, 22 August 2012 (EST)

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Remember: textbooks are a good foundation, but articles are best to gain info from.

--[[User:Z3332337|Z3332337]] 11:32, 29 August 2012 (EST)

Hey, Just need somewhere to put this:
*[http://embryology.med.unsw.edu.au/embryology/index.php?title=Sensory_-_Taste_Development Sensory Taste Development; UNSW Embryology]
*[http://www.ncbi.nlm.nih.gov/pubmed/8955790 Embryonic and early fetal development of human taste buds: a transmission electron microscopical study] <ref name=PMID8955790><pubmed>8955790</pubmed></ref> - Can't access full article!
*[http://www.ncbi.nlm.nih.gov/pubmed/9455607 Scanning electron microscopical studies of developing gustatory papillae in humans.] <ref><pubmed>9455607</pubmed></ref>
*[http://www.ncbi.nlm.nih.gov/pubmed/9541477 Innervation of developing human taste buds. An immunohistochemical study] <ref><pubmed>9541477</pubmed></ref>
*[http://www.ncbi.nlm.nih.gov/pubmed/8241557 Evidence for stimulus access to taste cells and nerves during development: an electron microscopic study.] <ref><pubmed>8241557</pubmed></ref>

--[[User:Z3289738|Z3289738]] 11:24, 19 September 2012 (EST)

== Headings==
* Introduction
* History of Major Discoveries (early researchers)
* Time line of Developmental processes
- this is the major focus of the project (ie: developmental processes)

- week by week
** Tongue
** Taste
* Final Structure and Function of the Tongue
* Abnormal structure and function
^ these 2 can be minor sections.
* Technologies to detect abnormalities during pregnancy?
* Current research (recent findings)
* Glossary and Abbreviations
* References

--[[User:Z3332337|Z3332337]] 11:30, 29 August 2012 (EST)

Notes from Mark Hill:
* Origins of sensory
* Central pathway for taste
* Neural crest contributions
* Overview diagram of sensory diagram (can be hand drawn)
* Journal of Cell biology - Taste [http://jcb.rupress.org/content/190/3/285.full JCB]
* Links between taste and smell
* Tongue has muscular and sensory functions - segregate the two

==Division of Work==

Natalie - Normal function & abnormal function

Liz - tongue & taste development

Jordan - time line of discoveries

Jared - structure & function; recent findings

==Topic Choice==

Hey guys,
Unfortunately a lot of other groups seem to want to do hearing & vision as well, so I thought maybe we should choose to do '''taste'''. Let me know what you think!

I also brainstormed a few topic headings... feel free to add to it or change the order around

Headings:
* Introduction (what is the project about?)
* Time line of major discoveries / History (early researchers)
* Structure & Function
* Tongue development (brief)
* Taste development - time line and detailed
* Normal function
* Abnormal function
* Current research (recent findings)
* Glossary and Abbreviations
* References

--[[User:Z3289738|Z3289738]] 11:42, 15 August 2012 (EST)

----

==Lets do: Sensory - Hearing==

From a bit of research this afternoon, I couldn't find much on skin development in terms of "sense organ"/"sense development". I suggest if we do Sensory we do hearing as there was alot of information (inner, middle, outer). And also there are specific screening procedures involved during pregancy.

Couple of link below with basic surface information that we could use as a starting point.

[http://cwx.prenhall.com/bookbind/pubbooks/martini10/chapter18/custom3/deluxe-content.html]

[http://www.spuc.org.uk/education/abortion/human-development]

----

Hi guys

Organ = liver

Sensory = vision / skin / hearing

--[[User:Z3289738|Z3289738]] 12:02, 8 August 2012 (EST)

really usefull website including information on phisiology etc
[http://www.cf.ac.uk/biosi/staffinfo/jacob/teaching/sensory/taste.html]

== Stucture & Function ==

'''Structure/ Parts'''
general including tissue type muslces + mucosa etc

- anterior 2/3 and posterior 1/3 (sculus terminulis)- we are manily concerned with 2/3 of tounge as it responsible for papillae + soft palate and epiglottis containing
- papillae, contain chemo-recpetors

'''Function'''
- direct vs indriect
- parts of tounge detecting differnt tastes/ flavours

'''Pathway'''
chmeorecpetors (translation/ transduction)
process of chemical to elecectrical

2012 Group Project 3

2012-09-30T12:14:09Z

Z3289738: /* Glossary */

=Taste Development=

== Introduction ==
**NEED TO ADD**

==Adult Tongue and Taste Buds – Structure and Function==

'''Structure'''

The tongue is located on the floor of the oral cavity, It is a muscular structure with sensory units crowning. The tongue is divided into an anterior two thirds and a posterior one third. These regions are divided by a V-shaped groove at the back of the tongue (sulcus terminalis). The anterior two thirds of the tongue is covered by stratified squamous epithelium, It contains a roughened surface and has projections called papillae that vary in shape and number.

''''The image below is a simplistic diagram of the surface of the tongue showing the locations of the different papillae and other important features'''

{|
| [[Image:Drawing of Tongue.png|500px]]

'''Papillae'''
[[File:Papillae.jpg|Left|thumb|200px|Close up of Human Tongue Papillae]]

There are 4 types of papillae on the tongue.
The most numerous papillae are the filiform papillae, which function to provide a surface that aids in holding food on the tongue during chewing but do not contain taste buds. The larger, less numerous fungiform papillae which contain taste buds, as do foliate papillae. Circumvallate papillae form a wide V at the sulcus terminalis also containing taste bus. There are no papillae or taste buds located on the posterior third of the tongue, having mucosal folds and the lingual tonsils instead.

'''Function'''

The tongue is for tasting, swallowing, and speech.
The functional unit of the taste bud is a taste cell, there are between 50 and 100 taste cells in each taste bud these taste cells represent all 5 different tastes. Historically is was believed that different areas of the tongue were responsible for different taste sensations although this has since been disregarded.[http://users.rcn.com/jkimball.ma.ultranet/BiologyPages/W/Welcome.html] The papillae contain taste buds which are connected to the oral cavity via a taste pore, the function of the taste bud is to transmit a chemical signal from the oral cavity to a taste cell, this chemical signal is the converted into an electrical impulse and delivered to the brain via nerve fibres for interpretation.

'''The image below is a simplistic hand-drawn cross section of a taste bud unit (not to scale)'''

[[File:Taste_bud_1.jpg|x400px|alt=Cross section of a taste bud unit|Cross section of a taste bud unit]]

==History of Discoveries==

{| cellpadding=5 style="border:1px solid #BBB"
|- bgcolor="#faecc8"
|''' Date'''|| '''Significant Discovery'''

|- bgcolor="#faf6ed"
|'''350BC'''
|| Aristotle writes about the basic tastes, sweet and bitter. He also notes that it can be modified by salty and acidic. <ref name="PMID22717400"><pubmed>22717400</pubmed></ref>

|- bgcolor="#faecc8"
|'''1901'''
|| D. Hanig publishes a paper describing taste sensitivity in different regions of the tongue.
''Interesting fact:'' The modern concept of a 'tongue map' is a misinterpretation of this study. <ref name="PMID22717400"/>

|- bgcolor="#faf6ed"
|style=white-space:nowrap|'''1908'''
|Kikunae Ikeda, a professor of the Tokyo Imperial University, discovered and identified the fifth basic taste: umami (savouriness), made palatable by glutamate. <ref><pubmed>12438213</pubmed></ref>
[http://chemse.oxfordjournals.org/content/27/9/847.long New Seasonings]

|- bgcolor="#faecc8"
|style=white-space:nowrap|'''1931-32'''
| A chemist named Arthur Fox and his college noted that they had different sensitivities to the bitter tasting Phenylthiocarbamide (PTC).<ref>Blakeslee AF, Fox AL. Our different taste worlds. J Hered. 1932;23:97–107.</ref> Geneticists later confirm these findings, and discover that non-tasting is a recessive genetic trait. <ref><pubmed>17782493</pubmed></ref>
[http://www.ncbi.nlm.nih.gov/pubmed/17782493 Inherited taste deficiency]

|- bgcolor="#faf6ed"
|style=white-space:nowrap|'''1965'''
|Farbman's study of the developing taste but in rat fungiform papilla was significant in increasing our understanding of taste bud development. <ref><pubmed>14300090</pubmed></ref>
[http://www.sciencedirect.com/science/article/pii/0012160665900400 Electron microscope study of the developing taste bud in rat fungiform papilla.]

|- bgcolor="#faecc8"
|style=white-space:nowrap|'''1992'''
|McLaughlin SK et al. discovery a taste cell-specific G-protein within the taste buds called Gustucon. This protein is later used to mark bitter, umami and sweet cells. <ref><pubmed>1608467 </pubmed></ref>
[http://www.nature.com/nature/journal/v357/n6379/abs/357563a0.html Gustducin is a taste-cell-specific G protein closely related to the transducins]

|- bgcolor="#faf6ed"
|style=white-space:nowrap|'''1995'''
|Barlow et al. experimented with Axolotl salamanders and concluded that taste buds from this species arise exclusively from epithelial tissue, "oropharyngeal [[#Glossary |'''epithelium''']]". <ref name="PMID17826760"><pubmed>17826760</pubmed></ref>
[http://www.ncbi.nlm.nih.gov/pubmed/17826760 Embryonic origin of gustatory cranial sensory neurons]

|- bgcolor="#faecc8"
|style=white-space:nowrap|'''1996'''
| Witt M and Reutter K of the Technical University Dresden in Germany, carried out a transmission electron microscopy study to investigate the embryonic and fetal development of Human taste buds. Their results suggest an "at least dual function of embryonic/fetal taste buds", including non-gustatory, paracrine functions prior to the 14th week and gustatory after the 14th week. <ref name="PMID8955790"><pubmed>8955790</pubmed></ref>
[http://www.ncbi.nlm.nih.gov/pubmed/8955790 Embryonic and early fetal development of human taste buds: a transmission electron microscopical study]

|- bgcolor="#faf6ed"
|style=white-space:nowrap|'''2000'''
|Chandrashekar, J. et al. discover the first taste sonsors, the T2R bitter taste receptors. <ref><pubmed>10761935</pubmed></ref>
[http://www.sciencedirect.com/science/article/pii/S0092867400807060 T2Rs Function as Bitter Taste Receptors]

|- bgcolor="#faecc8"
|style=white-space:nowrap|'''2001'''
|Nelson, G. et al. discover the sweet receptor: a combination of T1R2 and T1R3. <ref><pubmed>11509186</pubmed></ref>
[http://www.ncbi.nlm.nih.gov/pubmed/11509186?dopt=Abstract&holding=npg Mammalian sweet taste receptors.]

|- bgcolor="#faf6ed"
|style=white-space:nowrap|'''2002'''
|Nelson G. et al. discover the amino acid (umami) taste receptor: a combination of T1R1 and T1R3 identified. <ref><pubmed>11894099</pubmed></ref>
[http://www.ncbi.nlm.nih.gov/pubmed/11894099?dopt=Abstract&holding=npg An amino-acid taste receptor]

|- bgcolor="#faecc8"
|style=white-space:nowrap|'''2005'''
|Dyer, J. et al. discover sweet taste receptors in the GI tract. <ref><pubmed>17855558</pubmed></ref>
[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1986582/ Sweet taste signaling in the gut]

|- bgcolor="#faf6ed"
|style=white-space:nowrap|'''2006'''
|Huang, A. L et al. discover cells for sour taste, identified by PKD2L1 (a polycystic kidney disease-like ion channel). <ref><pubmed>16929298</pubmed></ref>
[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1571047/ The Cells and Logic for Mammalian Sour Taste detection]

|- bgcolor="#faecc8"
|style=white-space:nowrap|'''2007'''
|Harlow DE, Barlow LA of the University of Colorado Denver Health Sciences Center provide evidence of the "embryonic origin of gustatory cranial sensory neurons". <ref name="PMID17826760"/>
[http://www.ncbi.nlm.nih.gov/pubmed/17826760 Embryonic origin of gustatory cranial sensory neurons.]

|- bgcolor="#faf6ed"
|style=white-space:nowrap|'''2009'''
|A study by Hevezi P et al, presents "the first comprehensive characterization of gene expression in primate taste buds", as opposed to previous studies which focused on rodents. <ref><pubmed>19636377</pubmed></ref>
[http://www.ncbi.nlm.nih.gov/pubmed/19636377 Genome-wide analysis of gene expression in primate taste buds reveals links to diverse processes]

|- bgcolor="#faecc8"
|style=white-space:nowrap|'''2010'''
|Chandrashekar, J. et al. identify epithelial sodium channel (ENaC) as the sodium-salt taste receptor. <ref><pubmed>20107438</pubmed></ref>
[http://www.ncbi.nlm.nih.gov/pubmed/20107438?dopt=Abstract&holding=npg The cells and peripheral representation of sodium taste in mice]
|}

== Human Weekly Development - Two Prominent Studies ==
Martin Witt and Klaus Reutter of the University of Tubingen in Germany published two prominent studies regarding developing taste buds in humans. Their first study in 1996 was a transmission electron microscopical (TEM) study of the taste bud primordium and its morphological changes during the 8th-15th postovulatory week. Their next study in 1997 built on their previous findings by using Scanning Electron Microscopy (SEM) to observe the development of gustatory [[#Glossary |'''papillae''']] during postovulatory weeks 6-15.

The findings of these two studies are summarized in the table below. The figures provided relate to the images on their respective research papers.

# [http://onlinelibrary.wiley.com/doi/10.1002/(SICI)1097-0185(199612)246:4%3C507::AID-AR10%3E3.0.CO;2-S/pdf Embryonic and early fetal development of human taste buds: a transmission electron microscopical study, 1996]
# [http://chemse.oxfordjournals.org/content/22/6/601.long Scanning electron microscopical studies of developing gustatory papillae in humans, 1997]

===Timeline of Developmental Processes of Human Taste Buds===
{| cellpadding=5 style="border:1px solid #BBB"
|- bgcolor="#89CFF0"
|'''Postovulatory Week'''||'''Description'''

|- bgcolor="#BCD4E6"
|'''Week 6''' ||
The surface of the developing tongue is covered by nearly flat epithelium (1997, Figure 1). The first gustatory papillae of the tongue appear in the caudal mid-line near the foramen caecum and the first circumvallate papilla develops on the dorsal mid-line. <ref name="PMID9455607"><pubmed>9455607</pubmed></ref>

|- bgcolor="#89CFF0"
| '''Weeks 6 to 7'''||
Nerve fibers approach the basal lamina of lingual epithelium. At this stage the lingual epithelium consists of two to three cell layers and there is not yet any sign of cell specializations indicating early taste bud formation. <ref name=PMID8955790/>

|- bgcolor="#BCD4E6"
| '''Week 7 '''||
A series of irregular epithelial swellings in the anterior part and marginal parts of the tongue indicate early forming fungiform papillae. Furthermore, a V-like lane is observed anterior to the [[#Glossary |'''sulcus terminalis''']], which represents a smooth surface for developing circumvallate papillae (1997, Figure 2). Witt M et al observe that these circumvallate papillae are larger than the developing fungiform papillae of the same age, later noting that the fungiform papillae tend to increase in size over the 8-15th weeks of gestation, whilst the size of vallate papillae tend to remain constant during this period. <ref name=PMID9455607/>

|- bgcolor="#89CFF0"
| ''' Week 8 ''' ||
* The taste bud primordium are still differentiated, elongated epithelial cells, resting on a slightly developed core of young dermal papilla.
* The lingual epithelium shows first signs of taste bud development as nerve fibers coming from the dermal papilla penetrate the epithelial basal lamina and form synapses with taste bud progenitor cells (1996, Figure 1). These synapses demonstrate the neuronal connection between the taste bud primordium and the central nervous system, reaching a maximum around the 12th to 13th week. However, it is important to note that at this time these cells are still poorly differentiated, elongated epithelial cells.
* Ciliated cells also appear around the 8th week, however the significance of these cells which are scattered randomly across the lingual surface remains unclear. <ref name=PMID8955790/>

|- bgcolor="#BCD4E6"
|''' Week 9''' ||
By this stage, although a taste pore is not present, the surface of circumvallate papillae usually contains a taste pit partly filled with microvillus-like processes from the underlying taste bud cells (1997, Figure 10). <ref name=PMID9455607/>

|- bgcolor="#89CFF0"
|''' Weeks 10-11''' ||
At this stage, the lingual epithelium compromises of about four cell layers, and the first shallow grooves above the taste bud primordium are developed. Fungiform papillae appear on the lateral margins and the tip of the tongue, containing taste bud primordial that display the first signs of a primitive pore formation (1996, Figure 6). <ref name=PMID8955790/>

|- bgcolor="#BCD4E6"
|''' Week 12 ''' ||
Taste bud cells are more clearly differentiated into epithelial cell types II and III. <ref name=PMID8955790/>

|- bgcolor="#89CFF0"
|''' Weeks 12-13 ''' ||
At this stage the taste bud primordial are all located on the top of dermal papillae. There is also maximum synapses between cells and afferent nerve fibers, which intermingle with each other to form a plexus-like structure (1996, Figure 6a). <ref name=PMID8955790/>

|- bgcolor="#BCD4E6"
|''' Weeks 14 -15 ''' ||
The shape and size of the taste buds primordial begins to resemble those of adult taste buds (1996, Figure 9). By the 14th week the taste pores develop as the taste pits are filled by microvilli, and bubble like vesicles indicate the secretory activity of these cells (1996, Figure 10). However, the taste buds only achieve a fully developed function in week 15 of gestation with the development of type I cells to produce the mucous material in the taste pit. <ref name=PMID8955790/>
|}

==Abnormalities==

===Knocking out P2X Receptors===

[[File:Image of taste being evoked by visualizing ATP release.jpeg|Left|thumb|200px|Evoking taste - ATP release in tongue]]

Gustatory abnormalities has not been widely researched and what has been researched has been through animal testing, most commonly we have found on mice.

In Huang, 2008 this team used the release of the [[#Glossary |'''ectoderm''']], ATP (adenosine triphosphate) as a quantitative measurement of gustatory sensation and taste. This was done by using a comparison of wild type (WT) and double knockout (DKO) mice. P2X receptors, P2X2 and P2X3 were knocked out in the DKO mice. The premise of this article was that knocking out P2X receptors reduces transmitter secretion of ATP in taste buds, therefore they cannot taste.

It should be noted that the taste buds in DKO are functional, but are not stimulated by the administration of tastants.

The transmission of release of ATP is secretion through gap junction hemichannels (pannexin 1 gap junction).

When both P2X2 and P2X3 are knocked out, no taste is elicited. However they found that if either P2X2 OR P2X3 was knocked out there was a taste response. So the inference made from this is that if one of the two receptors from the P2X family was knocked out there still can have taste response. The WT mice showed significant stimulation by tastants whereas DKO had little to no stimulation of ATP release.<ref><pubmed>21940456</pubmed></ref>

===FGF signalling and genes===

Sprouty, or ''Srpy'', genes have been related to regulating the development of circumvallate papillae (CVP). The CVP are large dome shaped papillae, which form a 'V' just in front of the terminal sulcus.

By knocking out ''Spry'' genes using mice which had ''Spry1'' and ''Spry2'' knocked out showed that the number of CVP doubled. However, when Fibroblast [[#Glossary |'''Growth Factor''']] gene ("Fgf10") was absent, the number of CVP was significantly reduced, if not completely absent. The correlation between ''Spry1/2'' and ''Fgf10'' is that ''Spry1/2'' antagonizes "Fgf10" to limit the size of the CVP progenitor placode. Exclusive expression of ''Fgf10'' in the [[#Glossary |'''mesenchyme''']] is necessary for the formation of CVP.

'''This image shows the CVP stained with H&E and scanned by Scanning Electron Microscope (SEM)'''
[[File:CVP of WT(top) and DKO(bottom) mice with H&E and SEM.png]]

'''This image shows the location of the CVP and the increased number in DKO mice by SEM'''
[[File:Mouse circumvallate papilla 01.jpg|300px]]

Taste buds develop from the mesenchyme but require local signalling to properly differentiate. Some signalling factors for proper development of taste buds besides FGF are: [[#Glossary |'''Sonic Hedgehog''']] (SHH), Bone Morphogenetic Proteins (BMPs), Epidermal Growth Factor (EGF).

Additionally, this proves that the anterior and posterior developments of the tongue are derived from embryonic tissues, where the anterior tongue is derived from the [[#Glossary |'''ectoderm''']] and the posterior tongue is derived from the [[#Glossary |'''endoderm''']]. Taste buds develop from the mesenchyme but require local signalling to properly differentiate. Some signalling factors for proper development of taste buds besides FGF are: Sonic Hedgehog (SHH), Bone Morphogenetic Proteins (BMPs), Epidermal Growth Factor (EGF).

As mentioned above, this article shows that the anterior and posterior developments of the tongue are derived from embryonic tissues, where the anterior tongue is derived front the ectoderm and the posterior tongue is derived from the endoderm. Secondly, FGF is required to regulate the growth of taste buds, while ''Spry'' genes limit the number of CVP. ''Fgf10''& ''Spry 1&2''work antagonistically through receptor tyrosine kinase (RTK)signalling.

However, the deletion of ''Spry2''led to the increase of CVPs it should be noted that they found that a significant decrease in number of fungiform papillae. In contrast, the absence of ''Fgf10'', while leading to the absence of CVPs lead to an increase in number and size of fungiform papillae. Therefore these genes have different effects on the anterior and posterior developing tongue and taste buds.<ref><pubmed>21655085</pubmed></ref>

==Gustatory System==

[[Image:Taste qualities.gif|thumb|The five basic tastes]]

Taste or more appropriately gustation, is a fundamental survival tool in animals as it directs the consumption of essential nutrients. The five tastes that exist within the human gustatory system: salty, sweet, sour, bitter and umami, all signify basic physiological requirements. Salty tastes denote the presence of Na+, an important ion involved in the transportation and retention of water across cell membranes. Sweetness is the recognition of carbohydrates, essential for maintaining optimal brain function and providing the basis for energy production in muscle tissue via ATP [[#Glossary |'''hydrolysis''']]. Similarly umami codes for the presence of L-amino acids, especially L-glutamate which is an integral component of protein synthesis.

These different modalities not only function to maintain the proper intake of nutrients within the body but also, by way of aversion, prohibit the consumption of undesired or poisonous materials. The bitter modality for example is generally regarded as displeasing to the human palate. It represents a high acid content which may be a result of foods which have become rotten or are inherently poisonous to the body.<ref name=PMID20696704><pubmed>20696704</pubmed></ref>

Research has historically limited itself to investigating the mechanisms of these five taste qualities though it must be noted many other modalities may exist. Of particular conjecture is the existence of fatty acid recognition. In the past the detection of fat in food has been attributed to somatosensory inputs <ref name=PMID20696704/> from the tongue, that is, the oily feel and texture of fat rather than its actual ‘taste’ allows the brain to encode for its presence. Further research is therefore required to elicit the precise mechanisms of fat detection.

===Cell Biology===

The five taste qualities are not all detected by the same type of receptor cell located within the taste bud. Like rods and cones in the eye which detect different wavelengths of light, there are specific types of receptors for different tastes. For example, sweet, umami and bitter are recognized by Type II G-protein coupled receptors, whereas sour is related to Type III presynaptic cells. The cell type involved in salty taste transduction is unknown however it is known that sodium ions can enter the receptor cell membrane via ion channel permeation.

====Type II receptors====

When a bitter, sweet or umami ligand binds to a type II G-coupled receptor, a cascade of chemical reactions causes the release of Ca2+ which in turn mediates [[#Glossary |'''exocystosis''']] of ATP. The function of this ATP is threefold:

# Stimulates gustatory nerve afferents which project to gustatory nuclei in the spinal cord
# Excites Type III presynaptic nerve fibers to release serotonin.
# Has a positive feedback effect on type II receptor cells, increasing the level of ATP production.

The role of serotonin is believed to be in the form of lateral inhibition i.e. when a bitter quality is recognized, adjacent receptors for sweetness are deactivated and thus the two tastes may be clearly differentiated. It also has a negative feedback effect on receptor cells, inhibiting umami, bitter and sweet taste transduction.

==Taste Map==
[[Image:Taste map.png|thumb|left|250px|Obsolete idea of the tongue map]]
The idea of a tongue map has disseminated through society for many years. This concept purports that different areas of the tongue are specialized to detect either sweet, salty, sour and bitter tastes. Recent research however has completely nullified such claims and suggests instead that different forms of taste are recognized all over the tongue as well as via the palate. Thus the term ''taste map'' has come to take on a new meaning and that is, the precise areas of taste modalities processing in areas of cortex and its subsequent neural inputs.

===Neural Pathways===

'''First order [[#Glossary |'''neuron''']]''' - From the receptors located in the taste buds, gustatory nerve afferents project to the ipsilateral rostral 1/3 of the nucleus tractus solitarius (NTS), located in the medulla. This rostral 1/3 is commonly referred to as the ''gustatory nucleus''.

The ''gustatory nucleus'' receives input from cranial nerves VII (''Facial n.''), IX (''Hypglossal n.''), and X (''Vagus n.'') via special visceral afferent (SVA) nerve fibers. A summary of their functions is as follows:

* ''Facial nerve n''. - carries taste information from the anterior 2/3 of the tongue.
* ''Hypoglossal n.'' - carries taste information from the posterior 1/3 of the tongue.
* ''Vagus n''. - carries taste information from the palate

'''Second order neurons''' - From the NTS second order neurons carry taste information to the Ventral posteromedial (VPM) nucleus in the thalamus.<ref name=PMID21885776/>

Copious scientific conjecture surrounds how each taste modality is transmitted to the brain. The ‘labelled-line’ hypothesis suggests that there are taste specific neurons which exclusively carry that taste modality to cortical areas. In analogous terms it can be viewed like the pipelines leading toward a house. Each pipeline carries its own utility, there is one for gas, another for water and finally for electricity with each terminating in slightly different areas of the house. In the same way, on the tongues there are different receptors for each taste which concurrently have individual nerve tracts leading to the primary gustatory cortex.

Contrapuntally there is electrophysiological evidence that single nerve afferents carry multiple modalities. These studies show one nerve afferent may have both a strong and a weak activation in response to a multiple taste stimuli.

===Cortical Areas===

[[Image:Primary gustatory cortex.png|thumb|Primary gustatory cortex]]

The location of the taste perception centers has been observed via functional magnetic resonance imaging (fMRI) studies. The primary taste cortex has been identified as being located in the anterior insula/frontal operculum (I/fO)<ref name=PMID22245354><pubmed>22245354</pubmed></ref>, with the secondary taste cortex in the caudolateral orbitofrontal cortex.<ref name=PMID21305668><pubmed>21305668</pubmed></ref> Within the insula there are further subdivisions related to each taste modality. Two photon calcium imaging research has outlined certain ’hot-spots’ of activation which are clearly delineated in relation to each taste. For example, the bitter modality is represented on the insula cortex approximately 1mm posterior to the middle cerebral artery whereas the sweet modality is represented 2.5mm rostrodorsal to the bitter field with no apparent overlap.<ref name=PMID21885776><pubmed>21885776</pubmed></ref> These findings lend weight to the idea that there is only one receptor for each taste quality.

It is interesting to note the relationship between taste and the reward centers of the brain. There is evidence of neural input to the ventral tegmental area (the origin of the mesolimbic dopaminergic reward pathway) and nucleus accumbens (involved in the conversion of motivation into physical action).<ref name=PMID21885776/> Neural connections such as this provide the foundations in explaining concepts such as flavour learning and preference. It may also give some insight into chronic problems such as food addiction and craving. As of yet however the gustatory neural network is not well understood and more research is required to elucidate the relationship between pleasure and taste sensation

==Current Research==
We have an evolving understanding of Embryonic Taste development, through the use of state-of-the-art technology and research techniques we are able to make brilliant discoveries that continue to connect the dots of this amazing natural process of human development.
The majority of research in taste development is involving mice, these mammals show similar embryonic pathways to humans and research is performed in ethical and humane methods.

[[File:Histology.jpg|Left|thumb|200px|Image shows histological stains of a mice tongue showing dysplasia]]

'''Synergistic relationships of Six Genes '''

In an animal study using mice by Suzuki Y, Ikeda K, Kawakami K.(2011) Firstly nominating "[[#Glossary |'''Six Genes''']]" as a major component in [[#Glossary |'''gustatory ''']] development, stating that deficiencies in certain Six genes (specifically Six1 & Six4) leads to poor development. Their research also highlights evidence of cooperative relationships between Six genes for normal advance. This experiment involved breeding mice containing exclusively Six1 and Six4 genes and examining the expression of these genes in papillae under high powered microscope observation. Understanding the role of certain genes along with the intrinsic relationships they hold is crucial for the ability to identify possible causes and correction of any abnormalities <ref><pubmed>21978088</pubmed></ref>

'''Neural Crest responsibilities '''

Another Animal Study involving mice explores a new idea of [[#Glossary |'''Neural crest''']] (NC) contribution in taste development, specifically the development of papillae and taste buds. Liu HX, Komatsu Y, Mishina Y, Mistretta CM. (2012) suggest that Neural crest cells travel to the location of the tongue in early embryonic stages, gain epithelium phenotypes, multiply and then differentiate to eventually form taste papillae. The experiment involved the comparison of 2 different types of Cre line mice, which both express Cre gene in neural crest protocol, the different distribution patterns where observed in specific regions that NC is responsible for.<ref><pubmed>22659543</pubmed></ref>

'''Augmentation of Endoderm'''

In an animal study conducted by Rothova M, Thompson H, Lickert H, Tucker AS.(2012) exploring the historically debated issue of endoderm contribution to tongue development showed promising evidence that position of taste buds are patterned by the border of ectoderm and endoderm derivative epithelium. This study was accomplished via microscopic examination of previously stained specimens. Concluding endoderm has direct influence on gustatory development <ref><pubmed>22581563</pubmed></ref>

'''Changes in Taste Cells over time'''

Research by
Ozdener H, Spielman AI, Rawson NE.(2012) developing a culture which allows taste cells to survive for up to 12 months, empowers researchers to study the processes of proliferation, differentiation and function. This experiment will provide a precedent for future study of taste cells, as these cells are able to operate and grow normally. <ref><pubmed>22643728</pubmed></ref>

'''Shh key component of taste bud proginators'''

A [[#Glossary |'''tamoxifen''']] treatment which suppresses Sonic hedgehog (Shh) secretion in mice proving to reduce the number of cells visible within papillae, in contrast mice not treated with tamoxifen showed a mark increase of cells within papillae, these cells are assumed to become taste cells in later development.
Specific mice were bred to trace the destination of taste placode cells, the study concluded that Shh expressing placodes are taste bud proginators which in turn become taste cells within taste buds although do not have any precursors relationship with papillae. The results were obtain by examination of mice embryos using Bright-field or multichannel fluorescent images through the use of an "Axiocam CCD camera and Axioplan fluorescence microscope with Axiovision software" a study by Harlow, Yang, Williams, Barlow (2011)<ref><pubmed>PMC2674259</pubmed></ref>

'''WNT family exhibit various roles''' [[File:Abnormal of tongue.jpg|thumb|200px|Image shows an example of tongue abnormalities, this is called "double tongue" each side has independent movement!]]

The WNT gene family has a function of signally proteins for various reason such as development, In 2010 Liu, Staubach Grosse, Walton, Saims, Gumucio, Mistretta explored recent findings on the role of WNT's in tongue and papillae development, Concluding that WNT/β-catenin is essential for fungiform papillae differing to WNT5a which proved to be principle in tongue development. Intrinsic chemical mediators were considered by manipulating a tissue culture and then thoroughly examined by scanning photomicrograph. <ref><pubmed>PMC2768563</pubmed></ref>

[http://www.surgicalneurologyint.com/article.asp?issn=2152-7806;year=2012;volume=3;issue=1;spage=23;epage=23;aulast=Manjila]

==Glossary==

* '''Ectoderm'''- outer germ layer of embryo

* '''Endoderm''' - inner germ layer of embryo

* '''Epithelium''' - basic animal tissue that is composed of tightly packed cells, usually covering the outer portion of organs

* '''Exocystosis''' - movement of contents out of cell

* '''Ganglia''' - the accumulation of a nerve cell body

* '''Growth factor''' - a substance that stimulates the growth of cells

* '''Gustatory''' - anything that relates to the taste sense

* '''Hydrolysis''' - breakdown of a chemical when it reacts with water

* '''Mesoderm''' - middle germ layer of embryo

* '''Mesenchyme''' - multipotential cells

* '''Neural crest''' - a part of the ectoderm found on both sides of the neural tube

* '''Neuron''' - most simplistic unit of the nervous system

* '''Neurotransmitter''' - chemicals which allow the passing of signals from neuron to neuron via connecting part (synapse)

* '''Papillae''' - small rough surface projection

* '''Six genes''' - a family of genes

* '''Sonic hedgehog (Shh)''' - signalling protein involved in normal development

* '''Sulcus terminalis''' - describes a physical transition point separating the anterior 2/3 of the tongue from the posterior 1/3

* '''Tamoxifen''' - hormonal altering drug

== References ==
<references/>

==External Links==
{{External Links}}

http://www.webmd.com/oral-health/picture-of-the-tongue

http://www.tutorvista.com/content/biology/biology-iv/nervous-coordination/tongue-structure.php#parts-of-tongue

http://www.cf.ac.uk/biosi/staffinfo/jacob/teaching/sensory/taste.html

--[[User:Z8600021|Mark Hill]] 12:22, 15 August 2012 (EST) Please leave the content listed below the line at the bottom of your project page.

----

{{2012Projects}}

2012 Group Project 3

2012-09-30T12:12:28Z

Z3289738:

=Taste Development=

== Introduction ==
**NEED TO ADD**

==Adult Tongue and Taste Buds – Structure and Function==

'''Structure'''

The tongue is located on the floor of the oral cavity, It is a muscular structure with sensory units crowning. The tongue is divided into an anterior two thirds and a posterior one third. These regions are divided by a V-shaped groove at the back of the tongue (sulcus terminalis). The anterior two thirds of the tongue is covered by stratified squamous epithelium, It contains a roughened surface and has projections called papillae that vary in shape and number.

''''The image below is a simplistic diagram of the surface of the tongue showing the locations of the different papillae and other important features'''

{|
| [[Image:Drawing of Tongue.png|500px]]

'''Papillae'''
[[File:Papillae.jpg|Left|thumb|200px|Close up of Human Tongue Papillae]]

There are 4 types of papillae on the tongue.
The most numerous papillae are the filiform papillae, which function to provide a surface that aids in holding food on the tongue during chewing but do not contain taste buds. The larger, less numerous fungiform papillae which contain taste buds, as do foliate papillae. Circumvallate papillae form a wide V at the sulcus terminalis also containing taste bus. There are no papillae or taste buds located on the posterior third of the tongue, having mucosal folds and the lingual tonsils instead.

'''Function'''

The tongue is for tasting, swallowing, and speech.
The functional unit of the taste bud is a taste cell, there are between 50 and 100 taste cells in each taste bud these taste cells represent all 5 different tastes. Historically is was believed that different areas of the tongue were responsible for different taste sensations although this has since been disregarded.[http://users.rcn.com/jkimball.ma.ultranet/BiologyPages/W/Welcome.html] The papillae contain taste buds which are connected to the oral cavity via a taste pore, the function of the taste bud is to transmit a chemical signal from the oral cavity to a taste cell, this chemical signal is the converted into an electrical impulse and delivered to the brain via nerve fibres for interpretation.

'''The image below is a simplistic hand-drawn cross section of a taste bud unit (not to scale)'''

[[File:Taste_bud_1.jpg|x400px|alt=Cross section of a taste bud unit|Cross section of a taste bud unit]]

==History of Discoveries==

{| cellpadding=5 style="border:1px solid #BBB"
|- bgcolor="#faecc8"
|''' Date'''|| '''Significant Discovery'''

|- bgcolor="#faf6ed"
|'''350BC'''
|| Aristotle writes about the basic tastes, sweet and bitter. He also notes that it can be modified by salty and acidic. <ref name="PMID22717400"><pubmed>22717400</pubmed></ref>

|- bgcolor="#faecc8"
|'''1901'''
|| D. Hanig publishes a paper describing taste sensitivity in different regions of the tongue.
''Interesting fact:'' The modern concept of a 'tongue map' is a misinterpretation of this study. <ref name="PMID22717400"/>

|- bgcolor="#faf6ed"
|style=white-space:nowrap|'''1908'''
|Kikunae Ikeda, a professor of the Tokyo Imperial University, discovered and identified the fifth basic taste: umami (savouriness), made palatable by glutamate. <ref><pubmed>12438213</pubmed></ref>
[http://chemse.oxfordjournals.org/content/27/9/847.long New Seasonings]

|- bgcolor="#faecc8"
|style=white-space:nowrap|'''1931-32'''
| A chemist named Arthur Fox and his college noted that they had different sensitivities to the bitter tasting Phenylthiocarbamide (PTC).<ref>Blakeslee AF, Fox AL. Our different taste worlds. J Hered. 1932;23:97–107.</ref> Geneticists later confirm these findings, and discover that non-tasting is a recessive genetic trait. <ref><pubmed>17782493</pubmed></ref>
[http://www.ncbi.nlm.nih.gov/pubmed/17782493 Inherited taste deficiency]

|- bgcolor="#faf6ed"
|style=white-space:nowrap|'''1965'''
|Farbman's study of the developing taste but in rat fungiform papilla was significant in increasing our understanding of taste bud development. <ref><pubmed>14300090</pubmed></ref>
[http://www.sciencedirect.com/science/article/pii/0012160665900400 Electron microscope study of the developing taste bud in rat fungiform papilla.]

|- bgcolor="#faecc8"
|style=white-space:nowrap|'''1992'''
|McLaughlin SK et al. discovery a taste cell-specific G-protein within the taste buds called Gustucon. This protein is later used to mark bitter, umami and sweet cells. <ref><pubmed>1608467 </pubmed></ref>
[http://www.nature.com/nature/journal/v357/n6379/abs/357563a0.html Gustducin is a taste-cell-specific G protein closely related to the transducins]

|- bgcolor="#faf6ed"
|style=white-space:nowrap|'''1995'''
|Barlow et al. experimented with Axolotl salamanders and concluded that taste buds from this species arise exclusively from epithelial tissue, "oropharyngeal [[#Glossary |'''epithelium''']]". <ref name="PMID17826760"><pubmed>17826760</pubmed></ref>
[http://www.ncbi.nlm.nih.gov/pubmed/17826760 Embryonic origin of gustatory cranial sensory neurons]

|- bgcolor="#faecc8"
|style=white-space:nowrap|'''1996'''
| Witt M and Reutter K of the Technical University Dresden in Germany, carried out a transmission electron microscopy study to investigate the embryonic and fetal development of Human taste buds. Their results suggest an "at least dual function of embryonic/fetal taste buds", including non-gustatory, paracrine functions prior to the 14th week and gustatory after the 14th week. <ref name="PMID8955790"><pubmed>8955790</pubmed></ref>
[http://www.ncbi.nlm.nih.gov/pubmed/8955790 Embryonic and early fetal development of human taste buds: a transmission electron microscopical study]

|- bgcolor="#faf6ed"
|style=white-space:nowrap|'''2000'''
|Chandrashekar, J. et al. discover the first taste sonsors, the T2R bitter taste receptors. <ref><pubmed>10761935</pubmed></ref>
[http://www.sciencedirect.com/science/article/pii/S0092867400807060 T2Rs Function as Bitter Taste Receptors]

|- bgcolor="#faecc8"
|style=white-space:nowrap|'''2001'''
|Nelson, G. et al. discover the sweet receptor: a combination of T1R2 and T1R3. <ref><pubmed>11509186</pubmed></ref>
[http://www.ncbi.nlm.nih.gov/pubmed/11509186?dopt=Abstract&holding=npg Mammalian sweet taste receptors.]

|- bgcolor="#faf6ed"
|style=white-space:nowrap|'''2002'''
|Nelson G. et al. discover the amino acid (umami) taste receptor: a combination of T1R1 and T1R3 identified. <ref><pubmed>11894099</pubmed></ref>
[http://www.ncbi.nlm.nih.gov/pubmed/11894099?dopt=Abstract&holding=npg An amino-acid taste receptor]

|- bgcolor="#faecc8"
|style=white-space:nowrap|'''2005'''
|Dyer, J. et al. discover sweet taste receptors in the GI tract. <ref><pubmed>17855558</pubmed></ref>
[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1986582/ Sweet taste signaling in the gut]

|- bgcolor="#faf6ed"
|style=white-space:nowrap|'''2006'''
|Huang, A. L et al. discover cells for sour taste, identified by PKD2L1 (a polycystic kidney disease-like ion channel). <ref><pubmed>16929298</pubmed></ref>
[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1571047/ The Cells and Logic for Mammalian Sour Taste detection]

|- bgcolor="#faecc8"
|style=white-space:nowrap|'''2007'''
|Harlow DE, Barlow LA of the University of Colorado Denver Health Sciences Center provide evidence of the "embryonic origin of gustatory cranial sensory neurons". <ref name="PMID17826760"/>
[http://www.ncbi.nlm.nih.gov/pubmed/17826760 Embryonic origin of gustatory cranial sensory neurons.]

|- bgcolor="#faf6ed"
|style=white-space:nowrap|'''2009'''
|A study by Hevezi P et al, presents "the first comprehensive characterization of gene expression in primate taste buds", as opposed to previous studies which focused on rodents. <ref><pubmed>19636377</pubmed></ref>
[http://www.ncbi.nlm.nih.gov/pubmed/19636377 Genome-wide analysis of gene expression in primate taste buds reveals links to diverse processes]

|- bgcolor="#faecc8"
|style=white-space:nowrap|'''2010'''
|Chandrashekar, J. et al. identify epithelial sodium channel (ENaC) as the sodium-salt taste receptor. <ref><pubmed>20107438</pubmed></ref>
[http://www.ncbi.nlm.nih.gov/pubmed/20107438?dopt=Abstract&holding=npg The cells and peripheral representation of sodium taste in mice]
|}

== Human Weekly Development - Two Prominent Studies ==
Martin Witt and Klaus Reutter of the University of Tubingen in Germany published two prominent studies regarding developing taste buds in humans. Their first study in 1996 was a transmission electron microscopical (TEM) study of the taste bud primordium and its morphological changes during the 8th-15th postovulatory week. Their next study in 1997 built on their previous findings by using Scanning Electron Microscopy (SEM) to observe the development of gustatory [[#Glossary |'''papillae''']] during postovulatory weeks 6-15.

The findings of these two studies are summarized in the table below. The figures provided relate to the images on their respective research papers.

# [http://onlinelibrary.wiley.com/doi/10.1002/(SICI)1097-0185(199612)246:4%3C507::AID-AR10%3E3.0.CO;2-S/pdf Embryonic and early fetal development of human taste buds: a transmission electron microscopical study, 1996]
# [http://chemse.oxfordjournals.org/content/22/6/601.long Scanning electron microscopical studies of developing gustatory papillae in humans, 1997]

===Timeline of Developmental Processes of Human Taste Buds===
{| cellpadding=5 style="border:1px solid #BBB"
|- bgcolor="#89CFF0"
|'''Postovulatory Week'''||'''Description'''

|- bgcolor="#BCD4E6"
|'''Week 6''' ||
The surface of the developing tongue is covered by nearly flat epithelium (1997, Figure 1). The first gustatory papillae of the tongue appear in the caudal mid-line near the foramen caecum and the first circumvallate papilla develops on the dorsal mid-line. <ref name="PMID9455607"><pubmed>9455607</pubmed></ref>

|- bgcolor="#89CFF0"
| '''Weeks 6 to 7'''||
Nerve fibers approach the basal lamina of lingual epithelium. At this stage the lingual epithelium consists of two to three cell layers and there is not yet any sign of cell specializations indicating early taste bud formation. <ref name=PMID8955790/>

|- bgcolor="#BCD4E6"
| '''Week 7 '''||
A series of irregular epithelial swellings in the anterior part and marginal parts of the tongue indicate early forming fungiform papillae. Furthermore, a V-like lane is observed anterior to the [[#Glossary |'''sulcus terminalis''']], which represents a smooth surface for developing circumvallate papillae (1997, Figure 2). Witt M et al observe that these circumvallate papillae are larger than the developing fungiform papillae of the same age, later noting that the fungiform papillae tend to increase in size over the 8-15th weeks of gestation, whilst the size of vallate papillae tend to remain constant during this period. <ref name=PMID9455607/>

|- bgcolor="#89CFF0"
| ''' Week 8 ''' ||
* The taste bud primordium are still differentiated, elongated epithelial cells, resting on a slightly developed core of young dermal papilla.
* The lingual epithelium shows first signs of taste bud development as nerve fibers coming from the dermal papilla penetrate the epithelial basal lamina and form synapses with taste bud progenitor cells (1996, Figure 1). These synapses demonstrate the neuronal connection between the taste bud primordium and the central nervous system, reaching a maximum around the 12th to 13th week. However, it is important to note that at this time these cells are still poorly differentiated, elongated epithelial cells.
* Ciliated cells also appear around the 8th week, however the significance of these cells which are scattered randomly across the lingual surface remains unclear. <ref name=PMID8955790/>

|- bgcolor="#BCD4E6"
|''' Week 9''' ||
By this stage, although a taste pore is not present, the surface of circumvallate papillae usually contains a taste pit partly filled with microvillus-like processes from the underlying taste bud cells (1997, Figure 10). <ref name=PMID9455607/>

|- bgcolor="#89CFF0"
|''' Weeks 10-11''' ||
At this stage, the lingual epithelium compromises of about four cell layers, and the first shallow grooves above the taste bud primordium are developed. Fungiform papillae appear on the lateral margins and the tip of the tongue, containing taste bud primordial that display the first signs of a primitive pore formation (1996, Figure 6). <ref name=PMID8955790/>

|- bgcolor="#BCD4E6"
|''' Week 12 ''' ||
Taste bud cells are more clearly differentiated into epithelial cell types II and III. <ref name=PMID8955790/>

|- bgcolor="#89CFF0"
|''' Weeks 12-13 ''' ||
At this stage the taste bud primordial are all located on the top of dermal papillae. There is also maximum synapses between cells and afferent nerve fibers, which intermingle with each other to form a plexus-like structure (1996, Figure 6a). <ref name=PMID8955790/>

|- bgcolor="#BCD4E6"
|''' Weeks 14 -15 ''' ||
The shape and size of the taste buds primordial begins to resemble those of adult taste buds (1996, Figure 9). By the 14th week the taste pores develop as the taste pits are filled by microvilli, and bubble like vesicles indicate the secretory activity of these cells (1996, Figure 10). However, the taste buds only achieve a fully developed function in week 15 of gestation with the development of type I cells to produce the mucous material in the taste pit. <ref name=PMID8955790/>
|}

==Abnormalities==

===Knocking out P2X Receptors===

[[File:Image of taste being evoked by visualizing ATP release.jpeg|Left|thumb|200px|Evoking taste - ATP release in tongue]]

Gustatory abnormalities has not been widely researched and what has been researched has been through animal testing, most commonly we have found on mice.

In Huang, 2008 this team used the release of the [[#Glossary |'''ectoderm''']], ATP (adenosine triphosphate) as a quantitative measurement of gustatory sensation and taste. This was done by using a comparison of wild type (WT) and double knockout (DKO) mice. P2X receptors, P2X2 and P2X3 were knocked out in the DKO mice. The premise of this article was that knocking out P2X receptors reduces transmitter secretion of ATP in taste buds, therefore they cannot taste.

It should be noted that the taste buds in DKO are functional, but are not stimulated by the administration of tastants.

The transmission of release of ATP is secretion through gap junction hemichannels (pannexin 1 gap junction).

When both P2X2 and P2X3 are knocked out, no taste is elicited. However they found that if either P2X2 OR P2X3 was knocked out there was a taste response. So the inference made from this is that if one of the two receptors from the P2X family was knocked out there still can have taste response. The WT mice showed significant stimulation by tastants whereas DKO had little to no stimulation of ATP release.<ref><pubmed>21940456</pubmed></ref>

===FGF signalling and genes===

Sprouty, or ''Srpy'', genes have been related to regulating the development of circumvallate papillae (CVP). The CVP are large dome shaped papillae, which form a 'V' just in front of the terminal sulcus.

By knocking out ''Spry'' genes using mice which had ''Spry1'' and ''Spry2'' knocked out showed that the number of CVP doubled. However, when Fibroblast [[#Glossary |'''Growth Factor''']] gene ("Fgf10") was absent, the number of CVP was significantly reduced, if not completely absent. The correlation between ''Spry1/2'' and ''Fgf10'' is that ''Spry1/2'' antagonizes "Fgf10" to limit the size of the CVP progenitor placode. Exclusive expression of ''Fgf10'' in the [[#Glossary |'''mesenchyme''']] is necessary for the formation of CVP.

'''This image shows the CVP stained with H&E and scanned by Scanning Electron Microscope (SEM)'''
[[File:CVP of WT(top) and DKO(bottom) mice with H&E and SEM.png]]

'''This image shows the location of the CVP and the increased number in DKO mice by SEM'''
[[File:Mouse circumvallate papilla 01.jpg|300px]]

Taste buds develop from the mesenchyme but require local signalling to properly differentiate. Some signalling factors for proper development of taste buds besides FGF are: [[#Glossary |'''Sonic Hedgehog''']] (SHH), Bone Morphogenetic Proteins (BMPs), Epidermal Growth Factor (EGF).

Additionally, this proves that the anterior and posterior developments of the tongue are derived from embryonic tissues, where the anterior tongue is derived from the [[#Glossary |'''ectoderm''']] and the posterior tongue is derived from the [[#Glossary |'''endoderm''']]. Taste buds develop from the mesenchyme but require local signalling to properly differentiate. Some signalling factors for proper development of taste buds besides FGF are: Sonic Hedgehog (SHH), Bone Morphogenetic Proteins (BMPs), Epidermal Growth Factor (EGF).

As mentioned above, this article shows that the anterior and posterior developments of the tongue are derived from embryonic tissues, where the anterior tongue is derived front the ectoderm and the posterior tongue is derived from the endoderm. Secondly, FGF is required to regulate the growth of taste buds, while ''Spry'' genes limit the number of CVP. ''Fgf10''& ''Spry 1&2''work antagonistically through receptor tyrosine kinase (RTK)signalling.

However, the deletion of ''Spry2''led to the increase of CVPs it should be noted that they found that a significant decrease in number of fungiform papillae. In contrast, the absence of ''Fgf10'', while leading to the absence of CVPs lead to an increase in number and size of fungiform papillae. Therefore these genes have different effects on the anterior and posterior developing tongue and taste buds.<ref><pubmed>21655085</pubmed></ref>

==Gustatory System==

[[Image:Taste qualities.gif|thumb|The five basic tastes]]

Taste or more appropriately gustation, is a fundamental survival tool in animals as it directs the consumption of essential nutrients. The five tastes that exist within the human gustatory system: salty, sweet, sour, bitter and umami, all signify basic physiological requirements. Salty tastes denote the presence of Na+, an important ion involved in the transportation and retention of water across cell membranes. Sweetness is the recognition of carbohydrates, essential for maintaining optimal brain function and providing the basis for energy production in muscle tissue via ATP [[#Glossary |'''hydrolysis''']]. Similarly umami codes for the presence of L-amino acids, especially L-glutamate which is an integral component of protein synthesis.

These different modalities not only function to maintain the proper intake of nutrients within the body but also, by way of aversion, prohibit the consumption of undesired or poisonous materials. The bitter modality for example is generally regarded as displeasing to the human palate. It represents a high acid content which may be a result of foods which have become rotten or are inherently poisonous to the body.<ref name=PMID20696704><pubmed>20696704</pubmed></ref>

Research has historically limited itself to investigating the mechanisms of these five taste qualities though it must be noted many other modalities may exist. Of particular conjecture is the existence of fatty acid recognition. In the past the detection of fat in food has been attributed to somatosensory inputs <ref name=PMID20696704/> from the tongue, that is, the oily feel and texture of fat rather than its actual ‘taste’ allows the brain to encode for its presence. Further research is therefore required to elicit the precise mechanisms of fat detection.

===Cell Biology===

The five taste qualities are not all detected by the same type of receptor cell located within the taste bud. Like rods and cones in the eye which detect different wavelengths of light, there are specific types of receptors for different tastes. For example, sweet, umami and bitter are recognized by Type II G-protein coupled receptors, whereas sour is related to Type III presynaptic cells. The cell type involved in salty taste transduction is unknown however it is known that sodium ions can enter the receptor cell membrane via ion channel permeation.

====Type II receptors====

When a bitter, sweet or umami ligand binds to a type II G-coupled receptor, a cascade of chemical reactions causes the release of Ca2+ which in turn mediates [[#Glossary |'''exocystosis''']] of ATP. The function of this ATP is threefold:

# Stimulates gustatory nerve afferents which project to gustatory nuclei in the spinal cord
# Excites Type III presynaptic nerve fibers to release serotonin.
# Has a positive feedback effect on type II receptor cells, increasing the level of ATP production.

The role of serotonin is believed to be in the form of lateral inhibition i.e. when a bitter quality is recognized, adjacent receptors for sweetness are deactivated and thus the two tastes may be clearly differentiated. It also has a negative feedback effect on receptor cells, inhibiting umami, bitter and sweet taste transduction.

==Taste Map==
[[Image:Taste map.png|thumb|left|250px|Obsolete idea of the tongue map]]
The idea of a tongue map has disseminated through society for many years. This concept purports that different areas of the tongue are specialized to detect either sweet, salty, sour and bitter tastes. Recent research however has completely nullified such claims and suggests instead that different forms of taste are recognized all over the tongue as well as via the palate. Thus the term ''taste map'' has come to take on a new meaning and that is, the precise areas of taste modalities processing in areas of cortex and its subsequent neural inputs.

===Neural Pathways===

'''First order [[#Glossary |'''neuron''']]''' - From the receptors located in the taste buds, gustatory nerve afferents project to the ipsilateral rostral 1/3 of the nucleus tractus solitarius (NTS), located in the medulla. This rostral 1/3 is commonly referred to as the ''gustatory nucleus''.

The ''gustatory nucleus'' receives input from cranial nerves VII (''Facial n.''), IX (''Hypglossal n.''), and X (''Vagus n.'') via special visceral afferent (SVA) nerve fibers. A summary of their functions is as follows:

* ''Facial nerve n''. - carries taste information from the anterior 2/3 of the tongue.
* ''Hypoglossal n.'' - carries taste information from the posterior 1/3 of the tongue.
* ''Vagus n''. - carries taste information from the palate

'''Second order neurons''' - From the NTS second order neurons carry taste information to the Ventral posteromedial (VPM) nucleus in the thalamus.<ref name=PMID21885776/>

Copious scientific conjecture surrounds how each taste modality is transmitted to the brain. The ‘labelled-line’ hypothesis suggests that there are taste specific neurons which exclusively carry that taste modality to cortical areas. In analogous terms it can be viewed like the pipelines leading toward a house. Each pipeline carries its own utility, there is one for gas, another for water and finally for electricity with each terminating in slightly different areas of the house. In the same way, on the tongues there are different receptors for each taste which concurrently have individual nerve tracts leading to the primary gustatory cortex.

Contrapuntally there is electrophysiological evidence that single nerve afferents carry multiple modalities. These studies show one nerve afferent may have both a strong and a weak activation in response to a multiple taste stimuli.

===Cortical Areas===

[[Image:Primary gustatory cortex.png|thumb|Primary gustatory cortex]]

The location of the taste perception centers has been observed via functional magnetic resonance imaging (fMRI) studies. The primary taste cortex has been identified as being located in the anterior insula/frontal operculum (I/fO)<ref name=PMID22245354><pubmed>22245354</pubmed></ref>, with the secondary taste cortex in the caudolateral orbitofrontal cortex.<ref name=PMID21305668><pubmed>21305668</pubmed></ref> Within the insula there are further subdivisions related to each taste modality. Two photon calcium imaging research has outlined certain ’hot-spots’ of activation which are clearly delineated in relation to each taste. For example, the bitter modality is represented on the insula cortex approximately 1mm posterior to the middle cerebral artery whereas the sweet modality is represented 2.5mm rostrodorsal to the bitter field with no apparent overlap.<ref name=PMID21885776><pubmed>21885776</pubmed></ref> These findings lend weight to the idea that there is only one receptor for each taste quality.

It is interesting to note the relationship between taste and the reward centers of the brain. There is evidence of neural input to the ventral tegmental area (the origin of the mesolimbic dopaminergic reward pathway) and nucleus accumbens (involved in the conversion of motivation into physical action).<ref name=PMID21885776/> Neural connections such as this provide the foundations in explaining concepts such as flavour learning and preference. It may also give some insight into chronic problems such as food addiction and craving. As of yet however the gustatory neural network is not well understood and more research is required to elucidate the relationship between pleasure and taste sensation

==Current Research==
We have an evolving understanding of Embryonic Taste development, through the use of state-of-the-art technology and research techniques we are able to make brilliant discoveries that continue to connect the dots of this amazing natural process of human development.
The majority of research in taste development is involving mice, these mammals show similar embryonic pathways to humans and research is performed in ethical and humane methods.

[[File:Histology.jpg|Left|thumb|200px|Image shows histological stains of a mice tongue showing dysplasia]]

'''Synergistic relationships of Six Genes '''

In an animal study using mice by Suzuki Y, Ikeda K, Kawakami K.(2011) Firstly nominating "[[#Glossary |'''Six Genes''']]" as a major component in [[#Glossary |'''gustatory ''']] development, stating that deficiencies in certain Six genes (specifically Six1 & Six4) leads to poor development. Their research also highlights evidence of cooperative relationships between Six genes for normal advance. This experiment involved breeding mice containing exclusively Six1 and Six4 genes and examining the expression of these genes in papillae under high powered microscope observation. Understanding the role of certain genes along with the intrinsic relationships they hold is crucial for the ability to identify possible causes and correction of any abnormalities <ref><pubmed>21978088</pubmed></ref>

'''Neural Crest responsibilities '''

Another Animal Study involving mice explores a new idea of [[#Glossary |'''Neural crest''']] (NC) contribution in taste development, specifically the development of papillae and taste buds. Liu HX, Komatsu Y, Mishina Y, Mistretta CM. (2012) suggest that Neural crest cells travel to the location of the tongue in early embryonic stages, gain epithelium phenotypes, multiply and then differentiate to eventually form taste papillae. The experiment involved the comparison of 2 different types of Cre line mice, which both express Cre gene in neural crest protocol, the different distribution patterns where observed in specific regions that NC is responsible for.<ref><pubmed>22659543</pubmed></ref>

'''Augmentation of Endoderm'''

In an animal study conducted by Rothova M, Thompson H, Lickert H, Tucker AS.(2012) exploring the historically debated issue of endoderm contribution to tongue development showed promising evidence that position of taste buds are patterned by the border of ectoderm and endoderm derivative epithelium. This study was accomplished via microscopic examination of previously stained specimens. Concluding endoderm has direct influence on gustatory development <ref><pubmed>22581563</pubmed></ref>

'''Changes in Taste Cells over time'''

Research by
Ozdener H, Spielman AI, Rawson NE.(2012) developing a culture which allows taste cells to survive for up to 12 months, empowers researchers to study the processes of proliferation, differentiation and function. This experiment will provide a precedent for future study of taste cells, as these cells are able to operate and grow normally. <ref><pubmed>22643728</pubmed></ref>

'''Shh key component of taste bud proginators'''

A [[#Glossary |'''tamoxifen''']] treatment which suppresses Sonic hedgehog (Shh) secretion in mice proving to reduce the number of cells visible within papillae, in contrast mice not treated with tamoxifen showed a mark increase of cells within papillae, these cells are assumed to become taste cells in later development.
Specific mice were bred to trace the destination of taste placode cells, the study concluded that Shh expressing placodes are taste bud proginators which in turn become taste cells within taste buds although do not have any precursors relationship with papillae. The results were obtain by examination of mice embryos using Bright-field or multichannel fluorescent images through the use of an "Axiocam CCD camera and Axioplan fluorescence microscope with Axiovision software" a study by Harlow, Yang, Williams, Barlow (2011)<ref><pubmed>PMC2674259</pubmed></ref>

'''WNT family exhibit various roles''' [[File:Abnormal of tongue.jpg|thumb|200px|Image shows an example of tongue abnormalities, this is called "double tongue" each side has independent movement!]]

The WNT gene family has a function of signally proteins for various reason such as development, In 2010 Liu, Staubach Grosse, Walton, Saims, Gumucio, Mistretta explored recent findings on the role of WNT's in tongue and papillae development, Concluding that WNT/β-catenin is essential for fungiform papillae differing to WNT5a which proved to be principle in tongue development. Intrinsic chemical mediators were considered by manipulating a tissue culture and then thoroughly examined by scanning photomicrograph. <ref><pubmed>PMC2768563</pubmed></ref>

[http://www.surgicalneurologyint.com/article.asp?issn=2152-7806;year=2012;volume=3;issue=1;spage=23;epage=23;aulast=Manjila]

==Glossary==

* Ectoderm- outer germ layer of embryo

* Endoderm - inner germ layer of embryo

* Epithelium - basic animal tissue that is composed of tightly packed cells, usually covering the outer portion of organs

* Exocystosis - movement of contents out of cell

* Ganglia - the accumulation of a nerve cell body

* Growth factor - a substance that stimulates the growth of cells

* Gustatory - anything that relates to the taste sense

* Hydrolysis - breakdown of a chemical when it reacts with water

* Mesoderm - middle germ layer of embryo

* Mesenchyme - multipotential cells

* Neural crest - a part of the ectoderm found on both sides of the neural tube

* Neuron - most simplistic unit of the nervous system

* Neurotransmitter - chemicals which allow the passing of signals from neuron to neuron via connecting part (synapse)

* Papillae - small rough surface projection

* Six genes - a family of genes

* Sonic hedgehog (Shh) - signalling protein invloved in normal development

* Sulcus terminalis - describes a physical transition point separating the anterior 2/3 of the tongue from the posterior 1/3

* Tamoxifen - hormonal altering drug

== References ==
<references/>

==External Links==
{{External Links}}

http://www.webmd.com/oral-health/picture-of-the-tongue

http://www.tutorvista.com/content/biology/biology-iv/nervous-coordination/tongue-structure.php#parts-of-tongue

http://www.cf.ac.uk/biosi/staffinfo/jacob/teaching/sensory/taste.html

--[[User:Z8600021|Mark Hill]] 12:22, 15 August 2012 (EST) Please leave the content listed below the line at the bottom of your project page.

----

{{2012Projects}}

2012 Group Project 3

2012-09-30T12:03:18Z

Z3289738: /* Timeline of Developmental Processes of Human Taste Buds */

=Taste Development=

== Introduction ==
**NEED TO ADD**

==Adult Tongue and Taste Buds – Structure and Function==

'''Structure'''

The tongue is located on the floor of the oral cavity, It is a muscular structure with sensory units crowning. The tongue is divided into an anterior two thirds and a posterior one third. These regions are divided by a V-shaped groove at the back of the tongue (sulcus terminalis). The anterior two thirds of the tongue is covered by stratified squamous epithelium, It contains a roughened surface and has projections called papillae that vary in shape and number.

''''The image below is a simplistic diagram of the surface of the tongue showing the locations of the different papillae and other important features'''

{|
| [[Image:Drawing of Tongue.png|500px]]

'''Papillae'''
[[File:Papillae.jpg|Left|thumb|200px|Close up of Human Tongue Papillae]]

There are 4 types of papillae on the tongue.
The most numerous papillae are the filiform papillae, which function to provide a surface that aids in holding food on the tongue during chewing but do not contain taste buds. The larger, less numerous fungiform papillae which contain taste buds, as do foliate papillae. Circumvallate papillae form a wide V at the sulcus terminalis also containing taste bus. There are no papillae or taste buds located on the posterior third of the tongue, having mucosal folds and the lingual tonsils instead.

'''Function'''

The tongue is for tasting, swallowing, and speech.
The functional unit of the taste bud is a taste cell, there are between 50 and 100 taste cells in each taste bud these taste cells represent all 5 different tastes. Historically is was believed that different areas of the tongue were responsible for different taste sensations although this has since been disregarded.[http://users.rcn.com/jkimball.ma.ultranet/BiologyPages/W/Welcome.html] The papillae contain taste buds which are connected to the oral cavity via a taste pore, the function of the taste bud is to transmit a chemical signal from the oral cavity to a taste cell, this chemical signal is the converted into an electrical impulse and delivered to the brain via nerve fibres for interpretation.

'''The image below is a simplistic hand-drawn cross section of a taste bud unit (not to scale)'''

[[File:Taste_bud_1.jpg|x400px|alt=Cross section of a taste bud unit|Cross section of a taste bud unit]]

==History of Discoveries==

{| cellpadding=5 style="border:1px solid #BBB"
|- bgcolor="#faecc8"
|''' Date'''|| '''Significant Discovery'''

|- bgcolor="#faf6ed"
|'''350BC'''
|| Aristotle writes about the basic tastes, sweet and bitter. He also notes that it can be modified by salty and acidic. <ref name="PMID22717400"><pubmed>22717400</pubmed></ref>

|- bgcolor="#faecc8"
|'''1901'''
|| D. Hanig publishes a paper describing taste sensitivity in different regions of the tongue.
''Interesting fact:'' The modern concept of a 'tongue map' is a misinterpretation of this study. <ref name="PMID22717400"/>

|- bgcolor="#faf6ed"
|style=white-space:nowrap|'''1908'''
|Kikunae Ikeda, a professor of the Tokyo Imperial University, discovered and identified the fifth basic taste: umami (savouriness), made palatable by glutamate. <ref><pubmed>12438213</pubmed></ref>
[http://chemse.oxfordjournals.org/content/27/9/847.long New Seasonings]

|- bgcolor="#faecc8"
|style=white-space:nowrap|'''1931-32'''
| A chemist named Arthur Fox and his college noted that they had different sensitivities to the bitter tasting Phenylthiocarbamide (PTC).<ref>Blakeslee AF, Fox AL. Our different taste worlds. J Hered. 1932;23:97–107.</ref> Geneticists later confirm these findings, and discover that non-tasting is a recessive genetic trait. <ref><pubmed>17782493</pubmed></ref>
[http://www.ncbi.nlm.nih.gov/pubmed/17782493 Inherited taste deficiency]

|- bgcolor="#faf6ed"
|style=white-space:nowrap|'''1965'''
|Farbman's study of the developing taste but in rat fungiform papilla was significant in increasing our understanding of taste bud development. <ref><pubmed>14300090</pubmed></ref>
[http://www.sciencedirect.com/science/article/pii/0012160665900400 Electron microscope study of the developing taste bud in rat fungiform papilla.]

|- bgcolor="#faecc8"
|style=white-space:nowrap|'''1992'''
|McLaughlin SK et al. discovery a taste cell-specific G-protein within the taste buds called Gustucon. This protein is later used to mark bitter, umami and sweet cells. <ref><pubmed>1608467 </pubmed></ref>
[http://www.nature.com/nature/journal/v357/n6379/abs/357563a0.html Gustducin is a taste-cell-specific G protein closely related to the transducins]

|- bgcolor="#faf6ed"
|style=white-space:nowrap|'''1995'''
|Barlow et al. experimented with Axolotl salamanders and concluded that taste buds from this species arise exclusively from epithelial tissue, "oropharyngeal [[#Glossary |'''epithelium''']]". <ref name="PMID17826760"><pubmed>17826760</pubmed></ref>
[http://www.ncbi.nlm.nih.gov/pubmed/17826760 Embryonic origin of gustatory cranial sensory neurons]

|- bgcolor="#faecc8"
|style=white-space:nowrap|'''1996'''
| Witt M and Reutter K of the Technical University Dresden in Germany, carried out a transmission electron microscopy study to investigate the embryonic and fetal development of Human taste buds. Their results suggest an "at least dual function of embryonic/fetal taste buds", including non-gustatory, paracrine functions prior to the 14th week and gustatory after the 14th week. <ref name="PMID8955790"><pubmed>8955790</pubmed></ref>
[http://www.ncbi.nlm.nih.gov/pubmed/8955790 Embryonic and early fetal development of human taste buds: a transmission electron microscopical study]

|- bgcolor="#faf6ed"
|style=white-space:nowrap|'''2000'''
|Chandrashekar, J. et al. discover the first taste sonsors, the T2R bitter taste receptors. <ref><pubmed>10761935</pubmed></ref>
[http://www.sciencedirect.com/science/article/pii/S0092867400807060 T2Rs Function as Bitter Taste Receptors]

|- bgcolor="#faecc8"
|style=white-space:nowrap|'''2001'''
|Nelson, G. et al. discover the sweet receptor: a combination of T1R2 and T1R3. <ref><pubmed>11509186</pubmed></ref>
[http://www.ncbi.nlm.nih.gov/pubmed/11509186?dopt=Abstract&holding=npg Mammalian sweet taste receptors.]

|- bgcolor="#faf6ed"
|style=white-space:nowrap|'''2002'''
|Nelson G. et al. discover the amino acid (umami) taste receptor: a combination of T1R1 and T1R3 identified. <ref><pubmed>11894099</pubmed></ref>
[http://www.ncbi.nlm.nih.gov/pubmed/11894099?dopt=Abstract&holding=npg An amino-acid taste receptor]

|- bgcolor="#faecc8"
|style=white-space:nowrap|'''2005'''
|Dyer, J. et al. discover sweet taste receptors in the GI tract. <ref><pubmed>17855558</pubmed></ref>
[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1986582/ Sweet taste signaling in the gut]

|- bgcolor="#faf6ed"
|style=white-space:nowrap|'''2006'''
|Huang, A. L et al. discover cells for sour taste, identified by PKD2L1 (a polycystic kidney disease-like ion channel). <ref><pubmed>16929298</pubmed></ref>
[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1571047/ The Cells and Logic for Mammalian Sour Taste detection]

|- bgcolor="#faecc8"
|style=white-space:nowrap|'''2007'''
|Harlow DE, Barlow LA of the University of Colorado Denver Health Sciences Center provide evidence of the "embryonic origin of gustatory cranial sensory neurons". <ref name="PMID17826760"/>
[http://www.ncbi.nlm.nih.gov/pubmed/17826760 Embryonic origin of gustatory cranial sensory neurons.]

|- bgcolor="#faf6ed"
|style=white-space:nowrap|'''2009'''
|A study by Hevezi P et al, presents "the first comprehensive characterization of gene expression in primate taste buds", as opposed to previous studies which focused on rodents. <ref><pubmed>19636377</pubmed></ref>
[http://www.ncbi.nlm.nih.gov/pubmed/19636377 Genome-wide analysis of gene expression in primate taste buds reveals links to diverse processes]

|- bgcolor="#faecc8"
|style=white-space:nowrap|'''2010'''
|Chandrashekar, J. et al. identify epithelial sodium channel (ENaC) as the sodium-salt taste receptor. <ref><pubmed>20107438</pubmed></ref>
[http://www.ncbi.nlm.nih.gov/pubmed/20107438?dopt=Abstract&holding=npg The cells and peripheral representation of sodium taste in mice]
|}

== Human Weekly Development - Two Prominent Studies ==
Martin Witt and Klaus Reutter of the University of Tubingen in Germany published two prominent studies regarding developing taste buds in humans. Their first study in 1996 was a transmission electron microscopical (TEM) study of the taste bud primordium and its morphological changes during the 8th-15th postovulatory week. Their next study in 1997 built on their previous findings by using Scanning Electron Microscopy (SEM) to observe the development of gustatory [[#Glossary |'''papillae''']] during postovulatory weeks 6-15.

The findings of these two studies are summarized in the table below. The figures provided relate to the images on their respective research papers.

# [http://onlinelibrary.wiley.com/doi/10.1002/(SICI)1097-0185(199612)246:4%3C507::AID-AR10%3E3.0.CO;2-S/pdf Embryonic and early fetal development of human taste buds: a transmission electron microscopical study, 1996]
# [http://chemse.oxfordjournals.org/content/22/6/601.long Scanning electron microscopical studies of developing gustatory papillae in humans, 1997]

===Timeline of Developmental Processes of Human Taste Buds===
{| cellpadding=5 style="border:1px solid #BBB"
|- bgcolor="#89CFF0"
|'''Postovulatory Week'''||'''Description'''

|- bgcolor="#BCD4E6"
|'''Week 6''' ||
The surface of the developing tongue is covered by nearly flat epithelium (1997, Figure 1). The first gustatory papillae of the tongue appear in the caudal midline near the foramen caecum and the first circumvallate papilla develops on the dorsal midline. <ref name="PMID9455607"><pubmed>9455607</pubmed></ref>

|- bgcolor="#89CFF0"
| '''Weeks 6 to 7'''||
Nerve fibres approach the basal lamina of lingual epithelium. At this stage the lingual epithelium consists of two to three cell layers and there is not yet any sign of cell specializations indicating early taste bud formation. <ref name=PMID8955790/>

|- bgcolor="#BCD4E6"
| '''Week 7 '''||
A series of irregular epithelial swellings in the anterior part and marginal parts of the tongue indicate early forming fungiform papillae. Furthermore, a V-like lane is observed anterior to the [[#Glossary |'''sulcus terminalis''']], which represents a smooth surface for developing circumvallate papillae (1997, Figure 2). Witt M et al observe that these circumvallate papillae are larger than the developing fungiform papillae of the same age, later noting that the fungiform papillae tend to increase in size over the 8-15th weeks of gestation, whilst the size of vallate papillae tend to remain constant during this period. <ref name=PMID9455607/>

|- bgcolor="#89CFF0"
| ''' Week 8 ''' ||
* The taste bud primordium are still differentiated, elongated epithelial cells, resting on a slightly developed core of young dermal papilla.
* The lingual epithelium shows first signs of taste bud development as nerve fibres coming from the dermal papilla penetrate the epithelial basal lamina and form synapses with taste bud progenitor cells (1996, Figure 1). These synapses demonstrate the neuronal connection between the taste bud primordium and the central nervous system, reaching a maximum around the 12th to 13th week. However, it is important to note that at this time these cells are still poorly differentiated, elongated epithelial cells.
* Ciliated cells also appear around the 8th week, however the significance of these cells which are scattered randomly across the lingual surface remains unclear. <ref name=PMID8955790/>

|- bgcolor="#BCD4E6"
|''' Week 9''' ||
By this stage, although a taste pore is not present, the surface of circumvallate papillae usually contains a taste pit partly filled with microvillus-like processes from the underlying taste bud cells (1997, Figure 10). <ref name=PMID9455607/>

|- bgcolor="#89CFF0"
|''' Weeks 10-11''' ||
At this stage, the lingual epithelium compromises of about four cell layers, and the first shallow grooves above the taste bud primordium are developed. Fungiform papillae appear on the lateral margins and the tip of the tongue, containing taste bud primordial that display the first signs of a primitive pore formation (1996, Figure 6). <ref name=PMID8955790/>
||
Image

|- bgcolor="#BCD4E6"
|''' Week 12 ''' ||
Taste bud cells are more clearly differentiated into epithelial cell types II and III. <ref name=PMID8955790/>

|- bgcolor="#89CFF0"
|''' Weeks 12-13 ''' ||
At this stage the taste bud primordial are all located on the top of dermal papillae. There is also maximum synapses between cells and afferent nerve fibres, which intermingle with each other to form a plexus-like structure (1996, Figure 6a). <ref name=PMID8955790/>

|- bgcolor="#BCD4E6"
|''' Weeks 14 -15 ''' ||
The shape and size of the taste buds primordial begins to resemble those of adult taste buds (1996, Figure 9). By the 14th week the taste pores develop as the taste pits are filled by microvilli, and bubble like vesicles indicate the secretory activity of these cells (1996, Figure 10). However, the tastebuds only achieve a fully developed function in week 15 of gestation with the development of type I cells to produce the mucous material in the taste pit. <ref name=PMID8955790/>
|}

==Abnormalities==

===Knocking out P2X Receptors===

[[File:Image of taste being evoked by visualising ATP release.jpeg|Left|thumb|200px|Evoking taste - ATP release in tongue]]

Gustatory abnormalities has not been widely researched and what has been researched has been through animal testing, most commonly we have found on mice.

In Huang, 2008 this team used the release of the [[#Glossary |'''ectoderm''']], ATP (adenosine triphosphate) as a quantitative measurement of gustatory sensation and taste. This was done by using a comparison of wild type (WT) and double knockout (DKO) mice. P2X receptors, P2X2 and P2X3 were knocked out in the DKO mice. The premise of this article was that knocking out P2X receptors reduces transmitter secretion of ATP in taste buds, therefore they cannot taste.

It should be noted that the taste buds in DKO are functional, but are not stimulated by the administration of tastants.

The transmission of release of ATP is secretion through gap junction hemichannels (pannexin 1 gap junction).

When both P2X2 and P2X3 are knocked out, no taste is elicited. However they found that if either P2X2 OR P2X3 was knocked out there was a taste response. So the inference made from this is that if one of the two receptors from the P2X family was knocked out there still can have taste response. The WT mice showed significant stimulation by tastants whereas DKO had little to no stimulation of ATP release.<ref><pubmed>21940456</pubmed></ref>

===FGF signalling and genes===

Sprouty, or ''Srpy'', genes have been related to regulating the development of circumvillate papillae (CVP). The CVP are large dome shaped papillae, which form a 'V' just in front of the terminal sulcus.

By knocking out ''Spry'' genes using mice which had ''Spry1'' and ''Spry2'' knocked out showed that the number of CVP doubled. However, when Fibroblast [[#Glossary |'''Growth Factor''']] gene ("Fgf10") was absent, the number of CVP was significantly reduced, if not completely absent. The correlation between ''Spry1/2'' and ''Fgf10'' is that ''Spry1/2'' antagonises "Fgf10" to limit the size of the CVP progenitor placode. Exclusive expression of ''Fgf10'' in the [[#Glossary |'''mesenchyme''']] is necessary for the formation of CVP.

'''This image shows the CVP stained with H&E and scanned by Scanning Electron Microscope (SEM)'''
[[File:CVP of WT(top) and DKO(bottom) mice with H&E and SEM.png]]

'''This image shows the location of the CVP and the increased number in DKO mice by SEM'''
[[File:Mouse circumvallate papilla 01.jpg|300px]]

Taste buds develop from the mesenchyme but require local signalling to properly differentiate. Some signalling factors for proper development of taste buds besides FGF are: [[#Glossary |'''Sonic Hedgehog''']] (SHH), Bone Morphogenetic Proteins (BMPs), Epidermal Growth Factor (EGF).

Additionally, this proves that the anterior and posterior developments of the tongue are derived from embryonic tissues, where the anterior tongue is derived from the [[#Glossary |'''ectoderm''']] and the posterior tongue is derived from the [[#Glossary |'''endoderm''']]. Taste buds develop from the mesenchyme but require local signalling to properly differentiate. Some signalling factors for proper development of taste buds besides FGF are: Sonic Hedgehog (SHH), Bone Morphogenetic Proteins (BMPs), Epidermal Growth Factor (EGF).

As mentioned above, this article shows that the anterior and posterior developments of the tongue are derived from embryonic tissues, where the anterior tongue is derived front the ectoderm and the posterior tongue is derived from the endoderm. Secondly, FGF is required to regulate the growth of taste buds, while ''Spry'' genes limit the number of CVP. ''Fgf10''& ''Spry 1&2''work antagonistically through receptor tyrosine kinase (RTK)signalling.

However, the deletion of ''Spry2''led to the increase of CVPs it should be noted that they found that a significant decrease in number of fungiform papillae. Contrastingly, the absence of ''Fgf10'', while leading to the absence of CVPs lead to an increase in number and size of fungiform papillae. Therefore these genes have different effects on the anterior and posterior developing tongue and taste buds.<ref><pubmed>21655085</pubmed></ref>

==Gustatory System==

[[Image:Taste qualities.gif|thumb|The five basic tastes]]

Taste or more appropriately gustation, is a fundamental survival tool in animals as it directs the consumption of essential nutrients. The five tastes that exist within the human gustatory system: salty, sweet, sour, bitter and umami, all signify basic physiological requirements. Salty tastes denote the presence of Na+, an important ion involved in the transportation and retention of water across cell membranes. Sweetness is the recognition of carbohydrates, essential for maintaining optimal brain function and providing the basis for energy production in muscle tissue via ATP [[#Glossary |'''hydrolysis''']]. Similarly umami codes for the presence of L-amino acids, especially L-glutamate which is an integral component of protein synthesis.

These different modalities not only function to maintain the proper intake of nutrients within the body but also, by way of aversion, prohibit the consumption of undesired or poisonous materials. The bitter modality for example is generally regarded as displeasing to the human palate. It represents a high acid content which may be a result of foods which have become rotten or are inherently poisonous to the body.<ref name=PMID20696704><pubmed>20696704</pubmed></ref>

Research has historically limited itself to investigating the mechanisms of these five taste qualities though it must be noted many other modalities may exist. Of particular conjecture is the existence of fatty acid recognition. In the past the detection of fat in food has been attributed to somatosensory inputs <ref name=PMID20696704/> from the tongue, that is, the oily feel and texture of fat rather than its actual ‘taste’ allows the brain to encode for its presence. Further research is therefore required to elicit the precise mechanisms of fat detection.

===Cell Biology===

The five taste qualities are not all detected by the same type of receptor cell located within the taste bud. Like rods and cones in the eye which detect different wavelengths of light, there are specific types of receptors for different tastes. For example, sweet, umami and bitter are recognised by Type II G-protein coupled receptors, whereas sour is related to Type III presynaptic cells. The cell type involved in salty taste transduction is unknown however it is known that sodium ions can enter the receptor cell membrane via ion channel permeation.

====Type II receptors====

When a bitter, sweet or umami ligand binds to a type II G-coupled receptor, a cascade of chemical reactions causes the release of Ca2+ which in turn mediates [[#Glossary |'''exocystosis''']] of ATP. The function of this ATP is threefold:

# Stimulates gustatory nerve afferents which project to gustatory nuclei in the spinal cord
# Excites Type III presynaptic nerve fibres to release serotonin.
# Has a positive feedback effect on type II receptor cells, increasing the level of ATP production.

The role of serotonin is believed to be in the form of lateral inhibition i.e. when a bitter quality is recognised, adjacent receptors for sweetness are deactivated and thus the two tastes may be clearly differentiated. It also has a negative feedback effect on receptor cells, inhibiting umami, bitter and sweet taste transduction.

==Taste Map==
[[Image:Taste map.png|thumb|left|250px|Obsolete idea of the tongue map]]
The idea of a tongue map has disseminated through society for many years. This concept purports that different areas of the tongue are specialised to detect either sweet, salty, sour and bitter tastes. Recent research however has completely nullified such claims and suggests instead that different forms of taste are recognised all over the tongue as well as via the palate. Thus the term ''taste map'' has come to take on a new meaning and that is, the precise areas of taste modalities processing in areas of cortex and its subsequent neural inputs.

===Neural Pathways===

'''First order [[#Glossary |'''neuron''']]''' - From the receptors located in the taste buds, gustatory nerve afferents project to the ipsilateral rostral 1/3 of the nucleus tractus solitarius (NTS), located in the medulla. This rostral 1/3 is commonly referred to as the ''gustatory nucleus''.

The ''gustatory nucleus'' receives input from cranial nerves VII (''Facial n.''), IX (''Hypglossal n.''), and X (''Vagus n.'') via special visceral afferent (SVA) nerve fibres. A summary of their functions is as follows:

* ''Facial nerve n''. - carries taste information from the anterior 2/3 of the tongue.
* ''Hypoglossal n.'' - carries taste information from the posterior 1/3 of the tongue.
* ''Vagus n''. - carries taste information from the palate

'''Second order neurons''' - From the NTS second order neurons carry taste information to the Ventral posteromedial (VPM) nucleus in the thalamus.<ref name=PMID21885776/>

Copious scientific conjecture surrounds how each taste modality is transmitted to the brain. The ‘labelled-line’ hypothesis suggests that there are taste specific neurons which exclusively carry that taste modality to cortical areas. In analogous terms it can be viewed like the pipelines leading toward a house. Each pipeline carries its own utility, there is one for gas, another for water and finally for electricity with each terminating in slightly different areas of the house. In the same way, on the tongues there are different receptors for each taste which concurrently have individual nerve tracts leading to the primary gustatory cortex.

Contrapuntally there is electrophysiological evidence that single nerve afferents carry multiple modalities. These studies show one nerve afferent may have both a strong and a weak activation in response to a multiple taste stimuli.

===Cortical Areas===

[[Image:Primary gustatory cortex.png|thumb|Primary gustatory cortex]]

The location of the taste perception centres has been observed via functional magnetic resonance imaging (fMRI) studies. The primary taste cortex has been identified as being located in the anterior insula/frontal operculum (I/fO)<ref name=PMID22245354><pubmed>22245354</pubmed></ref>, with the secondary taste cortex in the caudolateral orbitofrontal cortex.<ref name=PMID21305668><pubmed>21305668</pubmed></ref> Within the insula there are further subdivisions related to each taste modality. Two photon calcium imaging research has outlined certain ’hot-spots’ of activation which are clearly delineated in relation to each taste. For example, the bitter modality is represented on the insula cortex approximately 1mm posterior to the middle cerebral artery whereas the sweet modality is represented 2.5mm rostrodorsal to the bitter field with no apparent overlap.<ref name=PMID21885776><pubmed>21885776</pubmed></ref> These findings lend weight to the idea that there is only one receptor for each taste quality.

It is interesting to note the relationship between taste and the reward centres of the brain. There is evidence of neural input to the ventral tegmental area (the origin of the mesolimbic dopaminergic reward pathway) and nucleus accumbens (involved in the conversion of motivation into physical action).<ref name=PMID21885776/> Neural connections such as this provide the foundations in explaining concepts such as flavour learning and preference. It may also give some insight into chronic problems such as food addiction and craving. As of yet however the gustatory neural network is not well understood and more research is required to elucidate the relationship between pleasure and taste sensation

==Current Research==
We have an evolving understanding of Embryonic Taste development, through the use of state-of-the-art technology and research techniques we are able to make brilliant discoveries that continue to connect the dots of this amazing natural process of human development.
The majority of research in taste development is involving mice, these mammals show similar embryonic pathways to humans and research is performed in ethical and humane methods.

[[File:Histology.jpg|Left|thumb|200px|Image shows histological stains of a mice tongue showing dysplasia]]

'''Synergistic relationships of Six Genes '''

In an animal study using mice by Suzuki Y, Ikeda K, Kawakami K.(2011) Firstly nominating "[[#Glossary |'''Six Genes''']]" as a major component in [[#Glossary |'''gustatory ''']] development, stating that deficiencies in certain Six genes (specifically Six1 & Six4) leads to poor development. Their research also highlights evidence of cooperative relationships between Six genes for normal advance. This experiment involved breeding mice containing exclusively Six1 and Six4 genes and examining the expression of these genes in papillae under high powered microscope observation. Understanding the role of certain genes along with the intrinsic relationships they hold is crucial for the ability to identify possible causes and correction of any abnormalities <ref><pubmed>21978088</pubmed></ref>

'''Neural Crest responsibilities '''

Another Animal Study involving mice explores a new idea of [[#Glossary |'''Neural crest''']] (NC) contribution in taste development, specifically the development of papillae and taste buds. Liu HX, Komatsu Y, Mishina Y, Mistretta CM. (2012) suggest that Neural crest cells travel to the location of the tongue in early embryonic stages, gain epithelium phenotypes, multiply and then differentiate to eventually form taste papillae. The experiment involved the comparison of 2 different types of Cre line mice, which both express Cre gene in neural crest protocol, the different distribution patterns where observed in specific regions that NC is responsible for.<ref><pubmed>22659543</pubmed></ref>

'''Augmentation of Endoderm'''

In an animal study conducted by Rothova M, Thompson H, Lickert H, Tucker AS.(2012) exploring the historically debated issue of endoderm contribution to tongue development showed promising evidence that position of taste buds are patterned by the border of ectoderm and endoderm derivative epithelium. This study was accomplished via microscopic examination of previously stained specimens. Concluding endoderm has direct influence on gustatory develoment <ref><pubmed>22581563</pubmed></ref>

'''Changes in Taste Cells over time'''

Research by
Ozdener H, Spielman AI, Rawson NE.(2012) developing a culture which allows taste cells to survive for up to 12 months, empowers researchers to study the processes of proliferation, differentiation and function. This experiment will provide a precidnet for future study of taste cells, as these cells are able to operate and grow normally. <ref><pubmed>22643728</pubmed></ref>

'''Shh key component of taste bud proginators'''

A [[#Glossary |'''tamoxifen''']] treatment which supresses Sonic hedgehog (Shh) secretion in mice proving to reduce the number of cells visable within papillae, in contrast mice not treated with tamoxifen showed a mark increase of cells within papillae, these cells are assumed to become taste cells in later development.
Specific mice were bred to trace the destination of taste placode cells, the study concluded that Shh expressing placodes are taste bud proginators which in turn become taste cells within taste buds although do not have any prescuros relationship with pappilae. The results were obtain by examination of mice embryos using Bright-field or multichannel fluorescent images through the use of an "Axiocam CCD camera and Axioplan fluorescence microscope with Axiovision software" a study by Harlow, Yang, Williams, Barlow (2011)<ref><pubmed>PMC2674259</pubmed></ref>

'''WNT family exhibit various roles''' [[File:Abnormal of tongue.jpg|thumb|200px|Image shows an example of tongue abnormalities, this is called "double tongue" each side has independent movement!]]

The WNT gene family has a function of signally proteins for various reason such as development, In 2010 Liu, Staubach Grosse, Walton, Saims, Gumucio, Mistretta explored recent findings on the role of WNT's in tongue and papillae development, Concluding that WNT/β-catenin is essential for fungiform papillae differing to WNT5a which proved to be principle in tongue development. Intrinsic chemical mediators were considered by manipulating a tissue culture and then throughaly examined by scanning photomicrograph. <ref><pubmed>PMC2768563</pubmed></ref>

[http://www.surgicalneurologyint.com/article.asp?issn=2152-7806;year=2012;volume=3;issue=1;spage=23;epage=23;aulast=Manjila]

==Glossary==

* Ectoderm- outer germ layer of embryo

* Endoderm - inner germ layer of embryo

* Epithelium - basic animal tissue that is composed of tightly packed cells, usually covering the outer portion of organs

* Exocystosis - movement of contents out of cell

* Ganglia - the accumulation of a nerve cell body

* Growth factor - a substance that stimulates the growth of cells

* Gustatory - anything that relates to the taste sense

* Hydrolysis - breakdown of a chemical when it reacts with water

* Mesoderm - middle germ layer of embryo

* Mesenchyme - multipotential cells

* Neural crest - a part of the ectoderm found on both sides of the neural tube

* Neuron - most simplistic unit of the nervous system

* Neurotransmitter - chemicals which allow the passing of signals from neuron to neuron via connecting part (synapse)

* Papillae - small rough surface projection

* Six genes - a family of genes

* Sonic hedgehog (Shh) - signalling protein invloved in normal development

* Sulcus terminalis - describes a physical transition point separating the anterior 2/3 of the tongue from the posterior 1/3

* Tamoxifen - hormonal altering drug

== References ==
<references/>

==External Links==
{{External Links}}

http://www.webmd.com/oral-health/picture-of-the-tongue

http://www.tutorvista.com/content/biology/biology-iv/nervous-coordination/tongue-structure.php#parts-of-tongue

http://www.cf.ac.uk/biosi/staffinfo/jacob/teaching/sensory/taste.html

--[[User:Z8600021|Mark Hill]] 12:22, 15 August 2012 (EST) Please leave the content listed below the line at the bottom of your project page.

----

{{2012Projects}}

2012 Group Project 3

2012-09-30T11:59:44Z

Z3289738:

=Taste Development=

== Introduction ==
**NEED TO ADD**

==Adult Tongue and Taste Buds – Structure and Function==

'''Structure'''

The tongue is located on the floor of the oral cavity, It is a muscular structure with sensory units crowning. The tongue is divided into an anterior two thirds and a posterior one third. These regions are divided by a V-shaped groove at the back of the tongue (sulcus terminalis). The anterior two thirds of the tongue is covered by stratified squamous epithelium, It contains a roughened surface and has projections called papillae that vary in shape and number.

''''The image below is a simplistic diagram of the surface of the tongue showing the locations of the different papillae and other important features'''

{|
| [[Image:Drawing of Tongue.png|500px]]

'''Papillae'''
[[File:Papillae.jpg|Left|thumb|200px|Close up of Human Tongue Papillae]]

There are 4 types of papillae on the tongue.
The most numerous papillae are the filiform papillae, which function to provide a surface that aids in holding food on the tongue during chewing but do not contain taste buds. The larger, less numerous fungiform papillae which contain taste buds, as do foliate papillae. Circumvallate papillae form a wide V at the sulcus terminalis also containing taste bus. There are no papillae or taste buds located on the posterior third of the tongue, having mucosal folds and the lingual tonsils instead.

'''Function'''

The tongue is for tasting, swallowing, and speech.
The functional unit of the taste bud is a taste cell, there are between 50 and 100 taste cells in each taste bud these taste cells represent all 5 different tastes. Historically is was believed that different areas of the tongue were responsible for different taste sensations although this has since been disregarded.[http://users.rcn.com/jkimball.ma.ultranet/BiologyPages/W/Welcome.html] The papillae contain taste buds which are connected to the oral cavity via a taste pore, the function of the taste bud is to transmit a chemical signal from the oral cavity to a taste cell, this chemical signal is the converted into an electrical impulse and delivered to the brain via nerve fibres for interpretation.

'''The image below is a simplistic hand-drawn cross section of a taste bud unit (not to scale)'''

[[File:Taste_bud_1.jpg|x400px|alt=Cross section of a taste bud unit|Cross section of a taste bud unit]]

==History of Discoveries==

{| cellpadding=5 style="border:1px solid #BBB"
|- bgcolor="#faecc8"
|''' Date'''|| '''Significant Discovery'''

|- bgcolor="#faf6ed"
|'''350BC'''
|| Aristotle writes about the basic tastes, sweet and bitter. He also notes that it can be modified by salty and acidic. <ref name="PMID22717400"><pubmed>22717400</pubmed></ref>

|- bgcolor="#faecc8"
|'''1901'''
|| D. Hanig publishes a paper describing taste sensitivity in different regions of the tongue.
''Interesting fact:'' The modern concept of a 'tongue map' is a misinterpretation of this study. <ref name="PMID22717400"/>

|- bgcolor="#faf6ed"
|style=white-space:nowrap|'''1908'''
|Kikunae Ikeda, a professor of the Tokyo Imperial University, discovered and identified the fifth basic taste: umami (savouriness), made palatable by glutamate. <ref><pubmed>12438213</pubmed></ref>
[http://chemse.oxfordjournals.org/content/27/9/847.long New Seasonings]

|- bgcolor="#faecc8"
|style=white-space:nowrap|'''1931-32'''
| A chemist named Arthur Fox and his college noted that they had different sensitivities to the bitter tasting Phenylthiocarbamide (PTC).<ref>Blakeslee AF, Fox AL. Our different taste worlds. J Hered. 1932;23:97–107.</ref> Geneticists later confirm these findings, and discover that non-tasting is a recessive genetic trait. <ref><pubmed>17782493</pubmed></ref>
[http://www.ncbi.nlm.nih.gov/pubmed/17782493 Inherited taste deficiency]

|- bgcolor="#faf6ed"
|style=white-space:nowrap|'''1965'''
|Farbman's study of the developing taste but in rat fungiform papilla was significant in increasing our understanding of taste bud development. <ref><pubmed>14300090</pubmed></ref>
[http://www.sciencedirect.com/science/article/pii/0012160665900400 Electron microscope study of the developing taste bud in rat fungiform papilla.]

|- bgcolor="#faecc8"
|style=white-space:nowrap|'''1992'''
|McLaughlin SK et al. discovery a taste cell-specific G-protein within the taste buds called Gustucon. This protein is later used to mark bitter, umami and sweet cells. <ref><pubmed>1608467 </pubmed></ref>
[http://www.nature.com/nature/journal/v357/n6379/abs/357563a0.html Gustducin is a taste-cell-specific G protein closely related to the transducins]

|- bgcolor="#faf6ed"
|style=white-space:nowrap|'''1995'''
|Barlow et al. experimented with Axolotl salamanders and concluded that taste buds from this species arise exclusively from epithelial tissue, "oropharyngeal [[#Glossary |'''epithelium''']]". <ref name="PMID17826760"><pubmed>17826760</pubmed></ref>
[http://www.ncbi.nlm.nih.gov/pubmed/17826760 Embryonic origin of gustatory cranial sensory neurons]

|- bgcolor="#faecc8"
|style=white-space:nowrap|'''1996'''
| Witt M and Reutter K of the Technical University Dresden in Germany, carried out a transmission electron microscopy study to investigate the embryonic and fetal development of Human taste buds. Their results suggest an "at least dual function of embryonic/fetal taste buds", including non-gustatory, paracrine functions prior to the 14th week and gustatory after the 14th week. <ref name="PMID8955790"><pubmed>8955790</pubmed></ref>
[http://www.ncbi.nlm.nih.gov/pubmed/8955790 Embryonic and early fetal development of human taste buds: a transmission electron microscopical study]

|- bgcolor="#faf6ed"
|style=white-space:nowrap|'''2000'''
|Chandrashekar, J. et al. discover the first taste sonsors, the T2R bitter taste receptors. <ref><pubmed>10761935</pubmed></ref>
[http://www.sciencedirect.com/science/article/pii/S0092867400807060 T2Rs Function as Bitter Taste Receptors]

|- bgcolor="#faecc8"
|style=white-space:nowrap|'''2001'''
|Nelson, G. et al. discover the sweet receptor: a combination of T1R2 and T1R3. <ref><pubmed>11509186</pubmed></ref>
[http://www.ncbi.nlm.nih.gov/pubmed/11509186?dopt=Abstract&holding=npg Mammalian sweet taste receptors.]

|- bgcolor="#faf6ed"
|style=white-space:nowrap|'''2002'''
|Nelson G. et al. discover the amino acid (umami) taste receptor: a combination of T1R1 and T1R3 identified. <ref><pubmed>11894099</pubmed></ref>
[http://www.ncbi.nlm.nih.gov/pubmed/11894099?dopt=Abstract&holding=npg An amino-acid taste receptor]

|- bgcolor="#faecc8"
|style=white-space:nowrap|'''2005'''
|Dyer, J. et al. discover sweet taste receptors in the GI tract. <ref><pubmed>17855558</pubmed></ref>
[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1986582/ Sweet taste signaling in the gut]

|- bgcolor="#faf6ed"
|style=white-space:nowrap|'''2006'''
|Huang, A. L et al. discover cells for sour taste, identified by PKD2L1 (a polycystic kidney disease-like ion channel). <ref><pubmed>16929298</pubmed></ref>
[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1571047/ The Cells and Logic for Mammalian Sour Taste detection]

|- bgcolor="#faecc8"
|style=white-space:nowrap|'''2007'''
|Harlow DE, Barlow LA of the University of Colorado Denver Health Sciences Center provide evidence of the "embryonic origin of gustatory cranial sensory neurons". <ref name="PMID17826760"/>
[http://www.ncbi.nlm.nih.gov/pubmed/17826760 Embryonic origin of gustatory cranial sensory neurons.]

|- bgcolor="#faf6ed"
|style=white-space:nowrap|'''2009'''
|A study by Hevezi P et al, presents "the first comprehensive characterization of gene expression in primate taste buds", as opposed to previous studies which focused on rodents. <ref><pubmed>19636377</pubmed></ref>
[http://www.ncbi.nlm.nih.gov/pubmed/19636377 Genome-wide analysis of gene expression in primate taste buds reveals links to diverse processes]

|- bgcolor="#faecc8"
|style=white-space:nowrap|'''2010'''
|Chandrashekar, J. et al. identify epithelial sodium channel (ENaC) as the sodium-salt taste receptor. <ref><pubmed>20107438</pubmed></ref>
[http://www.ncbi.nlm.nih.gov/pubmed/20107438?dopt=Abstract&holding=npg The cells and peripheral representation of sodium taste in mice]
|}

== Human Weekly Development - Two Prominent Studies ==
Martin Witt and Klaus Reutter of the University of Tubingen in Germany published two prominent studies regarding developing taste buds in humans. Their first study in 1996 was a transmission electron microscopical (TEM) study of the taste bud primordium and its morphological changes during the 8th-15th postovulatory week. Their next study in 1997 built on their previous findings by using Scanning Electron Microscopy (SEM) to observe the development of gustatory [[#Glossary |'''papillae''']] during postovulatory weeks 6-15.

The findings of these two studies are summarized in the table below. The figures provided relate to the images on their respective research papers.

# [http://onlinelibrary.wiley.com/doi/10.1002/(SICI)1097-0185(199612)246:4%3C507::AID-AR10%3E3.0.CO;2-S/pdf Embryonic and early fetal development of human taste buds: a transmission electron microscopical study, 1996]
# [http://chemse.oxfordjournals.org/content/22/6/601.long Scanning electron microscopical studies of developing gustatory papillae in humans, 1997]

===Timeline of Developmental Processes of Human Taste Buds===
{| cellpadding=5 style="border:1px solid #BBB"
|- bgcolor="#89CFF0"
|'''Postovulatory Week'''||'''Description'''||'''Image'''

|- bgcolor="#BCD4E6"
|'''Week 6''' ||
The surface of the developing tongue is covered by nearly flat epithelium (1997, Figure 1). The first gustatory papillae of the tongue appear in the caudal midline near the foramen caecum and the first circumvallate papilla develops on the dorsal midline. <ref name="PMID9455607"><pubmed>9455607</pubmed></ref>
||
image

|- bgcolor="#89CFF0"
| '''Weeks 6 to 7'''||
Nerve fibres approach the basal lamina of lingual epithelium. At this stage the lingual epithelium consists of two to three cell layers and there is not yet any sign of cell specializations indicating early taste bud formation. <ref name=PMID8955790/>
||
Image

|- bgcolor="#BCD4E6"
| '''Week 7 '''||
A series of irregular epithelial swellings in the anterior part and marginal parts of the tongue indicate early forming fungiform papillae. Furthermore, a V-like lane is observed anterior to the [[#Glossary |'''sulcus terminalis''']], which represents a smooth surface for developing circumvallate papillae (1997, Figure 2). Witt M et al observe that these circumvallate papillae are larger than the developing fungiform papillae of the same age, later noting that the fungiform papillae tend to increase in size over the 8-15th weeks of gestation, whilst the size of vallate papillae tend to remain constant during this period. <ref name=PMID9455607/>
||
Image

|- bgcolor="#89CFF0"
| ''' Week 8 ''' ||
* The taste bud primordium are still differentiated, elongated epithelial cells, resting on a slightly developed core of young dermal papilla.
* The lingual epithelium shows first signs of taste bud development as nerve fibres coming from the dermal papilla penetrate the epithelial basal lamina and form synapses with taste bud progenitor cells (1996, Figure 1). These synapses demonstrate the neuronal connection between the taste bud primordium and the central nervous system, reaching a maximum around the 12th to 13th week. However, it is important to note that at this time these cells are still poorly differentiated, elongated epithelial cells.
* Ciliated cells also appear around the 8th week, however the significance of these cells which are scattered randomly across the lingual surface remains unclear. <ref name=PMID8955790/>
||
Image

|- bgcolor="#BCD4E6"
|''' Week 9''' ||
By this stage, although a taste pore is not present, the surface of circumvallate papillae usually contains a taste pit partly filled with microvillus-like processes from the underlying taste bud cells (1997, Figure 10). <ref name=PMID9455607/>
||
Image

|- bgcolor="#89CFF0"
|''' Weeks 10-11''' ||
At this stage, the lingual epithelium compromises of about four cell layers, and the first shallow grooves above the taste bud primordium are developed. Fungiform papillae appear on the lateral margins and the tip of the tongue, containing taste bud primordial that display the first signs of a primitive pore formation (1996, Figure 6). <ref name=PMID8955790/>
||
Image

|- bgcolor="#BCD4E6"
|''' Week 12 ''' ||
Taste bud cells are more clearly differentiated into epithelial cell types II and III. <ref name=PMID8955790/>
||
Image

|- bgcolor="#89CFF0"
|''' Weeks 12-13 ''' ||
At this stage the taste bud primordial are all located on the top of dermal papillae. There is also maximum synapses between cells and afferent nerve fibres, which intermingle with each other to form a plexus-like structure (1996, Figure 6a). <ref name=PMID8955790/>
||
Image

|- bgcolor="#BCD4E6"
|''' Weeks 14 -15 ''' ||
The shape and size of the taste buds primordial begins to resemble those of adult taste buds (1996, Figure 9). By the 14th week the taste pores develop as the taste pits are filled by microvilli, and bubble like vesicles indicate the secretory activity of these cells (1996, Figure 10). However, the tastebuds only achieve a fully developed function in week 15 of gestation with the development of type I cells to produce the mucous material in the taste pit. <ref name=PMID8955790/>
||
Image
|}

==Abnormalities==

===Knocking out P2X Receptors===

[[File:Image of taste being evoked by visualising ATP release.jpeg|Left|thumb|200px|Evoking taste - ATP release in tongue]]

Gustatory abnormalities has not been widely researched and what has been researched has been through animal testing, most commonly we have found on mice.

In Huang, 2008 this team used the release of the [[#Glossary |'''ectoderm''']], ATP (adenosine triphosphate) as a quantitative measurement of gustatory sensation and taste. This was done by using a comparison of wild type (WT) and double knockout (DKO) mice. P2X receptors, P2X2 and P2X3 were knocked out in the DKO mice. The premise of this article was that knocking out P2X receptors reduces transmitter secretion of ATP in taste buds, therefore they cannot taste.

It should be noted that the taste buds in DKO are functional, but are not stimulated by the administration of tastants.

The transmission of release of ATP is secretion through gap junction hemichannels (pannexin 1 gap junction).

When both P2X2 and P2X3 are knocked out, no taste is elicited. However they found that if either P2X2 OR P2X3 was knocked out there was a taste response. So the inference made from this is that if one of the two receptors from the P2X family was knocked out there still can have taste response. The WT mice showed significant stimulation by tastants whereas DKO had little to no stimulation of ATP release.<ref><pubmed>21940456</pubmed></ref>

===FGF signalling and genes===

Sprouty, or ''Srpy'', genes have been related to regulating the development of circumvillate papillae (CVP). The CVP are large dome shaped papillae, which form a 'V' just in front of the terminal sulcus.

By knocking out ''Spry'' genes using mice which had ''Spry1'' and ''Spry2'' knocked out showed that the number of CVP doubled. However, when Fibroblast [[#Glossary |'''Growth Factor''']] gene ("Fgf10") was absent, the number of CVP was significantly reduced, if not completely absent. The correlation between ''Spry1/2'' and ''Fgf10'' is that ''Spry1/2'' antagonises "Fgf10" to limit the size of the CVP progenitor placode. Exclusive expression of ''Fgf10'' in the [[#Glossary |'''mesenchyme''']] is necessary for the formation of CVP.

'''This image shows the CVP stained with H&E and scanned by Scanning Electron Microscope (SEM)'''
[[File:CVP of WT(top) and DKO(bottom) mice with H&E and SEM.png]]

'''This image shows the location of the CVP and the increased number in DKO mice by SEM'''
[[File:Mouse circumvallate papilla 01.jpg|300px]]

Taste buds develop from the mesenchyme but require local signalling to properly differentiate. Some signalling factors for proper development of taste buds besides FGF are: [[#Glossary |'''Sonic Hedgehog''']] (SHH), Bone Morphogenetic Proteins (BMPs), Epidermal Growth Factor (EGF).

Additionally, this proves that the anterior and posterior developments of the tongue are derived from embryonic tissues, where the anterior tongue is derived from the [[#Glossary |'''ectoderm''']] and the posterior tongue is derived from the [[#Glossary |'''endoderm''']]. Taste buds develop from the mesenchyme but require local signalling to properly differentiate. Some signalling factors for proper development of taste buds besides FGF are: Sonic Hedgehog (SHH), Bone Morphogenetic Proteins (BMPs), Epidermal Growth Factor (EGF).

As mentioned above, this article shows that the anterior and posterior developments of the tongue are derived from embryonic tissues, where the anterior tongue is derived front the ectoderm and the posterior tongue is derived from the endoderm. Secondly, FGF is required to regulate the growth of taste buds, while ''Spry'' genes limit the number of CVP. ''Fgf10''& ''Spry 1&2''work antagonistically through receptor tyrosine kinase (RTK)signalling.

However, the deletion of ''Spry2''led to the increase of CVPs it should be noted that they found that a significant decrease in number of fungiform papillae. Contrastingly, the absence of ''Fgf10'', while leading to the absence of CVPs lead to an increase in number and size of fungiform papillae. Therefore these genes have different effects on the anterior and posterior developing tongue and taste buds.<ref><pubmed>21655085</pubmed></ref>

==Gustatory System==

[[Image:Taste qualities.gif|thumb|The five basic tastes]]

Taste or more appropriately gustation, is a fundamental survival tool in animals as it directs the consumption of essential nutrients. The five tastes that exist within the human gustatory system: salty, sweet, sour, bitter and umami, all signify basic physiological requirements. Salty tastes denote the presence of Na+, an important ion involved in the transportation and retention of water across cell membranes. Sweetness is the recognition of carbohydrates, essential for maintaining optimal brain function and providing the basis for energy production in muscle tissue via ATP [[#Glossary |'''hydrolysis''']]. Similarly umami codes for the presence of L-amino acids, especially L-glutamate which is an integral component of protein synthesis.

These different modalities not only function to maintain the proper intake of nutrients within the body but also, by way of aversion, prohibit the consumption of undesired or poisonous materials. The bitter modality for example is generally regarded as displeasing to the human palate. It represents a high acid content which may be a result of foods which have become rotten or are inherently poisonous to the body.<ref name=PMID20696704><pubmed>20696704</pubmed></ref>

Research has historically limited itself to investigating the mechanisms of these five taste qualities though it must be noted many other modalities may exist. Of particular conjecture is the existence of fatty acid recognition. In the past the detection of fat in food has been attributed to somatosensory inputs <ref name=PMID20696704/> from the tongue, that is, the oily feel and texture of fat rather than its actual ‘taste’ allows the brain to encode for its presence. Further research is therefore required to elicit the precise mechanisms of fat detection.

===Cell Biology===

The five taste qualities are not all detected by the same type of receptor cell located within the taste bud. Like rods and cones in the eye which detect different wavelengths of light, there are specific types of receptors for different tastes. For example, sweet, umami and bitter are recognised by Type II G-protein coupled receptors, whereas sour is related to Type III presynaptic cells. The cell type involved in salty taste transduction is unknown however it is known that sodium ions can enter the receptor cell membrane via ion channel permeation.

====Type II receptors====

When a bitter, sweet or umami ligand binds to a type II G-coupled receptor, a cascade of chemical reactions causes the release of Ca2+ which in turn mediates [[#Glossary |'''exocystosis''']] of ATP. The function of this ATP is threefold:

# Stimulates gustatory nerve afferents which project to gustatory nuclei in the spinal cord
# Excites Type III presynaptic nerve fibres to release serotonin.
# Has a positive feedback effect on type II receptor cells, increasing the level of ATP production.

The role of serotonin is believed to be in the form of lateral inhibition i.e. when a bitter quality is recognised, adjacent receptors for sweetness are deactivated and thus the two tastes may be clearly differentiated. It also has a negative feedback effect on receptor cells, inhibiting umami, bitter and sweet taste transduction.

==Taste Map==
[[Image:Taste map.png|thumb|left|250px|Obsolete idea of the tongue map]]
The idea of a tongue map has disseminated through society for many years. This concept purports that different areas of the tongue are specialised to detect either sweet, salty, sour and bitter tastes. Recent research however has completely nullified such claims and suggests instead that different forms of taste are recognised all over the tongue as well as via the palate. Thus the term ''taste map'' has come to take on a new meaning and that is, the precise areas of taste modalities processing in areas of cortex and its subsequent neural inputs.

===Neural Pathways===

'''First order [[#Glossary |'''neuron''']]''' - From the receptors located in the taste buds, gustatory nerve afferents project to the ipsilateral rostral 1/3 of the nucleus tractus solitarius (NTS), located in the medulla. This rostral 1/3 is commonly referred to as the ''gustatory nucleus''.

The ''gustatory nucleus'' receives input from cranial nerves VII (''Facial n.''), IX (''Hypglossal n.''), and X (''Vagus n.'') via special visceral afferent (SVA) nerve fibres. A summary of their functions is as follows:

* ''Facial nerve n''. - carries taste information from the anterior 2/3 of the tongue.
* ''Hypoglossal n.'' - carries taste information from the posterior 1/3 of the tongue.
* ''Vagus n''. - carries taste information from the palate

'''Second order neurons''' - From the NTS second order neurons carry taste information to the Ventral posteromedial (VPM) nucleus in the thalamus.<ref name=PMID21885776/>

Copious scientific conjecture surrounds how each taste modality is transmitted to the brain. The ‘labelled-line’ hypothesis suggests that there are taste specific neurons which exclusively carry that taste modality to cortical areas. In analogous terms it can be viewed like the pipelines leading toward a house. Each pipeline carries its own utility, there is one for gas, another for water and finally for electricity with each terminating in slightly different areas of the house. In the same way, on the tongues there are different receptors for each taste which concurrently have individual nerve tracts leading to the primary gustatory cortex.

Contrapuntally there is electrophysiological evidence that single nerve afferents carry multiple modalities. These studies show one nerve afferent may have both a strong and a weak activation in response to a multiple taste stimuli.

===Cortical Areas===

[[Image:Primary gustatory cortex.png|thumb|Primary gustatory cortex]]

The location of the taste perception centres has been observed via functional magnetic resonance imaging (fMRI) studies. The primary taste cortex has been identified as being located in the anterior insula/frontal operculum (I/fO)<ref name=PMID22245354><pubmed>22245354</pubmed></ref>, with the secondary taste cortex in the caudolateral orbitofrontal cortex.<ref name=PMID21305668><pubmed>21305668</pubmed></ref> Within the insula there are further subdivisions related to each taste modality. Two photon calcium imaging research has outlined certain ’hot-spots’ of activation which are clearly delineated in relation to each taste. For example, the bitter modality is represented on the insula cortex approximately 1mm posterior to the middle cerebral artery whereas the sweet modality is represented 2.5mm rostrodorsal to the bitter field with no apparent overlap.<ref name=PMID21885776><pubmed>21885776</pubmed></ref> These findings lend weight to the idea that there is only one receptor for each taste quality.

It is interesting to note the relationship between taste and the reward centres of the brain. There is evidence of neural input to the ventral tegmental area (the origin of the mesolimbic dopaminergic reward pathway) and nucleus accumbens (involved in the conversion of motivation into physical action).<ref name=PMID21885776/> Neural connections such as this provide the foundations in explaining concepts such as flavour learning and preference. It may also give some insight into chronic problems such as food addiction and craving. As of yet however the gustatory neural network is not well understood and more research is required to elucidate the relationship between pleasure and taste sensation

==Current Research==
We have an evolving understanding of Embryonic Taste development, through the use of state-of-the-art technology and research techniques we are able to make brilliant discoveries that continue to connect the dots of this amazing natural process of human development.
The majority of research in taste development is involving mice, these mammals show similar embryonic pathways to humans and research is performed in ethical and humane methods.

[[File:Histology.jpg|Left|thumb|200px|Image shows histological stains of a mice tongue showing dysplasia]]

'''Synergistic relationships of Six Genes '''

In an animal study using mice by Suzuki Y, Ikeda K, Kawakami K.(2011) Firstly nominating "[[#Glossary |'''Six Genes''']]" as a major component in [[#Glossary |'''gustatory ''']] development, stating that deficiencies in certain Six genes (specifically Six1 & Six4) leads to poor development. Their research also highlights evidence of cooperative relationships between Six genes for normal advance. This experiment involved breeding mice containing exclusively Six1 and Six4 genes and examining the expression of these genes in papillae under high powered microscope observation. Understanding the role of certain genes along with the intrinsic relationships they hold is crucial for the ability to identify possible causes and correction of any abnormalities <ref><pubmed>21978088</pubmed></ref>

'''Neural Crest responsibilities '''

Another Animal Study involving mice explores a new idea of [[#Glossary |'''Neural crest''']] (NC) contribution in taste development, specifically the development of papillae and taste buds. Liu HX, Komatsu Y, Mishina Y, Mistretta CM. (2012) suggest that Neural crest cells travel to the location of the tongue in early embryonic stages, gain epithelium phenotypes, multiply and then differentiate to eventually form taste papillae. The experiment involved the comparison of 2 different types of Cre line mice, which both express Cre gene in neural crest protocol, the different distribution patterns where observed in specific regions that NC is responsible for.<ref><pubmed>22659543</pubmed></ref>

'''Augmentation of Endoderm'''

In an animal study conducted by Rothova M, Thompson H, Lickert H, Tucker AS.(2012) exploring the historically debated issue of endoderm contribution to tongue development showed promising evidence that position of taste buds are patterned by the border of ectoderm and endoderm derivative epithelium. This study was accomplished via microscopic examination of previously stained specimens. Concluding endoderm has direct influence on gustatory develoment <ref><pubmed>22581563</pubmed></ref>

'''Changes in Taste Cells over time'''

Research by
Ozdener H, Spielman AI, Rawson NE.(2012) developing a culture which allows taste cells to survive for up to 12 months, empowers researchers to study the processes of proliferation, differentiation and function. This experiment will provide a precidnet for future study of taste cells, as these cells are able to operate and grow normally. <ref><pubmed>22643728</pubmed></ref>

'''Shh key component of taste bud proginators'''

A [[#Glossary |'''tamoxifen''']] treatment which supresses Sonic hedgehog (Shh) secretion in mice proving to reduce the number of cells visable within papillae, in contrast mice not treated with tamoxifen showed a mark increase of cells within papillae, these cells are assumed to become taste cells in later development.
Specific mice were bred to trace the destination of taste placode cells, the study concluded that Shh expressing placodes are taste bud proginators which in turn become taste cells within taste buds although do not have any prescuros relationship with pappilae. The results were obtain by examination of mice embryos using Bright-field or multichannel fluorescent images through the use of an "Axiocam CCD camera and Axioplan fluorescence microscope with Axiovision software" a study by Harlow, Yang, Williams, Barlow (2011)<ref><pubmed>PMC2674259</pubmed></ref>

'''WNT family exhibit various roles''' [[File:Abnormal of tongue.jpg|thumb|200px|Image shows an example of tongue abnormalities, this is called "double tongue" each side has independent movement!]]

The WNT gene family has a function of signally proteins for various reason such as development, In 2010 Liu, Staubach Grosse, Walton, Saims, Gumucio, Mistretta explored recent findings on the role of WNT's in tongue and papillae development, Concluding that WNT/β-catenin is essential for fungiform papillae differing to WNT5a which proved to be principle in tongue development. Intrinsic chemical mediators were considered by manipulating a tissue culture and then throughaly examined by scanning photomicrograph. <ref><pubmed>PMC2768563</pubmed></ref>

[http://www.surgicalneurologyint.com/article.asp?issn=2152-7806;year=2012;volume=3;issue=1;spage=23;epage=23;aulast=Manjila]

==Glossary==

* Ectoderm- outer germ layer of embryo

* Endoderm - inner germ layer of embryo

* Epithelium - basic animal tissue that is composed of tightly packed cells, usually covering the outer portion of organs

* Exocystosis - movement of contents out of cell

* Ganglia - the accumulation of a nerve cell body

* Growth factor - a substance that stimulates the growth of cells

* Gustatory - anything that relates to the taste sense

* Hydrolysis - breakdown of a chemical when it reacts with water

* Mesoderm - middle germ layer of embryo

* Mesenchyme - multipotential cells

* Neural crest - a part of the ectoderm found on both sides of the neural tube

* Neuron - most simplistic unit of the nervous system

* Neurotransmitter - chemicals which allow the passing of signals from neuron to neuron via connecting part (synapse)

* Papillae - small rough surface projection

* Six genes - a family of genes

* Sonic hedgehog (Shh) - signalling protein invloved in normal development

* Sulcus terminalis - describes a physical transition point separating the anterior 2/3 of the tongue from the posterior 1/3

* Tamoxifen - hormonal altering drug

== References ==
<references/>

==External Links==
{{External Links}}

http://www.webmd.com/oral-health/picture-of-the-tongue

http://www.tutorvista.com/content/biology/biology-iv/nervous-coordination/tongue-structure.php#parts-of-tongue

http://www.cf.ac.uk/biosi/staffinfo/jacob/teaching/sensory/taste.html

--[[User:Z8600021|Mark Hill]] 12:22, 15 August 2012 (EST) Please leave the content listed below the line at the bottom of your project page.

----

{{2012Projects}}

2012 Group Project 3

2012-09-30T11:57:38Z

Z3289738:

=Taste Development=

== Introduction ==
**NEED TO ADD**

==Adult Tongue and Taste Buds – Structure and Function==

'''Structure'''

The tongue is located on the floor of the oral cavity, It is a muscular structure with sensory units crowning. The tongue is divided into an anterior two thirds and a posterior one third. These regions are divided by a V-shaped groove at the back of the tongue (sulcus terminalis). The anterior two thirds of the tongue is covered by stratified squamous epithelium, It contains a roughened surface and has projections called papillae that vary in shape and number.

''''The image below is a simplistic diagram of the surface of the tongue showing the locations of the different papillae and other important features'''

{|
| [[Image:Drawing of Tongue.png|500px]]

'''Papillae'''
[[File:Papillae.jpg|Left|thumb|200px|Close up of Human Tongue Papillae]]

There are 4 types of papillae on the tongue.
The most numerous papillae are the filiform papillae, which function to provide a surface that aids in holding food on the tongue during chewing but do not contain taste buds. The larger, less numerous fungiform papillae which contain taste buds, as do foliate papillae. Circumvallate papillae form a wide V at the sulcus terminalis also containing taste bus. There are no papillae or taste buds located on the posterior third of the tongue, having mucosal folds and the lingual tonsils instead.

'''Function'''

The tongue is for tasting, swallowing, and speech.
The functional unit of the taste bud is a taste cell, there are between 50 and 100 taste cells in each taste bud these taste cells represent all 5 different tastes. Historically is was believed that different areas of the tongue were responsible for different taste sensations although this has since been disregarded.[http://users.rcn.com/jkimball.ma.ultranet/BiologyPages/W/Welcome.html] The papillae contain taste buds which are connected to the oral cavity via a taste pore, the function of the taste bud is to transmit a chemical signal from the oral cavity to a taste cell, this chemical signal is the converted into an electrical impulse and delivered to the brain via nerve fibres for interpretation.

'''The image below is a simplistic hand-drawn cross section of a taste bud unit (not to scale)'''

[[File:Taste_bud_1.jpg|x400px|alt=Cross section of a taste bud unit|Cross section of a taste bud unit]]

==History of Discoveries==

{| cellpadding=5 style="border:1px solid #BBB"
|- bgcolor="#faecc8"
|''' Date'''|| '''Significant Discovery'''

|- bgcolor="#faf6ed"
|'''350BC'''
|| Aristotle writes about the basic tastes, sweet and bitter. He also notes that it can be modified by salty and acidic. <ref name="PMID22717400"><pubmed>22717400</pubmed></ref>

|- bgcolor="#faecc8"
|'''1901'''
|| D. Hanig publishes a paper describing taste sensitivity in different regions of the tongue.
''Interesting fact:'' The modern concept of a 'tongue map' is a misinterpretation of this study. <ref name="PMID22717400"/>

|- bgcolor="#faf6ed"
|style=white-space:nowrap|'''1908'''
|Kikunae Ikeda, a professor of the Tokyo Imperial University, discovered and identified the fifth basic taste: umami (savouriness), made palatable by glutamate. <ref><pubmed>12438213</pubmed></ref>
[http://chemse.oxfordjournals.org/content/27/9/847.long New Seasonings]

|- bgcolor="#faecc8"
|style=white-space:nowrap|'''1931-32'''
| A chemist named Arthur Fox and his college noted that they had different sensitivities to the bitter tasting Phenylthiocarbamide (PTC).<ref>Blakeslee AF, Fox AL. Our different taste worlds. J Hered. 1932;23:97–107.</ref> Geneticists later confirm these findings, and discover that non-tasting is a recessive genetic trait. <ref><pubmed>17782493</pubmed></ref>
[http://www.ncbi.nlm.nih.gov/pubmed/17782493 Inherited taste deficiency]

|- bgcolor="#faf6ed"
|style=white-space:nowrap|'''1965'''
|Farbman's study of the developing taste but in rat fungiform papilla was significant in increasing our understanding of taste bud development. <ref><pubmed>14300090</pubmed></ref>
[http://www.sciencedirect.com/science/article/pii/0012160665900400 Electron microscope study of the developing taste bud in rat fungiform papilla.]

|- bgcolor="#faecc8"
|style=white-space:nowrap|'''1992'''
|McLaughlin SK et al. discovery a taste cell-specific G-protein within the taste buds called Gustucon. This protein is later used to mark bitter, umami and sweet cells. <ref><pubmed>1608467 </pubmed></ref>
[http://www.nature.com/nature/journal/v357/n6379/abs/357563a0.html Gustducin is a taste-cell-specific G protein closely related to the transducins]

|- bgcolor="#faf6ed"
|style=white-space:nowrap|'''1995'''
|Barlow et al. experimented with Axolotl salamanders and concluded that taste buds from this species arise exclusively from epithelial tissue, "oropharyngeal [[#Glossary |'''epithelium''']]". <ref name="PMID17826760"><pubmed>17826760</pubmed></ref>
[http://www.ncbi.nlm.nih.gov/pubmed/17826760 Embryonic origin of gustatory cranial sensory neurons]

|- bgcolor="#faecc8"
|style=white-space:nowrap|'''1996'''
| Witt M and Reutter K of the Technical University Dresden in Germany, carried out a transmission electron microscopy study to investigate the embryonic and fetal development of Human taste buds. Their results suggest an "at least dual function of embryonic/fetal taste buds", including non-gustatory, paracrine functions prior to the 14th week and gustatory after the 14th week. <ref name="PMID8955790"><pubmed>8955790</pubmed></ref>
[http://www.ncbi.nlm.nih.gov/pubmed/8955790 Embryonic and early fetal development of human taste buds: a transmission electron microscopical study]

|- bgcolor="#faf6ed"
|style=white-space:nowrap|'''2000'''
|Chandrashekar, J. et al. discover the first taste sonsors, the T2R bitter taste receptors. <ref><pubmed>10761935</pubmed></ref>
[http://www.sciencedirect.com/science/article/pii/S0092867400807060 T2Rs Function as Bitter Taste Receptors]

|- bgcolor="#faecc8"
|style=white-space:nowrap|'''2001'''
|Nelson, G. et al. discover the sweet receptor: a combination of T1R2 and T1R3. <ref><pubmed>11509186</pubmed></ref>
[http://www.ncbi.nlm.nih.gov/pubmed/11509186?dopt=Abstract&holding=npg Mammalian sweet taste receptors.]

|- bgcolor="#faf6ed"
|style=white-space:nowrap|'''2002'''
|Nelson G. et al. discover the amino acid (umami) taste receptor: a combination of T1R1 and T1R3 identified. <ref><pubmed>11894099</pubmed></ref>
[http://www.ncbi.nlm.nih.gov/pubmed/11894099?dopt=Abstract&holding=npg An amino-acid taste receptor]

|- bgcolor="#faecc8"
|style=white-space:nowrap|'''2005'''
|Dyer, J. et al. discover sweet taste receptors in the GI tract. <ref><pubmed>17855558</pubmed></ref>
[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1986582/ Sweet taste signaling in the gut]

|- bgcolor="#faf6ed"
|style=white-space:nowrap|'''2006'''
|Huang, A. L et al. discover cells for sour taste, identified by PKD2L1 (a polycystic kidney disease-like ion channel). <ref><pubmed>16929298</pubmed></ref>
[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1571047/ The Cells and Logic for Mammalian Sour Taste detection]

|- bgcolor="#faecc8"
|style=white-space:nowrap|'''2007'''
|Harlow DE, Barlow LA of the University of Colorado Denver Health Sciences Center provide evidence of the "embryonic origin of gustatory cranial sensory neurons". <ref name="PMID17826760"/>
[http://www.ncbi.nlm.nih.gov/pubmed/17826760 Embryonic origin of gustatory cranial sensory neurons.]

|- bgcolor="#faf6ed"
|style=white-space:nowrap|'''2009'''
|A study by Hevezi P et al, presents "the first comprehensive characterization of gene expression in primate taste buds", as opposed to previous studies which focused on rodents. <ref><pubmed>19636377</pubmed></ref>
[http://www.ncbi.nlm.nih.gov/pubmed/19636377 Genome-wide analysis of gene expression in primate taste buds reveals links to diverse processes]

|- bgcolor="#faecc8"
|style=white-space:nowrap|'''2010'''
|Chandrashekar, J. et al. identify epithelial sodium channel (ENaC) as the sodium-salt taste receptor. <ref><pubmed>20107438</pubmed></ref>
[http://www.ncbi.nlm.nih.gov/pubmed/20107438?dopt=Abstract&holding=npg The cells and peripheral representation of sodium taste in mice]
|}

== Human Weekly Development - Two Prominent Studies ==
Martin Witt and Klaus Reutter of the University of Tubingen in Germany published two prominent studies regarding developing taste buds in humans. Their first study in 1996 was a transmission electron microscopical (TEM) study of the taste bud primordium and its morphological changes during the 8th-15th postovulatory week. Their next study in 1997 built on their previous findings by using Scanning Electron Microscopy (SEM) to observe the development of gustatory [[#Glossary |'''papillae''']] during postovulatory weeks 6-15.

The findings of these two studies are summarized in the table below. The figures provided relate to the images on their respective research papers.

# [http://onlinelibrary.wiley.com/doi/10.1002/(SICI)1097-0185(199612)246:4%3C507::AID-AR10%3E3.0.CO;2-S/pdf Embryonic and early fetal development of human taste buds: a transmission electron microscopical study, 1996]
# [http://chemse.oxfordjournals.org/content/22/6/601.long Scanning electron microscopical studies of developing gustatory papillae in humans, 1997]

===Timeline of Developmental Processes of Human Taste Buds===
{| cellpadding=5 style="border:1px solid #BBB"
|- bgcolor="#89CFF0"
|'''Postovulatory Week'''||'''Description'''||'''Image'''

|- bgcolor="#BCD4E6"
|'''Week 6''' ||
The surface of the developing tongue is covered by nearly flat epithelium (1997, Figure 1). The first gustatory papillae of the tongue appear in the caudal midline near the foramen caecum and the first circumvallate papilla develops on the dorsal midline. <ref name="PMID9455607"><pubmed>9455607</pubmed></ref>
||
image

|- bgcolor="#89CFF0"
| '''Weeks 6 to 7'''||
Nerve fibres approach the basal lamina of lingual epithelium. At this stage the lingual epithelium consists of two to three cell layers and there is not yet any sign of cell specializations indicating early taste bud formation. <ref name=PMID8955790/>
||
Image

|- bgcolor="#BCD4E6"
| '''Week 7 '''||
A series of irregular epithelial swellings in the anterior part and marginal parts of the tongue indicate early forming fungiform papillae. Furthermore, a V-like lane is observed anterior to the [[#Glossary |'''sulcus terminalis''']], which represents a smooth surface for developing circumvallate papillae (1997, Figure 2). Witt M et al observe that these circumvallate papillae are larger than the developing fungiform papillae of the same age, later noting that the fungiform papillae tend to increase in size over the 8-15th weeks of gestation, whilst the size of vallate papillae tend to remain constant during this period. <ref name=PMID9455607/>
||
Image

|- bgcolor="#89CFF0"
| ''' Week 8 ''' ||
* The taste bud primordium are still differentiated, elongated epithelial cells, resting on a slightly developed core of young dermal papilla.
* The lingual epithelium shows first signs of taste bud development as nerve fibres coming from the dermal papilla penetrate the epithelial basal lamina and form synapses with taste bud progenitor cells (1996, Figure 1). These synapses demonstrate the neuronal connection between the taste bud primordium and the central nervous system, reaching a maximum around the 12th to 13th week. However, it is important to note that at this time these cells are still poorly differentiated, elongated epithelial cells.
* Ciliated cells also appear around the 8th week, however the significance of these cells which are scattered randomly across the lingual surface remains unclear. <ref name=PMID8955790/>
||
Image

|- bgcolor="#BCD4E6"
|''' Week 9''' ||
By this stage, although a taste pore is not present, the surface of circumvallate papillae usually contains a taste pit partly filled with microvillus-like processes from the underlying taste bud cells (1997, Figure 10). <ref name=PMID9455607/>
||
Image

|- bgcolor="#89CFF0"
|''' Weeks 10-11''' ||
At this stage, the lingual epithelium compromises of about four cell layers, and the first shallow grooves above the taste bud primordium are developed. Fungiform papillae appear on the lateral margins and the tip of the tongue, containing taste bud primordial that display the first signs of a primitive pore formation (1996, Figure 6). <ref name=PMID8955790/>
||
Image

|- bgcolor="#BCD4E6"
|''' Week 12 ''' ||
Taste bud cells are more clearly differentiated into epithelial cell types II and III. <ref name=PMID8955790/>
||
Image

|- bgcolor="#89CFF0"
|''' Weeks 12-13 ''' ||
At this stage the taste bud primordial are all located on the top of dermal papillae. There is also maximum synapses between cells and afferent nerve fibres, which intermingle with each other to form a plexus-like structure (1996, Figure 6a). <ref name=PMID8955790/>
||
Image

|- bgcolor="#BCD4E6"
|''' Weeks 14 -15 ''' ||
The shape and size of the taste buds primordial begins to resemble those of adult taste buds (1996, Figure 9). By the 14th week the taste pores develop as the taste pits are filled by microvilli, and bubble like vesicles indicate the secretory activity of these cells (1996, Figure 10). However, the tastebuds only achieve a fully developed function in week 15 of gestation with the development of type I cells to produce the mucous material in the taste pit. <ref name=PMID8955790/>
||
Image
|}

==Gustatory System==

[[Image:Taste qualities.gif|thumb|The five basic tastes]]

Taste or more appropriately gustation, is a fundamental survival tool in animals as it directs the consumption of essential nutrients. The five tastes that exist within the human gustatory system: salty, sweet, sour, bitter and umami, all signify basic physiological requirements. Salty tastes denote the presence of Na+, an important ion involved in the transportation and retention of water across cell membranes. Sweetness is the recognition of carbohydrates, essential for maintaining optimal brain function and providing the basis for energy production in muscle tissue via ATP [[#Glossary |'''hydrolysis''']]. Similarly umami codes for the presence of L-amino acids, especially L-glutamate which is an integral component of protein synthesis.

These different modalities not only function to maintain the proper intake of nutrients within the body but also, by way of aversion, prohibit the consumption of undesired or poisonous materials. The bitter modality for example is generally regarded as displeasing to the human palate. It represents a high acid content which may be a result of foods which have become rotten or are inherently poisonous to the body.<ref name=PMID20696704><pubmed>20696704</pubmed></ref>

Research has historically limited itself to investigating the mechanisms of these five taste qualities though it must be noted many other modalities may exist. Of particular conjecture is the existence of fatty acid recognition. In the past the detection of fat in food has been attributed to somatosensory inputs <ref name=PMID20696704/> from the tongue, that is, the oily feel and texture of fat rather than its actual ‘taste’ allows the brain to encode for its presence. Further research is therefore required to elicit the precise mechanisms of fat detection.

===Cell Biology===

The five taste qualities are not all detected by the same type of receptor cell located within the taste bud. Like rods and cones in the eye which detect different wavelengths of light, there are specific types of receptors for different tastes. For example, sweet, umami and bitter are recognised by Type II G-protein coupled receptors, whereas sour is related to Type III presynaptic cells. The cell type involved in salty taste transduction is unknown however it is known that sodium ions can enter the receptor cell membrane via ion channel permeation.

====Type II receptors====

When a bitter, sweet or umami ligand binds to a type II G-coupled receptor, a cascade of chemical reactions causes the release of Ca2+ which in turn mediates [[#Glossary |'''exocystosis''']] of ATP. The function of this ATP is threefold:

# Stimulates gustatory nerve afferents which project to gustatory nuclei in the spinal cord
# Excites Type III presynaptic nerve fibres to release serotonin.
# Has a positive feedback effect on type II receptor cells, increasing the level of ATP production.

The role of serotonin is believed to be in the form of lateral inhibition i.e. when a bitter quality is recognised, adjacent receptors for sweetness are deactivated and thus the two tastes may be clearly differentiated. It also has a negative feedback effect on receptor cells, inhibiting umami, bitter and sweet taste transduction.

==Taste Map==
[[Image:Taste map.png|thumb|left|250px|Obsolete idea of the tongue map]]
The idea of a tongue map has disseminated through society for many years. This concept purports that different areas of the tongue are specialised to detect either sweet, salty, sour and bitter tastes. Recent research however has completely nullified such claims and suggests instead that different forms of taste are recognised all over the tongue as well as via the palate. Thus the term ''taste map'' has come to take on a new meaning and that is, the precise areas of taste modalities processing in areas of cortex and its subsequent neural inputs.

===Neural Pathways===

'''First order [[#Glossary |'''neuron''']]''' - From the receptors located in the taste buds, gustatory nerve afferents project to the ipsilateral rostral 1/3 of the nucleus tractus solitarius (NTS), located in the medulla. This rostral 1/3 is commonly referred to as the ''gustatory nucleus''.

The ''gustatory nucleus'' receives input from cranial nerves VII (''Facial n.''), IX (''Hypglossal n.''), and X (''Vagus n.'') via special visceral afferent (SVA) nerve fibres. A summary of their functions is as follows:

* ''Facial nerve n''. - carries taste information from the anterior 2/3 of the tongue.
* ''Hypoglossal n.'' - carries taste information from the posterior 1/3 of the tongue.
* ''Vagus n''. - carries taste information from the palate

'''Second order neurons''' - From the NTS second order neurons carry taste information to the Ventral posteromedial (VPM) nucleus in the thalamus.<ref name=PMID21885776/>

Copious scientific conjecture surrounds how each taste modality is transmitted to the brain. The ‘labelled-line’ hypothesis suggests that there are taste specific neurons which exclusively carry that taste modality to cortical areas. In analogous terms it can be viewed like the pipelines leading toward a house. Each pipeline carries its own utility, there is one for gas, another for water and finally for electricity with each terminating in slightly different areas of the house. In the same way, on the tongues there are different receptors for each taste which concurrently have individual nerve tracts leading to the primary gustatory cortex.

Contrapuntally there is electrophysiological evidence that single nerve afferents carry multiple modalities. These studies show one nerve afferent may have both a strong and a weak activation in response to a multiple taste stimuli.

===Cortical Areas===

[[Image:Primary gustatory cortex.png|thumb|Primary gustatory cortex]]

The location of the taste perception centres has been observed via functional magnetic resonance imaging (fMRI) studies. The primary taste cortex has been identified as being located in the anterior insula/frontal operculum (I/fO)<ref name=PMID22245354><pubmed>22245354</pubmed></ref>, with the secondary taste cortex in the caudolateral orbitofrontal cortex.<ref name=PMID21305668><pubmed>21305668</pubmed></ref> Within the insula there are further subdivisions related to each taste modality. Two photon calcium imaging research has outlined certain ’hot-spots’ of activation which are clearly delineated in relation to each taste. For example, the bitter modality is represented on the insula cortex approximately 1mm posterior to the middle cerebral artery whereas the sweet modality is represented 2.5mm rostrodorsal to the bitter field with no apparent overlap.<ref name=PMID21885776><pubmed>21885776</pubmed></ref> These findings lend weight to the idea that there is only one receptor for each taste quality.

It is interesting to note the relationship between taste and the reward centres of the brain. There is evidence of neural input to the ventral tegmental area (the origin of the mesolimbic dopaminergic reward pathway) and nucleus accumbens (involved in the conversion of motivation into physical action).<ref name=PMID21885776/> Neural connections such as this provide the foundations in explaining concepts such as flavour learning and preference. It may also give some insight into chronic problems such as food addiction and craving. As of yet however the gustatory neural network is not well understood and more research is required to elucidate the relationship between pleasure and taste sensation

==Abnormalities==

===Knocking out P2X Receptors===

[[File:Image of taste being evoked by visualising ATP release.jpeg|Left|thumb|200px|Evoking taste - ATP release in tongue]]

Gustatory abnormalities has not been widely researched and what has been researched has been through animal testing, most commonly we have found on mice.

In Huang, 2008 this team used the release of the [[#Glossary |'''ectoderm''']], ATP (adenosine triphosphate) as a quantitative measurement of gustatory sensation and taste. This was done by using a comparison of wild type (WT) and double knockout (DKO) mice. P2X receptors, P2X2 and P2X3 were knocked out in the DKO mice. The premise of this article was that knocking out P2X receptors reduces transmitter secretion of ATP in taste buds, therefore they cannot taste.

It should be noted that the taste buds in DKO are functional, but are not stimulated by the administration of tastants.

The transmission of release of ATP is secretion through gap junction hemichannels (pannexin 1 gap junction).

When both P2X2 and P2X3 are knocked out, no taste is elicited. However they found that if either P2X2 OR P2X3 was knocked out there was a taste response. So the inference made from this is that if one of the two receptors from the P2X family was knocked out there still can have taste response. The WT mice showed significant stimulation by tastants whereas DKO had little to no stimulation of ATP release.<ref><pubmed>21940456</pubmed></ref>

===FGF signalling and genes===

Sprouty, or ''Srpy'', genes have been related to regulating the development of circumvillate papillae (CVP). The CVP are large dome shaped papillae, which form a 'V' just in front of the terminal sulcus.

By knocking out ''Spry'' genes using mice which had ''Spry1'' and ''Spry2'' knocked out showed that the number of CVP doubled. However, when Fibroblast [[#Glossary |'''Growth Factor''']] gene ("Fgf10") was absent, the number of CVP was significantly reduced, if not completely absent. The correlation between ''Spry1/2'' and ''Fgf10'' is that ''Spry1/2'' antagonises "Fgf10" to limit the size of the CVP progenitor placode. Exclusive expression of ''Fgf10'' in the [[#Glossary |'''mesenchyme''']] is necessary for the formation of CVP.

'''This image shows the CVP stained with H&E and scanned by Scanning Electron Microscope (SEM)'''
[[File:CVP of WT(top) and DKO(bottom) mice with H&E and SEM.png]]

'''This image shows the location of the CVP and the increased number in DKO mice by SEM'''
[[File:Mouse circumvallate papilla 01.jpg|300px]]

Taste buds develop from the mesenchyme but require local signalling to properly differentiate. Some signalling factors for proper development of taste buds besides FGF are: [[#Glossary |'''Sonic Hedgehog''']] (SHH), Bone Morphogenetic Proteins (BMPs), Epidermal Growth Factor (EGF).

Additionally, this proves that the anterior and posterior developments of the tongue are derived from embryonic tissues, where the anterior tongue is derived from the [[#Glossary |'''ectoderm''']] and the posterior tongue is derived from the [[#Glossary |'''endoderm''']]. Taste buds develop from the mesenchyme but require local signalling to properly differentiate. Some signalling factors for proper development of taste buds besides FGF are: Sonic Hedgehog (SHH), Bone Morphogenetic Proteins (BMPs), Epidermal Growth Factor (EGF).

As mentioned above, this article shows that the anterior and posterior developments of the tongue are derived from embryonic tissues, where the anterior tongue is derived front the ectoderm and the posterior tongue is derived from the endoderm. Secondly, FGF is required to regulate the growth of taste buds, while ''Spry'' genes limit the number of CVP. ''Fgf10''& ''Spry 1&2''work antagonistically through receptor tyrosine kinase (RTK)signalling.

However, the deletion of ''Spry2''led to the increase of CVPs it should be noted that they found that a significant decrease in number of fungiform papillae. Contrastingly, the absence of ''Fgf10'', while leading to the absence of CVPs lead to an increase in number and size of fungiform papillae. Therefore these genes have different effects on the anterior and posterior developing tongue and taste buds.<ref><pubmed>21655085</pubmed></ref>

==Current Research==
We have an evolving understanding of Embryonic Taste development, through the use of state-of-the-art technology and research techniques we are able to make brilliant discoveries that continue to connect the dots of this amazing natural process of human development.
The majority of research in taste development is involving mice, these mammals show similar embryonic pathways to humans and research is performed in ethical and humane methods.

[[File:Histology.jpg|Left|thumb|200px|Image shows histological stains of a mice tongue showing dysplasia]]

'''Synergistic relationships of Six Genes '''

In an animal study using mice by Suzuki Y, Ikeda K, Kawakami K.(2011) Firstly nominating "[[#Glossary |'''Six Genes''']]" as a major component in [[#Glossary |'''gustatory ''']] development, stating that deficiencies in certain Six genes (specifically Six1 & Six4) leads to poor development. Their research also highlights evidence of cooperative relationships between Six genes for normal advance. This experiment involved breeding mice containing exclusively Six1 and Six4 genes and examining the expression of these genes in papillae under high powered microscope observation. Understanding the role of certain genes along with the intrinsic relationships they hold is crucial for the ability to identify possible causes and correction of any abnormalities <ref><pubmed>21978088</pubmed></ref>

'''Neural Crest responsibilities '''

Another Animal Study involving mice explores a new idea of [[#Glossary |'''Neural crest''']] (NC) contribution in taste development, specifically the development of papillae and taste buds. Liu HX, Komatsu Y, Mishina Y, Mistretta CM. (2012) suggest that Neural crest cells travel to the location of the tongue in early embryonic stages, gain epithelium phenotypes, multiply and then differentiate to eventually form taste papillae. The experiment involved the comparison of 2 different types of Cre line mice, which both express Cre gene in neural crest protocol, the different distribution patterns where observed in specific regions that NC is responsible for.<ref><pubmed>22659543</pubmed></ref>

'''Augmentation of Endoderm'''

In an animal study conducted by Rothova M, Thompson H, Lickert H, Tucker AS.(2012) exploring the historically debated issue of endoderm contribution to tongue development showed promising evidence that position of taste buds are patterned by the border of ectoderm and endoderm derivative epithelium. This study was accomplished via microscopic examination of previously stained specimens. Concluding endoderm has direct influence on gustatory develoment <ref><pubmed>22581563</pubmed></ref>

'''Changes in Taste Cells over time'''

Research by
Ozdener H, Spielman AI, Rawson NE.(2012) developing a culture which allows taste cells to survive for up to 12 months, empowers researchers to study the processes of proliferation, differentiation and function. This experiment will provide a precidnet for future study of taste cells, as these cells are able to operate and grow normally. <ref><pubmed>22643728</pubmed></ref>

'''Shh key component of taste bud proginators'''

A [[#Glossary |'''tamoxifen''']] treatment which supresses Sonic hedgehog (Shh) secretion in mice proving to reduce the number of cells visable within papillae, in contrast mice not treated with tamoxifen showed a mark increase of cells within papillae, these cells are assumed to become taste cells in later development.
Specific mice were bred to trace the destination of taste placode cells, the study concluded that Shh expressing placodes are taste bud proginators which in turn become taste cells within taste buds although do not have any prescuros relationship with pappilae. The results were obtain by examination of mice embryos using Bright-field or multichannel fluorescent images through the use of an "Axiocam CCD camera and Axioplan fluorescence microscope with Axiovision software" a study by Harlow, Yang, Williams, Barlow (2011)<ref><pubmed>PMC2674259</pubmed></ref>

'''WNT family exhibit various roles''' [[File:Abnormal of tongue.jpg|thumb|200px|Image shows an example of tongue abnormalities, this is called "double tongue" each side has independent movement!]]

The WNT gene family has a function of signally proteins for various reason such as development, In 2010 Liu, Staubach Grosse, Walton, Saims, Gumucio, Mistretta explored recent findings on the role of WNT's in tongue and papillae development, Concluding that WNT/β-catenin is essential for fungiform papillae differing to WNT5a which proved to be principle in tongue development. Intrinsic chemical mediators were considered by manipulating a tissue culture and then throughaly examined by scanning photomicrograph. <ref><pubmed>PMC2768563</pubmed></ref>

[http://www.surgicalneurologyint.com/article.asp?issn=2152-7806;year=2012;volume=3;issue=1;spage=23;epage=23;aulast=Manjila]

==Glossary==

* Ectoderm- outer germ layer of embryo

* Endoderm - inner germ layer of embryo

* Epithelium - basic animal tissue that is composed of tightly packed cells, usually covering the outer portion of organs

* Exocystosis - movement of contents out of cell

* Ganglia - the accumulation of a nerve cell body

* Growth factor - a substance that stimulates the growth of cells

* Gustatory - anything that relates to the taste sense

* Hydrolysis - breakdown of a chemical when it reacts with water

* Mesoderm - middle germ layer of embryo

* Mesenchyme - multipotential cells

* Neural crest - a part of the ectoderm found on both sides of the neural tube

* Neuron - most simplistic unit of the nervous system

* Neurotransmitter - chemicals which allow the passing of signals from neuron to neuron via connecting part (synapse)

* Papillae - small rough surface projection

* Six genes - a family of genes

* Sonic hedgehog (Shh) - signalling protein invloved in normal development

* Sulcus terminalis - describes a physical transition point separating the anterior 2/3 of the tongue from the posterior 1/3

* Tamoxifen - hormonal altering drug

== References ==
<references/>

==External Links==
{{External Links}}

http://www.webmd.com/oral-health/picture-of-the-tongue

http://www.tutorvista.com/content/biology/biology-iv/nervous-coordination/tongue-structure.php#parts-of-tongue

http://www.cf.ac.uk/biosi/staffinfo/jacob/teaching/sensory/taste.html

--[[User:Z8600021|Mark Hill]] 12:22, 15 August 2012 (EST) Please leave the content listed below the line at the bottom of your project page.

----

{{2012Projects}}

2012 Group Project 3

2012-09-30T11:55:53Z

Z3289738:

=Taste Development=

== Introduction ==
**NEED TO ADD**

==Adult Tongue and Taste Buds – Structure and Function==

'''Structure'''

The tongue is located on the floor of the oral cavity, It is a muscular structure with sensory units crowning. The tongue is divided into an anterior two thirds and a posterior one third. These regions are divided by a V-shaped groove at the back of the tongue (sulcus terminalis). The anterior two thirds of the tongue is covered by stratified squamous epithelium, It contains a roughened surface and has projections called papillae that vary in shape and number.

''''The image below is a simplistic diagram of the surface of the tongue showing the locations of the different papillae and other important features'''

{|
| [[Image:Drawing of Tongue.png|500px]]

'''Papillae'''
[[File:Papillae.jpg|Left|thumb|200px|Close up of Human Tongue Papillae]]

There are 4 types of papillae on the tongue.
The most numerous papillae are the filiform papillae, which function to provide a surface that aids in holding food on the tongue during chewing but do not contain taste buds. The larger, less numerous fungiform papillae which contain taste buds, as do foliate papillae. Circumvallate papillae form a wide V at the sulcus terminalis also containing taste bus. There are no papillae or taste buds located on the posterior third of the tongue, having mucosal folds and the lingual tonsils instead.

'''Function'''

The tongue is for tasting, swallowing, and speech.
The functional unit of the taste bud is a taste cell, there are between 50 and 100 taste cells in each taste bud these taste cells represent all 5 different tastes. Historically is was believed that different areas of the tongue were responsible for different taste sensations although this has since been disregarded.[http://users.rcn.com/jkimball.ma.ultranet/BiologyPages/W/Welcome.html] The papillae contain taste buds which are connected to the oral cavity via a taste pore, the function of the taste bud is to transmit a chemical signal from the oral cavity to a taste cell, this chemical signal is the converted into an electrical impulse and delivered to the brain via nerve fibres for interpretation.

'''The image below is a simplistic hand-drawn cross section of a taste bud unit (not to scale)'''

[[File:Taste_bud_1.jpg|x400px|alt=Cross section of a taste bud unit|Cross section of a taste bud unit]]

==History of Discoveries==

{| cellpadding=5 style="border:1px solid #BBB"
|- bgcolor="#faecc8"
|''' Date'''|| '''Significant Discovery'''

|- bgcolor="#faf6ed"
|'''350BC'''
|| Aristotle writes about the basic tastes, sweet and bitter. He also notes that it can be modified by salty and acidic. <ref name="PMID22717400"><pubmed>22717400</pubmed></ref>

|- bgcolor="#faecc8"
|'''1901'''
|| D. Hanig publishes a paper describing taste sensitivity in different regions of the tongue.
''Interesting fact:'' The modern concept of a 'tongue map' is a misinterpretation of this study. <ref name="PMID22717400"/>

|- bgcolor="#faf6ed"
|style=white-space:nowrap|'''1908'''
|Kikunae Ikeda, a professor of the Tokyo Imperial University, discovered and identified the fifth basic taste: umami (savouriness), made palatable by glutamate. <ref><pubmed>12438213</pubmed></ref>
[http://chemse.oxfordjournals.org/content/27/9/847.long New Seasonings]

|- bgcolor="#faecc8"
|style=white-space:nowrap|'''1931-32'''
| A chemist named Arthur Fox and his college noted that they had different sensitivities to the bitter tasting Phenylthiocarbamide (PTC).<ref>Blakeslee AF, Fox AL. Our different taste worlds. J Hered. 1932;23:97–107.</ref> Geneticists later confirm these findings, and discover that non-tasting is a recessive genetic trait. <ref><pubmed>17782493</pubmed></ref>
[http://www.ncbi.nlm.nih.gov/pubmed/17782493 Inherited taste deficiency]

|- bgcolor="#faf6ed"
|style=white-space:nowrap|'''1965'''
|Farbman's study of the developing taste but in rat fungiform papilla was significant in increasing our understanding of taste bud development. <ref><pubmed>14300090</pubmed></ref>
[http://www.sciencedirect.com/science/article/pii/0012160665900400 Electron microscope study of the developing taste bud in rat fungiform papilla.]

|- bgcolor="#faecc8"
|style=white-space:nowrap|'''1992'''
|McLaughlin SK et al. discovery a taste cell-specific G-protein within the taste buds called Gustucon. This protein is later used to mark bitter, umami and sweet cells. <ref><pubmed>1608467 </pubmed></ref>
[http://www.nature.com/nature/journal/v357/n6379/abs/357563a0.html Gustducin is a taste-cell-specific G protein closely related to the transducins]

|- bgcolor="#faf6ed"
|style=white-space:nowrap|'''1995'''
|Barlow et al. experimented with Axolotl salamanders and concluded that taste buds from this species arise exclusively from epithelial tissue, "oropharyngeal [[#Glossary |'''epithelium''']]". <ref name="PMID17826760"><pubmed>17826760</pubmed></ref>
[http://www.ncbi.nlm.nih.gov/pubmed/17826760 Embryonic origin of gustatory cranial sensory neurons]

|- bgcolor="#faecc8"
|style=white-space:nowrap|'''1996'''
| Witt M and Reutter K of the Technical University Dresden in Germany, carried out a transmission electron microscopy study to investigate the embryonic and fetal development of Human taste buds. Their results suggest an "at least dual function of embryonic/fetal taste buds", including non-gustatory, paracrine functions prior to the 14th week and gustatory after the 14th week. <ref name="PMID8955790"><pubmed>8955790</pubmed></ref>
[http://www.ncbi.nlm.nih.gov/pubmed/8955790 Embryonic and early fetal development of human taste buds: a transmission electron microscopical study]

|- bgcolor="#faf6ed"
|style=white-space:nowrap|'''2000'''
|Chandrashekar, J. et al. discover the first taste sonsors, the T2R bitter taste receptors. <ref><pubmed>10761935</pubmed></ref>
[http://www.sciencedirect.com/science/article/pii/S0092867400807060 T2Rs Function as Bitter Taste Receptors]

|- bgcolor="#faecc8"
|style=white-space:nowrap|'''2001'''
|Nelson, G. et al. discover the sweet receptor: a combination of T1R2 and T1R3. <ref><pubmed>11509186</pubmed></ref>
[http://www.ncbi.nlm.nih.gov/pubmed/11509186?dopt=Abstract&holding=npg Mammalian sweet taste receptors.]

|- bgcolor="#faf6ed"
|style=white-space:nowrap|'''2002'''
|Nelson G. et al. discover the amino acid (umami) taste receptor: a combination of T1R1 and T1R3 identified. <ref><pubmed>11894099</pubmed></ref>
[http://www.ncbi.nlm.nih.gov/pubmed/11894099?dopt=Abstract&holding=npg An amino-acid taste receptor]

|- bgcolor="#faecc8"
|style=white-space:nowrap|'''2005'''
|Dyer, J. et al. discover sweet taste receptors in the GI tract. <ref><pubmed>17855558</pubmed></ref>
[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1986582/ Sweet taste signaling in the gut]

|- bgcolor="#faf6ed"
|style=white-space:nowrap|'''2006'''
|Huang, A. L et al. discover cells for sour taste, identified by PKD2L1 (a polycystic kidney disease-like ion channel). <ref><pubmed>16929298</pubmed></ref>
[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1571047/ The Cells and Logic for Mammalian Sour Taste detection]

|- bgcolor="#faecc8"
|style=white-space:nowrap|'''2007'''
|Harlow DE, Barlow LA of the University of Colorado Denver Health Sciences Center provide evidence of the "embryonic origin of gustatory cranial sensory neurons". <ref name="PMID17826760"/>
[http://www.ncbi.nlm.nih.gov/pubmed/17826760 Embryonic origin of gustatory cranial sensory neurons.]

|- bgcolor="#faf6ed"
|style=white-space:nowrap|'''2009'''
|A study by Hevezi P et al, presents "the first comprehensive characterization of gene expression in primate taste buds", as opposed to previous studies which focused on rodents. <ref><pubmed>19636377</pubmed></ref>
[http://www.ncbi.nlm.nih.gov/pubmed/19636377 Genome-wide analysis of gene expression in primate taste buds reveals links to diverse processes]

|- bgcolor="#faecc8"
|style=white-space:nowrap|'''2010'''
|Chandrashekar, J. et al. identify epithelial sodium channel (ENaC) as the sodium-salt taste receptor. <ref><pubmed>20107438</pubmed></ref>
[http://www.ncbi.nlm.nih.gov/pubmed/20107438?dopt=Abstract&holding=npg The cells and peripheral representation of sodium taste in mice]
|}

== Human Weekly Development - Two Prominent Studies ==
Martin Witt and Klaus Reutter of the University of Tubingen in Germany published two prominent studies regarding developing taste buds in humans. Their first study in 1996 was a transmission electron microscopical (TEM) study of the taste bud primordium and its morphological changes during the 8th-15th postovulatory week. Their next study in 1997 built on their previous findings by using Scanning Electron Microscopy (SEM) to observe the development of gustatory [[#Glossary |'''papillae''']]during postovulatory weeks 6-15.

The findings of these two studies are summarized in the table below. The figures provided relate to the images on their respective research papers.

# [http://onlinelibrary.wiley.com/doi/10.1002/(SICI)1097-0185(199612)246:4%3C507::AID-AR10%3E3.0.CO;2-S/pdf Embryonic and early fetal development of human taste buds: a transmission electron microscopical study, 1996]
# [http://chemse.oxfordjournals.org/content/22/6/601.long Scanning electron microscopical studies of developing gustatory papillae in humans, 1997]

===Timeline of Developmental Processes of Human Taste Buds===
{| cellpadding=5 style="border:1px solid #BBB"
|- bgcolor="#89CFF0"
|'''Postovulatory Week'''||'''Description'''||'''Image'''

|- bgcolor="#BCD4E6"
|'''Week 6''' ||
The surface of the developing tongue is covered by nearly flat epithelium (1997, Figure 1). The first gustatory papillae of the tongue appear in the caudal midline near the foramen caecum and the first circumvallate papilla develops on the dorsal midline. <ref name="PMID9455607"><pubmed>9455607</pubmed></ref>
||
image

|- bgcolor="#89CFF0"
| '''Weeks 6 to 7'''||
Nerve fibres approach the basal lamina of lingual epithelium. At this stage the lingual epithelium consists of two to three cell layers and there is not yet any sign of cell specializations indicating early taste bud formation. <ref name=PMID8955790/>
||
Image

|- bgcolor="#BCD4E6"
| '''Week 7 '''||
A series of irregular epithelial swellings in the anterior part and marginal parts of the tongue indicate early forming fungiform papillae. Furthermore, a V-like lane is observed anterior to the [[#Glossary |'''sulcus terminalis''']], which represents a smooth surface for developing circumvallate papillae (1997, Figure 2). Witt M et al observe that these circumvallate papillae are larger than the developing fungiform papillae of the same age, later noting that the fungiform papillae tend to increase in size over the 8-15th weeks of gestation, whilst the size of vallate papillae tend to remain constant during this period. <ref name=PMID9455607/>
||
Image

|- bgcolor="#89CFF0"
| ''' Week 8 ''' ||
* The taste bud primordium are still differentiated, elongated epithelial cells, resting on a slightly developed core of young dermal papilla.
* The lingual epithelium shows first signs of taste bud development as nerve fibres coming from the dermal papilla penetrate the epithelial basal lamina and form synapses with taste bud progenitor cells (1996, Figure 1). These synapses demonstrate the neuronal connection between the taste bud primordium and the central nervous system, reaching a maximum around the 12th to 13th week. However, it is important to note that at this time these cells are still poorly differentiated, elongated epithelial cells.
* Ciliated cells also appear around the 8th week, however the significance of these cells which are scattered randomly across the lingual surface remains unclear. <ref name=PMID8955790/>
||
Image

|- bgcolor="#BCD4E6"
|''' Week 9''' ||
By this stage, although a taste pore is not present, the surface of circumvallate papillae usually contains a taste pit partly filled with microvillus-like processes from the underlying taste bud cells (1997, Figure 10). <ref name=PMID9455607/>
||
Image

|- bgcolor="#89CFF0"
|''' Weeks 10-11''' ||
At this stage, the lingual epithelium compromises of about four cell layers, and the first shallow grooves above the taste bud primordium are developed. Fungiform papillae appear on the lateral margins and the tip of the tongue, containing taste bud primordial that display the first signs of a primitive pore formation (1996, Figure 6). <ref name=PMID8955790/>
||
Image

|- bgcolor="#BCD4E6"
|''' Week 12 ''' ||
Taste bud cells are more clearly differentiated into epithelial cell types II and III. <ref name=PMID8955790/>
||
Image

|- bgcolor="#89CFF0"
|''' Weeks 12-13 ''' ||
At this stage the taste bud primordial are all located on the top of dermal papillae. There is also maximum synapses between cells and afferent nerve fibres, which intermingle with each other to form a plexus-like structure (1996, Figure 6a). <ref name=PMID8955790/>
||
Image

|- bgcolor="#BCD4E6"
|''' Weeks 14 -15 ''' ||
The shape and size of the taste buds primordial begins to resemble those of adult taste buds (1996, Figure 9). By the 14th week the taste pores develop as the taste pits are filled by microvilli, and bubble like vesicles indicate the secretory activity of these cells (1996, Figure 10). However, the tastebuds only achieve a fully developed function in week 15 of gestation with the development of type I cells to produce the mucous material in the taste pit. <ref name=PMID8955790/>
||
Image
|}

==Gustatory System==

[[Image:Taste qualities.gif|thumb|The five basic tastes]]

Taste or more appropriately gustation, is a fundamental survival tool in animals as it directs the consumption of essential nutrients. The five tastes that exist within the human gustatory system: salty, sweet, sour, bitter and umami, all signify basic physiological requirements. Salty tastes denote the presence of Na+, an important ion involved in the transportation and retention of water across cell membranes. Sweetness is the recognition of carbohydrates, essential for maintaining optimal brain function and providing the basis for energy production in muscle tissue via ATP [[#Glossary |'''hydrolysis''']]. Similarly umami codes for the presence of L-amino acids, especially L-glutamate which is an integral component of protein synthesis.

These different modalities not only function to maintain the proper intake of nutrients within the body but also, by way of aversion, prohibit the consumption of undesired or poisonous materials. The bitter modality for example is generally regarded as displeasing to the human palate. It represents a high acid content which may be a result of foods which have become rotten or are inherently poisonous to the body.<ref name=PMID20696704><pubmed>20696704</pubmed></ref>

Research has historically limited itself to investigating the mechanisms of these five taste qualities though it must be noted many other modalities may exist. Of particular conjecture is the existence of fatty acid recognition. In the past the detection of fat in food has been attributed to somatosensory inputs <ref name=PMID20696704/> from the tongue, that is, the oily feel and texture of fat rather than its actual ‘taste’ allows the brain to encode for its presence. Further research is therefore required to elicit the precise mechanisms of fat detection.

===Cell Biology===

The five taste qualities are not all detected by the same type of receptor cell located within the taste bud. Like rods and cones in the eye which detect different wavelengths of light, there are specific types of receptors for different tastes. For example, sweet, umami and bitter are recognised by Type II G-protein coupled receptors, whereas sour is related to Type III presynaptic cells. The cell type involved in salty taste transduction is unknown however it is known that sodium ions can enter the receptor cell membrane via ion channel permeation.

====Type II receptors====

When a bitter, sweet or umami ligand binds to a type II G-coupled receptor, a cascade of chemical reactions causes the release of Ca2+ which in turn mediates [[#Glossary |'''exocystosis''']]of ATP. The function of this ATP is threefold:

# Stimulates gustatory nerve afferents which project to gustatory nuclei in the spinal cord
# Excites Type III presynaptic nerve fibres to release serotonin.
# Has a positive feedback effect on type II receptor cells, increasing the level of ATP production.

The role of serotonin is believed to be in the form of lateral inhibition i.e. when a bitter quality is recognised, adjacent receptors for sweetness are deactivated and thus the two tastes may be clearly differentiated. It also has a negative feedback effect on receptor cells, inhibiting umami, bitter and sweet taste transduction.

==Taste Map==
[[Image:Taste map.png|thumb|left|250px|Obsolete idea of the tongue map]]
The idea of a tongue map has disseminated through society for many years. This concept purports that different areas of the tongue are specialised to detect either sweet, salty, sour and bitter tastes. Recent research however has completely nullified such claims and suggests instead that different forms of taste are recognised all over the tongue as well as via the palate. Thus the term ''taste map'' has come to take on a new meaning and that is, the precise areas of taste modalities processing in areas of cortex and its subsequent neural inputs.

===Neural Pathways===

'''First order [[#Glossary |'''neuron''']]''' - From the receptors located in the taste buds, gustatory nerve afferents project to the ipsilateral rostral 1/3 of the nucleus tractus solitarius (NTS), located in the medulla. This rostral 1/3 is commonly referred to as the ''gustatory nucleus''.

The ''gustatory nucleus'' receives input from cranial nerves VII (''Facial n.''), IX (''Hypglossal n.''), and X (''Vagus n.'') via special visceral afferent (SVA) nerve fibres. A summary of their functions is as follows:

* ''Facial nerve n''. - carries taste information from the anterior 2/3 of the tongue.
* ''Hypoglossal n.'' - carries taste information from the posterior 1/3 of the tongue.
* ''Vagus n''. - carries taste information from the palate

'''Second order neurons''' - From the NTS second order neurons carry taste information to the Ventral posteromedial (VPM) nucleus in the thalamus.<ref name=PMID21885776/>

Copious scientific conjecture surrounds how each taste modality is transmitted to the brain. The ‘labelled-line’ hypothesis suggests that there are taste specific neurons which exclusively carry that taste modality to cortical areas. In analogous terms it can be viewed like the pipelines leading toward a house. Each pipeline carries its own utility, there is one for gas, another for water and finally for electricity with each terminating in slightly different areas of the house. In the same way, on the tongues there are different receptors for each taste which concurrently have individual nerve tracts leading to the primary gustatory cortex.

Contrapuntally there is electrophysiological evidence that single nerve afferents carry multiple modalities. These studies show one nerve afferent may have both a strong and a weak activation in response to a multiple taste stimuli.

===Cortical Areas===

[[Image:Primary gustatory cortex.png|thumb|Primary gustatory cortex]]

The location of the taste perception centres has been observed via functional magnetic resonance imaging (fMRI) studies. The primary taste cortex has been identified as being located in the anterior insula/frontal operculum (I/fO)<ref name=PMID22245354><pubmed>22245354</pubmed></ref>, with the secondary taste cortex in the caudolateral orbitofrontal cortex.<ref name=PMID21305668><pubmed>21305668</pubmed></ref> Within the insula there are further subdivisions related to each taste modality. Two photon calcium imaging research has outlined certain ’hot-spots’ of activation which are clearly delineated in relation to each taste. For example, the bitter modality is represented on the insula cortex approximately 1mm posterior to the middle cerebral artery whereas the sweet modality is represented 2.5mm rostrodorsal to the bitter field with no apparent overlap.<ref name=PMID21885776><pubmed>21885776</pubmed></ref> These findings lend weight to the idea that there is only one receptor for each taste quality.

It is interesting to note the relationship between taste and the reward centres of the brain. There is evidence of neural input to the ventral tegmental area (the origin of the mesolimbic dopaminergic reward pathway) and nucleus accumbens (involved in the conversion of motivation into physical action).<ref name=PMID21885776/> Neural connections such as this provide the foundations in explaining concepts such as flavour learning and preference. It may also give some insight into chronic problems such as food addiction and craving. As of yet however the gustatory neural network is not well understood and more research is required to elucidate the relationship between pleasure and taste sensation

==Abnormalities==

===Knocking out P2X Receptors===

[[File:Image of taste being evoked by visualising ATP release.jpeg|Left|thumb|200px|Evoking taste - ATP release in tongue]]

Gustatory abnormalities has not been widely researched and what has been researched has been through animal testing, most commonly we have found on mice.

In Huang, 2008 this team used the release of the [[#Glossary |'''ectoderm''']], ATP (adenosine triphosphate) as a quantitative measurement of gustatory sensation and taste. This was done by using a comparison of wild type (WT) and double knockout (DKO) mice. P2X receptors, P2X2 and P2X3 were knocked out in the DKO mice. The premise of this article was that knocking out P2X receptors reduces transmitter secretion of ATP in taste buds, therefore they cannot taste.

It should be noted that the taste buds in DKO are functional, but are not stimulated by the administration of tastants.

The transmission of release of ATP is secretion through gap junction hemichannels (pannexin 1 gap junction).

When both P2X2 and P2X3 are knocked out, no taste is elicited. However they found that if either P2X2 OR P2X3 was knocked out there was a taste response. So the inference made from this is that if one of the two receptors from the P2X family was knocked out there still can have taste response. The WT mice showed significant stimulation by tastants whereas DKO had little to no stimulation of ATP release.<ref><pubmed>21940456</pubmed></ref>

===FGF signalling and genes===

Sprouty, or ''Srpy'', genes have been related to regulating the development of circumvillate papillae (CVP). The CVP are large dome shaped papillae, which form a 'V' just in front of the terminal sulcus.

By knocking out ''Spry'' genes using mice which had ''Spry1'' and ''Spry2'' knocked out showed that the number of CVP doubled. However, when Fibroblast [[#Glossary |'''Growth Factor''']] gene ("Fgf10") was absent, the number of CVP was significantly reduced, if not completely absent. The correlation between ''Spry1/2'' and ''Fgf10'' is that ''Spry1/2'' antagonises "Fgf10" to limit the size of the CVP progenitor placode. Exclusive expression of ''Fgf10'' in the [[#Glossary |'''mesenchyme''']] is necessary for the formation of CVP.

'''This image shows the CVP stained with H&E and scanned by Scanning Electron Microscope (SEM)'''
[[File:CVP of WT(top) and DKO(bottom) mice with H&E and SEM.png]]

'''This image shows the location of the CVP and the increased number in DKO mice by SEM'''
[[File:Mouse circumvallate papilla 01.jpg|300px]]

Taste buds develop from the mesenchyme but require local signalling to properly differentiate. Some signalling factors for proper development of taste buds besides FGF are: [[#Glossary |'''Sonic Hedgehog''']] (SHH), Bone Morphogenetic Proteins (BMPs), Epidermal Growth Factor (EGF).

Additionally, this proves that the anterior and posterior developments of the tongue are derived from embryonic tissues, where the anterior tongue is derived from the [[#Glossary |'''ectoderm''']] and the posterior tongue is derived from the [[#Glossary |'''endoderm''']]. Taste buds develop from the mesenchyme but require local signalling to properly differentiate. Some signalling factors for proper development of taste buds besides FGF are: Sonic Hedgehog (SHH), Bone Morphogenetic Proteins (BMPs), Epidermal Growth Factor (EGF).

As mentioned above, this article shows that the anterior and posterior developments of the tongue are derived from embryonic tissues, where the anterior tongue is derived front the ectoderm and the posterior tongue is derived from the endoderm. Secondly, FGF is required to regulate the growth of taste buds, while ''Spry'' genes limit the number of CVP. ''Fgf10''& ''Spry 1&2''work antagonistically through receptor tyrosine kinase (RTK)signalling.

However, the deletion of ''Spry2''led to the increase of CVPs it should be noted that they found that a significant decrease in number of fungiform papillae. Contrastingly, the absence of ''Fgf10'', while leading to the absence of CVPs lead to an increase in number and size of fungiform papillae. Therefore these genes have different effects on the anterior and posterior developing tongue and taste buds.<ref><pubmed>21655085</pubmed></ref>

==Current Research==
We have an evolving understanding of Embryonic Taste development, through the use of state-of-the-art technology and research techniques we are able to make brilliant discoveries that continue to connect the dots of this amazing natural process of human development.
The majority of research in taste development is involving mice, these mammals show similar embryonic pathways to humans and research is performed in ethical and humane methods.

[[File:Histology.jpg|Left|thumb|200px|Image shows histological stains of a mice tongue showing dysplasia]]

'''Synergistic relationships of Six Genes '''

In an animal study using mice by Suzuki Y, Ikeda K, Kawakami K.(2011) Firstly nominating "[[#Glossary |'''Six Genes''']]" as a major component in [[#Glossary |'''gustatory ''']] development, stating that deficiencies in certain Six genes (specifically Six1 & Six4) leads to poor development. Their research also highlights evidence of cooperative relationships between Six genes for normal advance. This experiment involved breeding mice containing exclusively Six1 and Six4 genes and examining the expression of these genes in papillae under high powered microscope observation. Understanding the role of certain genes along with the intrinsic relationships they hold is crucial for the ability to identify possible causes and correction of any abnormalities <ref><pubmed>21978088</pubmed></ref>

'''Neural Crest responsibilities '''

Another Animal Study involving mice explores a new idea of [[#Glossary |'''Neural crest''']] (NC) contribution in taste development, specifically the development of papillae and taste buds. Liu HX, Komatsu Y, Mishina Y, Mistretta CM. (2012) suggest that Neural crest cells travel to the location of the tongue in early embryonic stages, gain epithelium phenotypes, multiply and then differentiate to eventually form taste papillae. The experiment involved the comparison of 2 different types of Cre line mice, which both express Cre gene in neural crest protocol, the different distribution patterns where observed in specific regions that NC is responsible for.<ref><pubmed>22659543</pubmed></ref>

'''Augmentation of Endoderm'''

In an animal study conducted by Rothova M, Thompson H, Lickert H, Tucker AS.(2012) exploring the historically debated issue of endoderm contribution to tongue development showed promising evidence that position of taste buds are patterned by the border of ectoderm and endoderm derivative epithelium. This study was accomplished via microscopic examination of previously stained specimens. Concluding endoderm has direct influence on gustatory develoment <ref><pubmed>22581563</pubmed></ref>

'''Changes in Taste Cells over time'''

Research by
Ozdener H, Spielman AI, Rawson NE.(2012) developing a culture which allows taste cells to survive for up to 12 months, empowers researchers to study the processes of proliferation, differentiation and function. This experiment will provide a precidnet for future study of taste cells, as these cells are able to operate and grow normally. <ref><pubmed>22643728</pubmed></ref>

'''Shh key component of taste bud proginators'''

A [[#Glossary |'''tamoxifen''']]treatment which supresses Sonic hedgehog (Shh) secretion in mice proving to reduce the number of cells visable within papillae, in contrast mice not treated with tamoxifen showed a mark increase of cells within papillae, these cells are assumed to become taste cells in later development.
Specific mice were bred to trace the destination of taste placode cells, the study concluded that Shh expressing placodes are taste bud proginators which in turn become taste cells within taste buds although do not have any prescuros relationship with pappilae. The results were obtain by examination of mice embryos using Bright-field or multichannel fluorescent images through the use of an "Axiocam CCD camera and Axioplan fluorescence microscope with Axiovision software" a study by Harlow, Yang, Williams, Barlow (2011)<ref><pubmed>PMC2674259</pubmed></ref>

'''WNT family exhibit various roles''' [[File:Abnormal of tongue.jpg|thumb|200px|Image shows an example of tongue abnormalities, this is called "double tongue" each side has independent movement!]]

The WNT gene family has a function of signally proteins for various reason such as development, In 2010 Liu, Staubach Grosse, Walton, Saims, Gumucio, Mistretta explored recent findings on the role of WNT's in tongue and papillae development, Concluding that WNT/β-catenin is essential for fungiform papillae differing to WNT5a which proved to be principle in tongue development. Intrinsic chemical mediators were considered by manipulating a tissue culture and then throughaly examined by scanning photomicrograph. <ref><pubmed>PMC2768563</pubmed></ref>

[http://www.surgicalneurologyint.com/article.asp?issn=2152-7806;year=2012;volume=3;issue=1;spage=23;epage=23;aulast=Manjila]

==Glossary==

* Ectoderm- outer germ layer of embryo

* Endoderm - inner germ layer of embryo

* Epithelium - basic animal tissue that is composed of tightly packed cells, usually covering the outer portion of organs

* Exocystosis - movement of contents out of cell

* Ganglia - the accumulation of a nerve cell body

* Growth factor - a substance that stimulates the growth of cells

* Gustatory - anything that relates to the taste sense

* Hydrolysis - breakdown of a chemical when it reacts with water

* Mesoderm - middle germ layer of embryo

* Mesenchyme - multipotential cells

* Neural crest - a part of the ectoderm found on both sides of the neural tube

* Neuron - most simplistic unit of the nervous system

* Neurotransmitter - chemicals which allow the passing of signals from neuron to neuron via connecting part (synapse)

* Papillae - small rough surface projection

* Six genes - a family of genes

* Sonic hedgehog (Shh) - signalling protein invloved in normal development

* Sulcus terminalis - describes a physical transition point separating the anterior 2/3 of the tongue from the posterior 1/3

* Tamoxifen - hormonal altering drug

== References ==
<references/>

==External Links==
{{External Links}}

http://www.webmd.com/oral-health/picture-of-the-tongue

http://www.tutorvista.com/content/biology/biology-iv/nervous-coordination/tongue-structure.php#parts-of-tongue

http://www.cf.ac.uk/biosi/staffinfo/jacob/teaching/sensory/taste.html

--[[User:Z8600021|Mark Hill]] 12:22, 15 August 2012 (EST) Please leave the content listed below the line at the bottom of your project page.

----

{{2012Projects}}

2012 Group Project 3

2012-09-30T11:46:26Z

Z3289738:

=Taste Development=

== Introduction ==
**NEED TO ADD**

==History of Discoveries==

{| cellpadding=5 style="border:1px solid #BBB"
|- bgcolor="#faecc8"
|''' Date'''|| '''Significant Discovery'''

|- bgcolor="#faf6ed"
|'''350BC'''
|| Aristotle writes about the basic tastes, sweet and bitter. He also notes that it can be modified by salty and acidic. <ref name="PMID22717400"><pubmed>22717400</pubmed></ref>

|- bgcolor="#faecc8"
|'''1901'''
|| D. Hanig publishes a paper describing taste sensitivity in different regions of the tongue.
''Interesting fact:'' The modern concept of a 'tongue map' is a misinterpretation of this study. <ref name="PMID22717400"/>

|- bgcolor="#faf6ed"
|style=white-space:nowrap|'''1908'''
|Kikunae Ikeda, a professor of the Tokyo Imperial University, discovered and identified the fifth basic taste: umami (savouriness), made palatable by glutamate. <ref><pubmed>12438213</pubmed></ref>
[http://chemse.oxfordjournals.org/content/27/9/847.long New Seasonings]

|- bgcolor="#faecc8"
|style=white-space:nowrap|'''1931-32'''
| A chemist named Arthur Fox and his college noted that they had different sensitivities to the bitter tasting Phenylthiocarbamide (PTC).<ref>Blakeslee AF, Fox AL. Our different taste worlds. J Hered. 1932;23:97–107.</ref> Geneticists later confirm these findings, and discover that non-tasting is a recessive genetic trait. <ref><pubmed>17782493</pubmed></ref>
[http://www.ncbi.nlm.nih.gov/pubmed/17782493 Inherited taste deficiency]

|- bgcolor="#faf6ed"
|style=white-space:nowrap|'''1965'''
|Farbman's study of the developing taste but in rat fungiform papilla was significant in increasing our understanding of taste bud development. <ref><pubmed>14300090</pubmed></ref>
[http://www.sciencedirect.com/science/article/pii/0012160665900400 Electron microscope study of the developing taste bud in rat fungiform papilla.]

|- bgcolor="#faecc8"
|style=white-space:nowrap|'''1992'''
|McLaughlin SK et al. discovery a taste cell-specific G-protein within the taste buds called Gustucon. This protein is later used to mark bitter, umami and sweet cells. <ref><pubmed>1608467 </pubmed></ref>
[http://www.nature.com/nature/journal/v357/n6379/abs/357563a0.html Gustducin is a taste-cell-specific G protein closely related to the transducins]

|- bgcolor="#faf6ed"
|style=white-space:nowrap|'''1995'''
|Barlow et al. experimented with Axolotl salamanders and concluded that taste buds from this species arise exclusively from epithelial tissue, "oropharyngeal [[#Glossary |'''epithelium''']]". <ref name="PMID17826760"><pubmed>17826760</pubmed></ref>
[http://www.ncbi.nlm.nih.gov/pubmed/17826760 Embryonic origin of gustatory cranial sensory neurons]

|- bgcolor="#faecc8"
|style=white-space:nowrap|'''1996'''
| Witt M and Reutter K of the Technical University Dresden in Germany, carried out a transmission electron microscopy study to investigate the embryonic and fetal development of Human taste buds. Their results suggest an "at least dual function of embryonic/fetal taste buds", including non-gustatory, paracrine functions prior to the 14th week and gustatory after the 14th week. <ref name="PMID8955790"><pubmed>8955790</pubmed></ref>
[http://www.ncbi.nlm.nih.gov/pubmed/8955790 Embryonic and early fetal development of human taste buds: a transmission electron microscopical study]

|- bgcolor="#faf6ed"
|style=white-space:nowrap|'''2000'''
|Chandrashekar, J. et al. discover the first taste sonsors, the T2R bitter taste receptors. <ref><pubmed>10761935</pubmed></ref>
[http://www.sciencedirect.com/science/article/pii/S0092867400807060 T2Rs Function as Bitter Taste Receptors]

|- bgcolor="#faecc8"
|style=white-space:nowrap|'''2001'''
|Nelson, G. et al. discover the sweet receptor: a combination of T1R2 and T1R3. <ref><pubmed>11509186</pubmed></ref>
[http://www.ncbi.nlm.nih.gov/pubmed/11509186?dopt=Abstract&holding=npg Mammalian sweet taste receptors.]

|- bgcolor="#faf6ed"
|style=white-space:nowrap|'''2002'''
|Nelson G. et al. discover the amino acid (umami) taste receptor: a combination of T1R1 and T1R3 identified. <ref><pubmed>11894099</pubmed></ref>
[http://www.ncbi.nlm.nih.gov/pubmed/11894099?dopt=Abstract&holding=npg An amino-acid taste receptor]

|- bgcolor="#faecc8"
|style=white-space:nowrap|'''2005'''
|Dyer, J. et al. discover sweet taste receptors in the GI tract. <ref><pubmed>17855558</pubmed></ref>
[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1986582/ Sweet taste signaling in the gut]

|- bgcolor="#faf6ed"
|style=white-space:nowrap|'''2006'''
|Huang, A. L et al. discover cells for sour taste, identified by PKD2L1 (a polycystic kidney disease-like ion channel). <ref><pubmed>16929298</pubmed></ref>
[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1571047/ The Cells and Logic for Mammalian Sour Taste detection]

|- bgcolor="#faecc8"
|style=white-space:nowrap|'''2007'''
|Harlow DE, Barlow LA of the University of Colorado Denver Health Sciences Center provide evidence of the "embryonic origin of gustatory cranial sensory neurons". <ref name="PMID17826760"/>
[http://www.ncbi.nlm.nih.gov/pubmed/17826760 Embryonic origin of gustatory cranial sensory neurons.]

|- bgcolor="#faf6ed"
|style=white-space:nowrap|'''2009'''
|A study by Hevezi P et al, presents "the first comprehensive characterization of gene expression in primate taste buds", as opposed to previous studies which focused on rodents. <ref><pubmed>19636377</pubmed></ref>
[http://www.ncbi.nlm.nih.gov/pubmed/19636377 Genome-wide analysis of gene expression in primate taste buds reveals links to diverse processes]

|- bgcolor="#faecc8"
|style=white-space:nowrap|'''2010'''
|Chandrashekar, J. et al. identify epithelial sodium channel (ENaC) as the sodium-salt taste receptor. <ref><pubmed>20107438</pubmed></ref>
[http://www.ncbi.nlm.nih.gov/pubmed/20107438?dopt=Abstract&holding=npg The cells and peripheral representation of sodium taste in mice]
|}

==Adult Tongue and Taste Buds – Structure and Function==

'''Structure'''

The tongue is located on the floor of the oral cavity, It is a muscular structure with sensory units crowning. The tongue is divided into an anterior two thirds and a posterior one third. These regions are divided by a V-shaped groove at the back of the tongue (sulcus terminalis). The anterior two thirds of the tongue is covered by stratified squamous epithelium, It contains a roughened surface and has projections called papillae that vary in shape and number.

''''The Image Below is a very simplistic Diagram of the surface of the Tongue showing the locations of the different papillae and other important features'''

{|
| [[Image:Drawing of Tongue.png|500px]]

'''Papillae'''
[[File:Papillae.jpg|Left|thumb|200px|Close up of Human Tongue Papillae]]

There are 4 types of papillae on the tongue.
The most numerous papillae are the filiform papillae, which function to provide a surface that aids in holding food on the tongue during chewing but do not contain taste buds. The larger, less numerous fungiform papillae which contain taste buds, as do foliate papillae. Circumvallate papillae form a wide V at the sulcus terminalis also containing taste bus. There are no papillae or taste buds located on the posterior third of the tongue, having mucosal folds and the lingual tonsils instead.

'''Function'''

The tongue is for tasting, swallowing, and speech.
The functional unit of the taste bud is a taste cell, there are between 50 and 100 taste cells in each taste bud these taste cells represent all 5 different tastes. Historically is was believed that different areas of the tongue were responsible for different taste sensations although this has since been disregarded.[http://users.rcn.com/jkimball.ma.ultranet/BiologyPages/W/Welcome.html] The papillae contain taste buds which are connected to the oral cavity via a taste pore, the function of the taste bud is to transmit a chemical signal from the oral cavity to a taste cell, this chemical signal is the converted into an electrical impulse and delivered to the brain via nerve fibres for interpretation.

'''The image below is a simplistic hand-drawn cross section of a taste bud unit (not to scale)'''

[[File:Taste_bud_1.jpg|x400px|alt=Cross section of a taste bud unit|Cross section of a taste bud unit]]

== Human Weekly Development - Two Prominent Studies ==
Martin Witt and Klaus Reutter of the University of Tubingen in Germany published two prominent studies regarding developing taste buds in humans. Their first study in 1996 was a transmission electron microscopical (TEM) study of the taste bud primordium and its morphological changes during the 8th-15th postovulatory week. Their next study in 1997 built on their previous findings by using Scanning Electron Microscopy (SEM) to observe the development of gustatory [[#Glossary |'''papillae''']]during postovulatory weeks 6-15.

The findings of these two studies are summarized in the table below. The figures provided relate to the images on their respective research papers.

# [http://onlinelibrary.wiley.com/doi/10.1002/(SICI)1097-0185(199612)246:4%3C507::AID-AR10%3E3.0.CO;2-S/pdf Embryonic and early fetal development of human taste buds: a transmission electron microscopical study, 1996]
# [http://chemse.oxfordjournals.org/content/22/6/601.long Scanning electron microscopical studies of developing gustatory papillae in humans, 1997]

===Timeline of Developmental Processes of Human Taste Buds===
{| cellpadding=5 style="border:1px solid #BBB"
|- bgcolor="#89CFF0"
|'''Postovulatory Week'''||'''Description'''||'''Image'''

|- bgcolor="#BCD4E6"
|'''Week 6''' ||
The surface of the developing tongue is covered by nearly flat epithelium (1997, Figure 1). The first gustatory papillae of the tongue appear in the caudal midline near the foramen caecum and the first circumvallate papilla develops on the dorsal midline. <ref name="PMID9455607"><pubmed>9455607</pubmed></ref>
||
image

|- bgcolor="#89CFF0"
| '''Weeks 6 to 7'''||
Nerve fibres approach the basal lamina of lingual epithelium. At this stage the lingual epithelium consists of two to three cell layers and there is not yet any sign of cell specializations indicating early taste bud formation. <ref name=PMID8955790/>
||
Image

|- bgcolor="#BCD4E6"
| '''Week 7 '''||
A series of irregular epithelial swellings in the anterior part and marginal parts of the tongue indicate early forming fungiform papillae. Furthermore, a V-like lane is observed anterior to the [[#Glossary |'''sulcus terminalis''']], which represents a smooth surface for developing circumvallate papillae (1997, Figure 2). Witt M et al observe that these circumvallate papillae are larger than the developing fungiform papillae of the same age, later noting that the fungiform papillae tend to increase in size over the 8-15th weeks of gestation, whilst the size of vallate papillae tend to remain constant during this period. <ref name=PMID9455607/>
||
Image

|- bgcolor="#89CFF0"
| ''' Week 8 ''' ||
* The taste bud primordium are still differentiated, elongated epithelial cells, resting on a slightly developed core of young dermal papilla.
* The lingual epithelium shows first signs of taste bud development as nerve fibres coming from the dermal papilla penetrate the epithelial basal lamina and form synapses with taste bud progenitor cells (1996, Figure 1). These synapses demonstrate the neuronal connection between the taste bud primordium and the central nervous system, reaching a maximum around the 12th to 13th week. However, it is important to note that at this time these cells are still poorly differentiated, elongated epithelial cells.
* Ciliated cells also appear around the 8th week, however the significance of these cells which are scattered randomly across the lingual surface remains unclear. <ref name=PMID8955790/>
||
Image

|- bgcolor="#BCD4E6"
|''' Week 9''' ||
By this stage, although a taste pore is not present, the surface of circumvallate papillae usually contains a taste pit partly filled with microvillus-like processes from the underlying taste bud cells (1997, Figure 10). <ref name=PMID9455607/>
||
Image

|- bgcolor="#89CFF0"
|''' Weeks 10-11''' ||
At this stage, the lingual epithelium compromises of about four cell layers, and the first shallow grooves above the taste bud primordium are developed. Fungiform papillae appear on the lateral margins and the tip of the tongue, containing taste bud primordial that display the first signs of a primitive pore formation (1996, Figure 6). <ref name=PMID8955790/>
||
Image

|- bgcolor="#BCD4E6"
|''' Week 12 ''' ||
Taste bud cells are more clearly differentiated into epithelial cell types II and III. <ref name=PMID8955790/>
||
Image

|- bgcolor="#89CFF0"
|''' Weeks 12-13 ''' ||
At this stage the taste bud primordial are all located on the top of dermal papillae. There is also maximum synapses between cells and afferent nerve fibres, which intermingle with each other to form a plexus-like structure (1996, Figure 6a). <ref name=PMID8955790/>
||
Image

|- bgcolor="#BCD4E6"
|''' Weeks 14 -15 ''' ||
The shape and size of the taste buds primordial begins to resemble those of adult taste buds (1996, Figure 9). By the 14th week the taste pores develop as the taste pits are filled by microvilli, and bubble like vesicles indicate the secretory activity of these cells (1996, Figure 10). However, the tastebuds only achieve a fully developed function in week 15 of gestation with the development of type I cells to produce the mucous material in the taste pit. <ref name=PMID8955790/>
||
Image
|}

==Gustatory System==

[[Image:Taste qualities.gif|thumb|The five basic tastes]]

Taste or more appropriately gustation, is a fundamental survival tool in animals as it directs the consumption of essential nutrients. The five tastes that exist within the human gustatory system: salty, sweet, sour, bitter and umami, all signify basic physiological requirements. Salty tastes denote the presence of Na+, an important ion involved in the transportation and retention of water across cell membranes. Sweetness is the recognition of carbohydrates, essential for maintaining optimal brain function and providing the basis for energy production in muscle tissue via ATP [[#Glossary |'''hydrolysis''']]. Similarly umami codes for the presence of L-amino acids, especially L-glutamate which is an integral component of protein synthesis.

These different modalities not only function to maintain the proper intake of nutrients within the body but also, by way of aversion, prohibit the consumption of undesired or poisonous materials. The bitter modality for example is generally regarded as displeasing to the human palate. It represents a high acid content which may be a result of foods which have become rotten or are inherently poisonous to the body.<ref name=PMID20696704><pubmed>20696704</pubmed></ref>

Research has historically limited itself to investigating the mechanisms of these five taste qualities though it must be noted many other modalities may exist. Of particular conjecture is the existence of fatty acid recognition. In the past the detection of fat in food has been attributed to somatosensory inputs <ref name=PMID20696704/> from the tongue, that is, the oily feel and texture of fat rather than its actual ‘taste’ allows the brain to encode for its presence. Further research is therefore required to elicit the precise mechanisms of fat detection.

===Cell Biology===

The five taste qualities are not all detected by the same type of receptor cell located within the taste bud. Like rods and cones in the eye which detect different wavelengths of light, there are specific types of receptors for different tastes. For example, sweet, umami and bitter are recognised by Type II G-protein coupled receptors, whereas sour is related to Type III presynaptic cells. The cell type involved in salty taste transduction is unknown however it is known that sodium ions can enter the receptor cell membrane via ion channel permeation.

====Type II receptors====

When a bitter, sweet or umami ligand binds to a type II G-coupled receptor, a cascade of chemical reactions causes the release of Ca2+ which in turn mediates [[#Glossary |'''exocystosis''']]of ATP. The function of this ATP is threefold:

# Stimulates gustatory nerve afferents which project to gustatory nuclei in the spinal cord
# Excites Type III presynaptic nerve fibres to release serotonin.
# Has a positive feedback effect on type II receptor cells, increasing the level of ATP production.

The role of serotonin is believed to be in the form of lateral inhibition i.e. when a bitter quality is recognised, adjacent receptors for sweetness are deactivated and thus the two tastes may be clearly differentiated. It also has a negative feedback effect on receptor cells, inhibiting umami, bitter and sweet taste transduction.

==Taste Map==
[[Image:Taste map.png|thumb|left|250px|Obsolete idea of the tongue map]]
The idea of a tongue map has disseminated through society for many years. This concept purports that different areas of the tongue are specialised to detect either sweet, salty, sour and bitter tastes. Recent research however has completely nullified such claims and suggests instead that different forms of taste are recognised all over the tongue as well as via the palate. Thus the term ''taste map'' has come to take on a new meaning and that is, the precise areas of taste modalities processing in areas of cortex and its subsequent neural inputs.

===Neural Pathways===

'''First order [[#Glossary |'''neuron''']]''' - From the receptors located in the taste buds, gustatory nerve afferents project to the ipsilateral rostral 1/3 of the nucleus tractus solitarius (NTS), located in the medulla. This rostral 1/3 is commonly referred to as the ''gustatory nucleus''.

The ''gustatory nucleus'' receives input from cranial nerves VII (''Facial n.''), IX (''Hypglossal n.''), and X (''Vagus n.'') via special visceral afferent (SVA) nerve fibres. A summary of their functions is as follows:

* ''Facial nerve n''. - carries taste information from the anterior 2/3 of the tongue.
* ''Hypoglossal n.'' - carries taste information from the posterior 1/3 of the tongue.
* ''Vagus n''. - carries taste information from the palate

'''Second order neurons''' - From the NTS second order neurons carry taste information to the Ventral posteromedial (VPM) nucleus in the thalamus.<ref name=PMID21885776/>

Copious scientific conjecture surrounds how each taste modality is transmitted to the brain. The ‘labelled-line’ hypothesis suggests that there are taste specific neurons which exclusively carry that taste modality to cortical areas. In analogous terms it can be viewed like the pipelines leading toward a house. Each pipeline carries its own utility, there is one for gas, another for water and finally for electricity with each terminating in slightly different areas of the house. In the same way, on the tongues there are different receptors for each taste which concurrently have individual nerve tracts leading to the primary gustatory cortex.

Contrapuntally there is electrophysiological evidence that single nerve afferents carry multiple modalities. These studies show one nerve afferent may have both a strong and a weak activation in response to a multiple taste stimuli.

===Cortical Areas===

[[Image:Primary gustatory cortex.png|thumb|Primary gustatory cortex]]

The location of the taste perception centres has been observed via functional magnetic resonance imaging (fMRI) studies. The primary taste cortex has been identified as being located in the anterior insula/frontal operculum (I/fO)<ref name=PMID22245354><pubmed>22245354</pubmed></ref>, with the secondary taste cortex in the caudolateral orbitofrontal cortex.<ref name=PMID21305668><pubmed>21305668</pubmed></ref> Within the insula there are further subdivisions related to each taste modality. Two photon calcium imaging research has outlined certain ’hot-spots’ of activation which are clearly delineated in relation to each taste. For example, the bitter modality is represented on the insula cortex approximately 1mm posterior to the middle cerebral artery whereas the sweet modality is represented 2.5mm rostrodorsal to the bitter field with no apparent overlap.<ref name=PMID21885776><pubmed>21885776</pubmed></ref> These findings lend weight to the idea that there is only one receptor for each taste quality.

It is interesting to note the relationship between taste and the reward centres of the brain. There is evidence of neural input to the ventral tegmental area (the origin of the mesolimbic dopaminergic reward pathway) and nucleus accumbens (involved in the conversion of motivation into physical action).<ref name=PMID21885776/> Neural connections such as this provide the foundations in explaining concepts such as flavour learning and preference. It may also give some insight into chronic problems such as food addiction and craving. As of yet however the gustatory neural network is not well understood and more research is required to elucidate the relationship between pleasure and taste sensation

==Abnormalities==

===Knocking out P2X Receptors===

[[File:Image of taste being evoked by visualising ATP release.jpeg|Left|thumb|200px|Evoking taste - ATP release in tongue]]

Gustatory abnormalities has not been widely researched and what has been researched has been through animal testing, most commonly we have found on mice.

In Huang, 2008 this team used the release of the [[#Glossary |'''ectoderm''']], ATP (adenosine triphosphate) as a quantitative measurement of gustatory sensation and taste. This was done by using a comparison of wild type (WT) and double knockout (DKO) mice. P2X receptors, P2X2 and P2X3 were knocked out in the DKO mice. The premise of this article was that knocking out P2X receptors reduces transmitter secretion of ATP in taste buds, therefore they cannot taste.

It should be noted that the taste buds in DKO are functional, but are not stimulated by the administration of tastants.

The transmission of release of ATP is secretion through gap junction hemichannels (pannexin 1 gap junction).

When both P2X2 and P2X3 are knocked out, no taste is elicited. However they found that if either P2X2 OR P2X3 was knocked out there was a taste response. So the inference made from this is that if one of the two receptors from the P2X family was knocked out there still can have taste response. The WT mice showed significant stimulation by tastants whereas DKO had little to no stimulation of ATP release.<ref><pubmed>21940456</pubmed></ref>

===FGF signalling and genes===

Sprouty, or ''Srpy'', genes have been related to regulating the development of circumvillate papillae (CVP). The CVP are large dome shaped papillae, which form a 'V' just in front of the terminal sulcus.

By knocking out ''Spry'' genes using mice which had ''Spry1'' and ''Spry2'' knocked out showed that the number of CVP doubled. However, when Fibroblast [[#Glossary |'''Growth Factor''']] gene ("Fgf10") was absent, the number of CVP was significantly reduced, if not completely absent. The correlation between ''Spry1/2'' and ''Fgf10'' is that ''Spry1/2'' antagonises "Fgf10" to limit the size of the CVP progenitor placode. Exclusive expression of ''Fgf10'' in the [[#Glossary |'''mesenchyme''']] is necessary for the formation of CVP.

'''This image shows the CVP stained with H&E and scanned by Scanning Electron Microscope (SEM)'''
[[File:CVP of WT(top) and DKO(bottom) mice with H&E and SEM.png]]

'''This image shows the location of the CVP and the increased number in DKO mice by SEM'''
[[File:Mouse circumvallate papilla 01.jpg|300px]]

Taste buds develop from the mesenchyme but require local signalling to properly differentiate. Some signalling factors for proper development of taste buds besides FGF are: [[#Glossary |'''Sonic Hedgehog''']] (SHH), Bone Morphogenetic Proteins (BMPs), Epidermal Growth Factor (EGF).

Additionally, this proves that the anterior and posterior developments of the tongue are derived from embryonic tissues, where the anterior tongue is derived from the [[#Glossary |'''ectoderm''']] and the posterior tongue is derived from the [[#Glossary |'''endoderm''']]. Taste buds develop from the mesenchyme but require local signalling to properly differentiate. Some signalling factors for proper development of taste buds besides FGF are: Sonic Hedgehog (SHH), Bone Morphogenetic Proteins (BMPs), Epidermal Growth Factor (EGF).

As mentioned above, this article shows that the anterior and posterior developments of the tongue are derived from embryonic tissues, where the anterior tongue is derived front the ectoderm and the posterior tongue is derived from the endoderm. Secondly, FGF is required to regulate the growth of taste buds, while ''Spry'' genes limit the number of CVP. ''Fgf10''& ''Spry 1&2''work antagonistically through receptor tyrosine kinase (RTK)signalling.

However, the deletion of ''Spry2''led to the increase of CVPs it should be noted that they found that a significant decrease in number of fungiform papillae. Contrastingly, the absence of ''Fgf10'', while leading to the absence of CVPs lead to an increase in number and size of fungiform papillae. Therefore these genes have different effects on the anterior and posterior developing tongue and taste buds.<ref><pubmed>21655085</pubmed></ref>

==Current Research==
We have an evolving understanding of Embryonic Taste development, through the use of state-of-the-art technology and research techniques we are able to make brilliant discoveries that continue to connect the dots of this amazing natural process of human development.
The majority of research in taste development is involving mice, these mammals show similar embryonic pathways to humans and research is performed in ethical and humane methods.

[[File:Histology.jpg|Left|thumb|200px|Image shows histological stains of a mice tongue showing dysplasia]]

'''Synergistic relationships of Six Genes '''

In an animal study using mice by Suzuki Y, Ikeda K, Kawakami K.(2011) Firstly nominating "[[#Glossary |'''Six Genes''']]" as a major component in [[#Glossary |'''gustatory ''']] development, stating that deficiencies in certain Six genes (specifically Six1 & Six4) leads to poor development. Their research also highlights evidence of cooperative relationships between Six genes for normal advance. This experiment involved breeding mice containing exclusively Six1 and Six4 genes and examining the expression of these genes in papillae under high powered microscope observation. Understanding the role of certain genes along with the intrinsic relationships they hold is crucial for the ability to identify possible causes and correction of any abnormalities <ref><pubmed>21978088</pubmed></ref>

'''Neural Crest responsibilities '''

Another Animal Study involving mice explores a new idea of [[#Glossary |'''Neural crest''']] (NC) contribution in taste development, specifically the development of papillae and taste buds. Liu HX, Komatsu Y, Mishina Y, Mistretta CM. (2012) suggest that Neural crest cells travel to the location of the tongue in early embryonic stages, gain epithelium phenotypes, multiply and then differentiate to eventually form taste papillae. The experiment involved the comparison of 2 different types of Cre line mice, which both express Cre gene in neural crest protocol, the different distribution patterns where observed in specific regions that NC is responsible for.<ref><pubmed>22659543</pubmed></ref>

'''Augmentation of Endoderm'''

In an animal study conducted by Rothova M, Thompson H, Lickert H, Tucker AS.(2012) exploring the historically debated issue of endoderm contribution to tongue development showed promising evidence that position of taste buds are patterned by the border of ectoderm and endoderm derivative epithelium. This study was accomplished via microscopic examination of previously stained specimens. Concluding endoderm has direct influence on gustatory develoment <ref><pubmed>22581563</pubmed></ref>

'''Changes in Taste Cells over time'''

Research by
Ozdener H, Spielman AI, Rawson NE.(2012) developing a culture which allows taste cells to survive for up to 12 months, empowers researchers to study the processes of proliferation, differentiation and function. This experiment will provide a precidnet for future study of taste cells, as these cells are able to operate and grow normally. <ref><pubmed>22643728</pubmed></ref>

'''Shh key component of taste bud proginators'''

A [[#Glossary |'''tamoxifen''']]treatment which supresses Sonic hedgehog (Shh) secretion in mice proving to reduce the number of cells visable within papillae, in contrast mice not treated with tamoxifen showed a mark increase of cells within papillae, these cells are assumed to become taste cells in later development.
Specific mice were bred to trace the destination of taste placode cells, the study concluded that Shh expressing placodes are taste bud proginators which in turn become taste cells within taste buds although do not have any prescuros relationship with pappilae. The results were obtain by examination of mice embryos using Bright-field or multichannel fluorescent images through the use of an "Axiocam CCD camera and Axioplan fluorescence microscope with Axiovision software" a study by Harlow, Yang, Williams, Barlow (2011)<ref><pubmed>PMC2674259</pubmed></ref>

'''WNT family exhibit various roles'''

The WNT gene family has a function of signally proteins for various reason such as development, In 2010 Liu, Staubach Grosse, Walton, Saims, Gumucio, Mistretta explored recent findings on the role of WNT's in tongue and papillae development, Concluding that WNT/β-catenin is essential for fungiform papillae differing to WNT5a which proved to be principle in tongue development. Intrinsic chemical mediators were considered by manipulating a tissue culture and then throughaly examined by scanning photomicrograph. <ref><pubmed>PMC2768563</pubmed></ref>

[http://www.surgicalneurologyint.com/article.asp?issn=2152-7806;year=2012;volume=3;issue=1;spage=23;epage=23;aulast=Manjila]
[[File:Abnormal of tongue.jpg|Left|thumb|200px|Image shows and example of tongue abnormalities, this is called "double tongue" each side has independent movement!]]

==Glossary==

ectoderm- outer germ layer of embryo

endoderm - inner germ layer of embryo

epithelium - basic animal tissue that is composed of tightly packed cells, usually covering the outer portion of organs

exocystosis - movement of contents out of cell

ganglia - the accumulation of a nerve cell body

growth factor - a substance that stimulates the growth of cells

gustatory - anything that relates to the taste sense

hydrolysis - breakdown of a chemical when it reacts with water

mesoderm - middle germ layer of embryo

mesenchyme - multipotential cells

neural crest - a part of the ectoderm found on both sides of the neural tube

neuron - most simplistic unit of the nervous system

neurotransmitter - chemicals which allow the passing of signals from neuron to neuron via connecting part (synapse)

papillae - small rough surface projection

six genes - a family of genes

Sonic hedgehog (Shh) - signalling protein invloved in normal development

sulcus terminalis - describes a physical transition point separating the anterior 2/3 of the tongue from the posterior 1/3

tamoxifen - hormonal altering drug

== References ==
<references/>

==External Links==
{{External Links}}

http://www.webmd.com/oral-health/picture-of-the-tongue

http://www.tutorvista.com/content/biology/biology-iv/nervous-coordination/tongue-structure.php#parts-of-tongue

http://www.cf.ac.uk/biosi/staffinfo/jacob/teaching/sensory/taste.html

--[[User:Z8600021|Mark Hill]] 12:22, 15 August 2012 (EST) Please leave the content listed below the line at the bottom of your project page.

----

{{2012Projects}}

2012 Group Project 3

2012-09-30T11:42:12Z

Z3289738:

=Taste Development=

== Introduction ==
**NEED TO ADD**

==History of Discoveries==

{| cellpadding=5 style="border:1px solid #BBB"
|- bgcolor="#faecc8"
|''' Date'''|| '''Significant Discovery'''

|- bgcolor="#faf6ed"
|'''350BC'''
|| Aristotle writes about the basic tastes, sweet and bitter. He also notes that it can be modified by salty and acidic. <ref name="PMID22717400"><pubmed>22717400</pubmed></ref>

|- bgcolor="#faecc8"
|'''1901'''
|| D. Hanig publishes a paper describing taste sensitivity in different regions of the tongue.
''Interesting fact:'' The modern concept of a 'tongue map' is a misinterpretation of this study. <ref name="PMID22717400"/>

|- bgcolor="#faf6ed"
|style=white-space:nowrap|'''1908'''
|Kikunae Ikeda, a professor of the Tokyo Imperial University, discovered and identified the fifth basic taste: umami (savouriness), made palatable by glutamate. <ref><pubmed>12438213</pubmed></ref>
[http://chemse.oxfordjournals.org/content/27/9/847.long New Seasonings]

|- bgcolor="#faecc8"
|style=white-space:nowrap|'''1931-32'''
| A chemist named Arthur Fox and his college noted that they had different sensitivities to the bitter tasting Phenylthiocarbamide (PTC).<ref>Blakeslee AF, Fox AL. Our different taste worlds. J Hered. 1932;23:97–107.</ref> Geneticists later confirm these findings, and discover that non-tasting is a recessive genetic trait. <ref><pubmed>17782493</pubmed></ref>
[http://www.ncbi.nlm.nih.gov/pubmed/17782493 Inherited taste deficiency]

|- bgcolor="#faf6ed"
|style=white-space:nowrap|'''1965'''
|Farbman's study of the developing taste but in rat fungiform papilla was significant in increasing our understanding of taste bud development. <ref><pubmed>14300090</pubmed></ref>
[http://www.sciencedirect.com/science/article/pii/0012160665900400 Electron microscope study of the developing taste bud in rat fungiform papilla.]

|- bgcolor="#faecc8"
|style=white-space:nowrap|'''1992'''
|McLaughlin SK et al. discovery a taste cell-specific G-protein within the taste buds called Gustucon. This protein is later used to mark bitter, umami and sweet cells. <ref><pubmed>1608467 </pubmed></ref>
[http://www.nature.com/nature/journal/v357/n6379/abs/357563a0.html Gustducin is a taste-cell-specific G protein closely related to the transducins]

|- bgcolor="#faf6ed"
|style=white-space:nowrap|'''1995'''
|Barlow et al. experimented with Axolotl salamanders and concluded that taste buds from this species arise exclusively from epithelial tissue, "oropharyngeal [[#Glossary |'''epithelium''']]". <ref name="PMID17826760"><pubmed>17826760</pubmed></ref>
[http://www.ncbi.nlm.nih.gov/pubmed/17826760 Embryonic origin of gustatory cranial sensory neurons]

|- bgcolor="#faecc8"
|style=white-space:nowrap|'''1996'''
| Witt M and Reutter K of the Technical University Dresden in Germany, carried out a transmission electron microscopy study to investigate the embryonic and fetal development of Human taste buds. Their results suggest an "at least dual function of embryonic/fetal taste buds", including non-gustatory, paracrine functions prior to the 14th week and gustatory after the 14th week. <ref name="PMID8955790"><pubmed>8955790</pubmed></ref>
[http://www.ncbi.nlm.nih.gov/pubmed/8955790 Embryonic and early fetal development of human taste buds: a transmission electron microscopical study]

|- bgcolor="#faf6ed"
|style=white-space:nowrap|'''2000'''
|Chandrashekar, J. et al. discover the first taste sonsors, the T2R bitter taste receptors. <ref><pubmed>10761935</pubmed></ref>
[http://www.sciencedirect.com/science/article/pii/S0092867400807060 T2Rs Function as Bitter Taste Receptors]

|- bgcolor="#faecc8"
|style=white-space:nowrap|'''2001'''
|Nelson, G. et al. discover the sweet receptor: a combination of T1R2 and T1R3. <ref><pubmed>11509186</pubmed></ref>
[http://www.ncbi.nlm.nih.gov/pubmed/11509186?dopt=Abstract&holding=npg Mammalian sweet taste receptors.]

|- bgcolor="#faf6ed"
|style=white-space:nowrap|'''2002'''
|Nelson G. et al. discover the amino acid (umami) taste receptor: a combination of T1R1 and T1R3 identified. <ref><pubmed>11894099</pubmed></ref>
[http://www.ncbi.nlm.nih.gov/pubmed/11894099?dopt=Abstract&holding=npg An amino-acid taste receptor]

|- bgcolor="#faecc8"
|style=white-space:nowrap|'''2005'''
|Dyer, J. et al. discover sweet taste receptors in the GI tract. <ref><pubmed>17855558</pubmed></ref>
[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1986582/ Sweet taste signaling in the gut]

|- bgcolor="#faf6ed"
|style=white-space:nowrap|'''2006'''
|Huang, A. L et al. discover cells for sour taste, identified by PKD2L1 (a polycystic kidney disease-like ion channel). <ref><pubmed>16929298</pubmed></ref>
[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1571047/ The Cells and Logic for Mammalian Sour Taste detection]

|- bgcolor="#faecc8"
|style=white-space:nowrap|'''2007'''
|Harlow DE, Barlow LA of the University of Colorado Denver Health Sciences Center provide evidence of the "embryonic origin of gustatory cranial sensory neurons". <ref name="PMID17826760"/>
[http://www.ncbi.nlm.nih.gov/pubmed/17826760 Embryonic origin of gustatory cranial sensory neurons.]

|- bgcolor="#faf6ed"
|style=white-space:nowrap|'''2009'''
|A study by Hevezi P et al, presents "the first comprehensive characterization of gene expression in primate taste buds", as opposed to previous studies which focused on rodents. <ref><pubmed>19636377</pubmed></ref>
[http://www.ncbi.nlm.nih.gov/pubmed/19636377 Genome-wide analysis of gene expression in primate taste buds reveals links to diverse processes]

|- bgcolor="#faecc8"
|style=white-space:nowrap|'''2010'''
|Chandrashekar, J. et al. identify epithelial sodium channel (ENaC) as the sodium-salt taste receptor. <ref><pubmed>20107438</pubmed></ref>
[http://www.ncbi.nlm.nih.gov/pubmed/20107438?dopt=Abstract&holding=npg The cells and peripheral representation of sodium taste in mice]
|}

==Gustatory System==

[[Image:Taste qualities.gif|thumb|The five basic tastes]]

Taste or more appropriately gustation, is a fundamental survival tool in animals as it directs the consumption of essential nutrients. The five tastes that exist within the human gustatory system: salty, sweet, sour, bitter and umami, all signify basic physiological requirements. Salty tastes denote the presence of Na+, an important ion involved in the transportation and retention of water across cell membranes. Sweetness is the recognition of carbohydrates, essential for maintaining optimal brain function and providing the basis for energy production in muscle tissue via ATP [[#Glossary |'''hydrolysis''']]. Similarly umami codes for the presence of L-amino acids, especially L-glutamate which is an integral component of protein synthesis.

These different modalities not only function to maintain the proper intake of nutrients within the body but also, by way of aversion, prohibit the consumption of undesired or poisonous materials. The bitter modality for example is generally regarded as displeasing to the human palate. It represents a high acid content which may be a result of foods which have become rotten or are inherently poisonous to the body.<ref name=PMID20696704><pubmed>20696704</pubmed></ref>

Research has historically limited itself to investigating the mechanisms of these five taste qualities though it must be noted many other modalities may exist. Of particular conjecture is the existence of fatty acid recognition. In the past the detection of fat in food has been attributed to somatosensory inputs <ref name=PMID20696704/> from the tongue, that is, the oily feel and texture of fat rather than its actual ‘taste’ allows the brain to encode for its presence. Further research is therefore required to elicit the precise mechanisms of fat detection.

===Cell Biology===

The five taste qualities are not all detected by the same type of receptor cell located within the taste bud. Like rods and cones in the eye which detect different wavelengths of light, there are specific types of receptors for different tastes. For example, sweet, umami and bitter are recognised by Type II G-protein coupled receptors, whereas sour is related to Type III presynaptic cells. The cell type involved in salty taste transduction is unknown however it is known that sodium ions can enter the receptor cell membrane via ion channel permeation.

====Type II receptors====

When a bitter, sweet or umami ligand binds to a type II G-coupled receptor, a cascade of chemical reactions causes the release of Ca2+ which in turn mediates [[#Glossary |'''exocystosis''']]of ATP. The function of this ATP is threefold:

# Stimulates gustatory nerve afferents which project to gustatory nuclei in the spinal cord
# Excites Type III presynaptic nerve fibres to release serotonin.
# Has a positive feedback effect on type II receptor cells, increasing the level of ATP production.

The role of serotonin is believed to be in the form of lateral inhibition i.e. when a bitter quality is recognised, adjacent receptors for sweetness are deactivated and thus the two tastes may be clearly differentiated. It also has a negative feedback effect on receptor cells, inhibiting umami, bitter and sweet taste transduction.

==Taste Map==
[[Image:Taste map.png|thumb|left|250px|Obsolete idea of the tongue map]]
The idea of a tongue map has disseminated through society for many years. This concept purports that different areas of the tongue are specialised to detect either sweet, salty, sour and bitter tastes. Recent research however has completely nullified such claims and suggests instead that different forms of taste are recognised all over the tongue as well as via the palate. Thus the term ''taste map'' has come to take on a new meaning and that is, the precise areas of taste modalities processing in areas of cortex and its subsequent neural inputs.

===Neural Pathways===

'''First order [[#Glossary |'''neuron''']]''' - From the receptors located in the taste buds, gustatory nerve afferents project to the ipsilateral rostral 1/3 of the nucleus tractus solitarius (NTS), located in the medulla. This rostral 1/3 is commonly referred to as the ''gustatory nucleus''.

The ''gustatory nucleus'' receives input from cranial nerves VII (''Facial n.''), IX (''Hypglossal n.''), and X (''Vagus n.'') via special visceral afferent (SVA) nerve fibres. A summary of their functions is as follows:

* ''Facial nerve n''. - carries taste information from the anterior 2/3 of the tongue.
* ''Hypoglossal n.'' - carries taste information from the posterior 1/3 of the tongue.
* ''Vagus n''. - carries taste information from the palate

'''Second order neurons''' - From the NTS second order neurons carry taste information to the Ventral posteromedial (VPM) nucleus in the thalamus.<ref name=PMID21885776/>

Copious scientific conjecture surrounds how each taste modality is transmitted to the brain. The ‘labelled-line’ hypothesis suggests that there are taste specific neurons which exclusively carry that taste modality to cortical areas. In analogous terms it can be viewed like the pipelines leading toward a house. Each pipeline carries its own utility, there is one for gas, another for water and finally for electricity with each terminating in slightly different areas of the house. In the same way, on the tongues there are different receptors for each taste which concurrently have individual nerve tracts leading to the primary gustatory cortex.

Contrapuntally there is electrophysiological evidence that single nerve afferents carry multiple modalities. These studies show one nerve afferent may have both a strong and a weak activation in response to a multiple taste stimuli.

===Cortical Areas===

[[Image:Primary gustatory cortex.png|thumb|Primary gustatory cortex]]

The location of the taste perception centres has been observed via functional magnetic resonance imaging (fMRI) studies. The primary taste cortex has been identified as being located in the anterior insula/frontal operculum (I/fO)<ref name=PMID22245354><pubmed>22245354</pubmed></ref>, with the secondary taste cortex in the caudolateral orbitofrontal cortex.<ref name=PMID21305668><pubmed>21305668</pubmed></ref> Within the insula there are further subdivisions related to each taste modality. Two photon calcium imaging research has outlined certain ’hot-spots’ of activation which are clearly delineated in relation to each taste. For example, the bitter modality is represented on the insula cortex approximately 1mm posterior to the middle cerebral artery whereas the sweet modality is represented 2.5mm rostrodorsal to the bitter field with no apparent overlap.<ref name=PMID21885776><pubmed>21885776</pubmed></ref> These findings lend weight to the idea that there is only one receptor for each taste quality.

It is interesting to note the relationship between taste and the reward centres of the brain. There is evidence of neural input to the ventral tegmental area (the origin of the mesolimbic dopaminergic reward pathway) and nucleus accumbens (involved in the conversion of motivation into physical action).<ref name=PMID21885776/> Neural connections such as this provide the foundations in explaining concepts such as flavour learning and preference. It may also give some insight into chronic problems such as food addiction and craving. As of yet however the gustatory neural network is not well understood and more research is required to elucidate the relationship between pleasure and taste sensation

== Human Weekly Development - Two Prominent Studies ==
Martin Witt and Klaus Reutter of the University of Tubingen in Germany published two prominent studies regarding developing taste buds in humans. Their first study in 1996 was a transmission electron microscopical (TEM) study of the taste bud primordium and its morphological changes during the 8th-15th postovulatory week. Their next study in 1997 built on their previous findings by using Scanning Electron Microscopy (SEM) to observe the development of gustatory [[#Glossary |'''papillae''']]during postovulatory weeks 6-15.

The findings of these two studies are summarized in the table below. The figures provided relate to the images on their respective research papers.

# [http://onlinelibrary.wiley.com/doi/10.1002/(SICI)1097-0185(199612)246:4%3C507::AID-AR10%3E3.0.CO;2-S/pdf Embryonic and early fetal development of human taste buds: a transmission electron microscopical study, 1996]
# [http://chemse.oxfordjournals.org/content/22/6/601.long Scanning electron microscopical studies of developing gustatory papillae in humans, 1997]

===Timeline of Developmental Processes of Human Taste Buds===
{| cellpadding=5 style="border:1px solid #BBB"
|- bgcolor="#89CFF0"
|'''Postovulatory Week'''||'''Description'''||'''Image'''

|- bgcolor="#BCD4E6"
|'''Week 6''' ||
The surface of the developing tongue is covered by nearly flat epithelium (1997, Figure 1). The first gustatory papillae of the tongue appear in the caudal midline near the foramen caecum and the first circumvallate papilla develops on the dorsal midline. <ref name="PMID9455607"><pubmed>9455607</pubmed></ref>
||
image

|- bgcolor="#89CFF0"
| '''Weeks 6 to 7'''||
Nerve fibres approach the basal lamina of lingual epithelium. At this stage the lingual epithelium consists of two to three cell layers and there is not yet any sign of cell specializations indicating early taste bud formation. <ref name=PMID8955790/>
||
Image

|- bgcolor="#BCD4E6"
| '''Week 7 '''||
A series of irregular epithelial swellings in the anterior part and marginal parts of the tongue indicate early forming fungiform papillae. Furthermore, a V-like lane is observed anterior to the [[#Glossary |'''sulcus terminalis''']], which represents a smooth surface for developing circumvallate papillae (1997, Figure 2). Witt M et al observe that these circumvallate papillae are larger than the developing fungiform papillae of the same age, later noting that the fungiform papillae tend to increase in size over the 8-15th weeks of gestation, whilst the size of vallate papillae tend to remain constant during this period. <ref name=PMID9455607/>
||
Image

|- bgcolor="#89CFF0"
| ''' Week 8 ''' ||
* The taste bud primordium are still differentiated, elongated epithelial cells, resting on a slightly developed core of young dermal papilla.
* The lingual epithelium shows first signs of taste bud development as nerve fibres coming from the dermal papilla penetrate the epithelial basal lamina and form synapses with taste bud progenitor cells (1996, Figure 1). These synapses demonstrate the neuronal connection between the taste bud primordium and the central nervous system, reaching a maximum around the 12th to 13th week. However, it is important to note that at this time these cells are still poorly differentiated, elongated epithelial cells.
* Ciliated cells also appear around the 8th week, however the significance of these cells which are scattered randomly across the lingual surface remains unclear. <ref name=PMID8955790/>
||
Image

|- bgcolor="#BCD4E6"
|''' Week 9''' ||
By this stage, although a taste pore is not present, the surface of circumvallate papillae usually contains a taste pit partly filled with microvillus-like processes from the underlying taste bud cells (1997, Figure 10). <ref name=PMID9455607/>
||
Image

|- bgcolor="#89CFF0"
|''' Weeks 10-11''' ||
At this stage, the lingual epithelium compromises of about four cell layers, and the first shallow grooves above the taste bud primordium are developed. Fungiform papillae appear on the lateral margins and the tip of the tongue, containing taste bud primordial that display the first signs of a primitive pore formation (1996, Figure 6). <ref name=PMID8955790/>
||
Image

|- bgcolor="#BCD4E6"
|''' Week 12 ''' ||
Taste bud cells are more clearly differentiated into epithelial cell types II and III. <ref name=PMID8955790/>
||
Image

|- bgcolor="#89CFF0"
|''' Weeks 12-13 ''' ||
At this stage the taste bud primordial are all located on the top of dermal papillae. There is also maximum synapses between cells and afferent nerve fibres, which intermingle with each other to form a plexus-like structure (1996, Figure 6a). <ref name=PMID8955790/>
||
Image

|- bgcolor="#BCD4E6"
|''' Weeks 14 -15 ''' ||
The shape and size of the taste buds primordial begins to resemble those of adult taste buds (1996, Figure 9). By the 14th week the taste pores develop as the taste pits are filled by microvilli, and bubble like vesicles indicate the secretory activity of these cells (1996, Figure 10). However, the tastebuds only achieve a fully developed function in week 15 of gestation with the development of type I cells to produce the mucous material in the taste pit. <ref name=PMID8955790/>
||
Image
|}

==Adult Tongue and Taste Buds – Structure and Function==

'''Structure'''

The tongue is located on the floor of the oral cavity, It is a muscular structure with sensory units crowning. The tongue is divided into an anterior two thirds and a posterior one third. These regions are divided by a V-shaped groove at the back of the tongue (sulcus terminalis). The anterior two thirds of the tongue is covered by stratified squamous epithelium, It contains a roughened surface and has projections called papillae that vary in shape and number.

''''The Image Below is a very simplistic Diagram of the surface of the Tongue showing the locations of the different papillae and other important features'''

{|
| [[Image:Drawing of Tongue.png|500px]]

'''Papillae'''
[[File:Papillae.jpg|Left|thumb|200px|Close up of Human Tongue Papillae]]

There are 4 types of papillae on the tongue.
The most numerous papillae are the filiform papillae, which function to provide a surface that aids in holding food on the tongue during chewing but do not contain taste buds. The larger, less numerous fungiform papillae which contain taste buds, as do foliate papillae. Circumvallate papillae form a wide V at the sulcus terminalis also containing taste bus. There are no papillae or taste buds located on the posterior third of the tongue, having mucosal folds and the lingual tonsils instead.

'''Function'''

The tongue is for tasting, swallowing, and speech.
The functional unit of the taste bud is a taste cell, there are between 50 and 100 taste cells in each taste bud these taste cells represent all 5 different tastes. Historically is was believed that different areas of the tongue were responsible for different taste sensations although this has since been disregarded.[http://users.rcn.com/jkimball.ma.ultranet/BiologyPages/W/Welcome.html] The papillae contain taste buds which are connected to the oral cavity via a taste pore, the function of the taste bud is to transmit a chemical signal from the oral cavity to a taste cell, this chemical signal is the converted into an electrical impulse and delivered to the brain via nerve fibres for interpretation.

'''The image below is a simplistic hand-drawn cross section of a taste bud unit (not to scale)'''

[[File:Taste_bud_1.jpg|x400px|alt=Cross section of a taste bud unit|Cross section of a taste bud unit]]

==Abnormalities==

===Knocking out P2X Receptors===

[[File:Image of taste being evoked by visualising ATP release.jpeg|Left|thumb|200px|Evoking taste - ATP release in tongue]]

Gustatory abnormalities has not been widely researched and what has been researched has been through animal testing, most commonly we have found on mice.

In Huang, 2008 this team used the release of the [[#Glossary |'''ectoderm''']], ATP (adenosine triphosphate) as a quantitative measurement of gustatory sensation and taste. This was done by using a comparison of wild type (WT) and double knockout (DKO) mice. P2X receptors, P2X2 and P2X3 were knocked out in the DKO mice. The premise of this article was that knocking out P2X receptors reduces transmitter secretion of ATP in taste buds, therefore they cannot taste.

It should be noted that the taste buds in DKO are functional, but are not stimulated by the administration of tastants.

The transmission of release of ATP is secretion through gap junction hemichannels (pannexin 1 gap junction).

When both P2X2 and P2X3 are knocked out, no taste is elicited. However they found that if either P2X2 OR P2X3 was knocked out there was a taste response. So the inference made from this is that if one of the two receptors from the P2X family was knocked out there still can have taste response. The WT mice showed significant stimulation by tastants whereas DKO had little to no stimulation of ATP release.<ref><pubmed>21940456</pubmed></ref>

===FGF signalling and genes===

Sprouty, or ''Srpy'', genes have been related to regulating the development of circumvillate papillae (CVP). The CVP are large dome shaped papillae, which form a 'V' just in front of the terminal sulcus.

By knocking out ''Spry'' genes using mice which had ''Spry1'' and ''Spry2'' knocked out showed that the number of CVP doubled. However, when Fibroblast [[#Glossary |'''Growth Factor''']] gene ("Fgf10") was absent, the number of CVP was significantly reduced, if not completely absent. The correlation between ''Spry1/2'' and ''Fgf10'' is that ''Spry1/2'' antagonises "Fgf10" to limit the size of the CVP progenitor placode. Exclusive expression of ''Fgf10'' in the [[#Glossary |'''mesenchyme''']] is necessary for the formation of CVP.

'''This image shows the CVP stained with H&E and scanned by Scanning Electron Microscope (SEM)'''
[[File:CVP of WT(top) and DKO(bottom) mice with H&E and SEM.png]]

'''This image shows the location of the CVP and the increased number in DKO mice by SEM'''
[[File:Mouse circumvallate papilla 01.jpg|300px]]

Taste buds develop from the mesenchyme but require local signalling to properly differentiate. Some signalling factors for proper development of taste buds besides FGF are: [[#Glossary |'''Sonic Hedgehog''']] (SHH), Bone Morphogenetic Proteins (BMPs), Epidermal Growth Factor (EGF).

Additionally, this proves that the anterior and posterior developments of the tongue are derived from embryonic tissues, where the anterior tongue is derived from the [[#Glossary |'''ectoderm''']] and the posterior tongue is derived from the [[#Glossary |'''endoderm''']]. Taste buds develop from the mesenchyme but require local signalling to properly differentiate. Some signalling factors for proper development of taste buds besides FGF are: Sonic Hedgehog (SHH), Bone Morphogenetic Proteins (BMPs), Epidermal Growth Factor (EGF).

As mentioned above, this article shows that the anterior and posterior developments of the tongue are derived from embryonic tissues, where the anterior tongue is derived front the ectoderm and the posterior tongue is derived from the endoderm. Secondly, FGF is required to regulate the growth of taste buds, while ''Spry'' genes limit the number of CVP. ''Fgf10''& ''Spry 1&2''work antagonistically through receptor tyrosine kinase (RTK)signalling.

However, the deletion of ''Spry2''led to the increase of CVPs it should be noted that they found that a significant decrease in number of fungiform papillae. Contrastingly, the absence of ''Fgf10'', while leading to the absence of CVPs lead to an increase in number and size of fungiform papillae. Therefore these genes have different effects on the anterior and posterior developing tongue and taste buds.<ref><pubmed>21655085</pubmed></ref>

==Current Research==
We have an evolving understanding of Embryonic Taste development, through the use of state-of-the-art technology and research techniques we are able to make brilliant discoveries that continue to connect the dots of this amazing natural process of human development.
The majority of research in taste development is involving mice, these mammals show similar embryonic pathways to humans and research is performed in ethical and humane methods.

[[File:Histology.jpg|Left|thumb|200px|Image shows histological stains of a mice tongue showing dysplasia]]

'''Synergistic relationships of Six Genes '''

In an animal study using mice by Suzuki Y, Ikeda K, Kawakami K.(2011) Firstly nominating "[[#Glossary |'''Six Genes''']]" as a major component in [[#Glossary |'''gustatory ''']] development, stating that deficiencies in certain Six genes (specifically Six1 & Six4) leads to poor development. Their research also highlights evidence of cooperative relationships between Six genes for normal advance. This experiment involved breeding mice containing exclusively Six1 and Six4 genes and examining the expression of these genes in papillae under high powered microscope observation. Understanding the role of certain genes along with the intrinsic relationships they hold is crucial for the ability to identify possible causes and correction of any abnormalities <ref><pubmed>21978088</pubmed></ref>

'''Neural Crest responsibilities '''

Another Animal Study involving mice explores a new idea of [[#Glossary |'''Neural crest''']] (NC) contribution in taste development, specifically the development of papillae and taste buds. Liu HX, Komatsu Y, Mishina Y, Mistretta CM. (2012) suggest that Neural crest cells travel to the location of the tongue in early embryonic stages, gain epithelium phenotypes, multiply and then differentiate to eventually form taste papillae. The experiment involved the comparison of 2 different types of Cre line mice, which both express Cre gene in neural crest protocol, the different distribution patterns where observed in specific regions that NC is responsible for.<ref><pubmed>22659543</pubmed></ref>

'''Augmentation of Endoderm'''

In an animal study conducted by Rothova M, Thompson H, Lickert H, Tucker AS.(2012) exploring the historically debated issue of endoderm contribution to tongue development showed promising evidence that position of taste buds are patterned by the border of ectoderm and endoderm derivative epithelium. This study was accomplished via microscopic examination of previously stained specimens. Concluding endoderm has direct influence on gustatory develoment <ref><pubmed>22581563</pubmed></ref>

'''Changes in Taste Cells over time'''

Research by
Ozdener H, Spielman AI, Rawson NE.(2012) developing a culture which allows taste cells to survive for up to 12 months, empowers researchers to study the processes of proliferation, differentiation and function. This experiment will provide a precidnet for future study of taste cells, as these cells are able to operate and grow normally. <ref><pubmed>22643728</pubmed></ref>

'''Shh key component of taste bud proginators'''

A [[#Glossary |'''tamoxifen''']]treatment which supresses Sonic hedgehog (Shh) secretion in mice proving to reduce the number of cells visable within papillae, in contrast mice not treated with tamoxifen showed a mark increase of cells within papillae, these cells are assumed to become taste cells in later development.
Specific mice were bred to trace the destination of taste placode cells, the study concluded that Shh expressing placodes are taste bud proginators which in turn become taste cells within taste buds although do not have any prescuros relationship with pappilae. The results were obtain by examination of mice embryos using Bright-field or multichannel fluorescent images through the use of an "Axiocam CCD camera and Axioplan fluorescence microscope with Axiovision software" a study by Harlow, Yang, Williams, Barlow (2011)<ref><pubmed>PMC2674259</pubmed></ref>

'''WNT family exhibit various roles'''

The WNT gene family has a function of signally proteins for various reason such as development, In 2010 Liu, Staubach Grosse, Walton, Saims, Gumucio, Mistretta explored recent findings on the role of WNT's in tongue and papillae development, Concluding that WNT/β-catenin is essential for fungiform papillae differing to WNT5a which proved to be principle in tongue development. Intrinsic chemical mediators were considered by manipulating a tissue culture and then throughaly examined by scanning photomicrograph. <ref><pubmed>PMC2768563</pubmed></ref>

[http://www.surgicalneurologyint.com/article.asp?issn=2152-7806;year=2012;volume=3;issue=1;spage=23;epage=23;aulast=Manjila]
[[File:Abnormal of tongue.jpg|Left|thumb|200px|Image shows and example of tongue abnormalities, this is called "double tongue" each side has independent movement!]]

==Useful links==

==Glossary==

ectoderm- outer germ layer of embryo

endoderm - inner germ layer of embryo

epithelium - basic animal tissue that is composed of tightly packed cells, usually covering the outer portion of organs

exocystosis - movement of contents out of cell

ganglia - the accumulation of a nerve cell body

growth factor - a substance that stimulates the growth of cells

gustatory - anything that relates to the taste sense

hydrolysis - breakdown of a chemical when it reacts with water

mesoderm - middle germ layer of embryo

mesenchyme - multipotential cells

neural crest - a part of the ectoderm found on both sides of the neural tube

neuron - most simplistic unit of the nervous system

neurotransmitter - chemicals which allow the passing of signals from neuron to neuron via connecting part (synapse)

papillae - small rough surface projection

six genes - a family of genes

Sonic hedgehog (Shh) - signalling protein invloved in normal development

sulcus terminalis - describes a physical transition point separating the anterior 2/3 of the tongue from the posterior 1/3

tamoxifen - hormonal altering drug

== References ==
<references/>

==External Links==
{{External Links}}

http://www.webmd.com/oral-health/picture-of-the-tongue

http://www.tutorvista.com/content/biology/biology-iv/nervous-coordination/tongue-structure.php#parts-of-tongue

http://www.cf.ac.uk/biosi/staffinfo/jacob/teaching/sensory/taste.html

--[[User:Z8600021|Mark Hill]] 12:22, 15 August 2012 (EST) Please leave the content listed below the line at the bottom of your project page.

----

{{2012Projects}}

2012 Group Project 3

2012-09-30T11:36:03Z

Z3289738: /* Adult Tongue and Taste Buds – Structure and Function */

=Taste Development=

== Introduction ==
**NEED TO ADD**

==History of Discoveries==

{| cellpadding=5 style="border:1px solid #BBB"
|- bgcolor="#faecc8"
|''' Date'''|| '''Significant Discovery'''

|- bgcolor="#faf6ed"
|'''350BC'''
|| Aristotle writes about the basic tastes, sweet and bitter. He also notes that it can be modified by salty and acidic. <ref name="PMID22717400"><pubmed>22717400</pubmed></ref>

|- bgcolor="#faecc8"
|'''1901'''
|| D. Hanig publishes a paper describing taste sensitivity in different regions of the tongue.
''Interesting fact:'' The modern concept of a 'tongue map' is a misinterpretation of this study. <ref name="PMID22717400"/>

|- bgcolor="#faf6ed"
|style=white-space:nowrap|'''1908'''
|Kikunae Ikeda, a professor of the Tokyo Imperial University, discovered and identified the fifth basic taste: umami (savouriness), made palatable by glutamate. <ref><pubmed>12438213</pubmed></ref>
[http://chemse.oxfordjournals.org/content/27/9/847.long New Seasonings]

|- bgcolor="#faecc8"
|style=white-space:nowrap|'''1931-32'''
| A chemist named Arthur Fox and his college noted that they had different sensitivities to the bitter tasting Phenylthiocarbamide (PTC).<ref>Blakeslee AF, Fox AL. Our different taste worlds. J Hered. 1932;23:97–107.</ref> Geneticists later confirm these findings, and discover that non-tasting is a recessive genetic trait. <ref><pubmed>17782493</pubmed></ref>
[http://www.ncbi.nlm.nih.gov/pubmed/17782493 Inherited taste deficiency]

|- bgcolor="#faf6ed"
|style=white-space:nowrap|'''1965'''
|Farbman's study of the developing taste but in rat fungiform papilla was significant in increasing our understanding of taste bud development. <ref><pubmed>14300090</pubmed></ref>
[http://www.sciencedirect.com/science/article/pii/0012160665900400 Electron microscope study of the developing taste bud in rat fungiform papilla.]

|- bgcolor="#faecc8"
|style=white-space:nowrap|'''1992'''
|McLaughlin SK et al. discovery a taste cell-specific G-protein within the taste buds called Gustucon. This protein is later used to mark bitter, umami and sweet cells. <ref><pubmed>1608467 </pubmed></ref>
[http://www.nature.com/nature/journal/v357/n6379/abs/357563a0.html Gustducin is a taste-cell-specific G protein closely related to the transducins]

|- bgcolor="#faf6ed"
|style=white-space:nowrap|'''1995'''
|Barlow et al. experimented with Axolotl salamanders and concluded that taste buds from this species arise exclusively from epithelial tissue, "oropharyngeal [[#Glossary |'''epithelium''']]". <ref name="PMID17826760"><pubmed>17826760</pubmed></ref>
[http://www.ncbi.nlm.nih.gov/pubmed/17826760 Embryonic origin of gustatory cranial sensory [[#Glossary |'''neuron''']]s.]

|- bgcolor="#faecc8"
|style=white-space:nowrap|'''1996'''
| Witt M and Reutter K of the Technical University Dresden in Germany, carried out a transmission electron microscopy study to investigate the embryonic and fetal development of Human taste buds. Their results suggest an "at least dual function of embryonic/fetal taste buds", including non-gustatory, paracrine functions prior to the 14th week and gustatory after the 14th week. <ref name="PMID8955790"><pubmed>8955790</pubmed></ref>
[http://www.ncbi.nlm.nih.gov/pubmed/8955790 Embryonic and early fetal development of human taste buds: a transmission electron microscopical study]

|- bgcolor="#faf6ed"
|style=white-space:nowrap|'''2000'''
|Chandrashekar, J. et al. discover the first taste sonsors, the T2R bitter taste receptors. <ref><pubmed>10761935</pubmed></ref>
[http://www.sciencedirect.com/science/article/pii/S0092867400807060 T2Rs Function as Bitter Taste Receptors]

|- bgcolor="#faecc8"
|style=white-space:nowrap|'''2001'''
|Nelson, G. et al. discover the sweet receptor: a combination of T1R2 and T1R3. <ref><pubmed>11509186</pubmed></ref>
[http://www.ncbi.nlm.nih.gov/pubmed/11509186?dopt=Abstract&holding=npg Mammalian sweet taste receptors.]

|- bgcolor="#faf6ed"
|style=white-space:nowrap|'''2002'''
|Nelson G. et al. discover the amino acid (umami) taste receptor: a combination of T1R1 and T1R3 identified. <ref><pubmed>11894099</pubmed></ref>
[http://www.ncbi.nlm.nih.gov/pubmed/11894099?dopt=Abstract&holding=npg An amino-acid taste receptor]

|- bgcolor="#faecc8"
|style=white-space:nowrap|'''2005'''
|Dyer, J. et al. discover sweet taste receptors in the GI tract. <ref><pubmed>17855558</pubmed></ref>
[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1986582/ Sweet taste signaling in the gut]

|- bgcolor="#faf6ed"
|style=white-space:nowrap|'''2006'''
|Huang, A. L et al. discover cells for sour taste, identified by PKD2L1 (a polycystic kidney disease-like ion channel). <ref><pubmed>16929298</pubmed></ref>
[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1571047/ The Cells and Logic for Mammalian Sour Taste detection]

|- bgcolor="#faecc8"
|style=white-space:nowrap|'''2007'''
|Harlow DE, Barlow LA of the University of Colorado Denver Health Sciences Center provide evidence of the "embryonic origin of gustatory cranial sensory neurons". <ref name="PMID17826760"/>
[http://www.ncbi.nlm.nih.gov/pubmed/17826760 Embryonic origin of gustatory cranial sensory neurons.]

|- bgcolor="#faf6ed"
|style=white-space:nowrap|'''2009'''
|A study by Hevezi P et al, presents "the first comprehensive characterization of gene expression in primate taste buds", as opposed to previous studies which focused on rodents. <ref><pubmed>19636377</pubmed></ref>
[http://www.ncbi.nlm.nih.gov/pubmed/19636377 Genome-wide analysis of gene expression in primate taste buds reveals links to diverse processes]

|- bgcolor="#faecc8"
|style=white-space:nowrap|'''2010'''
|Chandrashekar, J. et al. identify epithelial sodium channel (ENaC) as the sodium-salt taste receptor. <ref><pubmed>20107438</pubmed></ref>
[http://www.ncbi.nlm.nih.gov/pubmed/20107438?dopt=Abstract&holding=npg The cells and peripheral representation of sodium taste in mice]
|}

==Gustatory System==

[[Image:Taste qualities.gif|thumb|The five basic tastes]]

Taste or more appropriately gustation, is a fundamental survival tool in animals as it directs the consumption of essential nutrients. The five tastes that exist within the human gustatory system: salty, sweet, sour, bitter and umami, all signify basic physiological requirements. Salty tastes denote the presence of Na+, an important ion involved in the transportation and retention of water across cell membranes. Sweetness is the recognition of carbohydrates, essential for maintaining optimal brain function and providing the basis for energy production in muscle tissue via ATP [[#Glossary |'''hydrolysis''']]. Similarly umami codes for the presence of L-amino acids, especially L-glutamate which is an integral component of protein synthesis.

These different modalities not only function to maintain the proper intake of nutrients within the body but also, by way of aversion, prohibit the consumption of undesired or poisonous materials. The bitter modality for example is generally regarded as displeasing to the human palate. It represents a high acid content which may be a result of foods which have become rotten or are inherently poisonous to the body.<ref name=PMID20696704><pubmed>20696704</pubmed></ref>

Research has historically limited itself to investigating the mechanisms of these five taste qualities though it must be noted many other modalities may exist. Of particular conjecture is the existence of fatty acid recognition. In the past the detection of fat in food has been attributed to somatosensory inputs <ref name=PMID20696704/> from the tongue, that is, the oily feel and texture of fat rather than its actual ‘taste’ allows the brain to encode for its presence. Further research is therefore required to elicit the precise mechanisms of fat detection.

===Cell Biology===

The five taste qualities are not all detected by the same type of receptor cell located within the taste bud. Like rods and cones in the eye which detect different wavelengths of light, there are specific types of receptors for different tastes. For example, sweet, umami and bitter are recognised by Type II G-protein coupled receptors, whereas sour is related to Type III presynaptic cells. The cell type involved in salty taste transduction is unknown however it is known that sodium ions can enter the receptor cell membrane via ion channel permeation.

====Type II receptors====

When a bitter, sweet or umami ligand binds to a type II G-coupled receptor, a cascade of chemical reactions causes the release of Ca2+ which in turn mediates [[#Glossary |'''exocystosis''']]of ATP. The function of this ATP is threefold:

# Stimulates gustatory nerve afferents which project to gustatory nuclei in the spinal cord
# Excites Type III presynaptic nerve fibres to release serotonin.
# Has a positive feedback effect on type II receptor cells, increasing the level of ATP production.

The role of serotonin is believed to be in the form of lateral inhibition i.e. when a bitter quality is recognised, adjacent receptors for sweetness are deactivated and thus the two tastes may be clearly differentiated. It also has a negative feedback effect on receptor cells, inhibiting umami, bitter and sweet taste transduction.

==Taste Map==
[[Image:Taste map.png|thumb|left|250px|Obsolete idea of the tongue map]]
The idea of a tongue map has disseminated through society for many years. This concept purports that different areas of the tongue are specialised to detect either sweet, salty, sour and bitter tastes. Recent research however has completely nullified such claims and suggests instead that different forms of taste are recognised all over the tongue as well as via the palate. Thus the term ''taste map'' has come to take on a new meaning and that is, the precise areas of taste modalities processing in areas of cortex and its subsequent neural inputs.

===Neural Pathways===

'''First order neurons''' - From the receptors located in the taste buds, gustatory nerve afferents project to the ipsilateral rostral 1/3 of the nucleus tractus solitarius (NTS), located in the medulla. This rostral 1/3 is commonly referred to as the ''gustatory nucleus''.

The ''gustatory nucleus'' receives input from cranial nerves VII (''Facial n.''), IX (''Hypglossal n.''), and X (''Vagus n.'') via special visceral afferent (SVA) nerve fibres. A summary of their functions is as follows:

* ''Facial nerve n''. - carries taste information from the anterior 2/3 of the tongue.
* ''Hypoglossal n.'' - carries taste information from the posterior 1/3 of the tongue.
* ''Vagus n''. - carries taste information from the palate

'''Second order neurons''' - From the NTS second order neurons carry taste information to the Ventral posteromedial (VPM) nucleus in the thalamus.<ref name=PMID21885776/>

Copious scientific conjecture surrounds how each taste modality is transmitted to the brain. The ‘labelled-line’ hypothesis suggests that there are taste specific neurons which exclusively carry that taste modality to cortical areas. In analogous terms it can be viewed like the pipelines leading toward a house. Each pipeline carries its own utility, there is one for gas, another for water and finally for electricity with each terminating in slightly different areas of the house. In the same way, on the tongues there are different receptors for each taste which concurrently have individual nerve tracts leading to the primary gustatory cortex.

Contrapuntally there is electrophysiological evidence that single nerve afferents carry multiple modalities. These studies show one nerve afferent may have both a strong and a weak activation in response to a multiple taste stimuli.

===Cortical Areas===

[[Image:Primary gustatory cortex.png|thumb|Primary gustatory cortex]]

The location of the taste perception centres has been observed via functional magnetic resonance imaging (fMRI) studies. The primary taste cortex has been identified as being located in the anterior insula/frontal operculum (I/fO)<ref name=PMID22245354><pubmed>22245354</pubmed></ref>, with the secondary taste cortex in the caudolateral orbitofrontal cortex.<ref name=PMID21305668><pubmed>21305668</pubmed></ref> Within the insula there are further subdivisions related to each taste modality. Two photon calcium imaging research has outlined certain ’hot-spots’ of activation which are clearly delineated in relation to each taste. For example, the bitter modality is represented on the insula cortex approximately 1mm posterior to the middle cerebral artery whereas the sweet modality is represented 2.5mm rostrodorsal to the bitter field with no apparent overlap.<ref name=PMID21885776><pubmed>21885776</pubmed></ref> These findings lend weight to the idea that there is only one receptor for each taste quality.

It is interesting to note the relationship between taste and the reward centres of the brain. There is evidence of neural input to the ventral tegmental area (the origin of the mesolimbic dopaminergic reward pathway) and nucleus accumbens (involved in the conversion of motivation into physical action).<ref name=PMID21885776/> Neural connections such as this provide the foundations in explaining concepts such as flavour learning and preference. It may also give some insight into chronic problems such as food addiction and craving. As of yet however the gustatory neural network is not well understood and more research is required to elucidate the relationship between pleasure and taste sensation

== Human Weekly Development - Two Prominent Studies ==
Martin Witt and Klaus Reutter of the University of Tubingen in Germany published two prominent studies regarding developing taste buds in humans. Their first study in 1996 was a transmission electron microscopical (TEM) study of the taste bud primordium and its morphological changes during the 8th-15th postovulatory week. Their next study in 1997 built on their previous findings by using Scanning Electron Microscopy (SEM) to observe the development of gustatory [[#Glossary |'''papillae''']]during postovulatory weeks 6-15.

The findings of these two studies are summarized in the table below. The figures provided relate to the images on their respective research papers.

# [http://onlinelibrary.wiley.com/doi/10.1002/(SICI)1097-0185(199612)246:4%3C507::AID-AR10%3E3.0.CO;2-S/pdf Embryonic and early fetal development of human taste buds: a transmission electron microscopical study, 1996]
# [http://chemse.oxfordjournals.org/content/22/6/601.long Scanning electron microscopical studies of developing gustatory papillae in humans, 1997]

===Timeline of Developmental Processes of Human Taste Buds===
{| cellpadding=5 style="border:1px solid #BBB"
|- bgcolor="#89CFF0"
|'''Postovulatory Week'''||'''Description'''||'''Image'''

|- bgcolor="#BCD4E6"
|'''Week 6''' ||
The surface of the developing tongue is covered by nearly flat epithelium (1997, Figure 1). The first gustatory papillae of the tongue appear in the caudal midline near the foramen caecum and the first circumvallate papilla develops on the dorsal midline. <ref name="PMID9455607"><pubmed>9455607</pubmed></ref>
||
image

|- bgcolor="#89CFF0"
| '''Weeks 6 to 7'''||
Nerve fibres approach the basal lamina of lingual epithelium. At this stage the lingual epithelium consists of two to three cell layers and there is not yet any sign of cell specializations indicating early taste bud formation. <ref name=PMID8955790/>
||
Image

|- bgcolor="#BCD4E6"
| '''Week 7 '''||
A series of irregular epithelial swellings in the anterior part and marginal parts of the tongue indicate early forming fungiform papillae. Furthermore, a V-like lane is observed anterior to the [[#Glossary |'''sulcus terminalis''']], which represents a smooth surface for developing circumvallate papillae (1997, Figure 2). Witt M et al observe that these circumvallate papillae are larger than the developing fungiform papillae of the same age, later noting that the fungiform papillae tend to increase in size over the 8-15th weeks of gestation, whilst the size of vallate papillae tend to remain constant during this period. <ref name=PMID9455607/>
||
Image

|- bgcolor="#89CFF0"
| ''' Week 8 ''' ||
* The taste bud primordium are still differentiated, elongated epithelial cells, resting on a slightly developed core of young dermal papilla.
* The lingual epithelium shows first signs of taste bud development as nerve fibres coming from the dermal papilla penetrate the epithelial basal lamina and form synapses with taste bud progenitor cells (1996, Figure 1). These synapses demonstrate the neuronal connection between the taste bud primordium and the central nervous system, reaching a maximum around the 12th to 13th week. However, it is important to note that at this time these cells are still poorly differentiated, elongated epithelial cells.
* Ciliated cells also appear around the 8th week, however the significance of these cells which are scattered randomly across the lingual surface remains unclear. <ref name=PMID8955790/>
||
Image

|- bgcolor="#BCD4E6"
|''' Week 9''' ||
By this stage, although a taste pore is not present, the surface of circumvallate papillae usually contains a taste pit partly filled with microvillus-like processes from the underlying taste bud cells (1997, Figure 10). <ref name=PMID9455607/>
||
Image

|- bgcolor="#89CFF0"
|''' Weeks 10-11''' ||
At this stage, the lingual epithelium compromises of about four cell layers, and the first shallow grooves above the taste bud primordium are developed. Fungiform papillae appear on the lateral margins and the tip of the tongue, containing taste bud primordial that display the first signs of a primitive pore formation (1996, Figure 6). <ref name=PMID8955790/>
||
Image

|- bgcolor="#BCD4E6"
|''' Week 12 ''' ||
Taste bud cells are more clearly differentiated into epithelial cell types II and III. <ref name=PMID8955790/>
||
Image

|- bgcolor="#89CFF0"
|''' Weeks 12-13 ''' ||
At this stage the taste bud primordial are all located on the top of dermal papillae. There is also maximum synapses between cells and afferent nerve fibres, which intermingle with each other to form a plexus-like structure (1996, Figure 6a). <ref name=PMID8955790/>
||
Image

|- bgcolor="#BCD4E6"
|''' Weeks 14 -15 ''' ||
The shape and size of the taste buds primordial begins to resemble those of adult taste buds (1996, Figure 9). By the 14th week the taste pores develop as the taste pits are filled by microvilli, and bubble like vesicles indicate the secretory activity of these cells (1996, Figure 10). However, the tastebuds only achieve a fully developed function in week 15 of gestation with the development of type I cells to produce the mucous material in the taste pit. <ref name=PMID8955790/>
||
Image
|}

==Adult Tongue and Taste Buds – Structure and Function==

'''Structure'''

The tongue is located on the floor of the oral cavity, It is a muscular structure with sensory units crowning. The tongue is divided into an anterior two thirds and a posterior one third. These regions are divided by a V-shaped groove at the back of the tongue (sulcus terminalis). The anterior two thirds of the tongue is covered by stratified squamous epithelium, It contains a roughened surface and has projections called papillae that vary in shape and number.

''''The Image Below is a very simplistic Diagram of the surface of the Tongue showing the locations of the different papillae and other important features'''

{|
| [[Image:Drawing of Tongue.png|500px]]

'''Papillae'''
[[File:Papillae.jpg|Left|thumb|200px|Close up of Human Tongue Papillae]]

There are 4 types of papillae on the tongue.
The most numerous papillae are the filiform papillae, which function to provide a surface that aids in holding food on the tongue during chewing but do not contain taste buds. The larger, less numerous fungiform papillae which contain taste buds, as do foliate papillae. Circumvallate papillae form a wide V at the sulcus terminalis also containing taste bus. There are no papillae or taste buds located on the posterior third of the tongue, having mucosal folds and the lingual tonsils instead.

'''Function'''

The tongue is for tasting, swallowing, and speech.
The functional unit of the taste bud is a taste cell, there are between 50 and 100 taste cells in each taste bud these taste cells represent all 5 different tastes. Historically is was believed that different areas of the tongue were responsible for different taste sensations although this has since been disregarded.[http://users.rcn.com/jkimball.ma.ultranet/BiologyPages/W/Welcome.html] The papillae contain taste buds which are connected to the oral cavity via a taste pore, the function of the taste bud is to transmit a chemical signal from the oral cavity to a taste cell, this chemical signal is the converted into an electrical impulse and delivered to the brain via nerve fibres for interpretation.

'''The image below is a simplistic hand-drawn cross section of a taste bud unit (not to scale)'''

[[File:Taste_bud_1.jpg|x400px|alt=Cross section of a taste bud unit|Cross section of a taste bud unit]]

==Abnormalities==

===Knocking out P2X Receptors===

[[File:Image of taste being evoked by visualising ATP release.jpeg|Left|thumb|200px|Evoking taste - ATP release in tongue]]

Gustatory abnormalities has not been widely researched and what has been researched has been through animal testing, most commonly we have found on mice.

In Huang, 2008 this team used the release of the [[#Glossary |'''ectoderm''']], ATP (adenosine triphosphate) as a quantitative measurement of gustatory sensation and taste. This was done by using a comparison of wild type (WT) and double knockout (DKO) mice. P2X receptors, P2X2 and P2X3 were knocked out in the DKO mice. The premise of this article was that knocking out P2X receptors reduces transmitter secretion of ATP in taste buds, therefore they cannot taste.

It should be noted that the taste buds in DKO are functional, but are not stimulated by the administration of tastants.

The transmission of release of ATP is secretion through gap junction hemichannels (pannexin 1 gap junction).

When both P2X2 and P2X3 are knocked out, no taste is elicited. However they found that if either P2X2 OR P2X3 was knocked out there was a taste response. So the inference made from this is that if one of the two receptors from the P2X family was knocked out there still can have taste response. The WT mice showed significant stimulation by tastants whereas DKO had little to no stimulation of ATP release.<ref><pubmed>21940456</pubmed></ref>

===FGF signalling and genes===

Sprouty, or ''Srpy'', genes have been related to regulating the development of circumvillate papillae (CVP). The CVP are large dome shaped papillae, which form a 'V' just in front of the terminal sulcus.

By knocking out ''Spry'' genes using mice which had ''Spry1'' and ''Spry2'' knocked out showed that the number of CVP doubled. However, when Fibroblast [[#Glossary |'''Growth Factor''']] gene ("Fgf10") was absent, the number of CVP was significantly reduced, if not completely absent. The correlation between ''Spry1/2'' and ''Fgf10'' is that ''Spry1/2'' antagonises "Fgf10" to limit the size of the CVP progenitor placode. Exclusive expression of ''Fgf10'' in the [[#Glossary |'''mesenchyme''']] is necessary for the formation of CVP.

'''This image shows the CVP stained with H&E and scanned by Scanning Electron Microscope (SEM)'''
[[File:CVP of WT(top) and DKO(bottom) mice with H&E and SEM.png]]

'''This image shows the location of the CVP and the increased number in DKO mice by SEM'''
[[File:Mouse circumvallate papilla 01.jpg|300px]]

Taste buds develop from the mesenchyme but require local signalling to properly differentiate. Some signalling factors for proper development of taste buds besides FGF are: [[#Glossary |'''Sonic Hedgehog''']] (SHH), Bone Morphogenetic Proteins (BMPs), Epidermal Growth Factor (EGF).

Additionally, this proves that the anterior and posterior developments of the tongue are derived from embryonic tissues, where the anterior tongue is derived from the [[#Glossary |'''ectoderm''']] and the posterior tongue is derived from the [[#Glossary |'''endoderm''']]. Taste buds develop from the mesenchyme but require local signalling to properly differentiate. Some signalling factors for proper development of taste buds besides FGF are: Sonic Hedgehog (SHH), Bone Morphogenetic Proteins (BMPs), Epidermal Growth Factor (EGF).

As mentioned above, this article shows that the anterior and posterior developments of the tongue are derived from embryonic tissues, where the anterior tongue is derived front the ectoderm and the posterior tongue is derived from the endoderm. Secondly, FGF is required to regulate the growth of taste buds, while ''Spry'' genes limit the number of CVP. ''Fgf10''& ''Spry 1&2''work antagonistically through receptor tyrosine kinase (RTK)signalling.

However, the deletion of ''Spry2''led to the increase of CVPs it should be noted that they found that a significant decrease in number of fungiform papillae. Contrastingly, the absence of ''Fgf10'', while leading to the absence of CVPs lead to an increase in number and size of fungiform papillae. Therefore these genes have different effects on the anterior and posterior developing tongue and taste buds.<ref><pubmed>21655085</pubmed></ref>

==Current Research==
We have an evolving understanding of Embryonic Taste development, through the use of state-of-the-art technology and research techniques we are able to make brilliant discoveries that continue to connect the dots of this amazing natural process of human development.
The majority of research in taste development is involving mice, these mammals show similar embryonic pathways to humans and research is performed in ethical and humane methods.

[[File:Histology.jpg|Left|thumb|200px|Image shows histological stains of a mice tongue showing dysplasia]]

'''Synergistic relationships of Six Genes '''

In an animal study using mice by Suzuki Y, Ikeda K, Kawakami K.(2011) Firstly nominating "[[#Glossary |'''Six Genes''']]" as a major component in [[#Glossary |'''gustatory ''']] development, stating that deficiencies in certain Six genes (specifically Six1 & Six4) leads to poor development. Their research also highlights evidence of cooperative relationships between Six genes for normal advance. This experiment involved breeding mice containing exclusively Six1 and Six4 genes and examining the expression of these genes in papillae under high powered microscope observation. Understanding the role of certain genes along with the intrinsic relationships they hold is crucial for the ability to identify possible causes and correction of any abnormalities <ref><pubmed>21978088</pubmed></ref>

'''Neural Crest responsibilities '''

Another Animal Study involving mice explores a new idea of [[#Glossary |'''Neural crest''']] (NC) contribution in taste development, specifically the development of papillae and taste buds. Liu HX, Komatsu Y, Mishina Y, Mistretta CM. (2012) suggest that Neural crest cells travel to the location of the tongue in early embryonic stages, gain epithelium phenotypes, multiply and then differentiate to eventually form taste papillae. The experiment involved the comparison of 2 different types of Cre line mice, which both express Cre gene in neural crest protocol, the different distribution patterns where observed in specific regions that NC is responsible for.<ref><pubmed>22659543</pubmed></ref>

'''Augmentation of Endoderm'''

In an animal study conducted by Rothova M, Thompson H, Lickert H, Tucker AS.(2012) exploring the historically debated issue of endoderm contribution to tongue development showed promising evidence that position of taste buds are patterned by the border of ectoderm and endoderm derivative epithelium. This study was accomplished via microscopic examination of previously stained specimens. Concluding endoderm has direct influence on gustatory develoment <ref><pubmed>22581563</pubmed></ref>

'''Changes in Taste Cells over time'''

Research by
Ozdener H, Spielman AI, Rawson NE.(2012) developing a culture which allows taste cells to survive for up to 12 months, empowers researchers to study the processes of proliferation, differentiation and function. This experiment will provide a precidnet for future study of taste cells, as these cells are able to operate and grow normally. <ref><pubmed>22643728</pubmed></ref>

'''Shh key component of taste bud proginators'''

A [[#Glossary |'''tamoxifen''']]treatment which supresses Sonic hedgehog (Shh) secretion in mice proving to reduce the number of cells visable within papillae, in contrast mice not treated with tamoxifen showed a mark increase of cells within papillae, these cells are assumed to become taste cells in later development.
Specific mice were bred to trace the destination of taste placode cells, the study concluded that Shh expressing placodes are taste bud proginators which in turn become taste cells within taste buds although do not have any prescuros relationship with pappilae. The results were obtain by examination of mice embryos using Bright-field or multichannel fluorescent images through the use of an "Axiocam CCD camera and Axioplan fluorescence microscope with Axiovision software" a study by Harlow, Yang, Williams, Barlow (2011)<ref><pubmed>PMC2674259</pubmed></ref>

'''WNT family exhibit various roles'''

The WNT gene family has a function of signally proteins for various reason such as development, In 2010 Liu, Staubach Grosse, Walton, Saims, Gumucio, Mistretta explored recent findings on the role of WNT's in tongue and papillae development, Concluding that WNT/β-catenin is essential for fungiform papillae differing to WNT5a which proved to be principle in tongue development. Intrinsic chemical mediators were considered by manipulating a tissue culture and then throughaly examined by scanning photomicrograph. <ref><pubmed>PMC2768563</pubmed></ref>

[http://www.surgicalneurologyint.com/article.asp?issn=2152-7806;year=2012;volume=3;issue=1;spage=23;epage=23;aulast=Manjila]
[[File:Abnormal of tongue.jpg|Left|thumb|200px|Image shows and example of tongue abnormalities, this is called "double tongue" each side has independent movement!]]

==Useful links==

==Glossary==

ectoderm- outer germ layer of embryo

endoderm - inner germ layer of embryo

epithelium - basic animal tissue that is composed of tightly packed cells, usually covering the outer portion of organs

exocystosis - movement of contents out of cell

ganglia - the accumulation of a nerve cell body

growth factor - a substance that stimulates the growth of cells

gustatory - anything that relates to the taste sense

hydrolysis - breakdown of a chemical when it reacts with water

mesoderm - middle germ layer of embryo

mesenchyme - multipotential cells

neural crest - a part of the ectoderm found on both sides of the neural tube

neuron - most simplistic unit of the nervous system

neurotransmitter - chemicals which allow the passing of signals from neuron to neuron via connecting part (synapse)

papillae - small rough surface projection

six genes - a family of genes

Sonic hedgehog (Shh) - signalling protein invloved in normal development

sulcus terminalis - describes a physical transition point separating the anterior 2/3 of the tongue from the posterior 1/3

tamoxifen - hormonal altering drug

== References ==
<references/>

==External Links==
{{External Links}}

http://www.webmd.com/oral-health/picture-of-the-tongue

http://www.tutorvista.com/content/biology/biology-iv/nervous-coordination/tongue-structure.php#parts-of-tongue

http://www.cf.ac.uk/biosi/staffinfo/jacob/teaching/sensory/taste.html

--[[User:Z8600021|Mark Hill]] 12:22, 15 August 2012 (EST) Please leave the content listed below the line at the bottom of your project page.

----

{{2012Projects}}

2012 Group Project 3

2012-09-30T11:33:41Z

Z3289738: /* Adult Tongue and Taste Buds – Structure and Function */

=Taste Development=

== Introduction ==
**NEED TO ADD**

==History of Discoveries==

{| cellpadding=5 style="border:1px solid #BBB"
|- bgcolor="#faecc8"
|''' Date'''|| '''Significant Discovery'''

|- bgcolor="#faf6ed"
|'''350BC'''
|| Aristotle writes about the basic tastes, sweet and bitter. He also notes that it can be modified by salty and acidic. <ref name="PMID22717400"><pubmed>22717400</pubmed></ref>

|- bgcolor="#faecc8"
|'''1901'''
|| D. Hanig publishes a paper describing taste sensitivity in different regions of the tongue.
''Interesting fact:'' The modern concept of a 'tongue map' is a misinterpretation of this study. <ref name="PMID22717400"/>

|- bgcolor="#faf6ed"
|style=white-space:nowrap|'''1908'''
|Kikunae Ikeda, a professor of the Tokyo Imperial University, discovered and identified the fifth basic taste: umami (savouriness), made palatable by glutamate. <ref><pubmed>12438213</pubmed></ref>
[http://chemse.oxfordjournals.org/content/27/9/847.long New Seasonings]

|- bgcolor="#faecc8"
|style=white-space:nowrap|'''1931-32'''
| A chemist named Arthur Fox and his college noted that they had different sensitivities to the bitter tasting Phenylthiocarbamide (PTC).<ref>Blakeslee AF, Fox AL. Our different taste worlds. J Hered. 1932;23:97–107.</ref> Geneticists later confirm these findings, and discover that non-tasting is a recessive genetic trait. <ref><pubmed>17782493</pubmed></ref>
[http://www.ncbi.nlm.nih.gov/pubmed/17782493 Inherited taste deficiency]

|- bgcolor="#faf6ed"
|style=white-space:nowrap|'''1965'''
|Farbman's study of the developing taste but in rat fungiform papilla was significant in increasing our understanding of taste bud development. <ref><pubmed>14300090</pubmed></ref>
[http://www.sciencedirect.com/science/article/pii/0012160665900400 Electron microscope study of the developing taste bud in rat fungiform papilla.]

|- bgcolor="#faecc8"
|style=white-space:nowrap|'''1992'''
|McLaughlin SK et al. discovery a taste cell-specific G-protein within the taste buds called Gustucon. This protein is later used to mark bitter, umami and sweet cells. <ref><pubmed>1608467 </pubmed></ref>
[http://www.nature.com/nature/journal/v357/n6379/abs/357563a0.html Gustducin is a taste-cell-specific G protein closely related to the transducins]

|- bgcolor="#faf6ed"
|style=white-space:nowrap|'''1995'''
|Barlow et al. experimented with Axolotl salamanders and concluded that taste buds from this species arise exclusively from epithelial tissue, "oropharyngeal [[#Glossary |'''epithelium''']]". <ref name="PMID17826760"><pubmed>17826760</pubmed></ref>
[http://www.ncbi.nlm.nih.gov/pubmed/17826760 Embryonic origin of gustatory cranial sensory [[#Glossary |'''neuron''']]s.]

|- bgcolor="#faecc8"
|style=white-space:nowrap|'''1996'''
| Witt M and Reutter K of the Technical University Dresden in Germany, carried out a transmission electron microscopy study to investigate the embryonic and fetal development of Human taste buds. Their results suggest an "at least dual function of embryonic/fetal taste buds", including non-gustatory, paracrine functions prior to the 14th week and gustatory after the 14th week. <ref name="PMID8955790"><pubmed>8955790</pubmed></ref>
[http://www.ncbi.nlm.nih.gov/pubmed/8955790 Embryonic and early fetal development of human taste buds: a transmission electron microscopical study]

|- bgcolor="#faf6ed"
|style=white-space:nowrap|'''2000'''
|Chandrashekar, J. et al. discover the first taste sonsors, the T2R bitter taste receptors. <ref><pubmed>10761935</pubmed></ref>
[http://www.sciencedirect.com/science/article/pii/S0092867400807060 T2Rs Function as Bitter Taste Receptors]

|- bgcolor="#faecc8"
|style=white-space:nowrap|'''2001'''
|Nelson, G. et al. discover the sweet receptor: a combination of T1R2 and T1R3. <ref><pubmed>11509186</pubmed></ref>
[http://www.ncbi.nlm.nih.gov/pubmed/11509186?dopt=Abstract&holding=npg Mammalian sweet taste receptors.]

|- bgcolor="#faf6ed"
|style=white-space:nowrap|'''2002'''
|Nelson G. et al. discover the amino acid (umami) taste receptor: a combination of T1R1 and T1R3 identified. <ref><pubmed>11894099</pubmed></ref>
[http://www.ncbi.nlm.nih.gov/pubmed/11894099?dopt=Abstract&holding=npg An amino-acid taste receptor]

|- bgcolor="#faecc8"
|style=white-space:nowrap|'''2005'''
|Dyer, J. et al. discover sweet taste receptors in the GI tract. <ref><pubmed>17855558</pubmed></ref>
[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1986582/ Sweet taste signaling in the gut]

|- bgcolor="#faf6ed"
|style=white-space:nowrap|'''2006'''
|Huang, A. L et al. discover cells for sour taste, identified by PKD2L1 (a polycystic kidney disease-like ion channel). <ref><pubmed>16929298</pubmed></ref>
[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1571047/ The Cells and Logic for Mammalian Sour Taste detection]

|- bgcolor="#faecc8"
|style=white-space:nowrap|'''2007'''
|Harlow DE, Barlow LA of the University of Colorado Denver Health Sciences Center provide evidence of the "embryonic origin of gustatory cranial sensory neurons". <ref name="PMID17826760"/>
[http://www.ncbi.nlm.nih.gov/pubmed/17826760 Embryonic origin of gustatory cranial sensory neurons.]

|- bgcolor="#faf6ed"
|style=white-space:nowrap|'''2009'''
|A study by Hevezi P et al, presents "the first comprehensive characterization of gene expression in primate taste buds", as opposed to previous studies which focused on rodents. <ref><pubmed>19636377</pubmed></ref>
[http://www.ncbi.nlm.nih.gov/pubmed/19636377 Genome-wide analysis of gene expression in primate taste buds reveals links to diverse processes]

|- bgcolor="#faecc8"
|style=white-space:nowrap|'''2010'''
|Chandrashekar, J. et al. identify epithelial sodium channel (ENaC) as the sodium-salt taste receptor. <ref><pubmed>20107438</pubmed></ref>
[http://www.ncbi.nlm.nih.gov/pubmed/20107438?dopt=Abstract&holding=npg The cells and peripheral representation of sodium taste in mice]
|}

==Gustatory System==

[[Image:Taste qualities.gif|thumb|The five basic tastes]]

Taste or more appropriately gustation, is a fundamental survival tool in animals as it directs the consumption of essential nutrients. The five tastes that exist within the human gustatory system: salty, sweet, sour, bitter and umami, all signify basic physiological requirements. Salty tastes denote the presence of Na+, an important ion involved in the transportation and retention of water across cell membranes. Sweetness is the recognition of carbohydrates, essential for maintaining optimal brain function and providing the basis for energy production in muscle tissue via ATP [[#Glossary |'''hydrolysis''']]. Similarly umami codes for the presence of L-amino acids, especially L-glutamate which is an integral component of protein synthesis.

These different modalities not only function to maintain the proper intake of nutrients within the body but also, by way of aversion, prohibit the consumption of undesired or poisonous materials. The bitter modality for example is generally regarded as displeasing to the human palate. It represents a high acid content which may be a result of foods which have become rotten or are inherently poisonous to the body.<ref name=PMID20696704><pubmed>20696704</pubmed></ref>

Research has historically limited itself to investigating the mechanisms of these five taste qualities though it must be noted many other modalities may exist. Of particular conjecture is the existence of fatty acid recognition. In the past the detection of fat in food has been attributed to somatosensory inputs <ref name=PMID20696704/> from the tongue, that is, the oily feel and texture of fat rather than its actual ‘taste’ allows the brain to encode for its presence. Further research is therefore required to elicit the precise mechanisms of fat detection.

===Cell Biology===

The five taste qualities are not all detected by the same type of receptor cell located within the taste bud. Like rods and cones in the eye which detect different wavelengths of light, there are specific types of receptors for different tastes. For example, sweet, umami and bitter are recognised by Type II G-protein coupled receptors, whereas sour is related to Type III presynaptic cells. The cell type involved in salty taste transduction is unknown however it is known that sodium ions can enter the receptor cell membrane via ion channel permeation.

====Type II receptors====

When a bitter, sweet or umami ligand binds to a type II G-coupled receptor, a cascade of chemical reactions causes the release of Ca2+ which in turn mediates [[#Glossary |'''exocystosis''']]of ATP. The function of this ATP is threefold:

# Stimulates gustatory nerve afferents which project to gustatory nuclei in the spinal cord
# Excites Type III presynaptic nerve fibres to release serotonin.
# Has a positive feedback effect on type II receptor cells, increasing the level of ATP production.

The role of serotonin is believed to be in the form of lateral inhibition i.e. when a bitter quality is recognised, adjacent receptors for sweetness are deactivated and thus the two tastes may be clearly differentiated. It also has a negative feedback effect on receptor cells, inhibiting umami, bitter and sweet taste transduction.

==Taste Map==
[[Image:Taste map.png|thumb|left|250px|Obsolete idea of the tongue map]]
The idea of a tongue map has disseminated through society for many years. This concept purports that different areas of the tongue are specialised to detect either sweet, salty, sour and bitter tastes. Recent research however has completely nullified such claims and suggests instead that different forms of taste are recognised all over the tongue as well as via the palate. Thus the term ''taste map'' has come to take on a new meaning and that is, the precise areas of taste modalities processing in areas of cortex and its subsequent neural inputs.

===Neural Pathways===

'''First order neurons''' - From the receptors located in the taste buds, gustatory nerve afferents project to the ipsilateral rostral 1/3 of the nucleus tractus solitarius (NTS), located in the medulla. This rostral 1/3 is commonly referred to as the ''gustatory nucleus''.

The ''gustatory nucleus'' receives input from cranial nerves VII (''Facial n.''), IX (''Hypglossal n.''), and X (''Vagus n.'') via special visceral afferent (SVA) nerve fibres. A summary of their functions is as follows:

* ''Facial nerve n''. - carries taste information from the anterior 2/3 of the tongue.
* ''Hypoglossal n.'' - carries taste information from the posterior 1/3 of the tongue.
* ''Vagus n''. - carries taste information from the palate

'''Second order neurons''' - From the NTS second order neurons carry taste information to the Ventral posteromedial (VPM) nucleus in the thalamus.<ref name=PMID21885776/>

Copious scientific conjecture surrounds how each taste modality is transmitted to the brain. The ‘labelled-line’ hypothesis suggests that there are taste specific neurons which exclusively carry that taste modality to cortical areas. In analogous terms it can be viewed like the pipelines leading toward a house. Each pipeline carries its own utility, there is one for gas, another for water and finally for electricity with each terminating in slightly different areas of the house. In the same way, on the tongues there are different receptors for each taste which concurrently have individual nerve tracts leading to the primary gustatory cortex.

Contrapuntally there is electrophysiological evidence that single nerve afferents carry multiple modalities. These studies show one nerve afferent may have both a strong and a weak activation in response to a multiple taste stimuli.

===Cortical Areas===

[[Image:Primary gustatory cortex.png|thumb|Primary gustatory cortex]]

The location of the taste perception centres has been observed via functional magnetic resonance imaging (fMRI) studies. The primary taste cortex has been identified as being located in the anterior insula/frontal operculum (I/fO)<ref name=PMID22245354><pubmed>22245354</pubmed></ref>, with the secondary taste cortex in the caudolateral orbitofrontal cortex.<ref name=PMID21305668><pubmed>21305668</pubmed></ref> Within the insula there are further subdivisions related to each taste modality. Two photon calcium imaging research has outlined certain ’hot-spots’ of activation which are clearly delineated in relation to each taste. For example, the bitter modality is represented on the insula cortex approximately 1mm posterior to the middle cerebral artery whereas the sweet modality is represented 2.5mm rostrodorsal to the bitter field with no apparent overlap.<ref name=PMID21885776><pubmed>21885776</pubmed></ref> These findings lend weight to the idea that there is only one receptor for each taste quality.

It is interesting to note the relationship between taste and the reward centres of the brain. There is evidence of neural input to the ventral tegmental area (the origin of the mesolimbic dopaminergic reward pathway) and nucleus accumbens (involved in the conversion of motivation into physical action).<ref name=PMID21885776/> Neural connections such as this provide the foundations in explaining concepts such as flavour learning and preference. It may also give some insight into chronic problems such as food addiction and craving. As of yet however the gustatory neural network is not well understood and more research is required to elucidate the relationship between pleasure and taste sensation

== Human Weekly Development - Two Prominent Studies ==
Martin Witt and Klaus Reutter of the University of Tubingen in Germany published two prominent studies regarding developing taste buds in humans. Their first study in 1996 was a transmission electron microscopical (TEM) study of the taste bud primordium and its morphological changes during the 8th-15th postovulatory week. Their next study in 1997 built on their previous findings by using Scanning Electron Microscopy (SEM) to observe the development of gustatory [[#Glossary |'''papillae''']]during postovulatory weeks 6-15.

The findings of these two studies are summarized in the table below. The figures provided relate to the images on their respective research papers.

# [http://onlinelibrary.wiley.com/doi/10.1002/(SICI)1097-0185(199612)246:4%3C507::AID-AR10%3E3.0.CO;2-S/pdf Embryonic and early fetal development of human taste buds: a transmission electron microscopical study, 1996]
# [http://chemse.oxfordjournals.org/content/22/6/601.long Scanning electron microscopical studies of developing gustatory papillae in humans, 1997]

===Timeline of Developmental Processes of Human Taste Buds===
{| cellpadding=5 style="border:1px solid #BBB"
|- bgcolor="#89CFF0"
|'''Postovulatory Week'''||'''Description'''||'''Image'''

|- bgcolor="#BCD4E6"
|'''Week 6''' ||
The surface of the developing tongue is covered by nearly flat epithelium (1997, Figure 1). The first gustatory papillae of the tongue appear in the caudal midline near the foramen caecum and the first circumvallate papilla develops on the dorsal midline. <ref name="PMID9455607"><pubmed>9455607</pubmed></ref>
||
image

|- bgcolor="#89CFF0"
| '''Weeks 6 to 7'''||
Nerve fibres approach the basal lamina of lingual epithelium. At this stage the lingual epithelium consists of two to three cell layers and there is not yet any sign of cell specializations indicating early taste bud formation. <ref name=PMID8955790/>
||
Image

|- bgcolor="#BCD4E6"
| '''Week 7 '''||
A series of irregular epithelial swellings in the anterior part and marginal parts of the tongue indicate early forming fungiform papillae. Furthermore, a V-like lane is observed anterior to the [[#Glossary |'''sulcus terminalis''']], which represents a smooth surface for developing circumvallate papillae (1997, Figure 2). Witt M et al observe that these circumvallate papillae are larger than the developing fungiform papillae of the same age, later noting that the fungiform papillae tend to increase in size over the 8-15th weeks of gestation, whilst the size of vallate papillae tend to remain constant during this period. <ref name=PMID9455607/>
||
Image

|- bgcolor="#89CFF0"
| ''' Week 8 ''' ||
* The taste bud primordium are still differentiated, elongated epithelial cells, resting on a slightly developed core of young dermal papilla.
* The lingual epithelium shows first signs of taste bud development as nerve fibres coming from the dermal papilla penetrate the epithelial basal lamina and form synapses with taste bud progenitor cells (1996, Figure 1). These synapses demonstrate the neuronal connection between the taste bud primordium and the central nervous system, reaching a maximum around the 12th to 13th week. However, it is important to note that at this time these cells are still poorly differentiated, elongated epithelial cells.
* Ciliated cells also appear around the 8th week, however the significance of these cells which are scattered randomly across the lingual surface remains unclear. <ref name=PMID8955790/>
||
Image

|- bgcolor="#BCD4E6"
|''' Week 9''' ||
By this stage, although a taste pore is not present, the surface of circumvallate papillae usually contains a taste pit partly filled with microvillus-like processes from the underlying taste bud cells (1997, Figure 10). <ref name=PMID9455607/>
||
Image

|- bgcolor="#89CFF0"
|''' Weeks 10-11''' ||
At this stage, the lingual epithelium compromises of about four cell layers, and the first shallow grooves above the taste bud primordium are developed. Fungiform papillae appear on the lateral margins and the tip of the tongue, containing taste bud primordial that display the first signs of a primitive pore formation (1996, Figure 6). <ref name=PMID8955790/>
||
Image

|- bgcolor="#BCD4E6"
|''' Week 12 ''' ||
Taste bud cells are more clearly differentiated into epithelial cell types II and III. <ref name=PMID8955790/>
||
Image

|- bgcolor="#89CFF0"
|''' Weeks 12-13 ''' ||
At this stage the taste bud primordial are all located on the top of dermal papillae. There is also maximum synapses between cells and afferent nerve fibres, which intermingle with each other to form a plexus-like structure (1996, Figure 6a). <ref name=PMID8955790/>
||
Image

|- bgcolor="#BCD4E6"
|''' Weeks 14 -15 ''' ||
The shape and size of the taste buds primordial begins to resemble those of adult taste buds (1996, Figure 9). By the 14th week the taste pores develop as the taste pits are filled by microvilli, and bubble like vesicles indicate the secretory activity of these cells (1996, Figure 10). However, the tastebuds only achieve a fully developed function in week 15 of gestation with the development of type I cells to produce the mucous material in the taste pit. <ref name=PMID8955790/>
||
Image
|}

==Adult Tongue and Taste Buds – Structure and Function==

'''Structure'''

The tongue is located on the floor of the oral cavity, It is a muscular structure with sensory units crowning. The tongue is divided into an anterior two thirds and a posterior one third. These regions are divided by a V-shaped groove at the back of the tongue (sulcus terminalis). The anterior two thirds of the tongue is covered by stratified squamous epithelium, It contains a roughened surface and has projections called papillae that vary in shape and number.

''''The Image Below is a very simplistic Diagram of the surface of the Tongue showing the locations of the different papillae and other important features'''

{|
| [[Image:Drawing of Tongue.png|500px]]

'''Papillae'''
[[File:Papillae.jpg|Left|thumb|200px|Close up of Human Tongue Papillae]]

There are 4 types of papillae on the tongue.
The most numerous papillae are the filiform papillae, which function to provide a surface that aids in holding food on the tongue during chewing but do not contain taste buds. The larger, less numerous fungiform papillae which contain taste buds, as do foliate papillae. Circumvallate papillae form a wide V at the sulcus terminalis also containing taste bus. There are no papillae or taste buds located on the posterior third of the tongue, having mucosal folds and the lingual tonsils instead.

'''Function'''

The tongue is for tasting, swallowing, and speech.
The functional unit of the taste bud is a taste cell, there are between 50 and 100 taste cells in each taste bud these taste cells represent all 5 different tastes. Historically is was believed that different areas of the tongue were responsible for different taste sensations although this has since been disregarded.[http://users.rcn.com/jkimball.ma.ultranet/BiologyPages/W/Welcome.html] The papillae contain taste buds which are connected to the oral cavity via a taste pore, the function of the taste bud is to transmit a chemical signal from the oral cavity to a taste cell, this chemical signal is the converted into an electrical impulse and delivered to the brain via nerve fibres for interpretation.

'''The image below is a simplistic hand-drawn cross section of a taste bud unit (not to scale)'''

[[File:Taste_bud_1.jpg|left|x400px|alt=Cross section of a taste bud unit|Cross section of a taste bud unit]]

==Abnormalities==

===Knocking out P2X Receptors===

[[File:Image of taste being evoked by visualising ATP release.jpeg|Left|thumb|200px|Evoking taste - ATP release in tongue]]

Gustatory abnormalities has not been widely researched and what has been researched has been through animal testing, most commonly we have found on mice.

In Huang, 2008 this team used the release of the [[#Glossary |'''ectoderm''']], ATP (adenosine triphosphate) as a quantitative measurement of gustatory sensation and taste. This was done by using a comparison of wild type (WT) and double knockout (DKO) mice. P2X receptors, P2X2 and P2X3 were knocked out in the DKO mice. The premise of this article was that knocking out P2X receptors reduces transmitter secretion of ATP in taste buds, therefore they cannot taste.

It should be noted that the taste buds in DKO are functional, but are not stimulated by the administration of tastants.

The transmission of release of ATP is secretion through gap junction hemichannels (pannexin 1 gap junction).

When both P2X2 and P2X3 are knocked out, no taste is elicited. However they found that if either P2X2 OR P2X3 was knocked out there was a taste response. So the inference made from this is that if one of the two receptors from the P2X family was knocked out there still can have taste response. The WT mice showed significant stimulation by tastants whereas DKO had little to no stimulation of ATP release.<ref><pubmed>21940456</pubmed></ref>

===FGF signalling and genes===

Sprouty, or ''Srpy'', genes have been related to regulating the development of circumvillate papillae (CVP). The CVP are large dome shaped papillae, which form a 'V' just in front of the terminal sulcus.

By knocking out ''Spry'' genes using mice which had ''Spry1'' and ''Spry2'' knocked out showed that the number of CVP doubled. However, when Fibroblast [[#Glossary |'''Growth Factor''']] gene ("Fgf10") was absent, the number of CVP was significantly reduced, if not completely absent. The correlation between ''Spry1/2'' and ''Fgf10'' is that ''Spry1/2'' antagonises "Fgf10" to limit the size of the CVP progenitor placode. Exclusive expression of ''Fgf10'' in the [[#Glossary |'''mesenchyme''']] is necessary for the formation of CVP.

'''This image shows the CVP stained with H&E and scanned by Scanning Electron Microscope (SEM)'''
[[File:CVP of WT(top) and DKO(bottom) mice with H&E and SEM.png]]

'''This image shows the location of the CVP and the increased number in DKO mice by SEM'''
[[File:Mouse circumvallate papilla 01.jpg|300px]]

Taste buds develop from the mesenchyme but require local signalling to properly differentiate. Some signalling factors for proper development of taste buds besides FGF are: [[#Glossary |'''Sonic Hedgehog''']] (SHH), Bone Morphogenetic Proteins (BMPs), Epidermal Growth Factor (EGF).

Additionally, this proves that the anterior and posterior developments of the tongue are derived from embryonic tissues, where the anterior tongue is derived from the [[#Glossary |'''ectoderm''']] and the posterior tongue is derived from the [[#Glossary |'''endoderm''']]. Taste buds develop from the mesenchyme but require local signalling to properly differentiate. Some signalling factors for proper development of taste buds besides FGF are: Sonic Hedgehog (SHH), Bone Morphogenetic Proteins (BMPs), Epidermal Growth Factor (EGF).

As mentioned above, this article shows that the anterior and posterior developments of the tongue are derived from embryonic tissues, where the anterior tongue is derived front the ectoderm and the posterior tongue is derived from the endoderm. Secondly, FGF is required to regulate the growth of taste buds, while ''Spry'' genes limit the number of CVP. ''Fgf10''& ''Spry 1&2''work antagonistically through receptor tyrosine kinase (RTK)signalling.

However, the deletion of ''Spry2''led to the increase of CVPs it should be noted that they found that a significant decrease in number of fungiform papillae. Contrastingly, the absence of ''Fgf10'', while leading to the absence of CVPs lead to an increase in number and size of fungiform papillae. Therefore these genes have different effects on the anterior and posterior developing tongue and taste buds.<ref><pubmed>21655085</pubmed></ref>

==Current Research==
We have an evolving understanding of Embryonic Taste development, through the use of state-of-the-art technology and research techniques we are able to make brilliant discoveries that continue to connect the dots of this amazing natural process of human development.
The majority of research in taste development is involving mice, these mammals show similar embryonic pathways to humans and research is performed in ethical and humane methods.

[[File:Histology.jpg|Left|thumb|200px|Image shows histological stains of a mice tongue showing dysplasia]]

'''Synergistic relationships of Six Genes '''

In an animal study using mice by Suzuki Y, Ikeda K, Kawakami K.(2011) Firstly nominating "[[#Glossary |'''Six Genes''']]" as a major component in [[#Glossary |'''gustatory ''']] development, stating that deficiencies in certain Six genes (specifically Six1 & Six4) leads to poor development. Their research also highlights evidence of cooperative relationships between Six genes for normal advance. This experiment involved breeding mice containing exclusively Six1 and Six4 genes and examining the expression of these genes in papillae under high powered microscope observation. Understanding the role of certain genes along with the intrinsic relationships they hold is crucial for the ability to identify possible causes and correction of any abnormalities <ref><pubmed>21978088</pubmed></ref>

'''Neural Crest responsibilities '''

Another Animal Study involving mice explores a new idea of [[#Glossary |'''Neural crest''']] (NC) contribution in taste development, specifically the development of papillae and taste buds. Liu HX, Komatsu Y, Mishina Y, Mistretta CM. (2012) suggest that Neural crest cells travel to the location of the tongue in early embryonic stages, gain epithelium phenotypes, multiply and then differentiate to eventually form taste papillae. The experiment involved the comparison of 2 different types of Cre line mice, which both express Cre gene in neural crest protocol, the different distribution patterns where observed in specific regions that NC is responsible for.<ref><pubmed>22659543</pubmed></ref>

'''Augmentation of Endoderm'''

In an animal study conducted by Rothova M, Thompson H, Lickert H, Tucker AS.(2012) exploring the historically debated issue of endoderm contribution to tongue development showed promising evidence that position of taste buds are patterned by the border of ectoderm and endoderm derivative epithelium. This study was accomplished via microscopic examination of previously stained specimens. Concluding endoderm has direct influence on gustatory develoment <ref><pubmed>22581563</pubmed></ref>

'''Changes in Taste Cells over time'''

Research by
Ozdener H, Spielman AI, Rawson NE.(2012) developing a culture which allows taste cells to survive for up to 12 months, empowers researchers to study the processes of proliferation, differentiation and function. This experiment will provide a precidnet for future study of taste cells, as these cells are able to operate and grow normally. <ref><pubmed>22643728</pubmed></ref>

'''Shh key component of taste bud proginators'''

A [[#Glossary |'''tamoxifen''']]treatment which supresses Sonic hedgehog (Shh) secretion in mice proving to reduce the number of cells visable within papillae, in contrast mice not treated with tamoxifen showed a mark increase of cells within papillae, these cells are assumed to become taste cells in later development.
Specific mice were bred to trace the destination of taste placode cells, the study concluded that Shh expressing placodes are taste bud proginators which in turn become taste cells within taste buds although do not have any prescuros relationship with pappilae. The results were obtain by examination of mice embryos using Bright-field or multichannel fluorescent images through the use of an "Axiocam CCD camera and Axioplan fluorescence microscope with Axiovision software" a study by Harlow, Yang, Williams, Barlow (2011)<ref><pubmed>PMC2674259</pubmed></ref>

'''WNT family exhibit various roles'''

The WNT gene family has a function of signally proteins for various reason such as development, In 2010 Liu, Staubach Grosse, Walton, Saims, Gumucio, Mistretta explored recent findings on the role of WNT's in tongue and papillae development, Concluding that WNT/β-catenin is essential for fungiform papillae differing to WNT5a which proved to be principle in tongue development. Intrinsic chemical mediators were considered by manipulating a tissue culture and then throughaly examined by scanning photomicrograph. <ref><pubmed>PMC2768563</pubmed></ref>

[http://www.surgicalneurologyint.com/article.asp?issn=2152-7806;year=2012;volume=3;issue=1;spage=23;epage=23;aulast=Manjila]
[[File:Abnormal of tongue.jpg|Left|thumb|200px|Image shows and example of tongue abnormalities, this is called "double tongue" each side has independent movement!]]

==Useful links==

==Glossary==

ectoderm- outer germ layer of embryo

endoderm - inner germ layer of embryo

epithelium - basic animal tissue that is composed of tightly packed cells, usually covering the outer portion of organs

exocystosis - movement of contents out of cell

ganglia - the accumulation of a nerve cell body

growth factor - a substance that stimulates the growth of cells

gustatory - anything that relates to the taste sense

hydrolysis - breakdown of a chemical when it reacts with water

mesoderm - middle germ layer of embryo

mesenchyme - multipotential cells

neural crest - a part of the ectoderm found on both sides of the neural tube

neuron - most simplistic unit of the nervous system

neurotransmitter - chemicals which allow the passing of signals from neuron to neuron via connecting part (synapse)

papillae - small rough surface projection

six genes - a family of genes

Sonic hedgehog (Shh) - signalling protein invloved in normal development

sulcus terminalis - describes a physical transition point separating the anterior 2/3 of the tongue from the posterior 1/3

tamoxifen - hormonal altering drug

== References ==
<references/>

==External Links==
{{External Links}}

http://www.webmd.com/oral-health/picture-of-the-tongue

http://www.tutorvista.com/content/biology/biology-iv/nervous-coordination/tongue-structure.php#parts-of-tongue

http://www.cf.ac.uk/biosi/staffinfo/jacob/teaching/sensory/taste.html

--[[User:Z8600021|Mark Hill]] 12:22, 15 August 2012 (EST) Please leave the content listed below the line at the bottom of your project page.

----

{{2012Projects}}

2012 Group Project 3

2012-09-30T11:11:24Z

Z3289738: /* Image gallery */

=Taste Development=

== Introduction ==
**NEED TO ADD**

==History of Discoveries==

{| cellpadding=5 style="border:1px solid #BBB"
|- bgcolor="#faecc8"
|''' Date'''|| '''Significant Discovery'''

|- bgcolor="#faf6ed"
|'''350BC'''
|| Aristotle writes about the basic tastes, sweet and bitter. He also notes that it can be modified by salty and acidic. <ref name="PMID22717400"><pubmed>22717400</pubmed></ref>

|- bgcolor="#faecc8"
|'''1901'''
|| D. Hanig publishes a paper describing taste sensitivity in different regions of the tongue.
''Interesting fact:'' The modern concept of a 'tongue map' is a misinterpretation of this study. <ref name="PMID22717400"/>

|- bgcolor="#faf6ed"
|style=white-space:nowrap|'''1908'''
|Kikunae Ikeda, a professor of the Tokyo Imperial University, discovered and identified the fifth basic taste: umami (savouriness), made palatable by glutamate. <ref><pubmed>12438213</pubmed></ref>
[http://chemse.oxfordjournals.org/content/27/9/847.long New Seasonings]

|- bgcolor="#faecc8"
|style=white-space:nowrap|'''1931-32'''
| A chemist named Arthur Fox and his college noted that they had different sensitivities to the bitter tasting Phenylthiocarbamide (PTC).<ref>Blakeslee AF, Fox AL. Our different taste worlds. J Hered. 1932;23:97–107.</ref> Geneticists later confirm these findings, and discover that non-tasting is a recessive genetic trait. <ref><pubmed>17782493</pubmed></ref>
[http://www.ncbi.nlm.nih.gov/pubmed/17782493 Inherited taste deficiency]

|- bgcolor="#faf6ed"
|style=white-space:nowrap|'''1965'''
|Farbman's study of the developing taste but in rat fungiform papilla was significant in increasing our understanding of taste bud development. <ref><pubmed>14300090</pubmed></ref>
[http://www.sciencedirect.com/science/article/pii/0012160665900400 Electron microscope study of the developing taste bud in rat fungiform papilla.]

|- bgcolor="#faecc8"
|style=white-space:nowrap|'''1992'''
|McLaughlin SK et al. discovery a taste cell-specific G-protein within the taste buds called Gustucon. This protein is later used to mark bitter, umami and sweet cells. <ref><pubmed>1608467 </pubmed></ref>
[http://www.nature.com/nature/journal/v357/n6379/abs/357563a0.html Gustducin is a taste-cell-specific G protein closely related to the transducins]

|- bgcolor="#faf6ed"
|style=white-space:nowrap|'''1995'''
|Barlow et al. experimented with Axolotl salamanders and concluded that taste buds from this species arise exclusively from epithelial tissue, "oropharyngeal [[#Glossary |'''epithelium''']]". <ref name="PMID17826760"><pubmed>17826760</pubmed></ref>
[http://www.ncbi.nlm.nih.gov/pubmed/17826760 Embryonic origin of gustatory cranial sensory [[#Glossary |'''neuron''']]s.]

|- bgcolor="#faecc8"
|style=white-space:nowrap|'''1996'''
| Witt M and Reutter K of the Technical University Dresden in Germany, carried out a transmission electron microscopy study to investigate the embryonic and fetal development of Human taste buds. Their results suggest an "at least dual function of embryonic/fetal taste buds", including non-gustatory, paracrine functions prior to the 14th week and gustatory after the 14th week. <ref name="PMID8955790"><pubmed>8955790</pubmed></ref>
[http://www.ncbi.nlm.nih.gov/pubmed/8955790 Embryonic and early fetal development of human taste buds: a transmission electron microscopical study]

|- bgcolor="#faf6ed"
|style=white-space:nowrap|'''2000'''
|Chandrashekar, J. et al. discover the first taste sonsors, the T2R bitter taste receptors. <ref><pubmed>10761935</pubmed></ref>
[http://www.sciencedirect.com/science/article/pii/S0092867400807060 T2Rs Function as Bitter Taste Receptors]

|- bgcolor="#faecc8"
|style=white-space:nowrap|'''2001'''
|Nelson, G. et al. discover the sweet receptor: a combination of T1R2 and T1R3. <ref><pubmed>11509186</pubmed></ref>
[http://www.ncbi.nlm.nih.gov/pubmed/11509186?dopt=Abstract&holding=npg Mammalian sweet taste receptors.]

|- bgcolor="#faf6ed"
|style=white-space:nowrap|'''2002'''
|Nelson G. et al. discover the amino acid (umami) taste receptor: a combination of T1R1 and T1R3 identified. <ref><pubmed>11894099</pubmed></ref>
[http://www.ncbi.nlm.nih.gov/pubmed/11894099?dopt=Abstract&holding=npg An amino-acid taste receptor]

|- bgcolor="#faecc8"
|style=white-space:nowrap|'''2005'''
|Dyer, J. et al. discover sweet taste receptors in the GI tract. <ref><pubmed>17855558</pubmed></ref>
[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1986582/ Sweet taste signaling in the gut]

|- bgcolor="#faf6ed"
|style=white-space:nowrap|'''2006'''
|Huang, A. L et al. discover cells for sour taste, identified by PKD2L1 (a polycystic kidney disease-like ion channel). <ref><pubmed>16929298</pubmed></ref>
[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1571047/ The Cells and Logic for Mammalian Sour Taste detection]

|- bgcolor="#faecc8"
|style=white-space:nowrap|'''2007'''
|Harlow DE, Barlow LA of the University of Colorado Denver Health Sciences Center provide evidence of the "embryonic origin of gustatory cranial sensory neurons". <ref name="PMID17826760"/>
[http://www.ncbi.nlm.nih.gov/pubmed/17826760 Embryonic origin of gustatory cranial sensory neurons.]

|- bgcolor="#faf6ed"
|style=white-space:nowrap|'''2009'''
|A study by Hevezi P et al, presents "the first comprehensive characterization of gene expression in primate taste buds", as opposed to previous studies which focused on rodents. <ref><pubmed>19636377</pubmed></ref>
[http://www.ncbi.nlm.nih.gov/pubmed/19636377 Genome-wide analysis of gene expression in primate taste buds reveals links to diverse processes]

|- bgcolor="#faecc8"
|style=white-space:nowrap|'''2010'''
|Chandrashekar, J. et al. identify epithelial sodium channel (ENaC) as the sodium-salt taste receptor. <ref><pubmed>20107438</pubmed></ref>
[http://www.ncbi.nlm.nih.gov/pubmed/20107438?dopt=Abstract&holding=npg The cells and peripheral representation of sodium taste in mice]
|}

==Gustatory System==

[[Image:Taste qualities.gif|thumb|The five basic tastes]]

Taste or more appropriately gustation, is a fundamental survival tool in animals as it directs the consumption of essential nutrients. The five tastes that exist within the human gustatory system: salty, sweet, sour, bitter and umami, all signify basic physiological requirements. Salty tastes denote the presence of Na+, an important ion involved in the transportation and retention of water across cell membranes. Sweetness is the recognition of carbohydrates, essential for maintaining optimal brain function and providing the basis for energy production in muscle tissue via ATP [[#Glossary |'''hydrolysis''']]. Similarly umami codes for the presence of L-amino acids, especially L-glutamate which is an integral component of protein synthesis.

These different modalities not only function to maintain the proper intake of nutrients within the body but also, by way of aversion, prohibit the consumption of undesired or poisonous materials. The bitter modality for example is generally regarded as displeasing to the human palate. It represents a high acid content which may be a result of foods which have become rotten or are inherently poisonous to the body.<ref name=PMID20696704><pubmed>20696704</pubmed></ref>

Research has historically limited itself to investigating the mechanisms of these five taste qualities though it must be noted many other modalities may exist. Of particular conjecture is the existence of fatty acid recognition. In the past the detection of fat in food has been attributed to somatosensory inputs <ref name=PMID20696704/> from the tongue, that is, the oily feel and texture of fat rather than its actual ‘taste’ allows the brain to encode for its presence. Further research is therefore required to elicit the precise mechanisms of fat detection.

===Cell Biology===

The five taste qualities are not all detected by the same type of receptor cell located within the taste bud. Like rods and cones in the eye which detect different wavelengths of light, there are specific types of receptors for different tastes. For example, sweet, umami and bitter are recognised by Type II G-protein coupled receptors, whereas sour is related to Type III presynaptic cells. The cell type involved in salty taste transduction is unknown however it is known that sodium ions can enter the receptor cell membrane via ion channel permeation.

====Type II receptors====

When a bitter, sweet or umami ligand binds to a type II G-coupled receptor, a cascade of chemical reactions causes the release of Ca2+ which in turn mediates [[#Glossary |'''exocystosis''']]of ATP. The function of this ATP is threefold:

# Stimulates gustatory nerve afferents which project to gustatory nuclei in the spinal cord
# Excites Type III presynaptic nerve fibres to release serotonin.
# Has a positive feedback effect on type II receptor cells, increasing the level of ATP production.

The role of serotonin is believed to be in the form of lateral inhibition i.e. when a bitter quality is recognised, adjacent receptors for sweetness are deactivated and thus the two tastes may be clearly differentiated. It also has a negative feedback effect on receptor cells, inhibiting umami, bitter and sweet taste transduction.

==Taste Map==
[[Image:Taste map.png|thumb|left|250px|Obsolete idea of the tongue map]]
The idea of a tongue map has disseminated through society for many years. This concept purports that different areas of the tongue are specialised to detect either sweet, salty, sour and bitter tastes. Recent research however has completely nullified such claims and suggests instead that different forms of taste are recognised all over the tongue as well as via the palate. Thus the term ''taste map'' has come to take on a new meaning and that is, the precise areas of taste modalities processing in areas of cortex and its subsequent neural inputs.

===Neural Pathways===

'''First order neurons''' - From the receptors located in the taste buds, gustatory nerve afferents project to the ipsilateral rostral 1/3 of the nucleus tractus solitarius (NTS), located in the medulla. This rostral 1/3 is commonly referred to as the ''gustatory nucleus''.

The ''gustatory nucleus'' receives input from cranial nerves VII (''Facial n.''), IX (''Hypglossal n.''), and X (''Vagus n.'') via special visceral afferent (SVA) nerve fibres. A summary of their functions is as follows:

* ''Facial nerve n''. - carries taste information from the anterior 2/3 of the tongue.
* ''Hypoglossal n.'' - carries taste information from the posterior 1/3 of the tongue.
* ''Vagus n''. - carries taste information from the palate

'''Second order neurons''' - From the NTS second order neurons carry taste information to the Ventral posteromedial (VPM) nucleus in the thalamus.<ref name=PMID21885776/>

Copious scientific conjecture surrounds how each taste modality is transmitted to the brain. The ‘labelled-line’ hypothesis suggests that there are taste specific neurons which exclusively carry that taste modality to cortical areas. In analogous terms it can be viewed like the pipelines leading toward a house. Each pipeline carries its own utility, there is one for gas, another for water and finally for electricity with each terminating in slightly different areas of the house. In the same way, on the tongues there are different receptors for each taste which concurrently have individual nerve tracts leading to the primary gustatory cortex.

Contrapuntally there is electrophysiological evidence that single nerve afferents carry multiple modalities. These studies show one nerve afferent may have both a strong and a weak activation in response to a multiple taste stimuli.

===Cortical Areas===

[[Image:Primary gustatory cortex.png|thumb|Primary gustatory cortex]]

The location of the taste perception centres has been observed via functional magnetic resonance imaging (fMRI) studies. The primary taste cortex has been identified as being located in the anterior insula/frontal operculum (I/fO)<ref name=PMID22245354><pubmed>22245354</pubmed></ref>, with the secondary taste cortex in the caudolateral orbitofrontal cortex.<ref name=PMID21305668><pubmed>21305668</pubmed></ref> Within the insula there are further subdivisions related to each taste modality. Two photon calcium imaging research has outlined certain ’hot-spots’ of activation which are clearly delineated in relation to each taste. For example, the bitter modality is represented on the insula cortex approximately 1mm posterior to the middle cerebral artery whereas the sweet modality is represented 2.5mm rostrodorsal to the bitter field with no apparent overlap.<ref name=PMID21885776><pubmed>21885776</pubmed></ref> These findings lend weight to the idea that there is only one receptor for each taste quality.

It is interesting to note the relationship between taste and the reward centres of the brain. There is evidence of neural input to the ventral tegmental area (the origin of the mesolimbic dopaminergic reward pathway) and nucleus accumbens (involved in the conversion of motivation into physical action).<ref name=PMID21885776/> Neural connections such as this provide the foundations in explaining concepts such as flavour learning and preference. It may also give some insight into chronic problems such as food addiction and craving. As of yet however the gustatory neural network is not well understood and more research is required to elucidate the relationship between pleasure and taste sensation

== Human Weekly Development - Two Prominent Studies ==
Martin Witt and Klaus Reutter of the University of Tubingen in Germany published two prominent studies regarding developing taste buds in humans. Their first study in 1996 was a transmission electron microscopical (TEM) study of the taste bud primordium and its morphological changes during the 8th-15th postovulatory week. Their next study in 1997 built on their previous findings by using Scanning Electron Microscopy (SEM) to observe the development of gustatory [[#Glossary |'''papillae''']]during postovulatory weeks 6-15.

The findings of these two studies are summarized in the table below. The figures provided relate to the images on their respective research papers.

# [http://onlinelibrary.wiley.com/doi/10.1002/(SICI)1097-0185(199612)246:4%3C507::AID-AR10%3E3.0.CO;2-S/pdf Embryonic and early fetal development of human taste buds: a transmission electron microscopical study, 1996]
# [http://chemse.oxfordjournals.org/content/22/6/601.long Scanning electron microscopical studies of developing gustatory papillae in humans, 1997]

===Timeline of Developmental Processes of Human Taste Buds===
{| cellpadding=5 style="border:1px solid #BBB"
|- bgcolor="#89CFF0"
|'''Postovulatory Week'''||'''Description'''||'''Image'''

|- bgcolor="#BCD4E6"
|'''Week 6''' ||
The surface of the developing tongue is covered by nearly flat epithelium (1997, Figure 1). The first gustatory papillae of the tongue appear in the caudal midline near the foramen caecum and the first circumvallate papilla develops on the dorsal midline. <ref name="PMID9455607"><pubmed>9455607</pubmed></ref>
||
image

|- bgcolor="#89CFF0"
| '''Weeks 6 to 7'''||
Nerve fibres approach the basal lamina of lingual epithelium. At this stage the lingual epithelium consists of two to three cell layers and there is not yet any sign of cell specializations indicating early taste bud formation. <ref name=PMID8955790/>
||
Image

|- bgcolor="#BCD4E6"
| '''Week 7 '''||
A series of irregular epithelial swellings in the anterior part and marginal parts of the tongue indicate early forming fungiform papillae. Furthermore, a V-like lane is observed anterior to the [[#Glossary |'''sulcus terminalis''']], which represents a smooth surface for developing circumvallate papillae (1997, Figure 2). Witt M et al observe that these circumvallate papillae are larger than the developing fungiform papillae of the same age, later noting that the fungiform papillae tend to increase in size over the 8-15th weeks of gestation, whilst the size of vallate papillae tend to remain constant during this period. <ref name=PMID9455607/>
||
Image

|- bgcolor="#89CFF0"
| ''' Week 8 ''' ||
* The taste bud primordium are still differentiated, elongated epithelial cells, resting on a slightly developed core of young dermal papilla.
* The lingual epithelium shows first signs of taste bud development as nerve fibres coming from the dermal papilla penetrate the epithelial basal lamina and form synapses with taste bud progenitor cells (1996, Figure 1). These synapses demonstrate the neuronal connection between the taste bud primordium and the central nervous system, reaching a maximum around the 12th to 13th week. However, it is important to note that at this time these cells are still poorly differentiated, elongated epithelial cells.
* Ciliated cells also appear around the 8th week, however the significance of these cells which are scattered randomly across the lingual surface remains unclear. <ref name=PMID8955790/>
||
Image

|- bgcolor="#BCD4E6"
|''' Week 9''' ||
By this stage, although a taste pore is not present, the surface of circumvallate papillae usually contains a taste pit partly filled with microvillus-like processes from the underlying taste bud cells (1997, Figure 10). <ref name=PMID9455607/>
||
Image

|- bgcolor="#89CFF0"
|''' Weeks 10-11''' ||
At this stage, the lingual epithelium compromises of about four cell layers, and the first shallow grooves above the taste bud primordium are developed. Fungiform papillae appear on the lateral margins and the tip of the tongue, containing taste bud primordial that display the first signs of a primitive pore formation (1996, Figure 6). <ref name=PMID8955790/>
||
Image

|- bgcolor="#BCD4E6"
|''' Week 12 ''' ||
Taste bud cells are more clearly differentiated into epithelial cell types II and III. <ref name=PMID8955790/>
||
Image

|- bgcolor="#89CFF0"
|''' Weeks 12-13 ''' ||
At this stage the taste bud primordial are all located on the top of dermal papillae. There is also maximum synapses between cells and afferent nerve fibres, which intermingle with each other to form a plexus-like structure (1996, Figure 6a). <ref name=PMID8955790/>
||
Image

|- bgcolor="#BCD4E6"
|''' Weeks 14 -15 ''' ||
The shape and size of the taste buds primordial begins to resemble those of adult taste buds (1996, Figure 9). By the 14th week the taste pores develop as the taste pits are filled by microvilli, and bubble like vesicles indicate the secretory activity of these cells (1996, Figure 10). However, the tastebuds only achieve a fully developed function in week 15 of gestation with the development of type I cells to produce the mucous material in the taste pit. <ref name=PMID8955790/>
||
Image
|}

==Adult Tongue and Taste Buds – Structure and Function==

'''Structure'''

The tongue is located on the floor of the oral cavity, It is a muscular structure with sensory units crowning. The tongue is divided into an anterior two thirds and a posterior one third. These regions are divided by a V-shaped groove at the back of the tongue (sulcus terminalis). The anterior two thirds of the tongue is covered by stratified squamous epithelium, It contains a roughened surface and has projections called papillae that vary in shape and number.

''''The Image Below is a very simplistic Diagram of the surface of the Tongue showing the locations of the different papillae and other important features'''

{|
| [[Image:Drawing of Tongue.png|500px]]

'''Papillae'''
[[File:Papillae.jpg|Left|thumb|200px|Close up of Human Tongue Papillae]]

There are 4 types of papillae on the tongue.
The most numerous papillae are the filiform papillae, which function to provide a surface that aids in holding food on the tongue during chewing but do not contain taste buds. The larger, less numerous fungiform papillae which contain taste buds, as do foliate papillae. Circumvallate papillae form a wide V at the sulcus terminalis also containing taste bus. There are no papillae or taste buds located on the posterior third of the tongue, having mucosal folds and the lingual tonsils instead.

'''Function'''

The tongue is for tasting, swallowing, and speech.
The functional unit of the taste bud is a taste cell, there are between 50 and 100 taste cells in each taste bud these taste cells represent all 5 different tastes. Historically is was believed that different areas of the tongue were responsible for different taste sensations although this has since been disregarded.[http://users.rcn.com/jkimball.ma.ultranet/BiologyPages/W/Welcome.html] The papillae contain taste buds which are connected to the oral cavity via a taste pore, the function of the taste bud is to transmit a chemical signal from the oral cavity to a taste cell, this chemical signal is the converted into an electrical impulse and delivered to the brain via nerve fibres for interpretation.

'''The Image Below is a very simplistic Hand drawn Diagram of a taste bud, in an extreme close up, cross section view of the the taste bud unit, not to scale'''

[[File:Taste_bud_1.jpg]]

==Abnormalities==

===Knocking out P2X Receptors===

[[File:Image of taste being evoked by visualising ATP release.jpeg|Left|thumb|200px|Evoking taste - ATP release in tongue]]

Gustatory abnormalities has not been widely researched and what has been researched has been through animal testing, most commonly we have found on mice.

In Huang, 2008 this team used the release of the [[#Glossary |'''ectoderm''']], ATP (adenosine triphosphate) as a quantitative measurement of gustatory sensation and taste. This was done by using a comparison of wild type (WT) and double knockout (DKO) mice. P2X receptors, P2X2 and P2X3 were knocked out in the DKO mice. The premise of this article was that knocking out P2X receptors reduces transmitter secretion of ATP in taste buds, therefore they cannot taste.

It should be noted that the taste buds in DKO are functional, but are not stimulated by the administration of tastants.

The transmission of release of ATP is secretion through gap junction hemichannels (pannexin 1 gap junction).

When both P2X2 and P2X3 are knocked out, no taste is elicited. However they found that if either P2X2 OR P2X3 was knocked out there was a taste response. So the inference made from this is that if one of the two receptors from the P2X family was knocked out there still can have taste response. The WT mice showed significant stimulation by tastants whereas DKO had little to no stimulation of ATP release.<ref><pubmed>21940456</pubmed></ref>

===FGF signalling and genes===

Sprouty, or ''Srpy'', genes have been related to regulating the development of circumvillate papillae (CVP). The CVP are large dome shaped papillae, which form a 'V' just in front of the terminal sulcus.

By knocking out ''Spry'' genes using mice which had ''Spry1'' and ''Spry2'' knocked out showed that the number of CVP doubled. However, when Fibroblast [[#Glossary |'''Growth Factor''']] gene ("Fgf10") was absent, the number of CVP was significantly reduced, if not completely absent. The correlation between ''Spry1/2'' and ''Fgf10'' is that ''Spry1/2'' antagonises "Fgf10" to limit the size of the CVP progenitor placode. Exclusive expression of ''Fgf10'' in the [[#Glossary |'''mesenchyme''']] is necessary for the formation of CVP.

'''This image shows the CVP stained with H&E and scanned by Scanning Electron Microscope (SEM)'''
[[File:CVP of WT(top) and DKO(bottom) mice with H&E and SEM.png]]

'''This image shows the location of the CVP and the increased number in DKO mice by SEM'''
[[File:Mouse circumvallate papilla 01.jpg|300px]]

Taste buds develop from the mesenchyme but require local signalling to properly differentiate. Some signalling factors for proper development of taste buds besides FGF are: [[#Glossary |'''Sonic Hedgehog''']] (SHH), Bone Morphogenetic Proteins (BMPs), Epidermal Growth Factor (EGF).

Additionally, this proves that the anterior and posterior developments of the tongue are derived from embryonic tissues, where the anterior tongue is derived from the [[#Glossary |'''ectoderm''']] and the posterior tongue is derived from the [[#Glossary |'''endoderm''']]. Taste buds develop from the mesenchyme but require local signalling to properly differentiate. Some signalling factors for proper development of taste buds besides FGF are: Sonic Hedgehog (SHH), Bone Morphogenetic Proteins (BMPs), Epidermal Growth Factor (EGF).

As mentioned above, this article shows that the anterior and posterior developments of the tongue are derived from embryonic tissues, where the anterior tongue is derived front the ectoderm and the posterior tongue is derived from the endoderm. Secondly, FGF is required to regulate the growth of taste buds, while ''Spry'' genes limit the number of CVP. ''Fgf10''& ''Spry 1&2''work antagonistically through receptor tyrosine kinase (RTK)signalling.

However, the deletion of ''Spry2''led to the increase of CVPs it should be noted that they found that a significant decrease in number of fungiform papillae. Contrastingly, the absence of ''Fgf10'', while leading to the absence of CVPs lead to an increase in number and size of fungiform papillae. Therefore these genes have different effects on the anterior and posterior developing tongue and taste buds.<ref><pubmed>21655085</pubmed></ref>

==Current Research==
We have an evolving understanding of Embryonic Taste development, through the use of state-of-the-art technology and research techniques we are able to make brilliant discoveries that continue to connect the dots of this amazing natural process of human development.
The majority of research in taste development is involving mice, these mammals show similar embryonic pathways to humans and research is performed in ethical and humane methods.

[[File:Histology.jpg|Left|thumb|200px|Image shows histological stains of a mice tongue showing dysplasia]]

'''Synergistic relationships of Six Genes '''

In an animal study using mice by Suzuki Y, Ikeda K, Kawakami K.(2011) Firstly nominating "[[#Glossary |'''Six Genes''']]" as a major component in [[#Glossary |'''gustatory ''']] development, stating that deficiencies in certain Six genes (specifically Six1 & Six4) leads to poor development. Their research also highlights evidence of cooperative relationships between Six genes for normal advance. This experiment involved breeding mice containing exclusively Six1 and Six4 genes and examining the expression of these genes in papillae under high powered microscope observation. Understanding the role of certain genes along with the intrinsic relationships they hold is crucial for the ability to identify possible causes and correction of any abnormalities <ref><pubmed>21978088</pubmed></ref>

'''Neural Crest responsibilities '''

Another Animal Study involving mice explores a new idea of [[#Glossary |'''Neural crest''']] (NC) contribution in taste development, specifically the development of papillae and taste buds. Liu HX, Komatsu Y, Mishina Y, Mistretta CM. (2012) suggest that Neural crest cells travel to the location of the tongue in early embryonic stages, gain epithelium phenotypes, multiply and then differentiate to eventually form taste papillae. The experiment involved the comparison of 2 different types of Cre line mice, which both express Cre gene in neural crest protocol, the different distribution patterns where observed in specific regions that NC is responsible for.<ref><pubmed>22659543</pubmed></ref>

'''Augmentation of Endoderm'''

In an animal study conducted by Rothova M, Thompson H, Lickert H, Tucker AS.(2012) exploring the historically debated issue of endoderm contribution to tongue development showed promising evidence that position of taste buds are patterned by the border of ectoderm and endoderm derivative epithelium. This study was accomplished via microscopic examination of previously stained specimens. Concluding endoderm has direct influence on gustatory develoment <ref><pubmed>22581563</pubmed></ref>

'''Changes in Taste Cells over time'''

Research by
Ozdener H, Spielman AI, Rawson NE.(2012) developing a culture which allows taste cells to survive for up to 12 months, empowers researchers to study the processes of proliferation, differentiation and function. This experiment will provide a precidnet for future study of taste cells, as these cells are able to operate and grow normally. <ref><pubmed>22643728</pubmed></ref>

'''Shh key component of taste bud proginators'''

A [[#Glossary |'''tamoxifen''']]treatment which supresses Sonic hedgehog (Shh) secretion in mice proving to reduce the number of cells visable within papillae, in contrast mice not treated with tamoxifen showed a mark increase of cells within papillae, these cells are assumed to become taste cells in later development.
Specific mice were bred to trace the destination of taste placode cells, the study concluded that Shh expressing placodes are taste bud proginators which in turn become taste cells within taste buds although do not have any prescuros relationship with pappilae. The results were obtain by examination of mice embryos using Bright-field or multichannel fluorescent images through the use of an "Axiocam CCD camera and Axioplan fluorescence microscope with Axiovision software" a study by Harlow, Yang, Williams, Barlow (2011)<ref><pubmed>PMC2674259</pubmed></ref>

'''WNT family exhibit various roles'''

The WNT gene family has a function of signally proteins for various reason such as development, In 2010 Liu, Staubach Grosse, Walton, Saims, Gumucio, Mistretta explored recent findings on the role of WNT's in tongue and papillae development, Concluding that WNT/β-catenin is essential for fungiform papillae differing to WNT5a which proved to be principle in tongue development. Intrinsic chemical mediators were considered by manipulating a tissue culture and then throughaly examined by scanning photomicrograph. <ref><pubmed>PMC2768563</pubmed></ref>

[http://www.surgicalneurologyint.com/article.asp?issn=2152-7806;year=2012;volume=3;issue=1;spage=23;epage=23;aulast=Manjila]
[[File:Abnormal of tongue.jpg|Left|thumb|200px|Image shows and example of tongue abnormalities, this is called "double tongue" each side has independent movement!]]

==Useful links==

==Glossary==

ectoderm- outer germ layer of embryo

endoderm - inner germ layer of embryo

epithelium - basic animal tissue that is composed of tightly packed cells, usually covering the outer portion of organs

exocystosis - movement of contents out of cell

ganglia - the accumulation of a nerve cell body

growth factor - a substance that stimulates the growth of cells

gustatory - anything that relates to the taste sense

hydrolysis - breakdown of a chemical when it reacts with water

mesoderm - middle germ layer of embryo

mesenchyme - multipotential cells

neural crest - a part of the ectoderm found on both sides of the neural tube

neuron - most simplistic unit of the nervous system

neurotransmitter - chemicals which allow the passing of signals from neuron to neuron via connecting part (synapse)

papillae - small rough surface projection

six genes - a family of genes

Sonic hedgehog (Shh) - signalling protein invloved in normal development

sulcus terminalis - describes a physical transition point separating the anterior 2/3 of the tongue from the posterior 1/3

tamoxifen - hormonal altering drug

== References ==
<references/>

==External Links==
{{External Links}}

http://www.webmd.com/oral-health/picture-of-the-tongue

http://www.tutorvista.com/content/biology/biology-iv/nervous-coordination/tongue-structure.php#parts-of-tongue

http://www.cf.ac.uk/biosi/staffinfo/jacob/teaching/sensory/taste.html

--[[User:Z8600021|Mark Hill]] 12:22, 15 August 2012 (EST) Please leave the content listed below the line at the bottom of your project page.

----

{{2012Projects}}

2012 Group Project 3

2012-09-30T11:10:37Z

Z3289738:

=Taste Development=

== Introduction ==
**NEED TO ADD**

==History of Discoveries==

{| cellpadding=5 style="border:1px solid #BBB"
|- bgcolor="#faecc8"
|''' Date'''|| '''Significant Discovery'''

|- bgcolor="#faf6ed"
|'''350BC'''
|| Aristotle writes about the basic tastes, sweet and bitter. He also notes that it can be modified by salty and acidic. <ref name="PMID22717400"><pubmed>22717400</pubmed></ref>

|- bgcolor="#faecc8"
|'''1901'''
|| D. Hanig publishes a paper describing taste sensitivity in different regions of the tongue.
''Interesting fact:'' The modern concept of a 'tongue map' is a misinterpretation of this study. <ref name="PMID22717400"/>

|- bgcolor="#faf6ed"
|style=white-space:nowrap|'''1908'''
|Kikunae Ikeda, a professor of the Tokyo Imperial University, discovered and identified the fifth basic taste: umami (savouriness), made palatable by glutamate. <ref><pubmed>12438213</pubmed></ref>
[http://chemse.oxfordjournals.org/content/27/9/847.long New Seasonings]

|- bgcolor="#faecc8"
|style=white-space:nowrap|'''1931-32'''
| A chemist named Arthur Fox and his college noted that they had different sensitivities to the bitter tasting Phenylthiocarbamide (PTC).<ref>Blakeslee AF, Fox AL. Our different taste worlds. J Hered. 1932;23:97–107.</ref> Geneticists later confirm these findings, and discover that non-tasting is a recessive genetic trait. <ref><pubmed>17782493</pubmed></ref>
[http://www.ncbi.nlm.nih.gov/pubmed/17782493 Inherited taste deficiency]

|- bgcolor="#faf6ed"
|style=white-space:nowrap|'''1965'''
|Farbman's study of the developing taste but in rat fungiform papilla was significant in increasing our understanding of taste bud development. <ref><pubmed>14300090</pubmed></ref>
[http://www.sciencedirect.com/science/article/pii/0012160665900400 Electron microscope study of the developing taste bud in rat fungiform papilla.]

|- bgcolor="#faecc8"
|style=white-space:nowrap|'''1992'''
|McLaughlin SK et al. discovery a taste cell-specific G-protein within the taste buds called Gustucon. This protein is later used to mark bitter, umami and sweet cells. <ref><pubmed>1608467 </pubmed></ref>
[http://www.nature.com/nature/journal/v357/n6379/abs/357563a0.html Gustducin is a taste-cell-specific G protein closely related to the transducins]

|- bgcolor="#faf6ed"
|style=white-space:nowrap|'''1995'''
|Barlow et al. experimented with Axolotl salamanders and concluded that taste buds from this species arise exclusively from epithelial tissue, "oropharyngeal [[#Glossary |'''epithelium''']]". <ref name="PMID17826760"><pubmed>17826760</pubmed></ref>
[http://www.ncbi.nlm.nih.gov/pubmed/17826760 Embryonic origin of gustatory cranial sensory [[#Glossary |'''neuron''']]s.]

|- bgcolor="#faecc8"
|style=white-space:nowrap|'''1996'''
| Witt M and Reutter K of the Technical University Dresden in Germany, carried out a transmission electron microscopy study to investigate the embryonic and fetal development of Human taste buds. Their results suggest an "at least dual function of embryonic/fetal taste buds", including non-gustatory, paracrine functions prior to the 14th week and gustatory after the 14th week. <ref name="PMID8955790"><pubmed>8955790</pubmed></ref>
[http://www.ncbi.nlm.nih.gov/pubmed/8955790 Embryonic and early fetal development of human taste buds: a transmission electron microscopical study]

|- bgcolor="#faf6ed"
|style=white-space:nowrap|'''2000'''
|Chandrashekar, J. et al. discover the first taste sonsors, the T2R bitter taste receptors. <ref><pubmed>10761935</pubmed></ref>
[http://www.sciencedirect.com/science/article/pii/S0092867400807060 T2Rs Function as Bitter Taste Receptors]

|- bgcolor="#faecc8"
|style=white-space:nowrap|'''2001'''
|Nelson, G. et al. discover the sweet receptor: a combination of T1R2 and T1R3. <ref><pubmed>11509186</pubmed></ref>
[http://www.ncbi.nlm.nih.gov/pubmed/11509186?dopt=Abstract&holding=npg Mammalian sweet taste receptors.]

|- bgcolor="#faf6ed"
|style=white-space:nowrap|'''2002'''
|Nelson G. et al. discover the amino acid (umami) taste receptor: a combination of T1R1 and T1R3 identified. <ref><pubmed>11894099</pubmed></ref>
[http://www.ncbi.nlm.nih.gov/pubmed/11894099?dopt=Abstract&holding=npg An amino-acid taste receptor]

|- bgcolor="#faecc8"
|style=white-space:nowrap|'''2005'''
|Dyer, J. et al. discover sweet taste receptors in the GI tract. <ref><pubmed>17855558</pubmed></ref>
[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1986582/ Sweet taste signaling in the gut]

|- bgcolor="#faf6ed"
|style=white-space:nowrap|'''2006'''
|Huang, A. L et al. discover cells for sour taste, identified by PKD2L1 (a polycystic kidney disease-like ion channel). <ref><pubmed>16929298</pubmed></ref>
[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1571047/ The Cells and Logic for Mammalian Sour Taste detection]

|- bgcolor="#faecc8"
|style=white-space:nowrap|'''2007'''
|Harlow DE, Barlow LA of the University of Colorado Denver Health Sciences Center provide evidence of the "embryonic origin of gustatory cranial sensory neurons". <ref name="PMID17826760"/>
[http://www.ncbi.nlm.nih.gov/pubmed/17826760 Embryonic origin of gustatory cranial sensory neurons.]

|- bgcolor="#faf6ed"
|style=white-space:nowrap|'''2009'''
|A study by Hevezi P et al, presents "the first comprehensive characterization of gene expression in primate taste buds", as opposed to previous studies which focused on rodents. <ref><pubmed>19636377</pubmed></ref>
[http://www.ncbi.nlm.nih.gov/pubmed/19636377 Genome-wide analysis of gene expression in primate taste buds reveals links to diverse processes]

|- bgcolor="#faecc8"
|style=white-space:nowrap|'''2010'''
|Chandrashekar, J. et al. identify epithelial sodium channel (ENaC) as the sodium-salt taste receptor. <ref><pubmed>20107438</pubmed></ref>
[http://www.ncbi.nlm.nih.gov/pubmed/20107438?dopt=Abstract&holding=npg The cells and peripheral representation of sodium taste in mice]
|}

==Gustatory System==

[[Image:Taste qualities.gif|thumb|The five basic tastes]]

Taste or more appropriately gustation, is a fundamental survival tool in animals as it directs the consumption of essential nutrients. The five tastes that exist within the human gustatory system: salty, sweet, sour, bitter and umami, all signify basic physiological requirements. Salty tastes denote the presence of Na+, an important ion involved in the transportation and retention of water across cell membranes. Sweetness is the recognition of carbohydrates, essential for maintaining optimal brain function and providing the basis for energy production in muscle tissue via ATP [[#Glossary |'''hydrolysis''']]. Similarly umami codes for the presence of L-amino acids, especially L-glutamate which is an integral component of protein synthesis.

These different modalities not only function to maintain the proper intake of nutrients within the body but also, by way of aversion, prohibit the consumption of undesired or poisonous materials. The bitter modality for example is generally regarded as displeasing to the human palate. It represents a high acid content which may be a result of foods which have become rotten or are inherently poisonous to the body.<ref name=PMID20696704><pubmed>20696704</pubmed></ref>

Research has historically limited itself to investigating the mechanisms of these five taste qualities though it must be noted many other modalities may exist. Of particular conjecture is the existence of fatty acid recognition. In the past the detection of fat in food has been attributed to somatosensory inputs <ref name=PMID20696704/> from the tongue, that is, the oily feel and texture of fat rather than its actual ‘taste’ allows the brain to encode for its presence. Further research is therefore required to elicit the precise mechanisms of fat detection.

===Cell Biology===

The five taste qualities are not all detected by the same type of receptor cell located within the taste bud. Like rods and cones in the eye which detect different wavelengths of light, there are specific types of receptors for different tastes. For example, sweet, umami and bitter are recognised by Type II G-protein coupled receptors, whereas sour is related to Type III presynaptic cells. The cell type involved in salty taste transduction is unknown however it is known that sodium ions can enter the receptor cell membrane via ion channel permeation.

====Type II receptors====

When a bitter, sweet or umami ligand binds to a type II G-coupled receptor, a cascade of chemical reactions causes the release of Ca2+ which in turn mediates [[#Glossary |'''exocystosis''']]of ATP. The function of this ATP is threefold:

# Stimulates gustatory nerve afferents which project to gustatory nuclei in the spinal cord
# Excites Type III presynaptic nerve fibres to release serotonin.
# Has a positive feedback effect on type II receptor cells, increasing the level of ATP production.

The role of serotonin is believed to be in the form of lateral inhibition i.e. when a bitter quality is recognised, adjacent receptors for sweetness are deactivated and thus the two tastes may be clearly differentiated. It also has a negative feedback effect on receptor cells, inhibiting umami, bitter and sweet taste transduction.

==Taste Map==
[[Image:Taste map.png|thumb|left|250px|Obsolete idea of the tongue map]]
The idea of a tongue map has disseminated through society for many years. This concept purports that different areas of the tongue are specialised to detect either sweet, salty, sour and bitter tastes. Recent research however has completely nullified such claims and suggests instead that different forms of taste are recognised all over the tongue as well as via the palate. Thus the term ''taste map'' has come to take on a new meaning and that is, the precise areas of taste modalities processing in areas of cortex and its subsequent neural inputs.

===Neural Pathways===

'''First order neurons''' - From the receptors located in the taste buds, gustatory nerve afferents project to the ipsilateral rostral 1/3 of the nucleus tractus solitarius (NTS), located in the medulla. This rostral 1/3 is commonly referred to as the ''gustatory nucleus''.

The ''gustatory nucleus'' receives input from cranial nerves VII (''Facial n.''), IX (''Hypglossal n.''), and X (''Vagus n.'') via special visceral afferent (SVA) nerve fibres. A summary of their functions is as follows:

* ''Facial nerve n''. - carries taste information from the anterior 2/3 of the tongue.
* ''Hypoglossal n.'' - carries taste information from the posterior 1/3 of the tongue.
* ''Vagus n''. - carries taste information from the palate

'''Second order neurons''' - From the NTS second order neurons carry taste information to the Ventral posteromedial (VPM) nucleus in the thalamus.<ref name=PMID21885776/>

Copious scientific conjecture surrounds how each taste modality is transmitted to the brain. The ‘labelled-line’ hypothesis suggests that there are taste specific neurons which exclusively carry that taste modality to cortical areas. In analogous terms it can be viewed like the pipelines leading toward a house. Each pipeline carries its own utility, there is one for gas, another for water and finally for electricity with each terminating in slightly different areas of the house. In the same way, on the tongues there are different receptors for each taste which concurrently have individual nerve tracts leading to the primary gustatory cortex.

Contrapuntally there is electrophysiological evidence that single nerve afferents carry multiple modalities. These studies show one nerve afferent may have both a strong and a weak activation in response to a multiple taste stimuli.

===Cortical Areas===

[[Image:Primary gustatory cortex.png|thumb|Primary gustatory cortex]]

The location of the taste perception centres has been observed via functional magnetic resonance imaging (fMRI) studies. The primary taste cortex has been identified as being located in the anterior insula/frontal operculum (I/fO)<ref name=PMID22245354><pubmed>22245354</pubmed></ref>, with the secondary taste cortex in the caudolateral orbitofrontal cortex.<ref name=PMID21305668><pubmed>21305668</pubmed></ref> Within the insula there are further subdivisions related to each taste modality. Two photon calcium imaging research has outlined certain ’hot-spots’ of activation which are clearly delineated in relation to each taste. For example, the bitter modality is represented on the insula cortex approximately 1mm posterior to the middle cerebral artery whereas the sweet modality is represented 2.5mm rostrodorsal to the bitter field with no apparent overlap.<ref name=PMID21885776><pubmed>21885776</pubmed></ref> These findings lend weight to the idea that there is only one receptor for each taste quality.

It is interesting to note the relationship between taste and the reward centres of the brain. There is evidence of neural input to the ventral tegmental area (the origin of the mesolimbic dopaminergic reward pathway) and nucleus accumbens (involved in the conversion of motivation into physical action).<ref name=PMID21885776/> Neural connections such as this provide the foundations in explaining concepts such as flavour learning and preference. It may also give some insight into chronic problems such as food addiction and craving. As of yet however the gustatory neural network is not well understood and more research is required to elucidate the relationship between pleasure and taste sensation

== Human Weekly Development - Two Prominent Studies ==
Martin Witt and Klaus Reutter of the University of Tubingen in Germany published two prominent studies regarding developing taste buds in humans. Their first study in 1996 was a transmission electron microscopical (TEM) study of the taste bud primordium and its morphological changes during the 8th-15th postovulatory week. Their next study in 1997 built on their previous findings by using Scanning Electron Microscopy (SEM) to observe the development of gustatory [[#Glossary |'''papillae''']]during postovulatory weeks 6-15.

The findings of these two studies are summarized in the table below. The figures provided relate to the images on their respective research papers.

# [http://onlinelibrary.wiley.com/doi/10.1002/(SICI)1097-0185(199612)246:4%3C507::AID-AR10%3E3.0.CO;2-S/pdf Embryonic and early fetal development of human taste buds: a transmission electron microscopical study, 1996]
# [http://chemse.oxfordjournals.org/content/22/6/601.long Scanning electron microscopical studies of developing gustatory papillae in humans, 1997]

===Timeline of Developmental Processes of Human Taste Buds===
{| cellpadding=5 style="border:1px solid #BBB"
|- bgcolor="#89CFF0"
|'''Postovulatory Week'''||'''Description'''||'''Image'''

|- bgcolor="#BCD4E6"
|'''Week 6''' ||
The surface of the developing tongue is covered by nearly flat epithelium (1997, Figure 1). The first gustatory papillae of the tongue appear in the caudal midline near the foramen caecum and the first circumvallate papilla develops on the dorsal midline. <ref name="PMID9455607"><pubmed>9455607</pubmed></ref>
||
image

|- bgcolor="#89CFF0"
| '''Weeks 6 to 7'''||
Nerve fibres approach the basal lamina of lingual epithelium. At this stage the lingual epithelium consists of two to three cell layers and there is not yet any sign of cell specializations indicating early taste bud formation. <ref name=PMID8955790/>
||
Image

|- bgcolor="#BCD4E6"
| '''Week 7 '''||
A series of irregular epithelial swellings in the anterior part and marginal parts of the tongue indicate early forming fungiform papillae. Furthermore, a V-like lane is observed anterior to the [[#Glossary |'''sulcus terminalis''']], which represents a smooth surface for developing circumvallate papillae (1997, Figure 2). Witt M et al observe that these circumvallate papillae are larger than the developing fungiform papillae of the same age, later noting that the fungiform papillae tend to increase in size over the 8-15th weeks of gestation, whilst the size of vallate papillae tend to remain constant during this period. <ref name=PMID9455607/>
||
Image

|- bgcolor="#89CFF0"
| ''' Week 8 ''' ||
* The taste bud primordium are still differentiated, elongated epithelial cells, resting on a slightly developed core of young dermal papilla.
* The lingual epithelium shows first signs of taste bud development as nerve fibres coming from the dermal papilla penetrate the epithelial basal lamina and form synapses with taste bud progenitor cells (1996, Figure 1). These synapses demonstrate the neuronal connection between the taste bud primordium and the central nervous system, reaching a maximum around the 12th to 13th week. However, it is important to note that at this time these cells are still poorly differentiated, elongated epithelial cells.
* Ciliated cells also appear around the 8th week, however the significance of these cells which are scattered randomly across the lingual surface remains unclear. <ref name=PMID8955790/>
||
Image

|- bgcolor="#BCD4E6"
|''' Week 9''' ||
By this stage, although a taste pore is not present, the surface of circumvallate papillae usually contains a taste pit partly filled with microvillus-like processes from the underlying taste bud cells (1997, Figure 10). <ref name=PMID9455607/>
||
Image

|- bgcolor="#89CFF0"
|''' Weeks 10-11''' ||
At this stage, the lingual epithelium compromises of about four cell layers, and the first shallow grooves above the taste bud primordium are developed. Fungiform papillae appear on the lateral margins and the tip of the tongue, containing taste bud primordial that display the first signs of a primitive pore formation (1996, Figure 6). <ref name=PMID8955790/>
||
Image

|- bgcolor="#BCD4E6"
|''' Week 12 ''' ||
Taste bud cells are more clearly differentiated into epithelial cell types II and III. <ref name=PMID8955790/>
||
Image

|- bgcolor="#89CFF0"
|''' Weeks 12-13 ''' ||
At this stage the taste bud primordial are all located on the top of dermal papillae. There is also maximum synapses between cells and afferent nerve fibres, which intermingle with each other to form a plexus-like structure (1996, Figure 6a). <ref name=PMID8955790/>
||
Image

|- bgcolor="#BCD4E6"
|''' Weeks 14 -15 ''' ||
The shape and size of the taste buds primordial begins to resemble those of adult taste buds (1996, Figure 9). By the 14th week the taste pores develop as the taste pits are filled by microvilli, and bubble like vesicles indicate the secretory activity of these cells (1996, Figure 10). However, the tastebuds only achieve a fully developed function in week 15 of gestation with the development of type I cells to produce the mucous material in the taste pit. <ref name=PMID8955790/>
||
Image
|}

==Adult Tongue and Taste Buds – Structure and Function==

'''Structure'''

The tongue is located on the floor of the oral cavity, It is a muscular structure with sensory units crowning. The tongue is divided into an anterior two thirds and a posterior one third. These regions are divided by a V-shaped groove at the back of the tongue (sulcus terminalis). The anterior two thirds of the tongue is covered by stratified squamous epithelium, It contains a roughened surface and has projections called papillae that vary in shape and number.

''''The Image Below is a very simplistic Diagram of the surface of the Tongue showing the locations of the different papillae and other important features'''

{|
| [[Image:Drawing of Tongue.png|500px]]

'''Papillae'''
[[File:Papillae.jpg|Left|thumb|200px|Close up of Human Tongue Papillae]]

There are 4 types of papillae on the tongue.
The most numerous papillae are the filiform papillae, which function to provide a surface that aids in holding food on the tongue during chewing but do not contain taste buds. The larger, less numerous fungiform papillae which contain taste buds, as do foliate papillae. Circumvallate papillae form a wide V at the sulcus terminalis also containing taste bus. There are no papillae or taste buds located on the posterior third of the tongue, having mucosal folds and the lingual tonsils instead.

'''Function'''

The tongue is for tasting, swallowing, and speech.
The functional unit of the taste bud is a taste cell, there are between 50 and 100 taste cells in each taste bud these taste cells represent all 5 different tastes. Historically is was believed that different areas of the tongue were responsible for different taste sensations although this has since been disregarded.[http://users.rcn.com/jkimball.ma.ultranet/BiologyPages/W/Welcome.html] The papillae contain taste buds which are connected to the oral cavity via a taste pore, the function of the taste bud is to transmit a chemical signal from the oral cavity to a taste cell, this chemical signal is the converted into an electrical impulse and delivered to the brain via nerve fibres for interpretation.

'''The Image Below is a very simplistic Hand drawn Diagram of a taste bud, in an extreme close up, cross section view of the the taste bud unit, not to scale'''

[[File:Taste_bud_1.jpg]]

==Abnormalities==

===Knocking out P2X Receptors===

[[File:Image of taste being evoked by visualising ATP release.jpeg|Left|thumb|200px|Evoking taste - ATP release in tongue]]

Gustatory abnormalities has not been widely researched and what has been researched has been through animal testing, most commonly we have found on mice.

In Huang, 2008 this team used the release of the [[#Glossary |'''ectoderm''']], ATP (adenosine triphosphate) as a quantitative measurement of gustatory sensation and taste. This was done by using a comparison of wild type (WT) and double knockout (DKO) mice. P2X receptors, P2X2 and P2X3 were knocked out in the DKO mice. The premise of this article was that knocking out P2X receptors reduces transmitter secretion of ATP in taste buds, therefore they cannot taste.

It should be noted that the taste buds in DKO are functional, but are not stimulated by the administration of tastants.

The transmission of release of ATP is secretion through gap junction hemichannels (pannexin 1 gap junction).

When both P2X2 and P2X3 are knocked out, no taste is elicited. However they found that if either P2X2 OR P2X3 was knocked out there was a taste response. So the inference made from this is that if one of the two receptors from the P2X family was knocked out there still can have taste response. The WT mice showed significant stimulation by tastants whereas DKO had little to no stimulation of ATP release.<ref><pubmed>21940456</pubmed></ref>

===FGF signalling and genes===

Sprouty, or ''Srpy'', genes have been related to regulating the development of circumvillate papillae (CVP). The CVP are large dome shaped papillae, which form a 'V' just in front of the terminal sulcus.

By knocking out ''Spry'' genes using mice which had ''Spry1'' and ''Spry2'' knocked out showed that the number of CVP doubled. However, when Fibroblast [[#Glossary |'''Growth Factor''']] gene ("Fgf10") was absent, the number of CVP was significantly reduced, if not completely absent. The correlation between ''Spry1/2'' and ''Fgf10'' is that ''Spry1/2'' antagonises "Fgf10" to limit the size of the CVP progenitor placode. Exclusive expression of ''Fgf10'' in the [[#Glossary |'''mesenchyme''']] is necessary for the formation of CVP.

'''This image shows the CVP stained with H&E and scanned by Scanning Electron Microscope (SEM)'''
[[File:CVP of WT(top) and DKO(bottom) mice with H&E and SEM.png]]

'''This image shows the location of the CVP and the increased number in DKO mice by SEM'''
[[File:Mouse circumvallate papilla 01.jpg|300px]]

Taste buds develop from the mesenchyme but require local signalling to properly differentiate. Some signalling factors for proper development of taste buds besides FGF are: [[#Glossary |'''Sonic Hedgehog''']] (SHH), Bone Morphogenetic Proteins (BMPs), Epidermal Growth Factor (EGF).

Additionally, this proves that the anterior and posterior developments of the tongue are derived from embryonic tissues, where the anterior tongue is derived from the [[#Glossary |'''ectoderm''']] and the posterior tongue is derived from the [[#Glossary |'''endoderm''']]. Taste buds develop from the mesenchyme but require local signalling to properly differentiate. Some signalling factors for proper development of taste buds besides FGF are: Sonic Hedgehog (SHH), Bone Morphogenetic Proteins (BMPs), Epidermal Growth Factor (EGF).

As mentioned above, this article shows that the anterior and posterior developments of the tongue are derived from embryonic tissues, where the anterior tongue is derived front the ectoderm and the posterior tongue is derived from the endoderm. Secondly, FGF is required to regulate the growth of taste buds, while ''Spry'' genes limit the number of CVP. ''Fgf10''& ''Spry 1&2''work antagonistically through receptor tyrosine kinase (RTK)signalling.

However, the deletion of ''Spry2''led to the increase of CVPs it should be noted that they found that a significant decrease in number of fungiform papillae. Contrastingly, the absence of ''Fgf10'', while leading to the absence of CVPs lead to an increase in number and size of fungiform papillae. Therefore these genes have different effects on the anterior and posterior developing tongue and taste buds.<ref><pubmed>21655085</pubmed></ref>

==Current Research==
We have an evolving understanding of Embryonic Taste development, through the use of state-of-the-art technology and research techniques we are able to make brilliant discoveries that continue to connect the dots of this amazing natural process of human development.
The majority of research in taste development is involving mice, these mammals show similar embryonic pathways to humans and research is performed in ethical and humane methods.

[[File:Histology.jpg|Left|thumb|200px|Image shows histological stains of a mice tongue showing dysplasia]]

'''Synergistic relationships of Six Genes '''

In an animal study using mice by Suzuki Y, Ikeda K, Kawakami K.(2011) Firstly nominating "[[#Glossary |'''Six Genes''']]" as a major component in [[#Glossary |'''gustatory ''']] development, stating that deficiencies in certain Six genes (specifically Six1 & Six4) leads to poor development. Their research also highlights evidence of cooperative relationships between Six genes for normal advance. This experiment involved breeding mice containing exclusively Six1 and Six4 genes and examining the expression of these genes in papillae under high powered microscope observation. Understanding the role of certain genes along with the intrinsic relationships they hold is crucial for the ability to identify possible causes and correction of any abnormalities <ref><pubmed>21978088</pubmed></ref>

'''Neural Crest responsibilities '''

Another Animal Study involving mice explores a new idea of [[#Glossary |'''Neural crest''']] (NC) contribution in taste development, specifically the development of papillae and taste buds. Liu HX, Komatsu Y, Mishina Y, Mistretta CM. (2012) suggest that Neural crest cells travel to the location of the tongue in early embryonic stages, gain epithelium phenotypes, multiply and then differentiate to eventually form taste papillae. The experiment involved the comparison of 2 different types of Cre line mice, which both express Cre gene in neural crest protocol, the different distribution patterns where observed in specific regions that NC is responsible for.<ref><pubmed>22659543</pubmed></ref>

'''Augmentation of Endoderm'''

In an animal study conducted by Rothova M, Thompson H, Lickert H, Tucker AS.(2012) exploring the historically debated issue of endoderm contribution to tongue development showed promising evidence that position of taste buds are patterned by the border of ectoderm and endoderm derivative epithelium. This study was accomplished via microscopic examination of previously stained specimens. Concluding endoderm has direct influence on gustatory develoment <ref><pubmed>22581563</pubmed></ref>

'''Changes in Taste Cells over time'''

Research by
Ozdener H, Spielman AI, Rawson NE.(2012) developing a culture which allows taste cells to survive for up to 12 months, empowers researchers to study the processes of proliferation, differentiation and function. This experiment will provide a precidnet for future study of taste cells, as these cells are able to operate and grow normally. <ref><pubmed>22643728</pubmed></ref>

'''Shh key component of taste bud proginators'''

A [[#Glossary |'''tamoxifen''']]treatment which supresses Sonic hedgehog (Shh) secretion in mice proving to reduce the number of cells visable within papillae, in contrast mice not treated with tamoxifen showed a mark increase of cells within papillae, these cells are assumed to become taste cells in later development.
Specific mice were bred to trace the destination of taste placode cells, the study concluded that Shh expressing placodes are taste bud proginators which in turn become taste cells within taste buds although do not have any prescuros relationship with pappilae. The results were obtain by examination of mice embryos using Bright-field or multichannel fluorescent images through the use of an "Axiocam CCD camera and Axioplan fluorescence microscope with Axiovision software" a study by Harlow, Yang, Williams, Barlow (2011)<ref><pubmed>PMC2674259</pubmed></ref>

'''WNT family exhibit various roles'''

The WNT gene family has a function of signally proteins for various reason such as development, In 2010 Liu, Staubach Grosse, Walton, Saims, Gumucio, Mistretta explored recent findings on the role of WNT's in tongue and papillae development, Concluding that WNT/β-catenin is essential for fungiform papillae differing to WNT5a which proved to be principle in tongue development. Intrinsic chemical mediators were considered by manipulating a tissue culture and then throughaly examined by scanning photomicrograph. <ref><pubmed>PMC2768563</pubmed></ref>

[http://www.surgicalneurologyint.com/article.asp?issn=2152-7806;year=2012;volume=3;issue=1;spage=23;epage=23;aulast=Manjila]
[[File:Abnormal of tongue.jpg|Left|thumb|200px|Image shows and example of tongue abnormalities, this is called "double tongue" each side has independent movement!]]

==Useful links==

==Glossary==

ectoderm- outer germ layer of embryo

endoderm - inner germ layer of embryo

epithelium - basic animal tissue that is composed of tightly packed cells, usually covering the outer portion of organs

exocystosis - movement of contents out of cell

ganglia - the accumulation of a nerve cell body

growth factor - a substance that stimulates the growth of cells

gustatory - anything that relates to the taste sense

hydrolysis - breakdown of a chemical when it reacts with water

mesoderm - middle germ layer of embryo

mesenchyme - multipotential cells

neural crest - a part of the ectoderm found on both sides of the neural tube

neuron - most simplistic unit of the nervous system

neurotransmitter - chemicals which allow the passing of signals from neuron to neuron via connecting part (synapse)

papillae - small rough surface projection

six genes - a family of genes

Sonic hedgehog (Shh) - signalling protein invloved in normal development

sulcus terminalis - describes a physical transition point separating the anterior 2/3 of the tongue from the posterior 1/3

tamoxifen - hormonal altering drug

==Image gallery==

== References ==
<references/>

==External Links==
{{External Links}}

http://www.webmd.com/oral-health/picture-of-the-tongue

http://www.tutorvista.com/content/biology/biology-iv/nervous-coordination/tongue-structure.php#parts-of-tongue

http://www.cf.ac.uk/biosi/staffinfo/jacob/teaching/sensory/taste.html

--[[User:Z8600021|Mark Hill]] 12:22, 15 August 2012 (EST) Please leave the content listed below the line at the bottom of your project page.

----

{{2012Projects}}

2012 Group Project 3

2012-09-30T11:02:13Z

Z3289738: /* FGF signalling and genes */

=Taste Development=

== Introduction ==
**NEED TO ADD**

==History of Discoveries==

{| cellpadding=5 style="border:1px solid #BBB"
|- bgcolor="#faecc8"
|''' Date'''|| '''Significant Discovery'''

|- bgcolor="#faf6ed"
|'''350BC'''
|| Aristotle writes about the basic tastes, sweet and bitter. He also notes that it can be modified by salty and acidic. <ref name="PMID22717400"><pubmed>22717400</pubmed></ref>

|- bgcolor="#faecc8"
|'''1901'''
|| D. Hanig publishes a paper describing taste sensitivity in different regions of the tongue.
''Interesting fact:'' The modern concept of a 'tongue map' is a misinterpretation of this study. <ref name="PMID22717400"/>

|- bgcolor="#faf6ed"
|style=white-space:nowrap|'''1908'''
|Kikunae Ikeda, a professor of the Tokyo Imperial University, discovered and identified the fifth basic taste: umami (savouriness), made palatable by glutamate. <ref><pubmed>12438213</pubmed></ref>
[http://chemse.oxfordjournals.org/content/27/9/847.long New Seasonings]

|- bgcolor="#faecc8"
|style=white-space:nowrap|'''1931-32'''
| A chemist named Arthur Fox and his college noted that they had different sensitivities to the bitter tasting Phenylthiocarbamide (PTC).<ref>Blakeslee AF, Fox AL. Our different taste worlds. J Hered. 1932;23:97–107.</ref> Geneticists later confirm these findings, and discover that non-tasting is a recessive genetic trait. <ref><pubmed>17782493</pubmed></ref>
[http://www.ncbi.nlm.nih.gov/pubmed/17782493 Inherited taste deficiency]

|- bgcolor="#faf6ed"
|style=white-space:nowrap|'''1965'''
|Farbman's study of the developing taste but in rat fungiform papilla was significant in increasing our understanding of taste bud development. <ref><pubmed>14300090</pubmed></ref>
[http://www.sciencedirect.com/science/article/pii/0012160665900400 Electron microscope study of the developing taste bud in rat fungiform papilla.]

|- bgcolor="#faecc8"
|style=white-space:nowrap|'''1992'''
|McLaughlin SK et al. discovery a taste cell-specific G-protein within the taste buds called Gustucon. This protein is later used to mark bitter, umami and sweet cells. <ref><pubmed>1608467 </pubmed></ref>
[http://www.nature.com/nature/journal/v357/n6379/abs/357563a0.html Gustducin is a taste-cell-specific G protein closely related to the transducins]

|- bgcolor="#faf6ed"
|style=white-space:nowrap|'''1995'''
|Barlow et al. experimented with Axolotl salamanders and concluded that taste buds from this species arise exclusively from epithelial tissue, "oropharyngeal epithelium". <ref name="PMID17826760"><pubmed>17826760</pubmed></ref>
[http://www.ncbi.nlm.nih.gov/pubmed/17826760 Embryonic origin of gustatory cranial sensory neurons.]

|- bgcolor="#faecc8"
|style=white-space:nowrap|'''1996'''
| Witt M and Reutter K of the Technical University Dresden in Germany, carried out a transmission electron microscopy study to investigate the embryonic and fetal development of Human taste buds. Their results suggest an "at least dual function of embryonic/fetal taste buds", including non-gustatory, paracrine functions prior to the 14th week and gustatory after the 14th week. <ref name="PMID8955790"><pubmed>8955790</pubmed></ref>
[http://www.ncbi.nlm.nih.gov/pubmed/8955790 Embryonic and early fetal development of human taste buds: a transmission electron microscopical study]

|- bgcolor="#faf6ed"
|style=white-space:nowrap|'''2000'''
|Chandrashekar, J. et al. discover the first taste sonsors, the T2R bitter taste receptors. <ref><pubmed>10761935</pubmed></ref>
[http://www.sciencedirect.com/science/article/pii/S0092867400807060 T2Rs Function as Bitter Taste Receptors]

|- bgcolor="#faecc8"
|style=white-space:nowrap|'''2001'''
|Nelson, G. et al. discover the sweet receptor: a combination of T1R2 and T1R3. <ref><pubmed>11509186</pubmed></ref>
[http://www.ncbi.nlm.nih.gov/pubmed/11509186?dopt=Abstract&holding=npg Mammalian sweet taste receptors.]

|- bgcolor="#faf6ed"
|style=white-space:nowrap|'''2002'''
|Nelson G. et al. discover the amino acid (umami) taste receptor: a combination of T1R1 and T1R3 identified. <ref><pubmed>11894099</pubmed></ref>
[http://www.ncbi.nlm.nih.gov/pubmed/11894099?dopt=Abstract&holding=npg An amino-acid taste receptor]

|- bgcolor="#faecc8"
|style=white-space:nowrap|'''2005'''
|Dyer, J. et al. discover sweet taste receptors in the GI tract. <ref><pubmed>17855558</pubmed></ref>
[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1986582/ Sweet taste signaling in the gut]

|- bgcolor="#faf6ed"
|style=white-space:nowrap|'''2006'''
|Huang, A. L et al. discover cells for sour taste, identified by PKD2L1 (a polycystic kidney disease-like ion channel). <ref><pubmed>16929298</pubmed></ref>
[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1571047/ The Cells and Logic for Mammalian Sour Taste detection]

|- bgcolor="#faecc8"
|style=white-space:nowrap|'''2007'''
|Harlow DE, Barlow LA of the University of Colorado Denver Health Sciences Center provide evidence of the "embryonic origin of gustatory cranial sensory neurons". <ref name="PMID17826760"/>
[http://www.ncbi.nlm.nih.gov/pubmed/17826760 Embryonic origin of gustatory cranial sensory neurons.]

|- bgcolor="#faf6ed"
|style=white-space:nowrap|'''2009'''
|A study by Hevezi P et al, presents "the first comprehensive characterization of gene expression in primate taste buds", as opposed to previous studies which focused on rodents. <ref><pubmed>19636377</pubmed></ref>
[http://www.ncbi.nlm.nih.gov/pubmed/19636377 Genome-wide analysis of gene expression in primate taste buds reveals links to diverse processes]

|- bgcolor="#faecc8"
|style=white-space:nowrap|'''2010'''
|Chandrashekar, J. et al. identify epithelial sodium channel (ENaC) as the sodium-salt taste receptor. <ref><pubmed>20107438</pubmed></ref>
[http://www.ncbi.nlm.nih.gov/pubmed/20107438?dopt=Abstract&holding=npg The cells and peripheral representation of sodium taste in mice]
|}

==Gustatory System==

[[Image:Taste qualities.gif|thumb|The five basic tastes]]

Taste or more appropriately gustation, is a fundamental survival tool in animals as it directs the consumption of essential nutrients. The five tastes that exist within the human gustatory system: salty, sweet, sour, bitter and umami, all signify basic physiological requirements. Salty tastes denote the presence of Na+, an important ion involved in the transportation and retention of water across cell membranes. Sweetness is the recognition of carbohydrates, essential for maintaining optimal brain function and providing the basis for energy production in muscle tissue via ATP hydrolysis. Similarly umami codes for the presence of L-amino acids, especially L-glutamate which is an integral component of protein synthesis.

These different modalities not only function to maintain the proper intake of nutrients within the body but also, by way of aversion, prohibit the consumption of undesired or poisonous materials. The bitter modality for example is generally regarded as displeasing to the human palate. It represents a high acid content which may be a result of foods which have become rotten or are inherently poisonous to the body.<ref name=PMID20696704><pubmed>20696704</pubmed></ref>

Research has historically limited itself to investigating the mechanisms of these five taste qualities though it must be noted many other modalities may exist. Of particular conjecture is the existence of fatty acid recognition. In the past the detection of fat in food has been attributed to somatosensory inputs <ref name=PMID20696704/> from the tongue, that is, the oily feel and texture of fat rather than its actual ‘taste’ allows the brain to encode for its presence. Further research is therefore required to elicit the precise mechanisms of fat detection.

===Cell Biology===

The five taste qualities are not all detected by the same type of receptor cell located within the taste bud. Like rods and cones in the eye which detect different wavelengths of light, there are specific types of receptors for different tastes. For example, sweet, umami and bitter are recognised by Type II G-protein coupled receptors, whereas sour is related to Type III presynaptic cells. The cell type involved in salty taste transduction is unknown however it is known that sodium ions can enter the receptor cell membrane via ion channel permeation.

====Type II receptors====

When a bitter, sweet or umami ligand binds to a type II G-coupled receptor, a cascade of chemical reactions causes the release of Ca2+ which in turn mediates exocystosis of ATP. The function of this ATP is threefold:

# Stimulates gustatory nerve afferents which project to gustatory nuclei in the spinal cord
# Excites Type III presynaptic nerve fibres to release serotonin.
# Has a positive feedback effect on type II receptor cells, increasing the level of ATP production.

The role of serotonin is believed to be in the form of lateral inhibition i.e. when a bitter quality is recognised, adjacent receptors for sweetness are deactivated and thus the two tastes may be clearly differentiated. It also has a negative feedback effect on receptor cells, inhibiting umami, bitter and sweet taste transduction.

==Taste Map==
[[Image:Taste map.png|thumb|left|250px|Obsolete idea of the tongue map]]
The idea of a tongue map has disseminated through society for many years. This concept purports that different areas of the tongue are specialised to detect either sweet, salty, sour and bitter tastes. Recent research however has completely nullified such claims and suggests instead that different forms of taste are recognised all over the tongue as well as via the palate. Thus the term ''taste map'' has come to take on a new meaning and that is, the precise areas of taste modalities processing in areas of cortex and its subsequent neural inputs.

===Neural Pathways===

'''First order neurons''' - From the receptors located in the taste buds, gustatory nerve afferents project to the ipsilateral rostral 1/3 of the nucleus tractus solitarius (NTS), located in the medulla. This rostral 1/3 is commonly referred to as the ''gustatory nucleus''.

The ''gustatory nucleus'' receives input from cranial nerves VII (''Facial n.''), IX (''Hypglossal n.''), and X (''Vagus n.'') via special visceral afferent (SVA) nerve fibres. A summary of their functions is as follows:

* ''Facial nerve n''. - carries taste information from the anterior 2/3 of the tongue.
* ''Hypoglossal n.'' - carries taste information from the posterior 1/3 of the tongue.
* ''Vagus n''. - carries taste information from the palate

'''Second order neurons''' - From the NTS second order neurons carry taste information to the Ventral posteromedial (VPM) nucleus in the thalamus.<ref name=PMID21885776/>

Copious scientific conjecture surrounds how each taste modality is transmitted to the brain. The ‘labelled-line’ hypothesis suggests that there are taste specific neurons which exclusively carry that taste modality to cortical areas. In analogous terms it can be viewed like the pipelines leading toward a house. Each pipeline carries its own utility, there is one for gas, another for water and finally for electricity with each terminating in slightly different areas of the house. In the same way, on the tongues there are different receptors for each taste which concurrently have individual nerve tracts leading to the primary gustatory cortex.

Contrapuntally there is electrophysiological evidence that single nerve afferents carry multiple modalities. These studies show one nerve afferent may have both a strong and a weak activation in response to a multiple taste stimuli.

===Cortical Areas===

[[Image:Primary gustatory cortex.png|thumb|Primary gustatory cortex]]

The location of the taste perception centres has been observed via functional magnetic resonance imaging (fMRI) studies. The primary taste cortex has been identified as being located in the anterior insula/frontal operculum (I/fO)<ref name=PMID22245354><pubmed>22245354</pubmed></ref>, with the secondary taste cortex in the caudolateral orbitofrontal cortex.<ref name=PMID21305668><pubmed>21305668</pubmed></ref> Within the insula there are further subdivisions related to each taste modality. Two photon calcium imaging research has outlined certain ’hot-spots’ of activation which are clearly delineated in relation to each taste. For example, the bitter modality is represented on the insula cortex approximately 1mm posterior to the middle cerebral artery whereas the sweet modality is represented 2.5mm rostrodorsal to the bitter field with no apparent overlap.<ref name=PMID21885776><pubmed>21885776</pubmed></ref> These findings lend weight to the idea that there is only one receptor for each taste quality.

It is interesting to note the relationship between taste and the reward centres of the brain. There is evidence of neural input to the ventral tegmental area (the origin of the mesolimbic dopaminergic reward pathway) and nucleus accumbens (involved in the conversion of motivation into physical action).<ref name=PMID21885776/> Neural connections such as this provide the foundations in explaining concepts such as flavour learning and preference. It may also give some insight into chronic problems such as food addiction and craving. As of yet however the gustatory neural network is not well understood and more research is required to elucidate the relationship between pleasure and taste sensation

== Human Weekly Development - Two Prominent Studies ==
Martin Witt and Klaus Reutter of the University of Tubingen in Germany published two prominent studies regarding developing taste buds in humans. Their first study in 1996 was a transmission electron microscopical (TEM) study of the taste bud primordium and its morphological changes during the 8th-15th postovulatory week. Their next study in 1997 built on their previous findings by using Scanning Electron Microscopy (SEM) to observe the development of gustatory papillae during postovulatory weeks 6-15.

The findings of these two studies are summarized in the table below. The figures provided relate to the images on their respective research papers.

# [http://onlinelibrary.wiley.com/doi/10.1002/(SICI)1097-0185(199612)246:4%3C507::AID-AR10%3E3.0.CO;2-S/pdf Embryonic and early fetal development of human taste buds: a transmission electron microscopical study, 1996]
# [http://chemse.oxfordjournals.org/content/22/6/601.long Scanning electron microscopical studies of developing gustatory papillae in humans, 1997]

===Timeline of Developmental Processes of Human Taste Buds===
{| cellpadding=5 style="border:1px solid #BBB"
|- bgcolor="#89CFF0"
|'''Postovulatory Week'''||'''Description'''||'''Image'''

|- bgcolor="#BCD4E6"
|'''Week 6''' ||
The surface of the developing tongue is covered by nearly flat epithelium (1997, Figure 1). The first gustatory papillae of the tongue appear in the caudal midline near the foramen caecum and the first circumvallate papilla develops on the dorsal midline. <ref name="PMID9455607"><pubmed>9455607</pubmed></ref>
||
image

|- bgcolor="#89CFF0"
| '''Weeks 6 to 7'''||
Nerve fibres approach the basal lamina of lingual epithelium. At this stage the lingual epithelium consists of two to three cell layers and there is not yet any sign of cell specializations indicating early taste bud formation. <ref name=PMID8955790/>
||
Image

|- bgcolor="#BCD4E6"
| '''Week 7 '''||
A series of irregular epithelial swellings in the anterior part and marginal parts of the tongue indicate early forming fungiform papillae. Furthermore, a V-like lane is observed anterior to the sulcus terminalis, which represents a smooth surface for developing circumvallate papillae (1997, Figure 2). Witt M et al observe that these circumvallate papillae are larger than the developing fungiform papillae of the same age, later noting that the fungiform papillae tend to increase in size over the 8-15th weeks of gestation, whilst the size of vallate papillae tend to remain constant during this period. <ref name=PMID9455607/>
||
Image

|- bgcolor="#89CFF0"
| ''' Week 8 ''' ||
* The taste bud primordium are still differentiated, elongated epithelial cells, resting on a slightly developed core of young dermal papilla.
* The lingual epithelium shows first signs of taste bud development as nerve fibres coming from the dermal papilla penetrate the epithelial basal lamina and form synapses with taste bud progenitor cells (1996, Figure 1). These synapses demonstrate the neuronal connection between the taste bud primordium and the central nervous system, reaching a maximum around the 12th to 13th week. However, it is important to note that at this time these cells are still poorly differentiated, elongated epithelial cells.
* Ciliated cells also appear around the 8th week, however the significance of these cells which are scattered randomly across the lingual surface remains unclear. <ref name=PMID8955790/>
||
Image

|- bgcolor="#BCD4E6"
|''' Week 9''' ||
By this stage, although a taste pore is not present, the surface of circumvallate papillae usually contains a taste pit partly filled with microvillus-like processes from the underlying taste bud cells (1997, Figure 10). <ref name=PMID9455607/>
||
Image

|- bgcolor="#89CFF0"
|''' Weeks 10-11''' ||
At this stage, the lingual epithelium compromises of about four cell layers, and the first shallow grooves above the taste bud primordium are developed. Fungiform papillae appear on the lateral margins and the tip of the tongue, containing taste bud primordial that display the first signs of a primitive pore formation (1996, Figure 6). <ref name=PMID8955790/>
||
Image

|- bgcolor="#BCD4E6"
|''' Week 12 ''' ||
Taste bud cells are more clearly differentiated into epithelial cell types II and III. <ref name=PMID8955790/>
||
Image

|- bgcolor="#89CFF0"
|''' Weeks 12-13 ''' ||
At this stage the taste bud primordial are all located on the top of dermal papillae. There is also maximum synapses between cells and afferent nerve fibres, which intermingle with each other to form a plexus-like structure (1996, Figure 6a). <ref name=PMID8955790/>
||
Image

|- bgcolor="#BCD4E6"
|''' Weeks 14 -15 ''' ||
The shape and size of the taste buds primordial begins to resemble those of adult taste buds (1996, Figure 9). By the 14th week the taste pores develop as the taste pits are filled by microvilli, and bubble like vesicles indicate the secretory activity of these cells (1996, Figure 10). However, the tastebuds only achieve a fully developed function in week 15 of gestation with the development of type I cells to produce the mucous material in the taste pit. <ref name=PMID8955790/>
||
Image
|}

==Adult Tongue and Taste Buds – Structure and Function==

'''Structure'''

The tongue is located on the floor of the oral cavity, It is a muscular structure with sensory units crowning. The tongue is divided into an anterior two thirds and a posterior one third. These regions are divided by a V-shaped groove at the back of the tongue (sulcus terminalis). The anterior two thirds of the tongue is covered by stratified squamous epithelium, It contains a roughened surface and has projections called papillae that vary in shape and number.

''''The Image Below is a very simplistic Diagram of the surface of the Tongue showing the locations of the different papillae and other important features'''

{|
| [[Image:Drawing of Tongue.png|500px]]

'''Papillae'''
[[File:Papillae.jpg|Left|thumb|200px|Close up of Human Tongue Papillae]]

There are 4 types of papillae on the tongue.
The most numerous papillae are the filiform papillae, which function to provide a surface that aids in holding food on the tongue during chewing but do not contain taste buds. The larger, less numerous fungiform papillae which contain taste buds, as do foliate papillae. Circumvallate papillae form a wide V at the sulcus terminalis also containing taste bus. There are no papillae or taste buds located on the posterior third of the tongue, having mucosal folds and the lingual tonsils instead.

'''Function'''

The tongue is for tasting, swallowing, and speech.
The functional unit of the taste bud is a taste cell, there are between 50 and 100 taste cells in each taste bud these taste cells represent all 5 different tastes. Historically is was believed that different areas of the tongue were responsible for different taste sensations although this has since been disregarded.[http://users.rcn.com/jkimball.ma.ultranet/BiologyPages/W/Welcome.html] The papillae contain taste buds which are connected to the oral cavity via a taste pore, the function of the taste bud is to transmit a chemical signal from the oral cavity to a taste cell, this chemical signal is the converted into an electrical impulse and delivered to the brain via nerve fibres for interpretation.

'''The Image Below is a very simplistic Hand drawn Diagram of a taste bud, in an extreme close up, cross section view of the the taste bud unit, not to scale'''

[[File:Taste_bud_1.jpg]]

==Abnormalities==

===Knocking out P2X Receptors===

[[File:Image of taste being evoked by visualising ATP release.jpeg|Left|thumb|200px|Evoking taste - ATP release in tongue]]

Gustatory abnormalities has not been widely researched and what has been researched has been through animal testing, most commonly we have found on mice.

In Huang, 2008 this team used the release of the neurotransmitter, ATP (adenosine triphosphate) as a quantitative measurement of gustatory sensation and taste. This was done by using a comparison of wild type (WT) and double knockout (DKO) mice. P2X receptors, P2X2 and P2X3 were knocked out in the DKO mice. The premise of this article was that knocking out P2X receptors reduces transmitter secretion of ATP in taste buds, therefore they cannot taste.

It should be noted that the taste buds in DKO are functional, but are not stimulated by the administration of tastants.

The transmission of release of ATP is secretion through gap junction hemichannels (pannexin 1 gap junction).

When both P2X2 and P2X3 are knocked out, no taste is elicited. However they found that if either P2X2 OR P2X3 was knocked out there was a taste response. So the inference made from this is that if one of the two receptors from the P2X family was knocked out there still can have taste response. The WT mice showed significant stimulation by tastants whereas DKO had little to no stimulation of ATP release.<ref><pubmed>21940456</pubmed></ref>

===FGF signalling and genes===

Sprouty, or ''Srpy'', genes have been related to regulating the development of circumvillate papillae (CVP). The CVP are large dome shaped papillae, which form a 'V' just in front of the terminal sulcus.

By knocking out ''Spry'' genes using mice which had ''Spry1'' and ''Spry2'' knocked out showed that the number of CVP doubled. However, when Fibroblast Growth Factor gene ("Fgf10") was absent, the number of CVP was significantly reduced, if not completely absent. The correlation between ''Spry1/2'' and ''Fgf10'' is that ''Spry1/2'' antagonises "Fgf10" to limit the size of the CVP progenitor placode. Exclusive expression of ''Fgf10'' in the mesenchyme is necessary for the formation of CVP.

'''This image shows the CVP stained with H&E and scanned by Scanning Electron Microscope (SEM)'''
[[File:CVP of WT(top) and DKO(bottom) mice with H&E and SEM.png]]

'''This image shows the location of the CVP and the increased number in DKO mice by SEM'''
[[File:Mouse circumvallate papilla 01.jpg|300px]]

Taste buds develop from the mesenchyme but require local signalling to properly differentiate. Some signalling factors for proper development of taste buds besides FGF are: Sonic Hedgehog (SHH), Bone Morphogenetic Proteins (BMPs), Epidermal Growth Factor (EGF).

Additionally, this proves that the anterior and posterior developments of the tongue are derived from embryonic tissues, where the anterior tongue is derived from the [[#Glossary |'''ectoderm''']] and the posterior tongue is derived from the [[#Glossary |'''endoderm''']]. Taste buds develop from the mesenchyme but require local signalling to properly differentiate. Some signalling factors for proper development of taste buds besides FGF are: Sonic Hedgehog (SHH), Bone Morphogenetic Proteins (BMPs), Epidermal Growth Factor (EGF).

As mentioned above, this article shows that the anterior and posterior developments of the tongue are derived from embryonic tissues, where the anterior tongue is derived front the ectoderm and the posterior tongue is derived from the endoderm. Secondly, FGF is required to regulate the growth of taste buds, while ''Spry'' genes limit the number of CVP. ''Fgf10''& ''Spry 1&2''work antagonistically through receptor tyrosine kinase (RTK)signalling.

However, the deletion of ''Spry2''led to the increase of CVPs it should be noted that they found that a significant decrease in number of fungiform papillae. Contrastingly, the absence of ''Fgf10'', while leading to the absence of CVPs lead to an increase in number and size of fungiform papillae. Therefore these genes have different effects on the anterior and posterior developing tongue and taste buds.<ref><pubmed>21655085</pubmed></ref>

==Current Research==
We have an evolving understanding of Embryonic Taste development, through the use of state-of-the-art technology and research techniques we are able to make brilliant discoveries that continue to connect the dots of this amazing natural process of human development.
The majority of research in taste development is involving mice, these mammals show similar embryonic pathways to humans and research is performed in ethical and humane methods.

[[File:Histology.jpg|Left|thumb|200px|Image shows histological stains of a mice tongue showing dysplasia]]

'''Synergistic relationships of Six Genes '''

In an animal study using mice by Suzuki Y, Ikeda K, Kawakami K.(2011) Firstly nominating "Six Genes" as a major component in gustatory development, stating that deficiencies in certain Six genes (specifically Six1 & Six4) leads to poor development. Their research also highlights evidence of cooperative relationships between Six genes for normal advance. This experiment involved breeding mice containing exclusively Six1 and Six4 genes and examining the expression of these genes in papillae under high powered microscope observation. Understanding the role of certain genes along with the intrinsic relationships they hold is crucial for the ability to identify possible causes and correction of any abnormalities <ref><pubmed>21978088</pubmed></ref>

'''Neural Crest responsibilities '''

Another Animal Study involving mice explores a new idea of Neural crest (NC) contribution in taste development, specifically the development of papillae and taste buds. Liu HX, Komatsu Y, Mishina Y, Mistretta CM. (2012) suggest that Neural crest cells travel to the location of the tongue in early embryonic stages, gain epithelium phenotypes, multiply and then differentiate to eventually form taste papillae. The experiment involved the comparison of 2 different types of Cre line mice, which both express Cre gene in neural crest protocol, the different distribution patterns where observed in specific regions that NC is responsible for.<ref><pubmed>22659543</pubmed></ref>

'''Augmentation of Endoderm'''

In an animal study conducted by Rothova M, Thompson H, Lickert H, Tucker AS.(2012) exploring the historically debated issue of endoderm contribution to tongue development showed promising evidence that position of taste buds are patterned by the border of ectoderm and endoderm derivative epithelium. This study was accomplished via microscopic examination of previously stained specimens. Concluding endoderm has direct influence on gustatory develoment <ref><pubmed>22581563</pubmed></ref>

'''Changes in Taste Cells over time'''

Research by
Ozdener H, Spielman AI, Rawson NE.(2012) developing a culture which allows taste cells to survive for up to 12 months, empowers researchers to study the processes of proliferation, differentiation and function. This experiment will provide a precidnet for future study of taste cells, as these cells are able to operate and grow normally. <ref><pubmed>22643728</pubmed></ref>

'''Shh key component of taste bud proginators'''

A tamoxifen treatment which supresses Sonic hedgehog (Shh) secretion in mice proving to reduce the number of cells visable within papillae, in contrast mice not treated with tamoxifen showed a mark increase of cells within papillae, these cells are assumed to become taste cells in later development.
Specific mice were bred to trace the destination of taste placode cells, the study concluded that Shh expressing placodes are taste bud proginators which in turn become taste cells within taste buds although do not have any prescuros relationship with pappilae. The results were obtain by examination of mice embryos using Bright-field or multichannel fluorescent images through the use of an "Axiocam CCD camera and Axioplan fluorescence microscope with Axiovision software" a study by Harlow, Yang, Williams, Barlow (2011)<ref><pubmed>PMC2674259</pubmed></ref>

'''WNT family exhibit various roles'''

The WNT gene family has a function of signally proteins for various reason such as development, In 2010 Liu, Staubach Grosse, Walton, Saims, Gumucio, Mistretta explored recent findings on the role of WNT's in tongue and papillae development, Concluding that WNT/β-catenin is essential for fungiform papillae differing to WNT5a which proved to be principle in tongue development. Intrinsic chemical mediators were considered by manipulating a tissue culture and then throughaly examined by scanning photomicrograph. <ref><pubmed>PMC2768563</pubmed></ref>

[http://www.surgicalneurologyint.com/article.asp?issn=2152-7806;year=2012;volume=3;issue=1;spage=23;epage=23;aulast=Manjila]
[[File:Abnormal of tongue.jpg|Left|thumb|200px|Image shows and example of tongue abnormalities, this is called "double tongue" each side has independent movement!]]

==Useful links==

==Glossary==

ectoderm- outer germ layer of embryo

endoderm - inner germ layer of embryo

epithelium - basic animal tissue that is composed of tightly packed cells, usually covering the outer portion of organs

exocystosis - movement of contents out of cell

ganglia - the accumulation of a nerve cell body

growth factor - a substance that stimulates the growth of cells

gustatory - anything that relates to the taste sense

hydrolysis - breakdown of a chemical when it reacts with water

mesoderm - middle germ layer of embryo

mesenchyme - multipotential cells

neural crest - a part of the ectoderm found on both sides of the neural tube

neuron - most simplistic unit of the nervous system

neurotransmitter - chemicals which allow the passing of signals from neuron to neuron via connecting part (synapse)

papillae - small rough surface projection

six genes - a family of genes

Sonic hedgehog (Shh) - signalling protein invloved in normal development

sulcus terminalis - describes a physical transition point separating the anterior 2/3 of the tongue from the posterior 1/3

tamoxifen - hormonal altering drug

==Image gallery==

== References ==
<references/>

==External Links==
{{External Links}}

http://www.webmd.com/oral-health/picture-of-the-tongue

http://www.tutorvista.com/content/biology/biology-iv/nervous-coordination/tongue-structure.php#parts-of-tongue

http://www.cf.ac.uk/biosi/staffinfo/jacob/teaching/sensory/taste.html

--[[User:Z8600021|Mark Hill]] 12:22, 15 August 2012 (EST) Please leave the content listed below the line at the bottom of your project page.

----

{{2012Projects}}

2012 Group Project 3

2012-09-30T11:00:04Z

Z3289738: /* FGF signalling and genes */

=Taste Development=

== Introduction ==
**NEED TO ADD**

==History of Discoveries==

{| cellpadding=5 style="border:1px solid #BBB"
|- bgcolor="#faecc8"
|''' Date'''|| '''Significant Discovery'''

|- bgcolor="#faf6ed"
|'''350BC'''
|| Aristotle writes about the basic tastes, sweet and bitter. He also notes that it can be modified by salty and acidic. <ref name="PMID22717400"><pubmed>22717400</pubmed></ref>

|- bgcolor="#faecc8"
|'''1901'''
|| D. Hanig publishes a paper describing taste sensitivity in different regions of the tongue.
''Interesting fact:'' The modern concept of a 'tongue map' is a misinterpretation of this study. <ref name="PMID22717400"/>

|- bgcolor="#faf6ed"
|style=white-space:nowrap|'''1908'''
|Kikunae Ikeda, a professor of the Tokyo Imperial University, discovered and identified the fifth basic taste: umami (savouriness), made palatable by glutamate. <ref><pubmed>12438213</pubmed></ref>
[http://chemse.oxfordjournals.org/content/27/9/847.long New Seasonings]

|- bgcolor="#faecc8"
|style=white-space:nowrap|'''1931-32'''
| A chemist named Arthur Fox and his college noted that they had different sensitivities to the bitter tasting Phenylthiocarbamide (PTC).<ref>Blakeslee AF, Fox AL. Our different taste worlds. J Hered. 1932;23:97–107.</ref> Geneticists later confirm these findings, and discover that non-tasting is a recessive genetic trait. <ref><pubmed>17782493</pubmed></ref>
[http://www.ncbi.nlm.nih.gov/pubmed/17782493 Inherited taste deficiency]

|- bgcolor="#faf6ed"
|style=white-space:nowrap|'''1965'''
|Farbman's study of the developing taste but in rat fungiform papilla was significant in increasing our understanding of taste bud development. <ref><pubmed>14300090</pubmed></ref>
[http://www.sciencedirect.com/science/article/pii/0012160665900400 Electron microscope study of the developing taste bud in rat fungiform papilla.]

|- bgcolor="#faecc8"
|style=white-space:nowrap|'''1992'''
|McLaughlin SK et al. discovery a taste cell-specific G-protein within the taste buds called Gustucon. This protein is later used to mark bitter, umami and sweet cells. <ref><pubmed>1608467 </pubmed></ref>
[http://www.nature.com/nature/journal/v357/n6379/abs/357563a0.html Gustducin is a taste-cell-specific G protein closely related to the transducins]

|- bgcolor="#faf6ed"
|style=white-space:nowrap|'''1995'''
|Barlow et al. experimented with Axolotl salamanders and concluded that taste buds from this species arise exclusively from epithelial tissue, "oropharyngeal epithelium". <ref name="PMID17826760"><pubmed>17826760</pubmed></ref>
[http://www.ncbi.nlm.nih.gov/pubmed/17826760 Embryonic origin of gustatory cranial sensory neurons.]

|- bgcolor="#faecc8"
|style=white-space:nowrap|'''1996'''
| Witt M and Reutter K of the Technical University Dresden in Germany, carried out a transmission electron microscopy study to investigate the embryonic and fetal development of Human taste buds. Their results suggest an "at least dual function of embryonic/fetal taste buds", including non-gustatory, paracrine functions prior to the 14th week and gustatory after the 14th week. <ref name="PMID8955790"><pubmed>8955790</pubmed></ref>
[http://www.ncbi.nlm.nih.gov/pubmed/8955790 Embryonic and early fetal development of human taste buds: a transmission electron microscopical study]

|- bgcolor="#faf6ed"
|style=white-space:nowrap|'''2000'''
|Chandrashekar, J. et al. discover the first taste sonsors, the T2R bitter taste receptors. <ref><pubmed>10761935</pubmed></ref>
[http://www.sciencedirect.com/science/article/pii/S0092867400807060 T2Rs Function as Bitter Taste Receptors]

|- bgcolor="#faecc8"
|style=white-space:nowrap|'''2001'''
|Nelson, G. et al. discover the sweet receptor: a combination of T1R2 and T1R3. <ref><pubmed>11509186</pubmed></ref>
[http://www.ncbi.nlm.nih.gov/pubmed/11509186?dopt=Abstract&holding=npg Mammalian sweet taste receptors.]

|- bgcolor="#faf6ed"
|style=white-space:nowrap|'''2002'''
|Nelson G. et al. discover the amino acid (umami) taste receptor: a combination of T1R1 and T1R3 identified. <ref><pubmed>11894099</pubmed></ref>
[http://www.ncbi.nlm.nih.gov/pubmed/11894099?dopt=Abstract&holding=npg An amino-acid taste receptor]

|- bgcolor="#faecc8"
|style=white-space:nowrap|'''2005'''
|Dyer, J. et al. discover sweet taste receptors in the GI tract. <ref><pubmed>17855558</pubmed></ref>
[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1986582/ Sweet taste signaling in the gut]

|- bgcolor="#faf6ed"
|style=white-space:nowrap|'''2006'''
|Huang, A. L et al. discover cells for sour taste, identified by PKD2L1 (a polycystic kidney disease-like ion channel). <ref><pubmed>16929298</pubmed></ref>
[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1571047/ The Cells and Logic for Mammalian Sour Taste detection]

|- bgcolor="#faecc8"
|style=white-space:nowrap|'''2007'''
|Harlow DE, Barlow LA of the University of Colorado Denver Health Sciences Center provide evidence of the "embryonic origin of gustatory cranial sensory neurons". <ref name="PMID17826760"/>
[http://www.ncbi.nlm.nih.gov/pubmed/17826760 Embryonic origin of gustatory cranial sensory neurons.]

|- bgcolor="#faf6ed"
|style=white-space:nowrap|'''2009'''
|A study by Hevezi P et al, presents "the first comprehensive characterization of gene expression in primate taste buds", as opposed to previous studies which focused on rodents. <ref><pubmed>19636377</pubmed></ref>
[http://www.ncbi.nlm.nih.gov/pubmed/19636377 Genome-wide analysis of gene expression in primate taste buds reveals links to diverse processes]

|- bgcolor="#faecc8"
|style=white-space:nowrap|'''2010'''
|Chandrashekar, J. et al. identify epithelial sodium channel (ENaC) as the sodium-salt taste receptor. <ref><pubmed>20107438</pubmed></ref>
[http://www.ncbi.nlm.nih.gov/pubmed/20107438?dopt=Abstract&holding=npg The cells and peripheral representation of sodium taste in mice]
|}

==Gustatory System==

[[Image:Taste qualities.gif|thumb|The five basic tastes]]

Taste or more appropriately gustation, is a fundamental survival tool in animals as it directs the consumption of essential nutrients. The five tastes that exist within the human gustatory system: salty, sweet, sour, bitter and umami, all signify basic physiological requirements. Salty tastes denote the presence of Na+, an important ion involved in the transportation and retention of water across cell membranes. Sweetness is the recognition of carbohydrates, essential for maintaining optimal brain function and providing the basis for energy production in muscle tissue via ATP hydrolysis. Similarly umami codes for the presence of L-amino acids, especially L-glutamate which is an integral component of protein synthesis.

These different modalities not only function to maintain the proper intake of nutrients within the body but also, by way of aversion, prohibit the consumption of undesired or poisonous materials. The bitter modality for example is generally regarded as displeasing to the human palate. It represents a high acid content which may be a result of foods which have become rotten or are inherently poisonous to the body.<ref name=PMID20696704><pubmed>20696704</pubmed></ref>

Research has historically limited itself to investigating the mechanisms of these five taste qualities though it must be noted many other modalities may exist. Of particular conjecture is the existence of fatty acid recognition. In the past the detection of fat in food has been attributed to somatosensory inputs <ref name=PMID20696704/> from the tongue, that is, the oily feel and texture of fat rather than its actual ‘taste’ allows the brain to encode for its presence. Further research is therefore required to elicit the precise mechanisms of fat detection.

===Cell Biology===

The five taste qualities are not all detected by the same type of receptor cell located within the taste bud. Like rods and cones in the eye which detect different wavelengths of light, there are specific types of receptors for different tastes. For example, sweet, umami and bitter are recognised by Type II G-protein coupled receptors, whereas sour is related to Type III presynaptic cells. The cell type involved in salty taste transduction is unknown however it is known that sodium ions can enter the receptor cell membrane via ion channel permeation.

====Type II receptors====

When a bitter, sweet or umami ligand binds to a type II G-coupled receptor, a cascade of chemical reactions causes the release of Ca2+ which in turn mediates exocystosis of ATP. The function of this ATP is threefold:

# Stimulates gustatory nerve afferents which project to gustatory nuclei in the spinal cord
# Excites Type III presynaptic nerve fibres to release serotonin.
# Has a positive feedback effect on type II receptor cells, increasing the level of ATP production.

The role of serotonin is believed to be in the form of lateral inhibition i.e. when a bitter quality is recognised, adjacent receptors for sweetness are deactivated and thus the two tastes may be clearly differentiated. It also has a negative feedback effect on receptor cells, inhibiting umami, bitter and sweet taste transduction.

==Taste Map==
[[Image:Taste map.png|thumb|left|250px|Obsolete idea of the tongue map]]
The idea of a tongue map has disseminated through society for many years. This concept purports that different areas of the tongue are specialised to detect either sweet, salty, sour and bitter tastes. Recent research however has completely nullified such claims and suggests instead that different forms of taste are recognised all over the tongue as well as via the palate. Thus the term ''taste map'' has come to take on a new meaning and that is, the precise areas of taste modalities processing in areas of cortex and its subsequent neural inputs.

===Neural Pathways===

'''First order neurons''' - From the receptors located in the taste buds, gustatory nerve afferents project to the ipsilateral rostral 1/3 of the nucleus tractus solitarius (NTS), located in the medulla. This rostral 1/3 is commonly referred to as the ''gustatory nucleus''.

The ''gustatory nucleus'' receives input from cranial nerves VII (''Facial n.''), IX (''Hypglossal n.''), and X (''Vagus n.'') via special visceral afferent (SVA) nerve fibres. A summary of their functions is as follows:

* ''Facial nerve n''. - carries taste information from the anterior 2/3 of the tongue.
* ''Hypoglossal n.'' - carries taste information from the posterior 1/3 of the tongue.
* ''Vagus n''. - carries taste information from the palate

'''Second order neurons''' - From the NTS second order neurons carry taste information to the Ventral posteromedial (VPM) nucleus in the thalamus.<ref name=PMID21885776/>

Copious scientific conjecture surrounds how each taste modality is transmitted to the brain. The ‘labelled-line’ hypothesis suggests that there are taste specific neurons which exclusively carry that taste modality to cortical areas. In analogous terms it can be viewed like the pipelines leading toward a house. Each pipeline carries its own utility, there is one for gas, another for water and finally for electricity with each terminating in slightly different areas of the house. In the same way, on the tongues there are different receptors for each taste which concurrently have individual nerve tracts leading to the primary gustatory cortex.

Contrapuntally there is electrophysiological evidence that single nerve afferents carry multiple modalities. These studies show one nerve afferent may have both a strong and a weak activation in response to a multiple taste stimuli.

===Cortical Areas===

[[Image:Primary gustatory cortex.png|thumb|Primary gustatory cortex]]

The location of the taste perception centres has been observed via functional magnetic resonance imaging (fMRI) studies. The primary taste cortex has been identified as being located in the anterior insula/frontal operculum (I/fO)<ref name=PMID22245354><pubmed>22245354</pubmed></ref>, with the secondary taste cortex in the caudolateral orbitofrontal cortex.<ref name=PMID21305668><pubmed>21305668</pubmed></ref> Within the insula there are further subdivisions related to each taste modality. Two photon calcium imaging research has outlined certain ’hot-spots’ of activation which are clearly delineated in relation to each taste. For example, the bitter modality is represented on the insula cortex approximately 1mm posterior to the middle cerebral artery whereas the sweet modality is represented 2.5mm rostrodorsal to the bitter field with no apparent overlap.<ref name=PMID21885776><pubmed>21885776</pubmed></ref> These findings lend weight to the idea that there is only one receptor for each taste quality.

It is interesting to note the relationship between taste and the reward centres of the brain. There is evidence of neural input to the ventral tegmental area (the origin of the mesolimbic dopaminergic reward pathway) and nucleus accumbens (involved in the conversion of motivation into physical action).<ref name=PMID21885776/> Neural connections such as this provide the foundations in explaining concepts such as flavour learning and preference. It may also give some insight into chronic problems such as food addiction and craving. As of yet however the gustatory neural network is not well understood and more research is required to elucidate the relationship between pleasure and taste sensation

== Human Weekly Development - Two Prominent Studies ==
Martin Witt and Klaus Reutter of the University of Tubingen in Germany published two prominent studies regarding developing taste buds in humans. Their first study in 1996 was a transmission electron microscopical (TEM) study of the taste bud primordium and its morphological changes during the 8th-15th postovulatory week. Their next study in 1997 built on their previous findings by using Scanning Electron Microscopy (SEM) to observe the development of gustatory papillae during postovulatory weeks 6-15.

The findings of these two studies are summarized in the table below. The figures provided relate to the images on their respective research papers.

# [http://onlinelibrary.wiley.com/doi/10.1002/(SICI)1097-0185(199612)246:4%3C507::AID-AR10%3E3.0.CO;2-S/pdf Embryonic and early fetal development of human taste buds: a transmission electron microscopical study, 1996]
# [http://chemse.oxfordjournals.org/content/22/6/601.long Scanning electron microscopical studies of developing gustatory papillae in humans, 1997]

===Timeline of Developmental Processes of Human Taste Buds===
{| cellpadding=5 style="border:1px solid #BBB"
|- bgcolor="#89CFF0"
|'''Postovulatory Week'''||'''Description'''||'''Image'''

|- bgcolor="#BCD4E6"
|'''Week 6''' ||
The surface of the developing tongue is covered by nearly flat epithelium (1997, Figure 1). The first gustatory papillae of the tongue appear in the caudal midline near the foramen caecum and the first circumvallate papilla develops on the dorsal midline. <ref name="PMID9455607"><pubmed>9455607</pubmed></ref>
||
image

|- bgcolor="#89CFF0"
| '''Weeks 6 to 7'''||
Nerve fibres approach the basal lamina of lingual epithelium. At this stage the lingual epithelium consists of two to three cell layers and there is not yet any sign of cell specializations indicating early taste bud formation. <ref name=PMID8955790/>
||
Image

|- bgcolor="#BCD4E6"
| '''Week 7 '''||
A series of irregular epithelial swellings in the anterior part and marginal parts of the tongue indicate early forming fungiform papillae. Furthermore, a V-like lane is observed anterior to the sulcus terminalis, which represents a smooth surface for developing circumvallate papillae (1997, Figure 2). Witt M et al observe that these circumvallate papillae are larger than the developing fungiform papillae of the same age, later noting that the fungiform papillae tend to increase in size over the 8-15th weeks of gestation, whilst the size of vallate papillae tend to remain constant during this period. <ref name=PMID9455607/>
||
Image

|- bgcolor="#89CFF0"
| ''' Week 8 ''' ||
* The taste bud primordium are still differentiated, elongated epithelial cells, resting on a slightly developed core of young dermal papilla.
* The lingual epithelium shows first signs of taste bud development as nerve fibres coming from the dermal papilla penetrate the epithelial basal lamina and form synapses with taste bud progenitor cells (1996, Figure 1). These synapses demonstrate the neuronal connection between the taste bud primordium and the central nervous system, reaching a maximum around the 12th to 13th week. However, it is important to note that at this time these cells are still poorly differentiated, elongated epithelial cells.
* Ciliated cells also appear around the 8th week, however the significance of these cells which are scattered randomly across the lingual surface remains unclear. <ref name=PMID8955790/>
||
Image

|- bgcolor="#BCD4E6"
|''' Week 9''' ||
By this stage, although a taste pore is not present, the surface of circumvallate papillae usually contains a taste pit partly filled with microvillus-like processes from the underlying taste bud cells (1997, Figure 10). <ref name=PMID9455607/>
||
Image

|- bgcolor="#89CFF0"
|''' Weeks 10-11''' ||
At this stage, the lingual epithelium compromises of about four cell layers, and the first shallow grooves above the taste bud primordium are developed. Fungiform papillae appear on the lateral margins and the tip of the tongue, containing taste bud primordial that display the first signs of a primitive pore formation (1996, Figure 6). <ref name=PMID8955790/>
||
Image

|- bgcolor="#BCD4E6"
|''' Week 12 ''' ||
Taste bud cells are more clearly differentiated into epithelial cell types II and III. <ref name=PMID8955790/>
||
Image

|- bgcolor="#89CFF0"
|''' Weeks 12-13 ''' ||
At this stage the taste bud primordial are all located on the top of dermal papillae. There is also maximum synapses between cells and afferent nerve fibres, which intermingle with each other to form a plexus-like structure (1996, Figure 6a). <ref name=PMID8955790/>
||
Image

|- bgcolor="#BCD4E6"
|''' Weeks 14 -15 ''' ||
The shape and size of the taste buds primordial begins to resemble those of adult taste buds (1996, Figure 9). By the 14th week the taste pores develop as the taste pits are filled by microvilli, and bubble like vesicles indicate the secretory activity of these cells (1996, Figure 10). However, the tastebuds only achieve a fully developed function in week 15 of gestation with the development of type I cells to produce the mucous material in the taste pit. <ref name=PMID8955790/>
||
Image
|}

==Adult Tongue and Taste Buds – Structure and Function==

'''Structure'''

The tongue is located on the floor of the oral cavity, It is a muscular structure with sensory units crowning. The tongue is divided into an anterior two thirds and a posterior one third. These regions are divided by a V-shaped groove at the back of the tongue (sulcus terminalis). The anterior two thirds of the tongue is covered by stratified squamous epithelium, It contains a roughened surface and has projections called papillae that vary in shape and number.

''''The Image Below is a very simplistic Diagram of the surface of the Tongue showing the locations of the different papillae and other important features'''

{|
| [[Image:Drawing of Tongue.png|500px]]

'''Papillae'''
[[File:Papillae.jpg|Left|thumb|200px|Close up of Human Tongue Papillae]]

There are 4 types of papillae on the tongue.
The most numerous papillae are the filiform papillae, which function to provide a surface that aids in holding food on the tongue during chewing but do not contain taste buds. The larger, less numerous fungiform papillae which contain taste buds, as do foliate papillae. Circumvallate papillae form a wide V at the sulcus terminalis also containing taste bus. There are no papillae or taste buds located on the posterior third of the tongue, having mucosal folds and the lingual tonsils instead.

'''Function'''

The tongue is for tasting, swallowing, and speech.
The functional unit of the taste bud is a taste cell, there are between 50 and 100 taste cells in each taste bud these taste cells represent all 5 different tastes. Historically is was believed that different areas of the tongue were responsible for different taste sensations although this has since been disregarded.[http://users.rcn.com/jkimball.ma.ultranet/BiologyPages/W/Welcome.html] The papillae contain taste buds which are connected to the oral cavity via a taste pore, the function of the taste bud is to transmit a chemical signal from the oral cavity to a taste cell, this chemical signal is the converted into an electrical impulse and delivered to the brain via nerve fibres for interpretation.

'''The Image Below is a very simplistic Hand drawn Diagram of a taste bud, in an extreme close up, cross section view of the the taste bud unit, not to scale'''

[[File:Taste_bud_1.jpg]]

==Abnormalities==

===Knocking out P2X Receptors===

[[File:Image of taste being evoked by visualising ATP release.jpeg|Left|thumb|200px|Evoking taste - ATP release in tongue]]

Gustatory abnormalities has not been widely researched and what has been researched has been through animal testing, most commonly we have found on mice.

In Huang, 2008 this team used the release of the neurotransmitter, ATP (adenosine triphosphate) as a quantitative measurement of gustatory sensation and taste. This was done by using a comparison of wild type (WT) and double knockout (DKO) mice. P2X receptors, P2X2 and P2X3 were knocked out in the DKO mice. The premise of this article was that knocking out P2X receptors reduces transmitter secretion of ATP in taste buds, therefore they cannot taste.

It should be noted that the taste buds in DKO are functional, but are not stimulated by the administration of tastants.

The transmission of release of ATP is secretion through gap junction hemichannels (pannexin 1 gap junction).

When both P2X2 and P2X3 are knocked out, no taste is elicited. However they found that if either P2X2 OR P2X3 was knocked out there was a taste response. So the inference made from this is that if one of the two receptors from the P2X family was knocked out there still can have taste response. The WT mice showed significant stimulation by tastants whereas DKO had little to no stimulation of ATP release.<ref><pubmed>21940456</pubmed></ref>

===FGF signalling and genes===

Sprouty, or ''Srpy'', genes have been related to regulating the development of circumvillate papillae (CVP). The CVP are large dome shaped papillae, which form a 'V' just in front of the terminal sulcus.

By knocking out ''Spry'' genes using mice which had ''Spry1'' and ''Spry2'' knocked out showed that the number of CVP doubled. However, when Fibroblast Growth Factor gene ("Fgf10") was absent, the number of CVP was significantly reduced, if not completely absent. The correlation between ''Spry1/2'' and ''Fgf10'' is that ''Spry1/2'' antagonises "Fgf10" to limit the size of the CVP progenitor placode. Exclusive expression of ''Fgf10'' in the mesenchyme is necessary for the formation of CVP.

'''This image shows the CVP stained with H&E and scanned by Scanning Electron Microscope (SEM)'''
[[File:CVP of WT(top) and DKO(bottom) mice with H&E and SEM.png]]

'''This image shows the location of the CVP and the increased number in DKO mice by SEM'''
[[File:Mouse circumvallate papilla 01.jpg|300px]]

Taste buds develop from the mesenchyme but require local signalling to properly differentiate. Some signalling factors for proper development of taste buds besides FGF are: Sonic Hedgehog (SHH), Bone Morphogenetic Proteins (BMPs), Epidermal Growth Factor (EGF).

Additionally, this proves that the anterior and posterior developments of the tongue are derived from embryonic tissues, where the anterior tongue is derived from the [[#Glossary |'''ectoderm''']]and the posterior tongue is derived from the endoderm. Taste buds develop from the mesenchyme but require local signalling to properly differentiate. Some signalling factors for proper development of taste buds besides FGF are: Sonic Hedgehog (SHH), Bone Morphogenetic Proteins (BMPs), Epidermal Growth Factor (EGF).

As mentioned above, this article shows that the anterior and posterior developments of the tongue are derived from embryonic tissues, where the anterior tongue is derived front the ectoderm and the posterior tongue is derived from the endoderm. Secondly, FGF is required to regulate the growth of taste buds, while ''Spry'' genes limit the number of CVP. ''Fgf10''& ''Spry 1&2''work antagonistically through receptor tyrosine kinase (RTK)signalling.

However, the deletion of ''Spry2''led to the increase of CVPs it should be noted that they found that a significant decrease in number of fungiform papillae. Contrastingly, the absence of ''Fgf10'', while leading to the absence of CVPs lead to an increase in number and size of fungiform papillae. Therefore these genes have different effects on the anterior and posterior developing tongue and taste buds.<ref><pubmed>21655085</pubmed></ref>

==Current Research==
We have an evolving understanding of Embryonic Taste development, through the use of state-of-the-art technology and research techniques we are able to make brilliant discoveries that continue to connect the dots of this amazing natural process of human development.
The majority of research in taste development is involving mice, these mammals show similar embryonic pathways to humans and research is performed in ethical and humane methods.

[[File:Histology.jpg|Left|thumb|200px|Image shows histological stains of a mice tongue showing dysplasia]]

'''Synergistic relationships of Six Genes '''

In an animal study using mice by Suzuki Y, Ikeda K, Kawakami K.(2011) Firstly nominating "Six Genes" as a major component in gustatory development, stating that deficiencies in certain Six genes (specifically Six1 & Six4) leads to poor development. Their research also highlights evidence of cooperative relationships between Six genes for normal advance. This experiment involved breeding mice containing exclusively Six1 and Six4 genes and examining the expression of these genes in papillae under high powered microscope observation. Understanding the role of certain genes along with the intrinsic relationships they hold is crucial for the ability to identify possible causes and correction of any abnormalities <ref><pubmed>21978088</pubmed></ref>

'''Neural Crest responsibilities '''

Another Animal Study involving mice explores a new idea of Neural crest (NC) contribution in taste development, specifically the development of papillae and taste buds. Liu HX, Komatsu Y, Mishina Y, Mistretta CM. (2012) suggest that Neural crest cells travel to the location of the tongue in early embryonic stages, gain epithelium phenotypes, multiply and then differentiate to eventually form taste papillae. The experiment involved the comparison of 2 different types of Cre line mice, which both express Cre gene in neural crest protocol, the different distribution patterns where observed in specific regions that NC is responsible for.<ref><pubmed>22659543</pubmed></ref>

'''Augmentation of Endoderm'''

In an animal study conducted by Rothova M, Thompson H, Lickert H, Tucker AS.(2012) exploring the historically debated issue of endoderm contribution to tongue development showed promising evidence that position of taste buds are patterned by the border of ectoderm and endoderm derivative epithelium. This study was accomplished via microscopic examination of previously stained specimens. Concluding endoderm has direct influence on gustatory develoment <ref><pubmed>22581563</pubmed></ref>

'''Changes in Taste Cells over time'''

Research by
Ozdener H, Spielman AI, Rawson NE.(2012) developing a culture which allows taste cells to survive for up to 12 months, empowers researchers to study the processes of proliferation, differentiation and function. This experiment will provide a precidnet for future study of taste cells, as these cells are able to operate and grow normally. <ref><pubmed>22643728</pubmed></ref>

'''Shh key component of taste bud proginators'''

A tamoxifen treatment which supresses Sonic hedgehog (Shh) secretion in mice proving to reduce the number of cells visable within papillae, in contrast mice not treated with tamoxifen showed a mark increase of cells within papillae, these cells are assumed to become taste cells in later development.
Specific mice were bred to trace the destination of taste placode cells, the study concluded that Shh expressing placodes are taste bud proginators which in turn become taste cells within taste buds although do not have any prescuros relationship with pappilae. The results were obtain by examination of mice embryos using Bright-field or multichannel fluorescent images through the use of an "Axiocam CCD camera and Axioplan fluorescence microscope with Axiovision software" a study by Harlow, Yang, Williams, Barlow (2011)<ref><pubmed>PMC2674259</pubmed></ref>

'''WNT family exhibit various roles'''

The WNT gene family has a function of signally proteins for various reason such as development, In 2010 Liu, Staubach Grosse, Walton, Saims, Gumucio, Mistretta explored recent findings on the role of WNT's in tongue and papillae development, Concluding that WNT/β-catenin is essential for fungiform papillae differing to WNT5a which proved to be principle in tongue development. Intrinsic chemical mediators were considered by manipulating a tissue culture and then throughaly examined by scanning photomicrograph. <ref><pubmed>PMC2768563</pubmed></ref>

[http://www.surgicalneurologyint.com/article.asp?issn=2152-7806;year=2012;volume=3;issue=1;spage=23;epage=23;aulast=Manjila]
[[File:Abnormal of tongue.jpg|Left|thumb|200px|Image shows and example of tongue abnormalities, this is called "double tongue" each side has independent movement!]]

==Useful links==

==Glossary==

ectoderm- outer germ layer of embryo

endoderm - inner germ layer of embryo

epithelium - basic animal tissue that is composed of tightly packed cells, usually covering the outer portion of organs

exocystosis - movement of contents out of cell

ganglia - the accumulation of a nerve cell body

growth factor - a substance that stimulates the growth of cells

gustatory - anything that relates to the taste sense

hydrolysis - breakdown of a chemical when it reacts with water

mesoderm - middle germ layer of embryo

mesenchyme - multipotential cells

neural crest - a part of the ectoderm found on both sides of the neural tube

neuron - most simplistic unit of the nervous system

neurotransmitter - chemicals which allow the passing of signals from neuron to neuron via connecting part (synapse)

papillae - small rough surface projection

six genes - a family of genes

Sonic hedgehog (Shh) - signalling protein invloved in normal development

sulcus terminalis - describes a physical transition point separating the anterior 2/3 of the tongue from the posterior 1/3

tamoxifen - hormonal altering drug

==Image gallery==

== References ==
<references/>

==External Links==
{{External Links}}

http://www.webmd.com/oral-health/picture-of-the-tongue

http://www.tutorvista.com/content/biology/biology-iv/nervous-coordination/tongue-structure.php#parts-of-tongue

http://www.cf.ac.uk/biosi/staffinfo/jacob/teaching/sensory/taste.html

--[[User:Z8600021|Mark Hill]] 12:22, 15 August 2012 (EST) Please leave the content listed below the line at the bottom of your project page.

----

{{2012Projects}}

2012 Group Project 3

2012-09-30T05:05:39Z

Z3289738: /* Human Weekly Development - Two Prominent Studies */

=Taste Development=

== Introduction ==
**NEED TO ADD**

==History of Discoveries==

{| cellpadding=5 style="border:1px solid #BBB"
|- bgcolor="#faecc8"
|''' Date'''|| '''Significant Discovery'''

|- bgcolor="#faf6ed"
|'''350BC'''
|| Aristotle writes about the basic tastes, sweet and bitter. He also notes that it can be modified by salty and acidic. <ref name="PMID22717400"><pubmed>22717400</pubmed></ref>

|- bgcolor="#faecc8"
|'''1901'''
|| D. Hanig publishes a paper describing taste sensitivity in different regions of the tongue.
''Interesting fact:'' The modern concept of a 'tongue map' is a misinterpretation of this study. <ref name="PMID22717400"/>

|- bgcolor="#faf6ed"
|style=white-space:nowrap|'''1908'''
|Kikunae Ikeda, a professor of the Tokyo Imperial University, discovered and identified the fifth basic taste: umami (savouriness), made palatable by glutamate. <ref><pubmed>12438213</pubmed></ref>
[http://chemse.oxfordjournals.org/content/27/9/847.long New Seasonings]

|- bgcolor="#faecc8"
|style=white-space:nowrap|'''1931-32'''
| A chemist named Arthur Fox and his college noted that they had different sensitivities to the bitter tasting Phenylthiocarbamide (PTC).<ref>Blakeslee AF, Fox AL. Our different taste worlds. J Hered. 1932;23:97–107.</ref> Geneticists later confirm these findings, and discover that non-tasting is a recessive genetic trait. <ref><pubmed>17782493</pubmed></ref>
[http://www.ncbi.nlm.nih.gov/pubmed/17782493 Inherited taste deficiency]

|- bgcolor="#faf6ed"
|style=white-space:nowrap|'''1965'''
|Farbman's study of the developing taste but in rat fungiform papilla was significant in increasing our understanding of taste bud development. <ref><pubmed>14300090</pubmed></ref>
[http://www.sciencedirect.com/science/article/pii/0012160665900400 Electron microscope study of the developing taste bud in rat fungiform papilla.]

|- bgcolor="#faecc8"
|style=white-space:nowrap|'''1992'''
|McLaughlin SK et al. discovery a taste cell-specific G-protein within the taste buds called Gustucon. This protein is later used to mark bitter, umami and sweet cells. <ref><pubmed>1608467 </pubmed></ref>
[http://www.nature.com/nature/journal/v357/n6379/abs/357563a0.html Gustducin is a taste-cell-specific G protein closely related to the transducins]

|- bgcolor="#faf6ed"
|style=white-space:nowrap|'''1995'''
|Barlow et al. experimented with Axolotl salamanders and concluded that taste buds from this species arise exclusively from epithelial tissue, "oropharyngeal epithelium". <ref name="PMID17826760"><pubmed>17826760</pubmed></ref>
[http://www.ncbi.nlm.nih.gov/pubmed/17826760 Embryonic origin of gustatory cranial sensory neurons.]

|- bgcolor="#faecc8"
|style=white-space:nowrap|'''1996'''
| Witt M and Reutter K of the Technical University Dresden in Germany, carried out a transmission electron microscopy study to investigate the embryonic and fetal development of Human taste buds. Their results suggest an "at least dual function of embryonic/fetal taste buds", including non-gustatory, paracrine functions prior to the 14th week and gustatory after the 14th week. <ref name="PMID8955790"><pubmed>8955790</pubmed></ref>
[http://www.ncbi.nlm.nih.gov/pubmed/8955790 Embryonic and early fetal development of human taste buds: a transmission electron microscopical study]

|- bgcolor="#faf6ed"
|style=white-space:nowrap|'''2000'''
|Chandrashekar, J. et al. discover the first taste sonsors, the T2R bitter taste receptors. <ref><pubmed>10761935</pubmed></ref>
[http://www.sciencedirect.com/science/article/pii/S0092867400807060 T2Rs Function as Bitter Taste Receptors]

|- bgcolor="#faecc8"
|style=white-space:nowrap|'''2001'''
|Nelson, G. et al. discover the sweet receptor: a combination of T1R2 and T1R3. <ref><pubmed>11509186</pubmed></ref>
[http://www.ncbi.nlm.nih.gov/pubmed/11509186?dopt=Abstract&holding=npg Mammalian sweet taste receptors.]

|- bgcolor="#faf6ed"
|style=white-space:nowrap|'''2002'''
|Nelson G. et al. discover the amino acid (umami) taste receptor: a combination of T1R1 and T1R3 identified. <ref><pubmed>11894099</pubmed></ref>
[http://www.ncbi.nlm.nih.gov/pubmed/11894099?dopt=Abstract&holding=npg An amino-acid taste receptor]

|- bgcolor="#faecc8"
|style=white-space:nowrap|'''2005'''
|Dyer, J. et al. discover sweet taste receptors in the GI tract. <ref><pubmed>17855558</pubmed></ref>
[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1986582/ Sweet taste signaling in the gut]

|- bgcolor="#faf6ed"
|style=white-space:nowrap|'''2006'''
|Huang, A. L et al. discover cells for sour taste, identified by PKD2L1 (a polycystic kidney disease-like ion channel). <ref><pubmed>16929298</pubmed></ref>
[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1571047/ The Cells and Logic for Mammalian Sour Taste detection]

|- bgcolor="#faecc8"
|style=white-space:nowrap|'''2007'''
|Harlow DE, Barlow LA of the University of Colorado Denver Health Sciences Center provide evidence of the "embryonic origin of gustatory cranial sensory neurons". <ref name="PMID17826760"/>
[http://www.ncbi.nlm.nih.gov/pubmed/17826760 Embryonic origin of gustatory cranial sensory neurons.]

|- bgcolor="#faf6ed"
|style=white-space:nowrap|'''2009'''
|A study by Hevezi P et al, presents "the first comprehensive characterization of gene expression in primate taste buds", as opposed to previous studies which focused on rodents. <ref><pubmed>19636377</pubmed></ref>
[http://www.ncbi.nlm.nih.gov/pubmed/19636377 Genome-wide analysis of gene expression in primate taste buds reveals links to diverse processes]

|- bgcolor="#faecc8"
|style=white-space:nowrap|'''2010'''
|Chandrashekar, J. et al. identify epithelial sodium channel (ENaC) as the sodium-salt taste receptor. <ref><pubmed>20107438</pubmed></ref>
[http://www.ncbi.nlm.nih.gov/pubmed/20107438?dopt=Abstract&holding=npg The cells and peripheral representation of sodium taste in mice]
|}

==Gustatory System==

[[Image:Taste qualities.gif|thumb|The five basic tastes]]

Taste or more appropriately gustation, is a fundamental survival tool in animals as it directs the consumption of essential nutrients. The five tastes that exist within the human gustatory system: salty, sweet, sour, bitter and umami, all signify basic physiological requirements. Salty tastes denote the presence of Na+, an important ion involved in the transportation and retention of water across cell membranes. Sweetness is the recognition of carbohydrates, essential for maintaining optimal brain function and providing the basis for energy production in muscle tissue via ATP hydrolysis. Similarly umami codes for the presence of L-amino acids, especially L-glutamate which is an integral component of protein synthesis.

These different modalities not only function to maintain the proper intake of nutrients within the body but also, by way of aversion, prohibit the consumption of undesired or poisonous materials. The bitter modality for example is generally regarded as displeasing to the human palate. It represents a high acid content which may be a result of foods which have become rotten or are inherently poisonous to the body.<ref name=PMID20696704><pubmed>20696704</pubmed></ref>

Research has historically limited itself to investigating the mechanisms of these five taste qualities though it must be noted many other modalities may exist. Of particular conjecture is the existence of fatty acid recognition. In the past the detection of fat in food has been attributed to somatosensory inputs <ref name=PMID20696704/> from the tongue, that is, the oily feel and texture of fat rather than its actual ‘taste’ allows the brain to encode for its presence. Further research is therefore required to elicit the precise mechanisms of fat detection.

===Cell Biology===

The five taste qualities are not all detected by the same type of receptor cell located within the taste bud. Like rods and cones in the eye which detect different wavelengths of light, there are specific types of receptors for different tastes. For example, sweet, umami and bitter are recognised by Type II G-protein coupled receptors, whereas sour is related to Type III presynaptic cells. The cell type involved in salty taste transduction is unknown however it is known that sodium ions can enter the receptor cell membrane via ion channel permeation.

====Type II receptors====

When a bitter, sweet or umami ligand binds to a type II G-coupled receptor, a cascade of chemical reactions causes the release of Ca2+ which in turn mediates exocystosis of ATP. The function of this ATP is threefold:

# Stimulates gustatory nerve afferents which project to gustatory nuclei in the spinal cord
# Excites Type III presynaptic nerve fibres to release serotonin.
# Has a positive feedback effect on type II receptor cells, increasing the level of ATP production.

The role of serotonin is believed to be in the form of lateral inhibition i.e. when a bitter quality is recognised, adjacent receptors for sweetness are deactivated and thus the two tastes may be clearly differentiated. It also has a negative feedback effect on receptor cells, inhibiting umami, bitter and sweet taste transduction.

==Taste Map==
[[Image:Taste map.png|thumb|left|250px|Obsolete idea of the tongue map]]
The idea of a tongue map has disseminated through society for many years. This concept purports that different areas of the tongue are specialised to detect either sweet, salty, sour and bitter tastes. Recent research however has completely nullified such claims and suggests instead that different forms of taste are recognised all over the tongue as well as via the palate. Thus the term ''taste map'' has come to take on a new meaning and that is, the precise areas of taste modalities processing in areas of cortex and its subsequent neural inputs.

===Neural Pathways===

'''First order neurons''' - From the receptors located in the taste buds, gustatory nerve afferents project to the ipsilateral rostral 1/3 of the nucleus tractus solitarius (NTS), located in the medulla. This rostral 1/3 is commonly referred to as the ''gustatory nucleus''.

The ''gustatory nucleus'' receives input from cranial nerves VII (''Facial n.''), IX (''Hypglossal n.''), and X (''Vagus n.'') via special visceral afferent (SVA) nerve fibres. A summary of their functions is as follows:

* ''Facial nerve n''. - carries taste information from the anterior 2/3 of the tongue.
* ''Hypoglossal n.'' - carries taste information from the posterior 1/3 of the tongue.
* ''Vagus n''. - carries taste information from the palate

'''Second order neurons''' - From the NTS second order neurons carry taste information to the Ventral posteromedial (VPM) nucleus in the thalamus.<ref name=PMID21885776/>

Copious scientific conjecture surrounds how each taste modality is transmitted to the brain. The ‘labelled-line’ hypothesis suggests that there are taste specific neurons which exclusively carry that taste modality to cortical areas. In analogous terms it can be viewed like the pipelines leading toward a house. Each pipeline carries its own utility, there is one for gas, another for water and finally for electricity with each terminating in slightly different areas of the house. In the same way, on the tongues there are different receptors for each taste which concurrently have individual nerve tracts leading to the primary gustatory cortex.

Contrapuntally there is electrophysiological evidence that single nerve afferents carry multiple modalities. These studies show one nerve afferent may have both a strong and a weak activation in response to a multiple taste stimuli.

===Cortical Areas===

[[Image:Primary gustatory cortex.png|thumb|Primary gustatory cortex]]

The location of the taste perception centres has been observed via functional magnetic resonance imaging (fMRI) studies. The primary taste cortex has been identified as being located in the anterior insula/frontal operculum (I/fO)<ref name=PMID22245354><pubmed>22245354</pubmed></ref>, with the secondary taste cortex in the caudolateral orbitofrontal cortex.<ref name=PMID21305668><pubmed>21305668</pubmed></ref> Within the insula there are further subdivisions related to each taste modality. Two photon calcium imaging research has outlined certain ’hot-spots’ of activation which are clearly delineated in relation to each taste. For example, the bitter modality is represented on the insula cortex approximately 1mm posterior to the middle cerebral artery whereas the sweet modality is represented 2.5mm rostrodorsal to the bitter field with no apparent overlap.<ref name=PMID21885776><pubmed>21885776</pubmed></ref> These findings lend weight to the idea that there is only one receptor for each taste quality.

It is interesting to note the relationship between taste and the reward centres of the brain. There is evidence of neural input to the ventral tegmental area (the origin of the mesolimbic dopaminergic reward pathway) and nucleus accumbens (involved in the conversion of motivation into physical action).<ref name=PMID21885776/> Neural connections such as this provide the foundations in explaining concepts such as flavour learning and preference. It may also give some insight into chronic problems such as food addiction and craving. As of yet however the gustatory neural network is not well understood and more research is required to elucidate the relationship between pleasure and taste sensation

== Human Weekly Development - Two Prominent Studies ==
Martin Witt and Klaus Reutter of the University of Tubingen in Germany published two prominent studies regarding developing taste buds in humans. Their first study in 1996 was a transmission electron microscopical (TEM) study of the taste bud primordium and its morphological changes during the 8th-15th postovulatory week. Their next study in 1997 built on their previous findings by using Scanning Electron Microscopy (SEM) to observe the development of gustatory papillae during postovulatory weeks 6-15.

The findings of these two studies are summarized in the table below. The figures provided relate to the images on their respective research papers.

# [http://onlinelibrary.wiley.com/doi/10.1002/(SICI)1097-0185(199612)246:4%3C507::AID-AR10%3E3.0.CO;2-S/pdf Embryonic and early fetal development of human taste buds: a transmission electron microscopical study, 1996]
# [http://chemse.oxfordjournals.org/content/22/6/601.long Scanning electron microscopical studies of developing gustatory papillae in humans, 1997]

===Timeline of Developmental Processes of Human Taste Buds===
{| cellpadding=5 style="border:1px solid #BBB"
|- bgcolor="#89CFF0"
|'''Postovulatory Week'''||'''Description'''||'''Image'''

|- bgcolor="#BCD4E6"
|'''Week 6''' ||
The surface of the developing tongue is covered by nearly flat epithelium (1997, Figure 1). The first gustatory papillae of the tongue appear in the caudal midline near the foramen caecum and the first circumvallate papilla develops on the dorsal midline. <ref name="PMID9455607"><pubmed>9455607</pubmed></ref>
||
image

|- bgcolor="#89CFF0"
| '''Weeks 6 to 7'''||
Nerve fibres approach the basal lamina of lingual epithelium. At this stage the lingual epithelium consists of two to three cell layers and there is not yet any sign of cell specializations indicating early taste bud formation. <ref name=PMID8955790/>
||
Image

|- bgcolor="#BCD4E6"
| '''Week 7 '''||
A series of irregular epithelial swellings in the anterior part and marginal parts of the tongue indicate early forming fungiform papillae. Furthermore, a V-like lane is observed anterior to the sulcus terminalis, which represents a smooth surface for developing circumvallate papillae (1997, Figure 2). Witt M et al observe that these circumvallate papillae are larger than the developing fungiform papillae of the same age, later noting that the fungiform papillae tend to increase in size over the 8-15th weeks of gestation, whilst the size of vallate papillae tend to remain constant during this period. <ref name=PMID9455607/>
||
Image

|- bgcolor="#89CFF0"
| ''' Week 8 ''' ||
* The taste bud primordium are still differentiated, elongated epithelial cells, resting on a slightly developed core of young dermal papilla.
* The lingual epithelium shows first signs of taste bud development as nerve fibres coming from the dermal papilla penetrate the epithelial basal lamina and form synapses with taste bud progenitor cells (1996, Figure 1). These synapses demonstrate the neuronal connection between the taste bud primordium and the central nervous system, reaching a maximum around the 12th to 13th week. However, it is important to note that at this time these cells are still poorly differentiated, elongated epithelial cells.
* Ciliated cells also appear around the 8th week, however the significance of these cells which are scattered randomly across the lingual surface remains unclear. <ref name=PMID8955790/>
||
Image

|- bgcolor="#BCD4E6"
|''' Week 9''' ||
By this stage, although a taste pore is not present, the surface of circumvallate papillae usually contains a taste pit partly filled with microvillus-like processes from the underlying taste bud cells (1997, Figure 10). <ref name=PMID9455607/>
||
Image

|- bgcolor="#89CFF0"
|''' Weeks 10-11''' ||
At this stage, the lingual epithelium compromises of about four cell layers, and the first shallow grooves above the taste bud primordium are developed. Fungiform papillae appear on the lateral margins and the tip of the tongue, containing taste bud primordial that display the first signs of a primitive pore formation (1996, Figure 6). <ref name=PMID8955790/>
||
Image

|- bgcolor="#BCD4E6"
|''' Week 12 ''' ||
Taste bud cells are more clearly differentiated into epithelial cell types II and III. <ref name=PMID8955790/>
||
Image

|- bgcolor="#89CFF0"
|''' Weeks 12-13 ''' ||
At this stage the taste bud primordial are all located on the top of dermal papillae. There is also maximum synapses between cells and afferent nerve fibres, which intermingle with each other to form a plexus-like structure (1996, Figure 6a). <ref name=PMID8955790/>
||
Image

|- bgcolor="#BCD4E6"
|''' Weeks 14 -15 ''' ||
The shape and size of the taste buds primordial begins to resemble those of adult taste buds (1996, Figure 9). By the 14th week the taste pores develop as the taste pits are filled by microvilli, and bubble like vesicles indicate the secretory activity of these cells (1996, Figure 10). However, the tastebuds only achieve a fully developed function in week 15 of gestation with the development of type I cells to produce the mucous material in the taste pit. <ref name=PMID8955790/>
||
Image
|}

==Adult Tongue and Taste Buds – Structure and Function==

'''Structure'''

The tongue is located on the floor of the oral cavity, It is a muscular structure with sensory units crowning. The tongue is divided into an anterior two thirds and a posterior one third. These regions are divided by a V-shaped groove at the back of the tongue (sulcus terminalis). The anterior two thirds of the tongue is covered by stratified squamous epithelium, It contains a roughened surface and has projections called papillae that vary in shape and number.

''''The Image Below is a very simplistic Diagram of the surface of the Tongue showing the locations of the different papillae and other important features'''

{|
| [[Image:Drawing of Tongue.png|500px]]

'''Papillae'''
[[File:Papillae.jpg|Left|thumb|200px|Close up of Human Tongue Papillae]]

There are 4 types of papillae on the tongue.
The most numerous papillae are the filiform papillae, which function to provide a surface that aids in holding food on the tongue during chewing but do not contain taste buds. The larger, less numerous fungiform papillae which contain taste buds, as do foliate papillae. Circumvallate papillae form a wide V at the sulcus terminalis also containing taste bus. There are no papillae or taste buds located on the posterior third of the tongue, having mucosal folds and the lingual tonsils instead.

'''Function'''

The tongue is for tasting, swallowing, and speech.
The functional unit of the taste bud is a taste cell, there are between 50 and 100 taste cells in each taste bud these taste cells represent all 5 different tastes. Historically is was believed that different areas of the tongue were responsible for different taste sensations although this has since been disregarded.[http://users.rcn.com/jkimball.ma.ultranet/BiologyPages/W/Welcome.html] The papillae contain taste buds which are connected to the oral cavity via a taste pore, the function of the taste bud is to transmit a chemical signal from the oral cavity to a taste cell, this chemical signal is the converted into an electrical impulse and delivered to the brain via nerve fibres for interpretation.

'''The Image Below is a very simplistic Hand drawn Diagram of a taste bud, in an extreme close up, cross section view of the the taste bud unit, not to scale'''

[[File:Taste_bud_1.jpg]]

==Abnormalities==

===Knocking out P2X Receptors===

[[File:Image of taste being evoked by visualising ATP release.jpeg|Left|thumb|200px|Evoking taste - ATP release in tongue]]

Gustatory abnormalities has not been widely researched and what has been researched has been through animal testing, most commonly we have found on mice.

In Huang, 2008 this team used the release of the neurotransmitter, ATP (adenosine triphosphate) as a quantitative measurement of gustatory sensation and taste. This was done by using a comparison of wild type (WT) and double knockout (DKO) mice. P2X receptors, P2X2 and P2X3 were knocked out in the DKO mice. The premise of this article was that knocking out P2X receptors reduces transmitter secretion of ATP in taste buds, therefore they cannot taste.

It should be noted that the taste buds in DKO are functional, but are not stimulated by the administration of tastants.

The transmission of release of ATP is secretion through gap junction hemichannels (pannexin 1 gap junction).

When both P2X2 and P2X3 are knocked out, no taste is elicited. However they found that if either P2X2 OR P2X3 was knocked out there was a taste response. So the inference made from this is that if one of the two receptors from the P2X family was knocked out there still can have taste response. The WT mice showed significant stimulation by tastants whereas DKO had little to no stimulation of ATP release.<ref><pubmed>21940456</pubmed></ref>

===FGF signalling and genes===

Sprouty, or ''Srpy'', genes have been related to regulating the development of circumvillate papillae (CVP). The CVP are large dome shaped papillae, which form a 'V' just in front of the terminal sulcus.

By knocking out ''Spry'' genes using mice which had ''Spry1'' and ''Spry2'' knocked out showed that the number of CVP doubled. However, when Fibroblast Growth Factor gene ("Fgf10") was absent, the number of CVP was significantly reduced, if not completely absent. The correlation between ''Spry1/2'' and ''Fgf10'' is that ''Spry1/2'' antagonises "Fgf10" to limit the size of the CVP progenitor placode. Exclusive expression of ''Fgf10'' in the mesenchyme is necessary for the formation of CVP.

'''This image shows the CVP stained with H&E and scanned by Scanning Electron Microscope (SEM)'''
[[File:CVP of WT(top) and DKO(bottom) mice with H&E and SEM.png]]

'''This image shows the location of the CVP and the increased number in DKO mice by SEM'''
[[File:Mouse circumvallate papilla 01.jpg|300px]]

Taste buds develop from the mesenchyme but require local signalling to properly differentiate. Some signalling factors for proper development of taste buds besides FGF are: Sonic Hedgehog (SHH), Bone Morphogenetic Proteins (BMPs), Epidermal Growth Factor (EGF).

Additionally, this proves that the anterior and posterior developments of the tongue are derived from embryonic tissues, where the anterior tongue is derived from the ectoderm and the posterior tongue is derived from the endoderm. Taste buds develop from the mesenchyme but require local signalling to properly differentiate. Some signalling factors for proper development of taste buds besides FGF are: Sonic Hedgehog (SHH), Bone Morphogenetic Proteins (BMPs), Epidermal Growth Factor (EGF).

As mentioned above, this article shows that the anterior and posterior developments of the tongue are derived from embryonic tissues, where the anterior tongue is derived front the ectoderm and the posterior tongue is derived from the endoderm. Secondly, FGF is required to regulate the growth of taste buds, while ''Spry'' genes limit the number of CVP. ''Fgf10''& ''Spry 1&2''work antagonistically through receptor tyrosine kinase (RTK)signalling.

However, the deletion of ''Spry2''led to the increase of CVPs it should be noted that they found that a significant decrease in number of fungiform papillae. Contrastingly, the absence of ''Fgf10'', while leading to the absence of CVPs lead to an increase in number and size of fungiform papillae. Therefore these genes have different effects on the anterior and posterior developing tongue and taste buds.<ref><pubmed>21655085</pubmed></ref>

==Current Research==
We have an evolving understanding of Embryonic Taste development, through the use of state-of-the-art technology and research techniques we are able to make brilliant discoveries that continue to connect the dots of this amazing natural process of human development.
The majority of research in taste development is involving mice, these mammals show similar embryonic pathways to humans and research is performed in ethical and humane methods.

[[File:Histology.jpg|Left|thumb|200px|Image shows histological stains of a mice tongue showing dysplasia]]

'''Synergistic relationships of Six Genes '''

In an animal study using mice by Suzuki Y, Ikeda K, Kawakami K.(2011) Firstly nominating "Six Genes" as a major component in gustatory development, stating that deficiencies in certain Six genes (specifically Six1 & Six4) leads to poor development. Their research also highlights evidence of cooperative relationships between Six genes for normal advance. This experiment involved breeding mice containing exclusively Six1 and Six4 genes and examining the expression of these genes in papillae under high powered microscope observation. Understanding the role of certain genes along with the intrinsic relationships they hold is crucial for the ability to identify possible causes and correction of any abnormalities <ref><pubmed>21978088</pubmed></ref>

'''Neural Crest responsibilities '''

Another Animal Study involving mice explores a new idea of Neural crest (NC) contribution in taste development, specifically the development of papillae and taste buds. Liu HX, Komatsu Y, Mishina Y, Mistretta CM. (2012) suggest that Neural crest cells travel to the location of the tongue in early embryonic stages, gain epithelium phenotypes, multiply and then differentiate to eventually form taste papillae. The experiment involved the comparison of 2 different types of Cre line mice, which both express Cre gene in neural crest protocol, the different distribution patterns where observed in specific regions that NC is responsible for.<ref><pubmed>22659543</pubmed></ref>

'''Augmentation of Endoderm'''

In an animal study conducted by Rothova M, Thompson H, Lickert H, Tucker AS.(2012) exploring the historically debated issue of endoderm contribution to tongue development showed promising evidence that position of taste buds are patterned by the border of ectoderm and endoderm derivative epithelium. This study was accomplished via microscopic examination of previously stained specimens. Concluding endoderm has direct influence on gustatory develoment <ref><pubmed>22581563</pubmed></ref>

'''Changes in Taste Cells over time'''

Research by
Ozdener H, Spielman AI, Rawson NE.(2012) developing a culture which allows taste cells to survive for up to 12 months, empowers researchers to study the processes of proliferation, differentiation and function. This experiment will provide a precidnet for future study of taste cells, as these cells are able to operate and grow normally. <ref><pubmed>22643728</pubmed></ref>

'''Shh key component of taste bud proginators'''

A tamoxifen treatment which supresses Sonic hedgehog (Shh) secretion in mice proving to reduce the number of cells visable within papillae, in contrast mice not treated with tamoxifen showed a mark increase of cells within papillae, these cells are assumed to become taste cells in later development.
Specific mice were bred to trace the destination of taste placode cells, the study concluded that Shh expressing placodes are taste bud proginators which in turn become taste cells within taste buds although do not have any prescuros relationship with pappilae. The results were obtain by examination of mice embryos using Bright-field or multichannel fluorescent images through the use of an "Axiocam CCD camera and Axioplan fluorescence microscope with Axiovision software" a study by Harlow, Yang, Williams, Barlow (2011)<ref><pubmed>PMC2674259</pubmed></ref>

'''WNT family exhibit various roles'''

The WNT gene family has a function of signally proteins for various reason such as development, In 2010 Liu, Staubach Grosse, Walton, Saims, Gumucio, Mistretta explored recent findings on the role of WNT's in tongue and papillae development, Concluding that WNT/β-catenin is essential for fungiform papillae differing to WNT5a which proved to be principle in tongue development. Intrinsic chemical mediators were considered by manipulating a tissue culture and then throughaly examined by scanning photomicrograph. <ref><pubmed>PMC2768563</pubmed></ref>

[http://www.surgicalneurologyint.com/article.asp?issn=2152-7806;year=2012;volume=3;issue=1;spage=23;epage=23;aulast=Manjila]
[[File:Abnormal of tongue.jpg|Left|thumb|200px|Image shows and example of tongue abnormalities, this is called "double tongue" each side has independent movement!]]

==Useful links==

==Glossary==

ectoderm- outer germ layer of embryo

endoderm - inner germ layer of embryo

epithelium - basic animal tissue that is composed of tightly packed cells, usually covering the outer portion of organs

exocystosis - movement of contents out of cell

ganglia - the accumulation of a nerve cell body

growth factor - a substance that stimulates the growth of cells

gustatory - anything that relates to the taste sense

hydrolysis - breakdown of a chemical when it reacts with water

mesoderm - middle germ layer of embryo

mesenchyme - multipotential cells

neural crest - a part of the ectoderm found on both sides of the neural tube

neuron - most simplistic unit of the nervous system

neurotransmitter - chemicals which allow the passing of signals from neuron to neuron via connecting part (synapse)

papillae - small rough surface projection

six genes - a family of genes

Sonic hedgehog (Shh) - signalling protein invloved in normal development

sulcus terminalis - describes a physical transition point separating the anterior 2/3 of the tongue from the posterior 1/3

tamoxifen - hormonal altering drug

==Image gallery==

== References ==
<references/>

==External Links==
{{External Links}}

http://www.webmd.com/oral-health/picture-of-the-tongue

http://www.tutorvista.com/content/biology/biology-iv/nervous-coordination/tongue-structure.php#parts-of-tongue

http://www.cf.ac.uk/biosi/staffinfo/jacob/teaching/sensory/taste.html

--[[User:Z8600021|Mark Hill]] 12:22, 15 August 2012 (EST) Please leave the content listed below the line at the bottom of your project page.

----

{{2012Projects}}

2012 Group Project 3

2012-09-30T04:59:00Z

Z3289738: /* Human Weekly Development - Two Prominent Studies */

=Taste Development=

== Introduction ==
**NEED TO ADD**

==History of Discoveries==

{| cellpadding=5 style="border:1px solid #BBB"
|- bgcolor="#faecc8"
|''' Date'''|| '''Significant Discovery'''

|- bgcolor="#faf6ed"
|'''350BC'''
|| Aristotle writes about the basic tastes, sweet and bitter. He also notes that it can be modified by salty and acidic. <ref name="PMID22717400"><pubmed>22717400</pubmed></ref>

|- bgcolor="#faecc8"
|'''1901'''
|| D. Hanig publishes a paper describing taste sensitivity in different regions of the tongue.
''Interesting fact:'' The modern concept of a 'tongue map' is a misinterpretation of this study. <ref name="PMID22717400"/>

|- bgcolor="#faf6ed"
|style=white-space:nowrap|'''1908'''
|Kikunae Ikeda, a professor of the Tokyo Imperial University, discovered and identified the fifth basic taste: umami (savouriness), made palatable by glutamate. <ref><pubmed>12438213</pubmed></ref>
[http://chemse.oxfordjournals.org/content/27/9/847.long New Seasonings]

|- bgcolor="#faecc8"
|style=white-space:nowrap|'''1931-32'''
| A chemist named Arthur Fox and his college noted that they had different sensitivities to the bitter tasting Phenylthiocarbamide (PTC).<ref>Blakeslee AF, Fox AL. Our different taste worlds. J Hered. 1932;23:97–107.</ref> Geneticists later confirm these findings, and discover that non-tasting is a recessive genetic trait. <ref><pubmed>17782493</pubmed></ref>
[http://www.ncbi.nlm.nih.gov/pubmed/17782493 Inherited taste deficiency]

|- bgcolor="#faf6ed"
|style=white-space:nowrap|'''1965'''
|Farbman's study of the developing taste but in rat fungiform papilla was significant in increasing our understanding of taste bud development. <ref><pubmed>14300090</pubmed></ref>
[http://www.sciencedirect.com/science/article/pii/0012160665900400 Electron microscope study of the developing taste bud in rat fungiform papilla.]

|- bgcolor="#faecc8"
|style=white-space:nowrap|'''1992'''
|McLaughlin SK et al. discovery a taste cell-specific G-protein within the taste buds called Gustucon. This protein is later used to mark bitter, umami and sweet cells. <ref><pubmed>1608467 </pubmed></ref>
[http://www.nature.com/nature/journal/v357/n6379/abs/357563a0.html Gustducin is a taste-cell-specific G protein closely related to the transducins]

|- bgcolor="#faf6ed"
|style=white-space:nowrap|'''1995'''
|Barlow et al. experimented with Axolotl salamanders and concluded that taste buds from this species arise exclusively from epithelial tissue, "oropharyngeal epithelium". <ref name="PMID17826760"><pubmed>17826760</pubmed></ref>
[http://www.ncbi.nlm.nih.gov/pubmed/17826760 Embryonic origin of gustatory cranial sensory neurons.]

|- bgcolor="#faecc8"
|style=white-space:nowrap|'''1996'''
| Witt M and Reutter K of the Technical University Dresden in Germany, carried out a transmission electron microscopy study to investigate the embryonic and fetal development of Human taste buds. Their results suggest an "at least dual function of embryonic/fetal taste buds", including non-gustatory, paracrine functions prior to the 14th week and gustatory after the 14th week. <ref name="PMID8955790"><pubmed>8955790</pubmed></ref>
[http://www.ncbi.nlm.nih.gov/pubmed/8955790 Embryonic and early fetal development of human taste buds: a transmission electron microscopical study]

|- bgcolor="#faf6ed"
|style=white-space:nowrap|'''2000'''
|Chandrashekar, J. et al. discover the first taste sonsors, the T2R bitter taste receptors. <ref><pubmed>10761935</pubmed></ref>
[http://www.sciencedirect.com/science/article/pii/S0092867400807060 T2Rs Function as Bitter Taste Receptors]

|- bgcolor="#faecc8"
|style=white-space:nowrap|'''2001'''
|Nelson, G. et al. discover the sweet receptor: a combination of T1R2 and T1R3. <ref><pubmed>11509186</pubmed></ref>
[http://www.ncbi.nlm.nih.gov/pubmed/11509186?dopt=Abstract&holding=npg Mammalian sweet taste receptors.]

|- bgcolor="#faf6ed"
|style=white-space:nowrap|'''2002'''
|Nelson G. et al. discover the amino acid (umami) taste receptor: a combination of T1R1 and T1R3 identified. <ref><pubmed>11894099</pubmed></ref>
[http://www.ncbi.nlm.nih.gov/pubmed/11894099?dopt=Abstract&holding=npg An amino-acid taste receptor]

|- bgcolor="#faecc8"
|style=white-space:nowrap|'''2005'''
|Dyer, J. et al. discover sweet taste receptors in the GI tract. <ref><pubmed>17855558</pubmed></ref>
[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1986582/ Sweet taste signaling in the gut]

|- bgcolor="#faf6ed"
|style=white-space:nowrap|'''2006'''
|Huang, A. L et al. discover cells for sour taste, identified by PKD2L1 (a polycystic kidney disease-like ion channel). <ref><pubmed>16929298</pubmed></ref>
[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1571047/ The Cells and Logic for Mammalian Sour Taste detection]

|- bgcolor="#faecc8"
|style=white-space:nowrap|'''2007'''
|Harlow DE, Barlow LA of the University of Colorado Denver Health Sciences Center provide evidence of the "embryonic origin of gustatory cranial sensory neurons". <ref name="PMID17826760"/>
[http://www.ncbi.nlm.nih.gov/pubmed/17826760 Embryonic origin of gustatory cranial sensory neurons.]

|- bgcolor="#faf6ed"
|style=white-space:nowrap|'''2009'''
|A study by Hevezi P et al, presents "the first comprehensive characterization of gene expression in primate taste buds", as opposed to previous studies which focused on rodents. <ref><pubmed>19636377</pubmed></ref>
[http://www.ncbi.nlm.nih.gov/pubmed/19636377 Genome-wide analysis of gene expression in primate taste buds reveals links to diverse processes]

|- bgcolor="#faecc8"
|style=white-space:nowrap|'''2010'''
|Chandrashekar, J. et al. identify epithelial sodium channel (ENaC) as the sodium-salt taste receptor. <ref><pubmed>20107438</pubmed></ref>
[http://www.ncbi.nlm.nih.gov/pubmed/20107438?dopt=Abstract&holding=npg The cells and peripheral representation of sodium taste in mice]
|}

==Gustatory System==

[[Image:Taste qualities.gif|thumb|The five basic tastes]]

Taste or more appropriately gustation, is a fundamental survival tool in animals as it directs the consumption of essential nutrients. The five tastes that exist within the human gustatory system: salty, sweet, sour, bitter and umami, all signify basic physiological requirements. Salty tastes denote the presence of Na+, an important ion involved in the transportation and retention of water across cell membranes. Sweetness is the recognition of carbohydrates, essential for maintaining optimal brain function and providing the basis for energy production in muscle tissue via ATP hydrolysis. Similarly umami codes for the presence of L-amino acids, especially L-glutamate which is an integral component of protein synthesis.

These different modalities not only function to maintain the proper intake of nutrients within the body but also, by way of aversion, prohibit the consumption of undesired or poisonous materials. The bitter modality for example is generally regarded as displeasing to the human palate. It represents a high acid content which may be a result of foods which have become rotten or are inherently poisonous to the body.<ref name=PMID20696704><pubmed>20696704</pubmed></ref>

Research has historically limited itself to investigating the mechanisms of these five taste qualities though it must be noted many other modalities may exist. Of particular conjecture is the existence of fatty acid recognition. In the past the detection of fat in food has been attributed to somatosensory inputs <ref name=PMID20696704/> from the tongue, that is, the oily feel and texture of fat rather than its actual ‘taste’ allows the brain to encode for its presence. Further research is therefore required to elicit the precise mechanisms of fat detection.

===Cell Biology===

The five taste qualities are not all detected by the same type of receptor cell located within the taste bud. Like rods and cones in the eye which detect different wavelengths of light, there are specific types of receptors for different tastes. For example, sweet, umami and bitter are recognised by Type II G-protein coupled receptors, whereas sour is related to Type III presynaptic cells. The cell type involved in salty taste transduction is unknown however it is known that sodium ions can enter the receptor cell membrane via ion channel permeation.

====Type II receptors====

When a bitter, sweet or umami ligand binds to a type II G-coupled receptor, a cascade of chemical reactions causes the release of Ca2+ which in turn mediates exocystosis of ATP. The function of this ATP is threefold:

# Stimulates gustatory nerve afferents which project to gustatory nuclei in the spinal cord
# Excites Type III presynaptic nerve fibres to release serotonin.
# Has a positive feedback effect on type II receptor cells, increasing the level of ATP production.

The role of serotonin is believed to be in the form of lateral inhibition i.e. when a bitter quality is recognised, adjacent receptors for sweetness are deactivated and thus the two tastes may be clearly differentiated. It also has a negative feedback effect on receptor cells, inhibiting umami, bitter and sweet taste transduction.

==Taste Map==
[[Image:Taste map.png|thumb|left|250px|Obsolete idea of the tongue map]]
The idea of a tongue map has disseminated through society for many years. This concept purports that different areas of the tongue are specialised to detect either sweet, salty, sour and bitter tastes. Recent research however has completely nullified such claims and suggests instead that different forms of taste are recognised all over the tongue as well as via the palate. Thus the term ''taste map'' has come to take on a new meaning and that is, the precise areas of taste modalities processing in areas of cortex and its subsequent neural inputs.

===Neural Pathways===

'''First order neurons''' - From the receptors located in the taste buds, gustatory nerve afferents project to the ipsilateral rostral 1/3 of the nucleus tractus solitarius (NTS), located in the medulla. This rostral 1/3 is commonly referred to as the ''gustatory nucleus''.

The ''gustatory nucleus'' receives input from cranial nerves VII (''Facial n.''), IX (''Hypglossal n.''), and X (''Vagus n.'') via special visceral afferent (SVA) nerve fibres. A summary of their functions is as follows:

* ''Facial nerve n''. - carries taste information from the anterior 2/3 of the tongue.
* ''Hypoglossal n.'' - carries taste information from the posterior 1/3 of the tongue.
* ''Vagus n''. - carries taste information from the palate

'''Second order neurons''' - From the NTS second order neurons carry taste information to the Ventral posteromedial (VPM) nucleus in the thalamus.<ref name=PMID21885776/>

Copious scientific conjecture surrounds how each taste modality is transmitted to the brain. The ‘labelled-line’ hypothesis suggests that there are taste specific neurons which exclusively carry that taste modality to cortical areas. In analogous terms it can be viewed like the pipelines leading toward a house. Each pipeline carries its own utility, there is one for gas, another for water and finally for electricity with each terminating in slightly different areas of the house. In the same way, on the tongues there are different receptors for each taste which concurrently have individual nerve tracts leading to the primary gustatory cortex.

Contrapuntally there is electrophysiological evidence that single nerve afferents carry multiple modalities. These studies show one nerve afferent may have both a strong and a weak activation in response to a multiple taste stimuli.

===Cortical Areas===

[[Image:Primary gustatory cortex.png|thumb|Primary gustatory cortex]]

The location of the taste perception centres has been observed via functional magnetic resonance imaging (fMRI) studies. The primary taste cortex has been identified as being located in the anterior insula/frontal operculum (I/fO)<ref name=PMID22245354><pubmed>22245354</pubmed></ref>, with the secondary taste cortex in the caudolateral orbitofrontal cortex.<ref name=PMID21305668><pubmed>21305668</pubmed></ref> Within the insula there are further subdivisions related to each taste modality. Two photon calcium imaging research has outlined certain ’hot-spots’ of activation which are clearly delineated in relation to each taste. For example, the bitter modality is represented on the insula cortex approximately 1mm posterior to the middle cerebral artery whereas the sweet modality is represented 2.5mm rostrodorsal to the bitter field with no apparent overlap.<ref name=PMID21885776><pubmed>21885776</pubmed></ref> These findings lend weight to the idea that there is only one receptor for each taste quality.

It is interesting to note the relationship between taste and the reward centres of the brain. There is evidence of neural input to the ventral tegmental area (the origin of the mesolimbic dopaminergic reward pathway) and nucleus accumbens (involved in the conversion of motivation into physical action).<ref name=PMID21885776/> Neural connections such as this provide the foundations in explaining concepts such as flavour learning and preference. It may also give some insight into chronic problems such as food addiction and craving. As of yet however the gustatory neural network is not well understood and more research is required to elucidate the relationship between pleasure and taste sensation

== Human Weekly Development - Two Prominent Studies ==
Martin Witt and Klaus Reutter of the University of Tubingen in Germany published two prominent studies regarding developing taste buds in humans. Their first study in 1996 was a transmission electron microscopical (TEM) study of the taste bud primordium and its morphological changes during the 8th-15th postovulatory week. Their next study in 1997 built on their previous findings by using Scanning Electron Microscopy (SEM) to observe the development of gustatory papillae during postovulatory weeks 6-15.

The findings of these two studies are summarized in the table below. The figures provided relate to the images on their respective research papers.

# [http://onlinelibrary.wiley.com/doi/10.1002/(SICI)1097-0185(199612)246:4%3C507::AID-AR10%3E3.0.CO;2-S/pdf Embryonic and early fetal development of human taste buds: a transmission electron microscopical study, 1996]
# [http://chemse.oxfordjournals.org/content/22/6/601.long Scanning electron microscopical studies of developing gustatory papillae in humans, 1997]

===Timeline of Developmental Processes of the Gustatory System===
{| cellpadding=5 style="border:1px solid #BBB"
|- bgcolor="#89CFF0"
|'''Postovulatory Week'''||'''Description'''||'''Image'''

|- bgcolor="#BCD4E6"
|'''Week 6''' ||
The surface of the developing tongue is covered by nearly flat epithelium (1997, Figure 1). The first gustatory papillae of the tongue appear in the caudal midline near the foramen caecum and the first circumvallate papilla develops on the dorsal midline. <ref name="PMID9455607"><pubmed>9455607</pubmed></ref>
||
image

|- bgcolor="#89CFF0"
| '''Weeks 6 to 7'''||
Nerve fibres approach the basal lamina of lingual epithelium. At this stage the lingual epithelium consists of two to three cell layers and there is not yet any sign of cell specializations indicating early taste bud formation. <ref name=PMID8955790/>
||
Image

|- bgcolor="#BCD4E6"
| '''Week 7 '''||
A series of irregular epithelial swellings in the anterior part and marginal parts of the tongue indicate early forming fungiform papillae. Furthermore, a V-like lane is observed anterior to the sulcus terminalis, which represents a smooth surface for developing circumvallate papillae (1997, Figure 2). Witt M et al observe that these circumvallate papillae are larger than the developing fungiform papillae of the same age, later noting that the fungiform papillae tend to increase in size over the 8-15th weeks of gestation, whilst the size of vallate papillae tend to remain constant during this period. <ref name=PMID9455607/>
||
Image

|- bgcolor="#89CFF0"
| ''' Week 8 ''' ||
* The taste bud primordium are still differentiated, elongated epithelial cells, resting on a slightly developed core of young dermal papilla.
* The lingual epithelium shows first signs of taste bud development as nerve fibres coming from the dermal papilla penetrate the epithelial basal lamina and form synapses with taste bud progenitor cells (1996, Figure 1). These synapses demonstrate the neuronal connection between the taste bud primordium and the central nervous system, reaching a maximum around the 12th to 13th week. However, it is important to note that at this time these cells are still poorly differentiated, elongated epithelial cells.
* Ciliated cells also appear around the 8th week, however the significance of these cells which are scattered randomly across the lingual surface remains unclear. <ref name=PMID8955790/>
||
Image

|- bgcolor="#BCD4E6"
|''' Week 9''' ||
By this stage, although a taste pore is not present, the surface of circumvallate papillae usually contains a taste pit partly filled with microvillus-like processes from the underlying taste bud cells (1997, Figure 10). <ref name=PMID9455607/>
||
Image

|- bgcolor="#89CFF0"
|''' Weeks 10-11''' ||
At this stage, the lingual epithelium compromises of about four cell layers, and the first shallow grooves above the taste bud primordium are developed. Fungiform papillae appear on the lateral margins and the tip of the tongue, containing taste bud primordial that display the first signs of a primitive pore formation (1996, Figure 6). <ref name=PMID8955790/>
||
Image

|- bgcolor="#BCD4E6"
|''' Week 12 ''' ||
Taste bud cells are more clearly differentiated into epithelial cell types II and III. <ref name=PMID8955790/>
||
Image

|- bgcolor="#89CFF0"
|''' Weeks 12-13 ''' ||
At this stage the taste bud primordial are all located on the top of dermal papillae. There is also maximum synapses between cells and afferent nerve fibres, which intermingle with each other to form a plexus-like structure (1996, Figure 6a). <ref name=PMID8955790/>
||
Image

|- bgcolor="#BCD4E6"
|''' Weeks 14 -15 ''' ||
The shape and size of the taste buds primordial begins to resemble those of adult taste buds (1996, Figure 9). By the 14th week the taste pores develop as the taste pits are filled by microvilli, and bubble like vesicles indicate the secretory activity of these cells (1996, Figure 10). However, the tastebuds only achieve a fully developed function in week 15 of gestation with the development of type I cells to produce the mucous material in the taste pit. <ref name=PMID8955790/>
||
Image
|}

==Adult Tongue and Taste Buds – Structure and Function==

'''Structure'''

The tongue is located on the floor of the oral cavity, It is a muscular structure with sensory units crowning. The tongue is divided into an anterior two thirds and a posterior one third. These regions are divided by a V-shaped groove at the back of the tongue (sulcus terminalis). The anterior two thirds of the tongue is covered by stratified squamous epithelium, It contains a roughened surface and has projections called papillae that vary in shape and number.

''''The Image Below is a very simplistic Diagram of the surface of the Tongue showing the locations of the different papillae and other important features'''

{|
| [[Image:Drawing of Tongue.png|500px]]

'''Papillae'''
[[File:Papillae.jpg|Left|thumb|200px|Close up of Human Tongue Papillae]]

There are 4 types of papillae on the tongue.
The most numerous papillae are the filiform papillae, which function to provide a surface that aids in holding food on the tongue during chewing but do not contain taste buds. The larger, less numerous fungiform papillae which contain taste buds, as do foliate papillae. Circumvallate papillae form a wide V at the sulcus terminalis also containing taste bus. There are no papillae or taste buds located on the posterior third of the tongue, having mucosal folds and the lingual tonsils instead.

'''Function'''

The tongue is for tasting, swallowing, and speech.
The functional unit of the taste bud is a taste cell, there are between 50 and 100 taste cells in each taste bud these taste cells represent all 5 different tastes. Historically is was believed that different areas of the tongue were responsible for different taste sensations although this has since been disregarded.[http://users.rcn.com/jkimball.ma.ultranet/BiologyPages/W/Welcome.html] The papillae contain taste buds which are connected to the oral cavity via a taste pore, the function of the taste bud is to transmit a chemical signal from the oral cavity to a taste cell, this chemical signal is the converted into an electrical impulse and delivered to the brain via nerve fibres for interpretation.

'''The Image Below is a very simplistic Hand drawn Diagram of a taste bud, in an extreme close up, cross section view of the the taste bud unit, not to scale'''

[[File:Taste_bud_1.jpg]]

==Abnormalities==

===Knocking out P2X Receptors===

[[File:Image of taste being evoked by visualising ATP release.jpeg|Left|thumb|200px|Evoking taste - ATP release in tongue]]

Gustatory abnormalities has not been widely researched and what has been researched has been through animal testing, most commonly we have found on mice.

In Huang, 2008 this team used the release of the neurotransmitter, ATP (adenosine triphosphate) as a quantitative measurement of gustatory sensation and taste. This was done by using a comparison of wild type (WT) and double knockout (DKO) mice. P2X receptors, P2X2 and P2X3 were knocked out in the DKO mice. The premise of this article was that knocking out P2X receptors reduces transmitter secretion of ATP in taste buds, therefore they cannot taste.

It should be noted that the taste buds in DKO are functional, but are not stimulated by the administration of tastants.

The transmission of release of ATP is secretion through gap junction hemichannels (pannexin 1 gap junction).

When both P2X2 and P2X3 are knocked out, no taste is elicited. However they found that if either P2X2 OR P2X3 was knocked out there was a taste response. So the inference made from this is that if one of the two receptors from the P2X family was knocked out there still can have taste response. The WT mice showed significant stimulation by tastants whereas DKO had little to no stimulation of ATP release.<ref><pubmed>21940456</pubmed></ref>

===FGF signalling and genes===

Sprouty, or ''Srpy'', genes have been related to regulating the development of circumvillate papillae (CVP). The CVP are large dome shaped papillae, which form a 'V' just in front of the terminal sulcus.

By knocking out ''Spry'' genes using mice which had ''Spry1'' and ''Spry2'' knocked out showed that the number of CVP doubled. However, when Fibroblast Growth Factor gene ("Fgf10") was absent, the number of CVP was significantly reduced, if not completely absent. The correlation between ''Spry1/2'' and ''Fgf10'' is that ''Spry1/2'' antagonises "Fgf10" to limit the size of the CVP progenitor placode. Exclusive expression of ''Fgf10'' in the mesenchyme is necessary for the formation of CVP.

'''This image shows the CVP stained with H&E and scanned by Scanning Electron Microscope (SEM)'''
[[File:CVP of WT(top) and DKO(bottom) mice with H&E and SEM.png]]

'''This image shows the location of the CVP and the increased number in DKO mice by SEM'''
[[File:Mouse circumvallate papilla 01.jpg|300px]]

Taste buds develop from the mesenchyme but require local signalling to properly differentiate. Some signalling factors for proper development of taste buds besides FGF are: Sonic Hedgehog (SHH), Bone Morphogenetic Proteins (BMPs), Epidermal Growth Factor (EGF).

Additionally, this proves that the anterior and posterior developments of the tongue are derived from embryonic tissues, where the anterior tongue is derived from the ectoderm and the posterior tongue is derived from the endoderm. Taste buds develop from the mesenchyme but require local signalling to properly differentiate. Some signalling factors for proper development of taste buds besides FGF are: Sonic Hedgehog (SHH), Bone Morphogenetic Proteins (BMPs), Epidermal Growth Factor (EGF).

As mentioned above, this article shows that the anterior and posterior developments of the tongue are derived from embryonic tissues, where the anterior tongue is derived front the ectoderm and the posterior tongue is derived from the endoderm. Secondly, FGF is required to regulate the growth of taste buds, while ''Spry'' genes limit the number of CVP. ''Fgf10''& ''Spry 1&2''work antagonistically through receptor tyrosine kinase (RTK)signalling.

However, the deletion of ''Spry2''led to the increase of CVPs it should be noted that they found that a significant decrease in number of fungiform papillae. Contrastingly, the absence of ''Fgf10'', while leading to the absence of CVPs lead to an increase in number and size of fungiform papillae. Therefore these genes have different effects on the anterior and posterior developing tongue and taste buds.<ref><pubmed>21655085</pubmed></ref>

==Current Research==
We have an evolving understanding of Embryonic Taste development, through the use of state-of-the-art technology and research techniques we are able to make brilliant discoveries that continue to connect the dots of this amazing natural process of human development.
The majority of research in taste development is involving mice, these mammals show similar embryonic pathways to humans and research is performed in ethical and humane methods.

[[File:Histology.jpg|Left|thumb|200px|Image shows histological stains of a mice tongue showing dysplasia]]

'''Synergistic relationships of Six Genes '''

In an animal study using mice by Suzuki Y, Ikeda K, Kawakami K.(2011) Firstly nominating "Six Genes" as a major component in gustatory development, stating that deficiencies in certain Six genes (specifically Six1 & Six4) leads to poor development. Their research also highlights evidence of cooperative relationships between Six genes for normal advance. This experiment involved breeding mice containing exclusively Six1 and Six4 genes and examining the expression of these genes in papillae under high powered microscope observation. Understanding the role of certain genes along with the intrinsic relationships they hold is crucial for the ability to identify possible causes and correction of any abnormalities <ref><pubmed>21978088</pubmed></ref>

'''Neural Crest responsibilities '''

Another Animal Study involving mice explores a new idea of Neural crest (NC) contribution in taste development, specifically the development of papillae and taste buds. Liu HX, Komatsu Y, Mishina Y, Mistretta CM. (2012) suggest that Neural crest cells travel to the location of the tongue in early embryonic stages, gain epithelium phenotypes, multiply and then differentiate to eventually form taste papillae. The experiment involved the comparison of 2 different types of Cre line mice, which both express Cre gene in neural crest protocol, the different distribution patterns where observed in specific regions that NC is responsible for.<ref><pubmed>22659543</pubmed></ref>

'''Augmentation of Endoderm'''

In an animal study conducted by Rothova M, Thompson H, Lickert H, Tucker AS.(2012) exploring the historically debated issue of endoderm contribution to tongue development showed promising evidence that position of taste buds are patterned by the border of ectoderm and endoderm derivative epithelium. This study was accomplished via microscopic examination of previously stained specimens. Concluding endoderm has direct influence on gustatory develoment <ref><pubmed>22581563</pubmed></ref>

'''Changes in Taste Cells over time'''

Research by
Ozdener H, Spielman AI, Rawson NE.(2012) developing a culture which allows taste cells to survive for up to 12 months, empowers researchers to study the processes of proliferation, differentiation and function. This experiment will provide a precidnet for future study of taste cells, as these cells are able to operate and grow normally. <ref><pubmed>22643728</pubmed></ref>

'''Shh key component of taste bud proginators'''

A tamoxifen treatment which supresses Sonic hedgehog (Shh) secretion in mice proving to reduce the number of cells visable within papillae, in contrast mice not treated with tamoxifen showed a mark increase of cells within papillae, these cells are assumed to become taste cells in later development.
Specific mice were bred to trace the destination of taste placode cells, the study concluded that Shh expressing placodes are taste bud proginators which in turn become taste cells within taste buds although do not have any prescuros relationship with pappilae. The results were obtain by examination of mice embryos using Bright-field or multichannel fluorescent images through the use of an "Axiocam CCD camera and Axioplan fluorescence microscope with Axiovision software" a study by Harlow, Yang, Williams, Barlow (2011)<ref><pubmed>PMC2674259</pubmed></ref>

'''WNT family exhibit various roles'''

The WNT gene family has a function of signally proteins for various reason such as development, In 2010 Liu, Staubach Grosse, Walton, Saims, Gumucio, Mistretta explored recent findings on the role of WNT's in tongue and papillae development, Concluding that WNT/β-catenin is essential for fungiform papillae differing to WNT5a which proved to be principle in tongue development. Intrinsic chemical mediators were considered by manipulating a tissue culture and then throughaly examined by scanning photomicrograph. <ref><pubmed>PMC2768563</pubmed></ref>

[http://www.surgicalneurologyint.com/article.asp?issn=2152-7806;year=2012;volume=3;issue=1;spage=23;epage=23;aulast=Manjila]
[[File:Abnormal of tongue.jpg|Left|thumb|200px|Image shows and example of tongue abnormalities, this is called "double tongue" each side has independent movement!]]

==Useful links==

==Glossary==

ectoderm- outer germ layer of embryo

endoderm - inner germ layer of embryo

epithelium - basic animal tissue that is composed of tightly packed cells, usually covering the outer portion of organs

exocystosis - movement of contents out of cell

ganglia - the accumulation of a nerve cell body

growth factor - a substance that stimulates the growth of cells

gustatory - anything that relates to the taste sense

hydrolysis - breakdown of a chemical when it reacts with water

mesoderm - middle germ layer of embryo

mesenchyme - multipotential cells

neural crest - a part of the ectoderm found on both sides of the neural tube

neuron - most simplistic unit of the nervous system

neurotransmitter - chemicals which allow the passing of signals from neuron to neuron via connecting part (synapse)

papillae - small rough surface projection

six genes - a family of genes

Sonic hedgehog (Shh) - signalling protein invloved in normal development

sulcus terminalis - describes a physical transition point separating the anterior 2/3 of the tongue from the posterior 1/3

tamoxifen - hormonal altering drug

==Image gallery==

== References ==
<references/>

==External Links==
{{External Links}}

http://www.webmd.com/oral-health/picture-of-the-tongue

http://www.tutorvista.com/content/biology/biology-iv/nervous-coordination/tongue-structure.php#parts-of-tongue

http://www.cf.ac.uk/biosi/staffinfo/jacob/teaching/sensory/taste.html

--[[User:Z8600021|Mark Hill]] 12:22, 15 August 2012 (EST) Please leave the content listed below the line at the bottom of your project page.

----

{{2012Projects}}

2012 Group Project 3

2012-09-30T04:58:13Z

Z3289738: /* Timeline of Developmental Processes of the Gustatory System */

=Taste Development=

== Introduction ==
**NEED TO ADD**

==History of Discoveries==

{| cellpadding=5 style="border:1px solid #BBB"
|- bgcolor="#faecc8"
|''' Date'''|| '''Significant Discovery'''

|- bgcolor="#faf6ed"
|'''350BC'''
|| Aristotle writes about the basic tastes, sweet and bitter. He also notes that it can be modified by salty and acidic. <ref name="PMID22717400"><pubmed>22717400</pubmed></ref>

|- bgcolor="#faecc8"
|'''1901'''
|| D. Hanig publishes a paper describing taste sensitivity in different regions of the tongue.
''Interesting fact:'' The modern concept of a 'tongue map' is a misinterpretation of this study. <ref name="PMID22717400"/>

|- bgcolor="#faf6ed"
|style=white-space:nowrap|'''1908'''
|Kikunae Ikeda, a professor of the Tokyo Imperial University, discovered and identified the fifth basic taste: umami (savouriness), made palatable by glutamate. <ref><pubmed>12438213</pubmed></ref>
[http://chemse.oxfordjournals.org/content/27/9/847.long New Seasonings]

|- bgcolor="#faecc8"
|style=white-space:nowrap|'''1931-32'''
| A chemist named Arthur Fox and his college noted that they had different sensitivities to the bitter tasting Phenylthiocarbamide (PTC).<ref>Blakeslee AF, Fox AL. Our different taste worlds. J Hered. 1932;23:97–107.</ref> Geneticists later confirm these findings, and discover that non-tasting is a recessive genetic trait. <ref><pubmed>17782493</pubmed></ref>
[http://www.ncbi.nlm.nih.gov/pubmed/17782493 Inherited taste deficiency]

|- bgcolor="#faf6ed"
|style=white-space:nowrap|'''1965'''
|Farbman's study of the developing taste but in rat fungiform papilla was significant in increasing our understanding of taste bud development. <ref><pubmed>14300090</pubmed></ref>
[http://www.sciencedirect.com/science/article/pii/0012160665900400 Electron microscope study of the developing taste bud in rat fungiform papilla.]

|- bgcolor="#faecc8"
|style=white-space:nowrap|'''1992'''
|McLaughlin SK et al. discovery a taste cell-specific G-protein within the taste buds called Gustucon. This protein is later used to mark bitter, umami and sweet cells. <ref><pubmed>1608467 </pubmed></ref>
[http://www.nature.com/nature/journal/v357/n6379/abs/357563a0.html Gustducin is a taste-cell-specific G protein closely related to the transducins]

|- bgcolor="#faf6ed"
|style=white-space:nowrap|'''1995'''
|Barlow et al. experimented with Axolotl salamanders and concluded that taste buds from this species arise exclusively from epithelial tissue, "oropharyngeal epithelium". <ref name="PMID17826760"><pubmed>17826760</pubmed></ref>
[http://www.ncbi.nlm.nih.gov/pubmed/17826760 Embryonic origin of gustatory cranial sensory neurons.]

|- bgcolor="#faecc8"
|style=white-space:nowrap|'''1996'''
| Witt M and Reutter K of the Technical University Dresden in Germany, carried out a transmission electron microscopy study to investigate the embryonic and fetal development of Human taste buds. Their results suggest an "at least dual function of embryonic/fetal taste buds", including non-gustatory, paracrine functions prior to the 14th week and gustatory after the 14th week. <ref name="PMID8955790"><pubmed>8955790</pubmed></ref>
[http://www.ncbi.nlm.nih.gov/pubmed/8955790 Embryonic and early fetal development of human taste buds: a transmission electron microscopical study]

|- bgcolor="#faf6ed"
|style=white-space:nowrap|'''2000'''
|Chandrashekar, J. et al. discover the first taste sonsors, the T2R bitter taste receptors. <ref><pubmed>10761935</pubmed></ref>
[http://www.sciencedirect.com/science/article/pii/S0092867400807060 T2Rs Function as Bitter Taste Receptors]

|- bgcolor="#faecc8"
|style=white-space:nowrap|'''2001'''
|Nelson, G. et al. discover the sweet receptor: a combination of T1R2 and T1R3. <ref><pubmed>11509186</pubmed></ref>
[http://www.ncbi.nlm.nih.gov/pubmed/11509186?dopt=Abstract&holding=npg Mammalian sweet taste receptors.]

|- bgcolor="#faf6ed"
|style=white-space:nowrap|'''2002'''
|Nelson G. et al. discover the amino acid (umami) taste receptor: a combination of T1R1 and T1R3 identified. <ref><pubmed>11894099</pubmed></ref>
[http://www.ncbi.nlm.nih.gov/pubmed/11894099?dopt=Abstract&holding=npg An amino-acid taste receptor]

|- bgcolor="#faecc8"
|style=white-space:nowrap|'''2005'''
|Dyer, J. et al. discover sweet taste receptors in the GI tract. <ref><pubmed>17855558</pubmed></ref>
[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1986582/ Sweet taste signaling in the gut]

|- bgcolor="#faf6ed"
|style=white-space:nowrap|'''2006'''
|Huang, A. L et al. discover cells for sour taste, identified by PKD2L1 (a polycystic kidney disease-like ion channel). <ref><pubmed>16929298</pubmed></ref>
[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1571047/ The Cells and Logic for Mammalian Sour Taste detection]

|- bgcolor="#faecc8"
|style=white-space:nowrap|'''2007'''
|Harlow DE, Barlow LA of the University of Colorado Denver Health Sciences Center provide evidence of the "embryonic origin of gustatory cranial sensory neurons". <ref name="PMID17826760"/>
[http://www.ncbi.nlm.nih.gov/pubmed/17826760 Embryonic origin of gustatory cranial sensory neurons.]

|- bgcolor="#faf6ed"
|style=white-space:nowrap|'''2009'''
|A study by Hevezi P et al, presents "the first comprehensive characterization of gene expression in primate taste buds", as opposed to previous studies which focused on rodents. <ref><pubmed>19636377</pubmed></ref>
[http://www.ncbi.nlm.nih.gov/pubmed/19636377 Genome-wide analysis of gene expression in primate taste buds reveals links to diverse processes]

|- bgcolor="#faecc8"
|style=white-space:nowrap|'''2010'''
|Chandrashekar, J. et al. identify epithelial sodium channel (ENaC) as the sodium-salt taste receptor. <ref><pubmed>20107438</pubmed></ref>
[http://www.ncbi.nlm.nih.gov/pubmed/20107438?dopt=Abstract&holding=npg The cells and peripheral representation of sodium taste in mice]
|}

==Gustatory System==

[[Image:Taste qualities.gif|thumb|The five basic tastes]]

Taste or more appropriately gustation, is a fundamental survival tool in animals as it directs the consumption of essential nutrients. The five tastes that exist within the human gustatory system: salty, sweet, sour, bitter and umami, all signify basic physiological requirements. Salty tastes denote the presence of Na+, an important ion involved in the transportation and retention of water across cell membranes. Sweetness is the recognition of carbohydrates, essential for maintaining optimal brain function and providing the basis for energy production in muscle tissue via ATP hydrolysis. Similarly umami codes for the presence of L-amino acids, especially L-glutamate which is an integral component of protein synthesis.

These different modalities not only function to maintain the proper intake of nutrients within the body but also, by way of aversion, prohibit the consumption of undesired or poisonous materials. The bitter modality for example is generally regarded as displeasing to the human palate. It represents a high acid content which may be a result of foods which have become rotten or are inherently poisonous to the body.<ref name=PMID20696704><pubmed>20696704</pubmed></ref>

Research has historically limited itself to investigating the mechanisms of these five taste qualities though it must be noted many other modalities may exist. Of particular conjecture is the existence of fatty acid recognition. In the past the detection of fat in food has been attributed to somatosensory inputs <ref name=PMID20696704/> from the tongue, that is, the oily feel and texture of fat rather than its actual ‘taste’ allows the brain to encode for its presence. Further research is therefore required to elicit the precise mechanisms of fat detection.

===Cell Biology===

The five taste qualities are not all detected by the same type of receptor cell located within the taste bud. Like rods and cones in the eye which detect different wavelengths of light, there are specific types of receptors for different tastes. For example, sweet, umami and bitter are recognised by Type II G-protein coupled receptors, whereas sour is related to Type III presynaptic cells. The cell type involved in salty taste transduction is unknown however it is known that sodium ions can enter the receptor cell membrane via ion channel permeation.

====Type II receptors====

When a bitter, sweet or umami ligand binds to a type II G-coupled receptor, a cascade of chemical reactions causes the release of Ca2+ which in turn mediates exocystosis of ATP. The function of this ATP is threefold:

# Stimulates gustatory nerve afferents which project to gustatory nuclei in the spinal cord
# Excites Type III presynaptic nerve fibres to release serotonin.
# Has a positive feedback effect on type II receptor cells, increasing the level of ATP production.

The role of serotonin is believed to be in the form of lateral inhibition i.e. when a bitter quality is recognised, adjacent receptors for sweetness are deactivated and thus the two tastes may be clearly differentiated. It also has a negative feedback effect on receptor cells, inhibiting umami, bitter and sweet taste transduction.

==Taste Map==
[[Image:Taste map.png|thumb|left|250px|Obsolete idea of the tongue map]]
The idea of a tongue map has disseminated through society for many years. This concept purports that different areas of the tongue are specialised to detect either sweet, salty, sour and bitter tastes. Recent research however has completely nullified such claims and suggests instead that different forms of taste are recognised all over the tongue as well as via the palate. Thus the term ''taste map'' has come to take on a new meaning and that is, the precise areas of taste modalities processing in areas of cortex and its subsequent neural inputs.

===Neural Pathways===

'''First order neurons''' - From the receptors located in the taste buds, gustatory nerve afferents project to the ipsilateral rostral 1/3 of the nucleus tractus solitarius (NTS), located in the medulla. This rostral 1/3 is commonly referred to as the ''gustatory nucleus''.

The ''gustatory nucleus'' receives input from cranial nerves VII (''Facial n.''), IX (''Hypglossal n.''), and X (''Vagus n.'') via special visceral afferent (SVA) nerve fibres. A summary of their functions is as follows:

* ''Facial nerve n''. - carries taste information from the anterior 2/3 of the tongue.
* ''Hypoglossal n.'' - carries taste information from the posterior 1/3 of the tongue.
* ''Vagus n''. - carries taste information from the palate

'''Second order neurons''' - From the NTS second order neurons carry taste information to the Ventral posteromedial (VPM) nucleus in the thalamus.<ref name=PMID21885776/>

Copious scientific conjecture surrounds how each taste modality is transmitted to the brain. The ‘labelled-line’ hypothesis suggests that there are taste specific neurons which exclusively carry that taste modality to cortical areas. In analogous terms it can be viewed like the pipelines leading toward a house. Each pipeline carries its own utility, there is one for gas, another for water and finally for electricity with each terminating in slightly different areas of the house. In the same way, on the tongues there are different receptors for each taste which concurrently have individual nerve tracts leading to the primary gustatory cortex.

Contrapuntally there is electrophysiological evidence that single nerve afferents carry multiple modalities. These studies show one nerve afferent may have both a strong and a weak activation in response to a multiple taste stimuli.

===Cortical Areas===

[[Image:Primary gustatory cortex.png|thumb|Primary gustatory cortex]]

The location of the taste perception centres has been observed via functional magnetic resonance imaging (fMRI) studies. The primary taste cortex has been identified as being located in the anterior insula/frontal operculum (I/fO)<ref name=PMID22245354><pubmed>22245354</pubmed></ref>, with the secondary taste cortex in the caudolateral orbitofrontal cortex.<ref name=PMID21305668><pubmed>21305668</pubmed></ref> Within the insula there are further subdivisions related to each taste modality. Two photon calcium imaging research has outlined certain ’hot-spots’ of activation which are clearly delineated in relation to each taste. For example, the bitter modality is represented on the insula cortex approximately 1mm posterior to the middle cerebral artery whereas the sweet modality is represented 2.5mm rostrodorsal to the bitter field with no apparent overlap.<ref name=PMID21885776><pubmed>21885776</pubmed></ref> These findings lend weight to the idea that there is only one receptor for each taste quality.

It is interesting to note the relationship between taste and the reward centres of the brain. There is evidence of neural input to the ventral tegmental area (the origin of the mesolimbic dopaminergic reward pathway) and nucleus accumbens (involved in the conversion of motivation into physical action).<ref name=PMID21885776/> Neural connections such as this provide the foundations in explaining concepts such as flavour learning and preference. It may also give some insight into chronic problems such as food addiction and craving. As of yet however the gustatory neural network is not well understood and more research is required to elucidate the relationship between pleasure and taste sensation

== Human Weekly Development - Two Prominent Studies ==
Martin Witt and Klaus Reutter of the University of Tubingen in Germany published two prominent studies regarding developing taste buds in humans. Their first study in 1996 was a transmission electron microscopical (TEM) study of the taste bud primordium and its morphological changes during the 8th-15th postovulatory week. Their next study in 1997 built on their previous findings by using Scanning Electron Microscopy (SEM) to observe the development of gustatory papillae during postovulatory weeks 6-15.

The findings of these two studies are summarized in the table below. The figures provided relate to the images on their respective research papers.

[http://onlinelibrary.wiley.com/doi/10.1002/(SICI)1097-0185(199612)246:4%3C507::AID-AR10%3E3.0.CO;2-S/pdf Embryonic and early fetal development of human taste buds: a transmission electron microscopical study, 1996] | [http://chemse.oxfordjournals.org/content/22/6/601.long Scanning electron microscopical studies of developing gustatory papillae in humans, 1997]

===Timeline of Developmental Processes of the Gustatory System===
{| cellpadding=5 style="border:1px solid #BBB"
|- bgcolor="#89CFF0"
|'''Postovulatory Week'''||'''Description'''||'''Image'''

|- bgcolor="#BCD4E6"
|'''Week 6''' ||
The surface of the developing tongue is covered by nearly flat epithelium (1997, Figure 1). The first gustatory papillae of the tongue appear in the caudal midline near the foramen caecum and the first circumvallate papilla develops on the dorsal midline. <ref name="PMID9455607"><pubmed>9455607</pubmed></ref>
||
image

|- bgcolor="#89CFF0"
| '''Weeks 6 to 7'''||
Nerve fibres approach the basal lamina of lingual epithelium. At this stage the lingual epithelium consists of two to three cell layers and there is not yet any sign of cell specializations indicating early taste bud formation. <ref name=PMID8955790/>
||
Image

|- bgcolor="#BCD4E6"
| '''Week 7 '''||
A series of irregular epithelial swellings in the anterior part and marginal parts of the tongue indicate early forming fungiform papillae. Furthermore, a V-like lane is observed anterior to the sulcus terminalis, which represents a smooth surface for developing circumvallate papillae (1997, Figure 2). Witt M et al observe that these circumvallate papillae are larger than the developing fungiform papillae of the same age, later noting that the fungiform papillae tend to increase in size over the 8-15th weeks of gestation, whilst the size of vallate papillae tend to remain constant during this period. <ref name=PMID9455607/>
||
Image

|- bgcolor="#89CFF0"
| ''' Week 8 ''' ||
* The taste bud primordium are still differentiated, elongated epithelial cells, resting on a slightly developed core of young dermal papilla.
* The lingual epithelium shows first signs of taste bud development as nerve fibres coming from the dermal papilla penetrate the epithelial basal lamina and form synapses with taste bud progenitor cells (1996, Figure 1). These synapses demonstrate the neuronal connection between the taste bud primordium and the central nervous system, reaching a maximum around the 12th to 13th week. However, it is important to note that at this time these cells are still poorly differentiated, elongated epithelial cells.
* Ciliated cells also appear around the 8th week, however the significance of these cells which are scattered randomly across the lingual surface remains unclear. <ref name=PMID8955790/>
||
Image

|- bgcolor="#BCD4E6"
|''' Week 9''' ||
By this stage, although a taste pore is not present, the surface of circumvallate papillae usually contains a taste pit partly filled with microvillus-like processes from the underlying taste bud cells (1997, Figure 10). <ref name=PMID9455607/>
||
Image

|- bgcolor="#89CFF0"
|''' Weeks 10-11''' ||
At this stage, the lingual epithelium compromises of about four cell layers, and the first shallow grooves above the taste bud primordium are developed. Fungiform papillae appear on the lateral margins and the tip of the tongue, containing taste bud primordial that display the first signs of a primitive pore formation (1996, Figure 6). <ref name=PMID8955790/>
||
Image

|- bgcolor="#BCD4E6"
|''' Week 12 ''' ||
Taste bud cells are more clearly differentiated into epithelial cell types II and III. <ref name=PMID8955790/>
||
Image

|- bgcolor="#89CFF0"
|''' Weeks 12-13 ''' ||
At this stage the taste bud primordial are all located on the top of dermal papillae. There is also maximum synapses between cells and afferent nerve fibres, which intermingle with each other to form a plexus-like structure (1996, Figure 6a). <ref name=PMID8955790/>
||
Image

|- bgcolor="#BCD4E6"
|''' Weeks 14 -15 ''' ||
The shape and size of the taste buds primordial begins to resemble those of adult taste buds (1996, Figure 9). By the 14th week the taste pores develop as the taste pits are filled by microvilli, and bubble like vesicles indicate the secretory activity of these cells (1996, Figure 10). However, the tastebuds only achieve a fully developed function in week 15 of gestation with the development of type I cells to produce the mucous material in the taste pit. <ref name=PMID8955790/>
||
Image
|}

==Adult Tongue and Taste Buds – Structure and Function==

'''Structure'''

The tongue is located on the floor of the oral cavity, It is a muscular structure with sensory units crowning. The tongue is divided into an anterior two thirds and a posterior one third. These regions are divided by a V-shaped groove at the back of the tongue (sulcus terminalis). The anterior two thirds of the tongue is covered by stratified squamous epithelium, It contains a roughened surface and has projections called papillae that vary in shape and number.

''''The Image Below is a very simplistic Diagram of the surface of the Tongue showing the locations of the different papillae and other important features'''

{|
| [[Image:Drawing of Tongue.png|500px]]

'''Papillae'''
[[File:Papillae.jpg|Left|thumb|200px|Close up of Human Tongue Papillae]]

There are 4 types of papillae on the tongue.
The most numerous papillae are the filiform papillae, which function to provide a surface that aids in holding food on the tongue during chewing but do not contain taste buds. The larger, less numerous fungiform papillae which contain taste buds, as do foliate papillae. Circumvallate papillae form a wide V at the sulcus terminalis also containing taste bus. There are no papillae or taste buds located on the posterior third of the tongue, having mucosal folds and the lingual tonsils instead.

'''Function'''

The tongue is for tasting, swallowing, and speech.
The functional unit of the taste bud is a taste cell, there are between 50 and 100 taste cells in each taste bud these taste cells represent all 5 different tastes. Historically is was believed that different areas of the tongue were responsible for different taste sensations although this has since been disregarded.[http://users.rcn.com/jkimball.ma.ultranet/BiologyPages/W/Welcome.html] The papillae contain taste buds which are connected to the oral cavity via a taste pore, the function of the taste bud is to transmit a chemical signal from the oral cavity to a taste cell, this chemical signal is the converted into an electrical impulse and delivered to the brain via nerve fibres for interpretation.

'''The Image Below is a very simplistic Hand drawn Diagram of a taste bud, in an extreme close up, cross section view of the the taste bud unit, not to scale'''

[[File:Taste_bud_1.jpg]]

==Abnormalities==

===Knocking out P2X Receptors===

[[File:Image of taste being evoked by visualising ATP release.jpeg|Left|thumb|200px|Evoking taste - ATP release in tongue]]

Gustatory abnormalities has not been widely researched and what has been researched has been through animal testing, most commonly we have found on mice.

In Huang, 2008 this team used the release of the neurotransmitter, ATP (adenosine triphosphate) as a quantitative measurement of gustatory sensation and taste. This was done by using a comparison of wild type (WT) and double knockout (DKO) mice. P2X receptors, P2X2 and P2X3 were knocked out in the DKO mice. The premise of this article was that knocking out P2X receptors reduces transmitter secretion of ATP in taste buds, therefore they cannot taste.

It should be noted that the taste buds in DKO are functional, but are not stimulated by the administration of tastants.

The transmission of release of ATP is secretion through gap junction hemichannels (pannexin 1 gap junction).

When both P2X2 and P2X3 are knocked out, no taste is elicited. However they found that if either P2X2 OR P2X3 was knocked out there was a taste response. So the inference made from this is that if one of the two receptors from the P2X family was knocked out there still can have taste response. The WT mice showed significant stimulation by tastants whereas DKO had little to no stimulation of ATP release.<ref><pubmed>21940456</pubmed></ref>

===FGF signalling and genes===

Sprouty, or ''Srpy'', genes have been related to regulating the development of circumvillate papillae (CVP). The CVP are large dome shaped papillae, which form a 'V' just in front of the terminal sulcus.

By knocking out ''Spry'' genes using mice which had ''Spry1'' and ''Spry2'' knocked out showed that the number of CVP doubled. However, when Fibroblast Growth Factor gene ("Fgf10") was absent, the number of CVP was significantly reduced, if not completely absent. The correlation between ''Spry1/2'' and ''Fgf10'' is that ''Spry1/2'' antagonises "Fgf10" to limit the size of the CVP progenitor placode. Exclusive expression of ''Fgf10'' in the mesenchyme is necessary for the formation of CVP.

'''This image shows the CVP stained with H&E and scanned by Scanning Electron Microscope (SEM)'''
[[File:CVP of WT(top) and DKO(bottom) mice with H&E and SEM.png]]

'''This image shows the location of the CVP and the increased number in DKO mice by SEM'''
[[File:Mouse circumvallate papilla 01.jpg|300px]]

Taste buds develop from the mesenchyme but require local signalling to properly differentiate. Some signalling factors for proper development of taste buds besides FGF are: Sonic Hedgehog (SHH), Bone Morphogenetic Proteins (BMPs), Epidermal Growth Factor (EGF).

Additionally, this proves that the anterior and posterior developments of the tongue are derived from embryonic tissues, where the anterior tongue is derived from the ectoderm and the posterior tongue is derived from the endoderm. Taste buds develop from the mesenchyme but require local signalling to properly differentiate. Some signalling factors for proper development of taste buds besides FGF are: Sonic Hedgehog (SHH), Bone Morphogenetic Proteins (BMPs), Epidermal Growth Factor (EGF).

As mentioned above, this article shows that the anterior and posterior developments of the tongue are derived from embryonic tissues, where the anterior tongue is derived front the ectoderm and the posterior tongue is derived from the endoderm. Secondly, FGF is required to regulate the growth of taste buds, while ''Spry'' genes limit the number of CVP. ''Fgf10''& ''Spry 1&2''work antagonistically through receptor tyrosine kinase (RTK)signalling.

However, the deletion of ''Spry2''led to the increase of CVPs it should be noted that they found that a significant decrease in number of fungiform papillae. Contrastingly, the absence of ''Fgf10'', while leading to the absence of CVPs lead to an increase in number and size of fungiform papillae. Therefore these genes have different effects on the anterior and posterior developing tongue and taste buds.<ref><pubmed>21655085</pubmed></ref>

==Current Research==
We have an evolving understanding of Embryonic Taste development, through the use of state-of-the-art technology and research techniques we are able to make brilliant discoveries that continue to connect the dots of this amazing natural process of human development.
The majority of research in taste development is involving mice, these mammals show similar embryonic pathways to humans and research is performed in ethical and humane methods.

[[File:Histology.jpg|Left|thumb|200px|Image shows histological stains of a mice tongue showing dysplasia]]

'''Synergistic relationships of Six Genes '''

In an animal study using mice by Suzuki Y, Ikeda K, Kawakami K.(2011) Firstly nominating "Six Genes" as a major component in gustatory development, stating that deficiencies in certain Six genes (specifically Six1 & Six4) leads to poor development. Their research also highlights evidence of cooperative relationships between Six genes for normal advance. This experiment involved breeding mice containing exclusively Six1 and Six4 genes and examining the expression of these genes in papillae under high powered microscope observation. Understanding the role of certain genes along with the intrinsic relationships they hold is crucial for the ability to identify possible causes and correction of any abnormalities <ref><pubmed>21978088</pubmed></ref>

'''Neural Crest responsibilities '''

Another Animal Study involving mice explores a new idea of Neural crest (NC) contribution in taste development, specifically the development of papillae and taste buds. Liu HX, Komatsu Y, Mishina Y, Mistretta CM. (2012) suggest that Neural crest cells travel to the location of the tongue in early embryonic stages, gain epithelium phenotypes, multiply and then differentiate to eventually form taste papillae. The experiment involved the comparison of 2 different types of Cre line mice, which both express Cre gene in neural crest protocol, the different distribution patterns where observed in specific regions that NC is responsible for.<ref><pubmed>22659543</pubmed></ref>

'''Augmentation of Endoderm'''

In an animal study conducted by Rothova M, Thompson H, Lickert H, Tucker AS.(2012) exploring the historically debated issue of endoderm contribution to tongue development showed promising evidence that position of taste buds are patterned by the border of ectoderm and endoderm derivative epithelium. This study was accomplished via microscopic examination of previously stained specimens. Concluding endoderm has direct influence on gustatory develoment <ref><pubmed>22581563</pubmed></ref>

'''Changes in Taste Cells over time'''

Research by
Ozdener H, Spielman AI, Rawson NE.(2012) developing a culture which allows taste cells to survive for up to 12 months, empowers researchers to study the processes of proliferation, differentiation and function. This experiment will provide a precidnet for future study of taste cells, as these cells are able to operate and grow normally. <ref><pubmed>22643728</pubmed></ref>

'''Shh key component of taste bud proginators'''

A tamoxifen treatment which supresses Sonic hedgehog (Shh) secretion in mice proving to reduce the number of cells visable within papillae, in contrast mice not treated with tamoxifen showed a mark increase of cells within papillae, these cells are assumed to become taste cells in later development.
Specific mice were bred to trace the destination of taste placode cells, the study concluded that Shh expressing placodes are taste bud proginators which in turn become taste cells within taste buds although do not have any prescuros relationship with pappilae. The results were obtain by examination of mice embryos using Bright-field or multichannel fluorescent images through the use of an "Axiocam CCD camera and Axioplan fluorescence microscope with Axiovision software" a study by Harlow, Yang, Williams, Barlow (2011)<ref><pubmed>PMC2674259</pubmed></ref>

'''WNT family exhibit various roles'''

The WNT gene family has a function of signally proteins for various reason such as development, In 2010 Liu, Staubach Grosse, Walton, Saims, Gumucio, Mistretta explored recent findings on the role of WNT's in tongue and papillae development, Concluding that WNT/β-catenin is essential for fungiform papillae differing to WNT5a which proved to be principle in tongue development. Intrinsic chemical mediators were considered by manipulating a tissue culture and then throughaly examined by scanning photomicrograph. <ref><pubmed>PMC2768563</pubmed></ref>

[http://www.surgicalneurologyint.com/article.asp?issn=2152-7806;year=2012;volume=3;issue=1;spage=23;epage=23;aulast=Manjila]
[[File:Abnormal of tongue.jpg|Left|thumb|200px|Image shows and example of tongue abnormalities, this is called "double tongue" each side has independent movement!]]

==Useful links==

==Glossary==

ectoderm- outer germ layer of embryo

endoderm - inner germ layer of embryo

epithelium - basic animal tissue that is composed of tightly packed cells, usually covering the outer portion of organs

exocystosis - movement of contents out of cell

ganglia - the accumulation of a nerve cell body

growth factor - a substance that stimulates the growth of cells

gustatory - anything that relates to the taste sense

hydrolysis - breakdown of a chemical when it reacts with water

mesoderm - middle germ layer of embryo

mesenchyme - multipotential cells

neural crest - a part of the ectoderm found on both sides of the neural tube

neuron - most simplistic unit of the nervous system

neurotransmitter - chemicals which allow the passing of signals from neuron to neuron via connecting part (synapse)

papillae - small rough surface projection

six genes - a family of genes

Sonic hedgehog (Shh) - signalling protein invloved in normal development

sulcus terminalis - describes a physical transition point separating the anterior 2/3 of the tongue from the posterior 1/3

tamoxifen - hormonal altering drug

==Image gallery==

== References ==
<references/>

==External Links==
{{External Links}}

http://www.webmd.com/oral-health/picture-of-the-tongue

http://www.tutorvista.com/content/biology/biology-iv/nervous-coordination/tongue-structure.php#parts-of-tongue

http://www.cf.ac.uk/biosi/staffinfo/jacob/teaching/sensory/taste.html

--[[User:Z8600021|Mark Hill]] 12:22, 15 August 2012 (EST) Please leave the content listed below the line at the bottom of your project page.

----

{{2012Projects}}

2012 Group Project 3

2012-09-30T04:57:33Z

Z3289738: /* Human Weekly Development - Two Prominent Studies */

=Taste Development=

== Introduction ==
**NEED TO ADD**

==History of Discoveries==

{| cellpadding=5 style="border:1px solid #BBB"
|- bgcolor="#faecc8"
|''' Date'''|| '''Significant Discovery'''

|- bgcolor="#faf6ed"
|'''350BC'''
|| Aristotle writes about the basic tastes, sweet and bitter. He also notes that it can be modified by salty and acidic. <ref name="PMID22717400"><pubmed>22717400</pubmed></ref>

|- bgcolor="#faecc8"
|'''1901'''
|| D. Hanig publishes a paper describing taste sensitivity in different regions of the tongue.
''Interesting fact:'' The modern concept of a 'tongue map' is a misinterpretation of this study. <ref name="PMID22717400"/>

|- bgcolor="#faf6ed"
|style=white-space:nowrap|'''1908'''
|Kikunae Ikeda, a professor of the Tokyo Imperial University, discovered and identified the fifth basic taste: umami (savouriness), made palatable by glutamate. <ref><pubmed>12438213</pubmed></ref>
[http://chemse.oxfordjournals.org/content/27/9/847.long New Seasonings]

|- bgcolor="#faecc8"
|style=white-space:nowrap|'''1931-32'''
| A chemist named Arthur Fox and his college noted that they had different sensitivities to the bitter tasting Phenylthiocarbamide (PTC).<ref>Blakeslee AF, Fox AL. Our different taste worlds. J Hered. 1932;23:97–107.</ref> Geneticists later confirm these findings, and discover that non-tasting is a recessive genetic trait. <ref><pubmed>17782493</pubmed></ref>
[http://www.ncbi.nlm.nih.gov/pubmed/17782493 Inherited taste deficiency]

|- bgcolor="#faf6ed"
|style=white-space:nowrap|'''1965'''
|Farbman's study of the developing taste but in rat fungiform papilla was significant in increasing our understanding of taste bud development. <ref><pubmed>14300090</pubmed></ref>
[http://www.sciencedirect.com/science/article/pii/0012160665900400 Electron microscope study of the developing taste bud in rat fungiform papilla.]

|- bgcolor="#faecc8"
|style=white-space:nowrap|'''1992'''
|McLaughlin SK et al. discovery a taste cell-specific G-protein within the taste buds called Gustucon. This protein is later used to mark bitter, umami and sweet cells. <ref><pubmed>1608467 </pubmed></ref>
[http://www.nature.com/nature/journal/v357/n6379/abs/357563a0.html Gustducin is a taste-cell-specific G protein closely related to the transducins]

|- bgcolor="#faf6ed"
|style=white-space:nowrap|'''1995'''
|Barlow et al. experimented with Axolotl salamanders and concluded that taste buds from this species arise exclusively from epithelial tissue, "oropharyngeal epithelium". <ref name="PMID17826760"><pubmed>17826760</pubmed></ref>
[http://www.ncbi.nlm.nih.gov/pubmed/17826760 Embryonic origin of gustatory cranial sensory neurons.]

|- bgcolor="#faecc8"
|style=white-space:nowrap|'''1996'''
| Witt M and Reutter K of the Technical University Dresden in Germany, carried out a transmission electron microscopy study to investigate the embryonic and fetal development of Human taste buds. Their results suggest an "at least dual function of embryonic/fetal taste buds", including non-gustatory, paracrine functions prior to the 14th week and gustatory after the 14th week. <ref name="PMID8955790"><pubmed>8955790</pubmed></ref>
[http://www.ncbi.nlm.nih.gov/pubmed/8955790 Embryonic and early fetal development of human taste buds: a transmission electron microscopical study]

|- bgcolor="#faf6ed"
|style=white-space:nowrap|'''2000'''
|Chandrashekar, J. et al. discover the first taste sonsors, the T2R bitter taste receptors. <ref><pubmed>10761935</pubmed></ref>
[http://www.sciencedirect.com/science/article/pii/S0092867400807060 T2Rs Function as Bitter Taste Receptors]

|- bgcolor="#faecc8"
|style=white-space:nowrap|'''2001'''
|Nelson, G. et al. discover the sweet receptor: a combination of T1R2 and T1R3. <ref><pubmed>11509186</pubmed></ref>
[http://www.ncbi.nlm.nih.gov/pubmed/11509186?dopt=Abstract&holding=npg Mammalian sweet taste receptors.]

|- bgcolor="#faf6ed"
|style=white-space:nowrap|'''2002'''
|Nelson G. et al. discover the amino acid (umami) taste receptor: a combination of T1R1 and T1R3 identified. <ref><pubmed>11894099</pubmed></ref>
[http://www.ncbi.nlm.nih.gov/pubmed/11894099?dopt=Abstract&holding=npg An amino-acid taste receptor]

|- bgcolor="#faecc8"
|style=white-space:nowrap|'''2005'''
|Dyer, J. et al. discover sweet taste receptors in the GI tract. <ref><pubmed>17855558</pubmed></ref>
[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1986582/ Sweet taste signaling in the gut]

|- bgcolor="#faf6ed"
|style=white-space:nowrap|'''2006'''
|Huang, A. L et al. discover cells for sour taste, identified by PKD2L1 (a polycystic kidney disease-like ion channel). <ref><pubmed>16929298</pubmed></ref>
[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1571047/ The Cells and Logic for Mammalian Sour Taste detection]

|- bgcolor="#faecc8"
|style=white-space:nowrap|'''2007'''
|Harlow DE, Barlow LA of the University of Colorado Denver Health Sciences Center provide evidence of the "embryonic origin of gustatory cranial sensory neurons". <ref name="PMID17826760"/>
[http://www.ncbi.nlm.nih.gov/pubmed/17826760 Embryonic origin of gustatory cranial sensory neurons.]

|- bgcolor="#faf6ed"
|style=white-space:nowrap|'''2009'''
|A study by Hevezi P et al, presents "the first comprehensive characterization of gene expression in primate taste buds", as opposed to previous studies which focused on rodents. <ref><pubmed>19636377</pubmed></ref>
[http://www.ncbi.nlm.nih.gov/pubmed/19636377 Genome-wide analysis of gene expression in primate taste buds reveals links to diverse processes]

|- bgcolor="#faecc8"
|style=white-space:nowrap|'''2010'''
|Chandrashekar, J. et al. identify epithelial sodium channel (ENaC) as the sodium-salt taste receptor. <ref><pubmed>20107438</pubmed></ref>
[http://www.ncbi.nlm.nih.gov/pubmed/20107438?dopt=Abstract&holding=npg The cells and peripheral representation of sodium taste in mice]
|}

==Gustatory System==

[[Image:Taste qualities.gif|thumb|The five basic tastes]]

Taste or more appropriately gustation, is a fundamental survival tool in animals as it directs the consumption of essential nutrients. The five tastes that exist within the human gustatory system: salty, sweet, sour, bitter and umami, all signify basic physiological requirements. Salty tastes denote the presence of Na+, an important ion involved in the transportation and retention of water across cell membranes. Sweetness is the recognition of carbohydrates, essential for maintaining optimal brain function and providing the basis for energy production in muscle tissue via ATP hydrolysis. Similarly umami codes for the presence of L-amino acids, especially L-glutamate which is an integral component of protein synthesis.

These different modalities not only function to maintain the proper intake of nutrients within the body but also, by way of aversion, prohibit the consumption of undesired or poisonous materials. The bitter modality for example is generally regarded as displeasing to the human palate. It represents a high acid content which may be a result of foods which have become rotten or are inherently poisonous to the body.<ref name=PMID20696704><pubmed>20696704</pubmed></ref>

Research has historically limited itself to investigating the mechanisms of these five taste qualities though it must be noted many other modalities may exist. Of particular conjecture is the existence of fatty acid recognition. In the past the detection of fat in food has been attributed to somatosensory inputs <ref name=PMID20696704/> from the tongue, that is, the oily feel and texture of fat rather than its actual ‘taste’ allows the brain to encode for its presence. Further research is therefore required to elicit the precise mechanisms of fat detection.

===Cell Biology===

The five taste qualities are not all detected by the same type of receptor cell located within the taste bud. Like rods and cones in the eye which detect different wavelengths of light, there are specific types of receptors for different tastes. For example, sweet, umami and bitter are recognised by Type II G-protein coupled receptors, whereas sour is related to Type III presynaptic cells. The cell type involved in salty taste transduction is unknown however it is known that sodium ions can enter the receptor cell membrane via ion channel permeation.

====Type II receptors====

When a bitter, sweet or umami ligand binds to a type II G-coupled receptor, a cascade of chemical reactions causes the release of Ca2+ which in turn mediates exocystosis of ATP. The function of this ATP is threefold:

# Stimulates gustatory nerve afferents which project to gustatory nuclei in the spinal cord
# Excites Type III presynaptic nerve fibres to release serotonin.
# Has a positive feedback effect on type II receptor cells, increasing the level of ATP production.

The role of serotonin is believed to be in the form of lateral inhibition i.e. when a bitter quality is recognised, adjacent receptors for sweetness are deactivated and thus the two tastes may be clearly differentiated. It also has a negative feedback effect on receptor cells, inhibiting umami, bitter and sweet taste transduction.

==Taste Map==
[[Image:Taste map.png|thumb|left|250px|Obsolete idea of the tongue map]]
The idea of a tongue map has disseminated through society for many years. This concept purports that different areas of the tongue are specialised to detect either sweet, salty, sour and bitter tastes. Recent research however has completely nullified such claims and suggests instead that different forms of taste are recognised all over the tongue as well as via the palate. Thus the term ''taste map'' has come to take on a new meaning and that is, the precise areas of taste modalities processing in areas of cortex and its subsequent neural inputs.

===Neural Pathways===

'''First order neurons''' - From the receptors located in the taste buds, gustatory nerve afferents project to the ipsilateral rostral 1/3 of the nucleus tractus solitarius (NTS), located in the medulla. This rostral 1/3 is commonly referred to as the ''gustatory nucleus''.

The ''gustatory nucleus'' receives input from cranial nerves VII (''Facial n.''), IX (''Hypglossal n.''), and X (''Vagus n.'') via special visceral afferent (SVA) nerve fibres. A summary of their functions is as follows:

* ''Facial nerve n''. - carries taste information from the anterior 2/3 of the tongue.
* ''Hypoglossal n.'' - carries taste information from the posterior 1/3 of the tongue.
* ''Vagus n''. - carries taste information from the palate

'''Second order neurons''' - From the NTS second order neurons carry taste information to the Ventral posteromedial (VPM) nucleus in the thalamus.<ref name=PMID21885776/>

Copious scientific conjecture surrounds how each taste modality is transmitted to the brain. The ‘labelled-line’ hypothesis suggests that there are taste specific neurons which exclusively carry that taste modality to cortical areas. In analogous terms it can be viewed like the pipelines leading toward a house. Each pipeline carries its own utility, there is one for gas, another for water and finally for electricity with each terminating in slightly different areas of the house. In the same way, on the tongues there are different receptors for each taste which concurrently have individual nerve tracts leading to the primary gustatory cortex.

Contrapuntally there is electrophysiological evidence that single nerve afferents carry multiple modalities. These studies show one nerve afferent may have both a strong and a weak activation in response to a multiple taste stimuli.

===Cortical Areas===

[[Image:Primary gustatory cortex.png|thumb|Primary gustatory cortex]]

The location of the taste perception centres has been observed via functional magnetic resonance imaging (fMRI) studies. The primary taste cortex has been identified as being located in the anterior insula/frontal operculum (I/fO)<ref name=PMID22245354><pubmed>22245354</pubmed></ref>, with the secondary taste cortex in the caudolateral orbitofrontal cortex.<ref name=PMID21305668><pubmed>21305668</pubmed></ref> Within the insula there are further subdivisions related to each taste modality. Two photon calcium imaging research has outlined certain ’hot-spots’ of activation which are clearly delineated in relation to each taste. For example, the bitter modality is represented on the insula cortex approximately 1mm posterior to the middle cerebral artery whereas the sweet modality is represented 2.5mm rostrodorsal to the bitter field with no apparent overlap.<ref name=PMID21885776><pubmed>21885776</pubmed></ref> These findings lend weight to the idea that there is only one receptor for each taste quality.

It is interesting to note the relationship between taste and the reward centres of the brain. There is evidence of neural input to the ventral tegmental area (the origin of the mesolimbic dopaminergic reward pathway) and nucleus accumbens (involved in the conversion of motivation into physical action).<ref name=PMID21885776/> Neural connections such as this provide the foundations in explaining concepts such as flavour learning and preference. It may also give some insight into chronic problems such as food addiction and craving. As of yet however the gustatory neural network is not well understood and more research is required to elucidate the relationship between pleasure and taste sensation

==Timeline of Developmental Processes of the Gustatory System==

{| cellpadding=5 style="border:1px solid #BBB"
|- bgcolor="#89CFF0"
|'''Postovulatory Week'''||'''Description'''||'''Image'''
|- bgcolor="#BCD4E6"
|'''Week 6''' ||
The surface of the developing tongue is covered by nearly flat epitheliuem (Figure 1). <ref name="PMID9455607"><pubmed>9455607</pubmed></ref> The first gustatory papillae of the tongue appears in the caudal midline near the foramen caecum and the first circumvallate papilla develop on the dorsal midline <ref name=PMID9455607/> .
||
image
|- bgcolor="#89CFF0"
| '''Weeks 6 to 7'''||
Nerve fibres approach the basal lamina of lingual epithelium <ref name=PMID8955790><pubmed>8955790</pubmed></ref>. At this stage the lingual epithelium consists of two to three cell layers and there is not yet any sign of cell specializations indicating early taste bud formation<ref name=PMID8955790/>.
||
Image
|- bgcolor="#BCD4E6"
| '''Week 7 '''||
A series of epithelial swellings in the anterior part and midline of the tongue indicate early forming fungiform papillae (figure 2) <ref name=PMID9455607/>.
||
Image
|- bgcolor="#89CFF0"
| ''' Week 8 ''' ||
The lingual epithelium shows first signs of taste bud development as nerve fibres penetrate epithelial basal lamina <ref name=PMID8955790/> and form synapses with taste bud progenitor cells. The synapses reach a maximum around the 12th to 13th week <ref name=PMID8955790/>. However, at this time these cells are still poorly differentiated, elongated epithelial cells <ref name=PMID8955790/> . The synapses demonstrate the neuronal connection between the taste bud primordium and the central nervous system <ref name=PMID8955790/>. Ciliated cells also appear around the 8th week, however the significance of these cells which are scattered randomly across the lingual surface remains unclear <ref name=PMID8955790/>.
||
Image
|- bgcolor="#BCD4E6"
|''' Weeks 8-9''' ||
“By this stage the top surface of circumvallate papillae usually contains a taste pit partly filled with microvilli of presumed underlying taste bud cells” (Figure 10) <ref name=PMID9455607/>
||
Image
|- bgcolor="#89CFF0"
|''' Weeks 10-11''' ||
At this stage, the lingual epithelium compromises of about four cell layers, and the first shallow grooves above the taste bud primordium are developed <ref name=PMID8955790/>.

Fungiform papillae appear on the lateral margins and the tip of the tongue <ref name=PMID9455607/>, containing taste bud primordial that display the first signs of a primitive pore formation <ref name=PMID8955790/>.

Untypically differentiated apical cellular processes extend onto the surface <ref name=PMID9455607/>

Some taste bud primordial contain cells that perforate the covering epithelial later with short, broad untypically differentiated apical cellular processes. (Figure 3,4) <ref name=PMID8955790/> <ref name=PMID9455607/>
||
Image
|- bgcolor="#BCD4E6"
|''' Week 12 ''' ||
Taste bud cells are more clearly differentiated into epithelial cell types II and III <ref name=PMID8955790/>.
||
Image
|- bgcolor="#89CFF0"
|''' Weeks 12-13 ''' ||
By this stage the taste bud primordial are all located on the top of dermal papillae (Fig 6a) <ref name=PMID8955790/>. There is also maximum synapses between cells and afferent nerve fibres, which intermingle with each other to form a plexus-like structure <ref name=PMID8955790/>.
||
Image
|- bgcolor="#BCD4E6"
|''' Weeks 14 -15 ''' ||
The shape of the taste buds primordial begins to resemble those of adult taste buds <ref name=PMID8955790/>. By the 14th week the taste pores develop as the taste pits are filled by microvilli <ref name=PMID8955790/>, indicating the possibility that the taste buds begin their gustatory function <ref name=PMID8955790/>, however they still lack an electron-dense mucous material (Fig.10) <ref name=PMID8955790/>. The tastebuds only achieve a fully developed function in week 15 of gestation with the development of type I cells to produce the mucous material in the taste pit <ref name=PMID8955790/>.
||
Image
|}

== Human Weekly Development - Two Prominent Studies ==
Martin Witt and Klaus Reutter of the University of Tubingen in Germany published two prominent studies regarding developing taste buds in humans. Their first study in 1996 was a transmission electron microscopical (TEM) study of the taste bud primordium and its morphological changes during the 8th-15th postovulatory week. Their next study in 1997 built on their previous findings by using Scanning Electron Microscopy (SEM) to observe the development of gustatory papillae during postovulatory weeks 6-15.

The findings of these two studies are summarized in the table below. The figures provided relate to the images on their respective research papers.

[http://onlinelibrary.wiley.com/doi/10.1002/(SICI)1097-0185(199612)246:4%3C507::AID-AR10%3E3.0.CO;2-S/pdf Embryonic and early fetal development of human taste buds: a transmission electron microscopical study, 1996] | [http://chemse.oxfordjournals.org/content/22/6/601.long Scanning electron microscopical studies of developing gustatory papillae in humans, 1997]

===Timeline of Developmental Processes of the Gustatory System===
{| cellpadding=5 style="border:1px solid #BBB"
|- bgcolor="#89CFF0"
|'''Postovulatory Week'''||'''Description'''||'''Image'''

|- bgcolor="#BCD4E6"
|'''Week 6''' ||
The surface of the developing tongue is covered by nearly flat epithelium (1997, Figure 1). The first gustatory papillae of the tongue appear in the caudal midline near the foramen caecum and the first circumvallate papilla develops on the dorsal midline. <ref name="PMID9455607"><pubmed>9455607</pubmed></ref>
||
image

|- bgcolor="#89CFF0"
| '''Weeks 6 to 7'''||
Nerve fibres approach the basal lamina of lingual epithelium. At this stage the lingual epithelium consists of two to three cell layers and there is not yet any sign of cell specializations indicating early taste bud formation. <ref name=PMID8955790/>
||
Image

|- bgcolor="#BCD4E6"
| '''Week 7 '''||
A series of irregular epithelial swellings in the anterior part and marginal parts of the tongue indicate early forming fungiform papillae. Furthermore, a V-like lane is observed anterior to the sulcus terminalis, which represents a smooth surface for developing circumvallate papillae (1997, Figure 2). Witt M et al observe that these circumvallate papillae are larger than the developing fungiform papillae of the same age, later noting that the fungiform papillae tend to increase in size over the 8-15th weeks of gestation, whilst the size of vallate papillae tend to remain constant during this period. <ref name=PMID9455607/>
||
Image

|- bgcolor="#89CFF0"
| ''' Week 8 ''' ||
* The taste bud primordium are still differentiated, elongated epithelial cells, resting on a slightly developed core of young dermal papilla.
* The lingual epithelium shows first signs of taste bud development as nerve fibres coming from the dermal papilla penetrate the epithelial basal lamina and form synapses with taste bud progenitor cells (1996, Figure 1). These synapses demonstrate the neuronal connection between the taste bud primordium and the central nervous system, reaching a maximum around the 12th to 13th week. However, it is important to note that at this time these cells are still poorly differentiated, elongated epithelial cells.
* Ciliated cells also appear around the 8th week, however the significance of these cells which are scattered randomly across the lingual surface remains unclear. <ref name=PMID8955790/>
||
Image

|- bgcolor="#BCD4E6"
|''' Week 9''' ||
By this stage, although a taste pore is not present, the surface of circumvallate papillae usually contains a taste pit partly filled with microvillus-like processes from the underlying taste bud cells (1997, Figure 10). <ref name=PMID9455607/>
||
Image

|- bgcolor="#89CFF0"
|''' Weeks 10-11''' ||
At this stage, the lingual epithelium compromises of about four cell layers, and the first shallow grooves above the taste bud primordium are developed. Fungiform papillae appear on the lateral margins and the tip of the tongue, containing taste bud primordial that display the first signs of a primitive pore formation (1996, Figure 6). <ref name=PMID8955790/>
||
Image

|- bgcolor="#BCD4E6"
|''' Week 12 ''' ||
Taste bud cells are more clearly differentiated into epithelial cell types II and III. <ref name=PMID8955790/>
||
Image

|- bgcolor="#89CFF0"
|''' Weeks 12-13 ''' ||
At this stage the taste bud primordial are all located on the top of dermal papillae. There is also maximum synapses between cells and afferent nerve fibres, which intermingle with each other to form a plexus-like structure (1996, Figure 6a). <ref name=PMID8955790/>
||
Image

|- bgcolor="#BCD4E6"
|''' Weeks 14 -15 ''' ||
The shape and size of the taste buds primordial begins to resemble those of adult taste buds (1996, Figure 9). By the 14th week the taste pores develop as the taste pits are filled by microvilli, and bubble like vesicles indicate the secretory activity of these cells (1996, Figure 10). However, the tastebuds only achieve a fully developed function in week 15 of gestation with the development of type I cells to produce the mucous material in the taste pit. <ref name=PMID8955790/>
||
Image
|}

==Adult Tongue and Taste Buds – Structure and Function==

'''Structure'''

The tongue is located on the floor of the oral cavity, It is a muscular structure with sensory units crowning. The tongue is divided into an anterior two thirds and a posterior one third. These regions are divided by a V-shaped groove at the back of the tongue (sulcus terminalis). The anterior two thirds of the tongue is covered by stratified squamous epithelium, It contains a roughened surface and has projections called papillae that vary in shape and number.

''''The Image Below is a very simplistic Diagram of the surface of the Tongue showing the locations of the different papillae and other important features'''

{|
| [[Image:Drawing of Tongue.png|500px]]

'''Papillae'''
[[File:Papillae.jpg|Left|thumb|200px|Close up of Human Tongue Papillae]]

There are 4 types of papillae on the tongue.
The most numerous papillae are the filiform papillae, which function to provide a surface that aids in holding food on the tongue during chewing but do not contain taste buds. The larger, less numerous fungiform papillae which contain taste buds, as do foliate papillae. Circumvallate papillae form a wide V at the sulcus terminalis also containing taste bus. There are no papillae or taste buds located on the posterior third of the tongue, having mucosal folds and the lingual tonsils instead.

'''Function'''

The tongue is for tasting, swallowing, and speech.
The functional unit of the taste bud is a taste cell, there are between 50 and 100 taste cells in each taste bud these taste cells represent all 5 different tastes. Historically is was believed that different areas of the tongue were responsible for different taste sensations although this has since been disregarded.[http://users.rcn.com/jkimball.ma.ultranet/BiologyPages/W/Welcome.html] The papillae contain taste buds which are connected to the oral cavity via a taste pore, the function of the taste bud is to transmit a chemical signal from the oral cavity to a taste cell, this chemical signal is the converted into an electrical impulse and delivered to the brain via nerve fibres for interpretation.

'''The Image Below is a very simplistic Hand drawn Diagram of a taste bud, in an extreme close up, cross section view of the the taste bud unit, not to scale'''

[[File:Taste_bud_1.jpg]]

==Abnormalities==

===Knocking out P2X Receptors===

[[File:Image of taste being evoked by visualising ATP release.jpeg|Left|thumb|200px|Evoking taste - ATP release in tongue]]

Gustatory abnormalities has not been widely researched and what has been researched has been through animal testing, most commonly we have found on mice.

In Huang, 2008 this team used the release of the neurotransmitter, ATP (adenosine triphosphate) as a quantitative measurement of gustatory sensation and taste. This was done by using a comparison of wild type (WT) and double knockout (DKO) mice. P2X receptors, P2X2 and P2X3 were knocked out in the DKO mice. The premise of this article was that knocking out P2X receptors reduces transmitter secretion of ATP in taste buds, therefore they cannot taste.

It should be noted that the taste buds in DKO are functional, but are not stimulated by the administration of tastants.

The transmission of release of ATP is secretion through gap junction hemichannels (pannexin 1 gap junction).

When both P2X2 and P2X3 are knocked out, no taste is elicited. However they found that if either P2X2 OR P2X3 was knocked out there was a taste response. So the inference made from this is that if one of the two receptors from the P2X family was knocked out there still can have taste response. The WT mice showed significant stimulation by tastants whereas DKO had little to no stimulation of ATP release.<ref><pubmed>21940456</pubmed></ref>

===FGF signalling and genes===

Sprouty, or ''Srpy'', genes have been related to regulating the development of circumvillate papillae (CVP). The CVP are large dome shaped papillae, which form a 'V' just in front of the terminal sulcus.

By knocking out ''Spry'' genes using mice which had ''Spry1'' and ''Spry2'' knocked out showed that the number of CVP doubled. However, when Fibroblast Growth Factor gene ("Fgf10") was absent, the number of CVP was significantly reduced, if not completely absent. The correlation between ''Spry1/2'' and ''Fgf10'' is that ''Spry1/2'' antagonises "Fgf10" to limit the size of the CVP progenitor placode. Exclusive expression of ''Fgf10'' in the mesenchyme is necessary for the formation of CVP.

'''This image shows the CVP stained with H&E and scanned by Scanning Electron Microscope (SEM)'''
[[File:CVP of WT(top) and DKO(bottom) mice with H&E and SEM.png]]

'''This image shows the location of the CVP and the increased number in DKO mice by SEM'''
[[File:Mouse circumvallate papilla 01.jpg|300px]]

Taste buds develop from the mesenchyme but require local signalling to properly differentiate. Some signalling factors for proper development of taste buds besides FGF are: Sonic Hedgehog (SHH), Bone Morphogenetic Proteins (BMPs), Epidermal Growth Factor (EGF).

Additionally, this proves that the anterior and posterior developments of the tongue are derived from embryonic tissues, where the anterior tongue is derived from the ectoderm and the posterior tongue is derived from the endoderm. Taste buds develop from the mesenchyme but require local signalling to properly differentiate. Some signalling factors for proper development of taste buds besides FGF are: Sonic Hedgehog (SHH), Bone Morphogenetic Proteins (BMPs), Epidermal Growth Factor (EGF).

As mentioned above, this article shows that the anterior and posterior developments of the tongue are derived from embryonic tissues, where the anterior tongue is derived front the ectoderm and the posterior tongue is derived from the endoderm. Secondly, FGF is required to regulate the growth of taste buds, while ''Spry'' genes limit the number of CVP. ''Fgf10''& ''Spry 1&2''work antagonistically through receptor tyrosine kinase (RTK)signalling.

However, the deletion of ''Spry2''led to the increase of CVPs it should be noted that they found that a significant decrease in number of fungiform papillae. Contrastingly, the absence of ''Fgf10'', while leading to the absence of CVPs lead to an increase in number and size of fungiform papillae. Therefore these genes have different effects on the anterior and posterior developing tongue and taste buds.<ref><pubmed>21655085</pubmed></ref>

==Current Research==
We have an evolving understanding of Embryonic Taste development, through the use of state-of-the-art technology and research techniques we are able to make brilliant discoveries that continue to connect the dots of this amazing natural process of human development.
The majority of research in taste development is involving mice, these mammals show similar embryonic pathways to humans and research is performed in ethical and humane methods.

[[File:Histology.jpg|Left|thumb|200px|Image shows histological stains of a mice tongue showing dysplasia]]

'''Synergistic relationships of Six Genes '''

In an animal study using mice by Suzuki Y, Ikeda K, Kawakami K.(2011) Firstly nominating "Six Genes" as a major component in gustatory development, stating that deficiencies in certain Six genes (specifically Six1 & Six4) leads to poor development. Their research also highlights evidence of cooperative relationships between Six genes for normal advance. This experiment involved breeding mice containing exclusively Six1 and Six4 genes and examining the expression of these genes in papillae under high powered microscope observation. Understanding the role of certain genes along with the intrinsic relationships they hold is crucial for the ability to identify possible causes and correction of any abnormalities <ref><pubmed>21978088</pubmed></ref>

'''Neural Crest responsibilities '''

Another Animal Study involving mice explores a new idea of Neural crest (NC) contribution in taste development, specifically the development of papillae and taste buds. Liu HX, Komatsu Y, Mishina Y, Mistretta CM. (2012) suggest that Neural crest cells travel to the location of the tongue in early embryonic stages, gain epithelium phenotypes, multiply and then differentiate to eventually form taste papillae. The experiment involved the comparison of 2 different types of Cre line mice, which both express Cre gene in neural crest protocol, the different distribution patterns where observed in specific regions that NC is responsible for.<ref><pubmed>22659543</pubmed></ref>

'''Augmentation of Endoderm'''

In an animal study conducted by Rothova M, Thompson H, Lickert H, Tucker AS.(2012) exploring the historically debated issue of endoderm contribution to tongue development showed promising evidence that position of taste buds are patterned by the border of ectoderm and endoderm derivative epithelium. This study was accomplished via microscopic examination of previously stained specimens. Concluding endoderm has direct influence on gustatory develoment <ref><pubmed>22581563</pubmed></ref>

'''Changes in Taste Cells over time'''

Research by
Ozdener H, Spielman AI, Rawson NE.(2012) developing a culture which allows taste cells to survive for up to 12 months, empowers researchers to study the processes of proliferation, differentiation and function. This experiment will provide a precidnet for future study of taste cells, as these cells are able to operate and grow normally. <ref><pubmed>22643728</pubmed></ref>

'''Shh key component of taste bud proginators'''

A tamoxifen treatment which supresses Sonic hedgehog (Shh) secretion in mice proving to reduce the number of cells visable within papillae, in contrast mice not treated with tamoxifen showed a mark increase of cells within papillae, these cells are assumed to become taste cells in later development.
Specific mice were bred to trace the destination of taste placode cells, the study concluded that Shh expressing placodes are taste bud proginators which in turn become taste cells within taste buds although do not have any prescuros relationship with pappilae. The results were obtain by examination of mice embryos using Bright-field or multichannel fluorescent images through the use of an "Axiocam CCD camera and Axioplan fluorescence microscope with Axiovision software" a study by Harlow, Yang, Williams, Barlow (2011)<ref><pubmed>PMC2674259</pubmed></ref>

'''WNT family exhibit various roles'''

The WNT gene family has a function of signally proteins for various reason such as development, In 2010 Liu, Staubach Grosse, Walton, Saims, Gumucio, Mistretta explored recent findings on the role of WNT's in tongue and papillae development, Concluding that WNT/β-catenin is essential for fungiform papillae differing to WNT5a which proved to be principle in tongue development. Intrinsic chemical mediators were considered by manipulating a tissue culture and then throughaly examined by scanning photomicrograph. <ref><pubmed>PMC2768563</pubmed></ref>

[http://www.surgicalneurologyint.com/article.asp?issn=2152-7806;year=2012;volume=3;issue=1;spage=23;epage=23;aulast=Manjila]
[[File:Abnormal of tongue.jpg|Left|thumb|200px|Image shows and example of tongue abnormalities, this is called "double tongue" each side has independent movement!]]

==Useful links==

==Glossary==

ectoderm- outer germ layer of embryo

endoderm - inner germ layer of embryo

epithelium - basic animal tissue that is composed of tightly packed cells, usually covering the outer portion of organs

exocystosis - movement of contents out of cell

ganglia - the accumulation of a nerve cell body

growth factor - a substance that stimulates the growth of cells

gustatory - anything that relates to the taste sense

hydrolysis - breakdown of a chemical when it reacts with water

mesoderm - middle germ layer of embryo

mesenchyme - multipotential cells

neural crest - a part of the ectoderm found on both sides of the neural tube

neuron - most simplistic unit of the nervous system

neurotransmitter - chemicals which allow the passing of signals from neuron to neuron via connecting part (synapse)

papillae - small rough surface projection

six genes - a family of genes

Sonic hedgehog (Shh) - signalling protein invloved in normal development

sulcus terminalis - describes a physical transition point separating the anterior 2/3 of the tongue from the posterior 1/3

tamoxifen - hormonal altering drug

==Image gallery==

== References ==
<references/>

==External Links==
{{External Links}}

http://www.webmd.com/oral-health/picture-of-the-tongue

http://www.tutorvista.com/content/biology/biology-iv/nervous-coordination/tongue-structure.php#parts-of-tongue

http://www.cf.ac.uk/biosi/staffinfo/jacob/teaching/sensory/taste.html

--[[User:Z8600021|Mark Hill]] 12:22, 15 August 2012 (EST) Please leave the content listed below the line at the bottom of your project page.

----

{{2012Projects}}

2012 Group Project 3

2012-09-30T04:50:57Z

Z3289738: /* Human Weekly Development - Two Prominent Studies */

=Taste Development=

== Introduction ==
**NEED TO ADD**

==History of Discoveries==

{| cellpadding=5 style="border:1px solid #BBB"
|- bgcolor="#faecc8"
|''' Date'''|| '''Significant Discovery'''

|- bgcolor="#faf6ed"
|'''350BC'''
|| Aristotle writes about the basic tastes, sweet and bitter. He also notes that it can be modified by salty and acidic. <ref name="PMID22717400"><pubmed>22717400</pubmed></ref>

|- bgcolor="#faecc8"
|'''1901'''
|| D. Hanig publishes a paper describing taste sensitivity in different regions of the tongue.
''Interesting fact:'' The modern concept of a 'tongue map' is a misinterpretation of this study. <ref name="PMID22717400"/>

|- bgcolor="#faf6ed"
|style=white-space:nowrap|'''1908'''
|Kikunae Ikeda, a professor of the Tokyo Imperial University, discovered and identified the fifth basic taste: umami (savouriness), made palatable by glutamate. <ref><pubmed>12438213</pubmed></ref>
[http://chemse.oxfordjournals.org/content/27/9/847.long New Seasonings]

|- bgcolor="#faecc8"
|style=white-space:nowrap|'''1931-32'''
| A chemist named Arthur Fox and his college noted that they had different sensitivities to the bitter tasting Phenylthiocarbamide (PTC).<ref>Blakeslee AF, Fox AL. Our different taste worlds. J Hered. 1932;23:97–107.</ref> Geneticists later confirm these findings, and discover that non-tasting is a recessive genetic trait. <ref><pubmed>17782493</pubmed></ref>
[http://www.ncbi.nlm.nih.gov/pubmed/17782493 Inherited taste deficiency]

|- bgcolor="#faf6ed"
|style=white-space:nowrap|'''1965'''
|Farbman's study of the developing taste but in rat fungiform papilla was significant in increasing our understanding of taste bud development. <ref><pubmed>14300090</pubmed></ref>
[http://www.sciencedirect.com/science/article/pii/0012160665900400 Electron microscope study of the developing taste bud in rat fungiform papilla.]

|- bgcolor="#faecc8"
|style=white-space:nowrap|'''1992'''
|McLaughlin SK et al. discovery a taste cell-specific G-protein within the taste buds called Gustucon. This protein is later used to mark bitter, umami and sweet cells. <ref><pubmed>1608467 </pubmed></ref>
[http://www.nature.com/nature/journal/v357/n6379/abs/357563a0.html Gustducin is a taste-cell-specific G protein closely related to the transducins]

|- bgcolor="#faf6ed"
|style=white-space:nowrap|'''1995'''
|Barlow et al. experimented with Axolotl salamanders and concluded that taste buds from this species arise exclusively from epithelial tissue, "oropharyngeal epithelium". <ref name="PMID17826760"><pubmed>17826760</pubmed></ref>
[http://www.ncbi.nlm.nih.gov/pubmed/17826760 Embryonic origin of gustatory cranial sensory neurons.]

|- bgcolor="#faecc8"
|style=white-space:nowrap|'''1996'''
| Witt M and Reutter K of the Technical University Dresden in Germany, carried out a transmission electron microscopy study to investigate the embryonic and fetal development of Human taste buds. Their results suggest an "at least dual function of embryonic/fetal taste buds", including non-gustatory, paracrine functions prior to the 14th week and gustatory after the 14th week. <ref name="PMID8955790"><pubmed>8955790</pubmed></ref>
[http://www.ncbi.nlm.nih.gov/pubmed/8955790 Embryonic and early fetal development of human taste buds: a transmission electron microscopical study]

|- bgcolor="#faf6ed"
|style=white-space:nowrap|'''2000'''
|Chandrashekar, J. et al. discover the first taste sonsors, the T2R bitter taste receptors. <ref><pubmed>10761935</pubmed></ref>
[http://www.sciencedirect.com/science/article/pii/S0092867400807060 T2Rs Function as Bitter Taste Receptors]

|- bgcolor="#faecc8"
|style=white-space:nowrap|'''2001'''
|Nelson, G. et al. discover the sweet receptor: a combination of T1R2 and T1R3. <ref><pubmed>11509186</pubmed></ref>
[http://www.ncbi.nlm.nih.gov/pubmed/11509186?dopt=Abstract&holding=npg Mammalian sweet taste receptors.]

|- bgcolor="#faf6ed"
|style=white-space:nowrap|'''2002'''
|Nelson G. et al. discover the amino acid (umami) taste receptor: a combination of T1R1 and T1R3 identified. <ref><pubmed>11894099</pubmed></ref>
[http://www.ncbi.nlm.nih.gov/pubmed/11894099?dopt=Abstract&holding=npg An amino-acid taste receptor]

|- bgcolor="#faecc8"
|style=white-space:nowrap|'''2005'''
|Dyer, J. et al. discover sweet taste receptors in the GI tract. <ref><pubmed>17855558</pubmed></ref>
[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1986582/ Sweet taste signaling in the gut]

|- bgcolor="#faf6ed"
|style=white-space:nowrap|'''2006'''
|Huang, A. L et al. discover cells for sour taste, identified by PKD2L1 (a polycystic kidney disease-like ion channel). <ref><pubmed>16929298</pubmed></ref>
[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1571047/ The Cells and Logic for Mammalian Sour Taste detection]

|- bgcolor="#faecc8"
|style=white-space:nowrap|'''2007'''
|Harlow DE, Barlow LA of the University of Colorado Denver Health Sciences Center provide evidence of the "embryonic origin of gustatory cranial sensory neurons". <ref name="PMID17826760"/>
[http://www.ncbi.nlm.nih.gov/pubmed/17826760 Embryonic origin of gustatory cranial sensory neurons.]

|- bgcolor="#faf6ed"
|style=white-space:nowrap|'''2009'''
|A study by Hevezi P et al, presents "the first comprehensive characterization of gene expression in primate taste buds", as opposed to previous studies which focused on rodents. <ref><pubmed>19636377</pubmed></ref>
[http://www.ncbi.nlm.nih.gov/pubmed/19636377 Genome-wide analysis of gene expression in primate taste buds reveals links to diverse processes]

|- bgcolor="#faecc8"
|style=white-space:nowrap|'''2010'''
|Chandrashekar, J. et al. identify epithelial sodium channel (ENaC) as the sodium-salt taste receptor. <ref><pubmed>20107438</pubmed></ref>
[http://www.ncbi.nlm.nih.gov/pubmed/20107438?dopt=Abstract&holding=npg The cells and peripheral representation of sodium taste in mice]
|}

==Gustatory System==

[[Image:Taste qualities.gif|thumb|The five basic tastes]]

Taste or more appropriately gustation, is a fundamental survival tool in animals as it directs the consumption of essential nutrients. The five tastes that exist within the human gustatory system: salty, sweet, sour, bitter and umami, all signify basic physiological requirements. Salty tastes denote the presence of Na+, an important ion involved in the transportation and retention of water across cell membranes. Sweetness is the recognition of carbohydrates, essential for maintaining optimal brain function and providing the basis for energy production in muscle tissue via ATP hydrolysis. Similarly umami codes for the presence of L-amino acids, especially L-glutamate which is an integral component of protein synthesis.

These different modalities not only function to maintain the proper intake of nutrients within the body but also, by way of aversion, prohibit the consumption of undesired or poisonous materials. The bitter modality for example is generally regarded as displeasing to the human palate. It represents a high acid content which may be a result of foods which have become rotten or are inherently poisonous to the body.<ref name=PMID20696704><pubmed>20696704</pubmed></ref>

Research has historically limited itself to investigating the mechanisms of these five taste qualities though it must be noted many other modalities may exist. Of particular conjecture is the existence of fatty acid recognition. In the past the detection of fat in food has been attributed to somatosensory inputs <ref name=PMID20696704/> from the tongue, that is, the oily feel and texture of fat rather than its actual ‘taste’ allows the brain to encode for its presence. Further research is therefore required to elicit the precise mechanisms of fat detection.

===Cell Biology===

The five taste qualities are not all detected by the same type of receptor cell located within the taste bud. Like rods and cones in the eye which detect different wavelengths of light, there are specific types of receptors for different tastes. For example, sweet, umami and bitter are recognised by Type II G-protein coupled receptors, whereas sour is related to Type III presynaptic cells. The cell type involved in salty taste transduction is unknown however it is known that sodium ions can enter the receptor cell membrane via ion channel permeation.

====Type II receptors====

When a bitter, sweet or umami ligand binds to a type II G-coupled receptor, a cascade of chemical reactions causes the release of Ca2+ which in turn mediates exocystosis of ATP. The function of this ATP is threefold:

# Stimulates gustatory nerve afferents which project to gustatory nuclei in the spinal cord
# Excites Type III presynaptic nerve fibres to release serotonin.
# Has a positive feedback effect on type II receptor cells, increasing the level of ATP production.

The role of serotonin is believed to be in the form of lateral inhibition i.e. when a bitter quality is recognised, adjacent receptors for sweetness are deactivated and thus the two tastes may be clearly differentiated. It also has a negative feedback effect on receptor cells, inhibiting umami, bitter and sweet taste transduction.

==Taste Map==
[[Image:Taste map.png|thumb|left|250px|Obsolete idea of the tongue map]]
The idea of a tongue map has disseminated through society for many years. This concept purports that different areas of the tongue are specialised to detect either sweet, salty, sour and bitter tastes. Recent research however has completely nullified such claims and suggests instead that different forms of taste are recognised all over the tongue as well as via the palate. Thus the term ''taste map'' has come to take on a new meaning and that is, the precise areas of taste modalities processing in areas of cortex and its subsequent neural inputs.

===Neural Pathways===

'''First order neurons''' - From the receptors located in the taste buds, gustatory nerve afferents project to the ipsilateral rostral 1/3 of the nucleus tractus solitarius (NTS), located in the medulla. This rostral 1/3 is commonly referred to as the ''gustatory nucleus''.

The ''gustatory nucleus'' receives input from cranial nerves VII (''Facial n.''), IX (''Hypglossal n.''), and X (''Vagus n.'') via special visceral afferent (SVA) nerve fibres. A summary of their functions is as follows:

* ''Facial nerve n''. - carries taste information from the anterior 2/3 of the tongue.
* ''Hypoglossal n.'' - carries taste information from the posterior 1/3 of the tongue.
* ''Vagus n''. - carries taste information from the palate

'''Second order neurons''' - From the NTS second order neurons carry taste information to the Ventral posteromedial (VPM) nucleus in the thalamus.<ref name=PMID21885776/>

Copious scientific conjecture surrounds how each taste modality is transmitted to the brain. The ‘labelled-line’ hypothesis suggests that there are taste specific neurons which exclusively carry that taste modality to cortical areas. In analogous terms it can be viewed like the pipelines leading toward a house. Each pipeline carries its own utility, there is one for gas, another for water and finally for electricity with each terminating in slightly different areas of the house. In the same way, on the tongues there are different receptors for each taste which concurrently have individual nerve tracts leading to the primary gustatory cortex.

Contrapuntally there is electrophysiological evidence that single nerve afferents carry multiple modalities. These studies show one nerve afferent may have both a strong and a weak activation in response to a multiple taste stimuli.

===Cortical Areas===

[[Image:Primary gustatory cortex.png|thumb|Primary gustatory cortex]]

The location of the taste perception centres has been observed via functional magnetic resonance imaging (fMRI) studies. The primary taste cortex has been identified as being located in the anterior insula/frontal operculum (I/fO)<ref name=PMID22245354><pubmed>22245354</pubmed></ref>, with the secondary taste cortex in the caudolateral orbitofrontal cortex.<ref name=PMID21305668><pubmed>21305668</pubmed></ref> Within the insula there are further subdivisions related to each taste modality. Two photon calcium imaging research has outlined certain ’hot-spots’ of activation which are clearly delineated in relation to each taste. For example, the bitter modality is represented on the insula cortex approximately 1mm posterior to the middle cerebral artery whereas the sweet modality is represented 2.5mm rostrodorsal to the bitter field with no apparent overlap.<ref name=PMID21885776><pubmed>21885776</pubmed></ref> These findings lend weight to the idea that there is only one receptor for each taste quality.

It is interesting to note the relationship between taste and the reward centres of the brain. There is evidence of neural input to the ventral tegmental area (the origin of the mesolimbic dopaminergic reward pathway) and nucleus accumbens (involved in the conversion of motivation into physical action).<ref name=PMID21885776/> Neural connections such as this provide the foundations in explaining concepts such as flavour learning and preference. It may also give some insight into chronic problems such as food addiction and craving. As of yet however the gustatory neural network is not well understood and more research is required to elucidate the relationship between pleasure and taste sensation

==Timeline of Developmental Processes of the Gustatory System==

{| cellpadding=5 style="border:1px solid #BBB"
|- bgcolor="#89CFF0"
|'''Postovulatory Week'''||'''Description'''||'''Image'''
|- bgcolor="#BCD4E6"
|'''Week 6''' ||
The surface of the developing tongue is covered by nearly flat epitheliuem (Figure 1). <ref name="PMID9455607"><pubmed>9455607</pubmed></ref> The first gustatory papillae of the tongue appears in the caudal midline near the foramen caecum and the first circumvallate papilla develop on the dorsal midline <ref name=PMID9455607/> .
||
image
|- bgcolor="#89CFF0"
| '''Weeks 6 to 7'''||
Nerve fibres approach the basal lamina of lingual epithelium <ref name=PMID8955790><pubmed>8955790</pubmed></ref>. At this stage the lingual epithelium consists of two to three cell layers and there is not yet any sign of cell specializations indicating early taste bud formation<ref name=PMID8955790/>.
||
Image
|- bgcolor="#BCD4E6"
| '''Week 7 '''||
A series of epithelial swellings in the anterior part and midline of the tongue indicate early forming fungiform papillae (figure 2) <ref name=PMID9455607/>.
||
Image
|- bgcolor="#89CFF0"
| ''' Week 8 ''' ||
The lingual epithelium shows first signs of taste bud development as nerve fibres penetrate epithelial basal lamina <ref name=PMID8955790/> and form synapses with taste bud progenitor cells. The synapses reach a maximum around the 12th to 13th week <ref name=PMID8955790/>. However, at this time these cells are still poorly differentiated, elongated epithelial cells <ref name=PMID8955790/> . The synapses demonstrate the neuronal connection between the taste bud primordium and the central nervous system <ref name=PMID8955790/>. Ciliated cells also appear around the 8th week, however the significance of these cells which are scattered randomly across the lingual surface remains unclear <ref name=PMID8955790/>.
||
Image
|- bgcolor="#BCD4E6"
|''' Weeks 8-9''' ||
“By this stage the top surface of circumvallate papillae usually contains a taste pit partly filled with microvilli of presumed underlying taste bud cells” (Figure 10) <ref name=PMID9455607/>
||
Image
|- bgcolor="#89CFF0"
|''' Weeks 10-11''' ||
At this stage, the lingual epithelium compromises of about four cell layers, and the first shallow grooves above the taste bud primordium are developed <ref name=PMID8955790/>.

Fungiform papillae appear on the lateral margins and the tip of the tongue <ref name=PMID9455607/>, containing taste bud primordial that display the first signs of a primitive pore formation <ref name=PMID8955790/>.

Untypically differentiated apical cellular processes extend onto the surface <ref name=PMID9455607/>

Some taste bud primordial contain cells that perforate the covering epithelial later with short, broad untypically differentiated apical cellular processes. (Figure 3,4) <ref name=PMID8955790/> <ref name=PMID9455607/>
||
Image
|- bgcolor="#BCD4E6"
|''' Week 12 ''' ||
Taste bud cells are more clearly differentiated into epithelial cell types II and III <ref name=PMID8955790/>.
||
Image
|- bgcolor="#89CFF0"
|''' Weeks 12-13 ''' ||
By this stage the taste bud primordial are all located on the top of dermal papillae (Fig 6a) <ref name=PMID8955790/>. There is also maximum synapses between cells and afferent nerve fibres, which intermingle with each other to form a plexus-like structure <ref name=PMID8955790/>.
||
Image
|- bgcolor="#BCD4E6"
|''' Weeks 14 -15 ''' ||
The shape of the taste buds primordial begins to resemble those of adult taste buds <ref name=PMID8955790/>. By the 14th week the taste pores develop as the taste pits are filled by microvilli <ref name=PMID8955790/>, indicating the possibility that the taste buds begin their gustatory function <ref name=PMID8955790/>, however they still lack an electron-dense mucous material (Fig.10) <ref name=PMID8955790/>. The tastebuds only achieve a fully developed function in week 15 of gestation with the development of type I cells to produce the mucous material in the taste pit <ref name=PMID8955790/>.
||
Image
|}

== Human Weekly Development - Two Prominent Studies ==
Martin Witt and Klaus Reutter of the University of Tubingen in Germany published two prominent studies regarding developing taste buds in humans. Their first study in 1996 was a transmission electron microscopical (TEM) study of the taste bud primordium and its morphological changes during the 8th-15th postovulatory week. Their next study in 1997 built on their previous findings by using Scanning Electron Microscopy (SEM) to observe the development of gustatory papillae during postovulatory weeks 6-15.

The findings of these two studies are summarized in the table below. The figures provided relate to the images on their respective research papers.

[http://chemse.oxfordjournals.org/content/22/6/601.long Scanning electron microscopical studies of developing gustatory papillae in humans] |

===Timeline of Developmental Processes of the Gustatory System===
{| cellpadding=5 style="border:1px solid #BBB"
|- bgcolor="#89CFF0"
|'''Postovulatory Week'''||'''Description'''||'''Image'''

|- bgcolor="#BCD4E6"
|'''Week 6''' ||
The surface of the developing tongue is covered by nearly flat epithelium (1997, Figure 1). The first gustatory papillae of the tongue appear in the caudal midline near the foramen caecum and the first circumvallate papilla develops on the dorsal midline. <ref name="PMID9455607"><pubmed>9455607</pubmed></ref>
||
image

|- bgcolor="#89CFF0"
| '''Weeks 6 to 7'''||
Nerve fibres approach the basal lamina of lingual epithelium. At this stage the lingual epithelium consists of two to three cell layers and there is not yet any sign of cell specializations indicating early taste bud formation. <ref name=PMID8955790/>
||
Image

|- bgcolor="#BCD4E6"
| '''Week 7 '''||
A series of irregular epithelial swellings in the anterior part and marginal parts of the tongue indicate early forming fungiform papillae. Furthermore, a V-like lane is observed anterior to the sulcus terminalis, which represents a smooth surface for developing circumvallate papillae (1997, Figure 2). Witt M et al observe that these circumvallate papillae are larger than the developing fungiform papillae of the same age, later noting that the fungiform papillae tend to increase in size over the 8-15th weeks of gestation, whilst the size of vallate papillae tend to remain constant during this period. <ref name=PMID9455607/>
||
Image

|- bgcolor="#89CFF0"
| ''' Week 8 ''' ||
* The taste bud primordium are still differentiated, elongated epithelial cells, resting on a slightly developed core of young dermal papilla.
* The lingual epithelium shows first signs of taste bud development as nerve fibres coming from the dermal papilla penetrate the epithelial basal lamina and form synapses with taste bud progenitor cells (1996, Figure 1). These synapses demonstrate the neuronal connection between the taste bud primordium and the central nervous system, reaching a maximum around the 12th to 13th week. However, it is important to note that at this time these cells are still poorly differentiated, elongated epithelial cells.
* Ciliated cells also appear around the 8th week, however the significance of these cells which are scattered randomly across the lingual surface remains unclear. <ref name=PMID8955790/>
||
Image

|- bgcolor="#BCD4E6"
|''' Week 9''' ||
By this stage, although a taste pore is not present, the surface of circumvallate papillae usually contains a taste pit partly filled with microvillus-like processes from the underlying taste bud cells (1997, Figure 10). <ref name=PMID9455607/>
||
Image

|- bgcolor="#89CFF0"
|''' Weeks 10-11''' ||
At this stage, the lingual epithelium compromises of about four cell layers, and the first shallow grooves above the taste bud primordium are developed. Fungiform papillae appear on the lateral margins and the tip of the tongue, containing taste bud primordial that display the first signs of a primitive pore formation (1996, Figure 6). <ref name=PMID8955790/>
||
Image

|- bgcolor="#BCD4E6"
|''' Week 12 ''' ||
Taste bud cells are more clearly differentiated into epithelial cell types II and III. <ref name=PMID8955790/>
||
Image

|- bgcolor="#89CFF0"
|''' Weeks 12-13 ''' ||
At this stage the taste bud primordial are all located on the top of dermal papillae. There is also maximum synapses between cells and afferent nerve fibres, which intermingle with each other to form a plexus-like structure (1996, Figure 6a). <ref name=PMID8955790/>
||
Image

|- bgcolor="#BCD4E6"
|''' Weeks 14 -15 ''' ||
The shape and size of the taste buds primordial begins to resemble those of adult taste buds (1996, Figure 9). By the 14th week the taste pores develop as the taste pits are filled by microvilli, and bubble like vesicles indicate the secretory activity of these cells (1996, Figure 10). However, the tastebuds only achieve a fully developed function in week 15 of gestation with the development of type I cells to produce the mucous material in the taste pit. <ref name=PMID8955790/>
||
Image
|}

==Adult Tongue and Taste Buds – Structure and Function==

'''Structure'''

The tongue is located on the floor of the oral cavity, It is a muscular structure with sensory units crowning. The tongue is divided into an anterior two thirds and a posterior one third. These regions are divided by a V-shaped groove at the back of the tongue (sulcus terminalis). The anterior two thirds of the tongue is covered by stratified squamous epithelium, It contains a roughened surface and has projections called papillae that vary in shape and number.

''''The Image Below is a very simplistic Diagram of the surface of the Tongue showing the locations of the different papillae and other important features'''

{|
| [[Image:Drawing of Tongue.png|500px]]

'''Papillae'''
[[File:Papillae.jpg|Left|thumb|200px|Close up of Human Tongue Papillae]]

There are 4 types of papillae on the tongue.
The most numerous papillae are the filiform papillae, which function to provide a surface that aids in holding food on the tongue during chewing but do not contain taste buds. The larger, less numerous fungiform papillae which contain taste buds, as do foliate papillae. Circumvallate papillae form a wide V at the sulcus terminalis also containing taste bus. There are no papillae or taste buds located on the posterior third of the tongue, having mucosal folds and the lingual tonsils instead.

'''Function'''

The tongue is for tasting, swallowing, and speech.
The functional unit of the taste bud is a taste cell, there are between 50 and 100 taste cells in each taste bud these taste cells represent all 5 different tastes. Historically is was believed that different areas of the tongue were responsible for different taste sensations although this has since been disregarded.[http://users.rcn.com/jkimball.ma.ultranet/BiologyPages/W/Welcome.html] The papillae contain taste buds which are connected to the oral cavity via a taste pore, the function of the taste bud is to transmit a chemical signal from the oral cavity to a taste cell, this chemical signal is the converted into an electrical impulse and delivered to the brain via nerve fibres for interpretation.

'''The Image Below is a very simplistic Hand drawn Diagram of a taste bud, in an extreme close up, cross section view of the the taste bud unit, not to scale'''

[[File:Taste_bud_1.jpg]]

==Abnormalities==

===Knocking out P2X Receptors===

[[File:Image of taste being evoked by visualising ATP release.jpeg|Left|thumb|200px|Evoking taste - ATP release in tongue]]

Gustatory abnormalities has not been widely researched and what has been researched has been through animal testing, most commonly we have found on mice.

In Huang, 2008 this team used the release of the neurotransmitter, ATP (adenosine triphosphate) as a quantitative measurement of gustatory sensation and taste. This was done by using a comparison of wild type (WT) and double knockout (DKO) mice. P2X receptors, P2X2 and P2X3 were knocked out in the DKO mice. The premise of this article was that knocking out P2X receptors reduces transmitter secretion of ATP in taste buds, therefore they cannot taste.

It should be noted that the taste buds in DKO are functional, but are not stimulated by the administration of tastants.

The transmission of release of ATP is secretion through gap junction hemichannels (pannexin 1 gap junction).

When both P2X2 and P2X3 are knocked out, no taste is elicited. However they found that if either P2X2 OR P2X3 was knocked out there was a taste response. So the inference made from this is that if one of the two receptors from the P2X family was knocked out there still can have taste response. The WT mice showed significant stimulation by tastants whereas DKO had little to no stimulation of ATP release.<ref><pubmed>21940456</pubmed></ref>

===FGF signalling and genes===

Sprouty, or ''Srpy'', genes have been related to regulating the development of circumvillate papillae (CVP). The CVP are large dome shaped papillae, which form a 'V' just in front of the terminal sulcus.

By knocking out ''Spry'' genes using mice which had ''Spry1'' and ''Spry2'' knocked out showed that the number of CVP doubled. However, when Fibroblast Growth Factor gene ("Fgf10") was absent, the number of CVP was significantly reduced, if not completely absent. The correlation between ''Spry1/2'' and ''Fgf10'' is that ''Spry1/2'' antagonises "Fgf10" to limit the size of the CVP progenitor placode. Exclusive expression of ''Fgf10'' in the mesenchyme is necessary for the formation of CVP.

'''This image shows the CVP stained with H&E and scanned by Scanning Electron Microscope (SEM)'''
[[File:CVP of WT(top) and DKO(bottom) mice with H&E and SEM.png]]

'''This image shows the location of the CVP and the increased number in DKO mice by SEM'''
[[File:Mouse circumvallate papilla 01.jpg|300px]]

Taste buds develop from the mesenchyme but require local signalling to properly differentiate. Some signalling factors for proper development of taste buds besides FGF are: Sonic Hedgehog (SHH), Bone Morphogenetic Proteins (BMPs), Epidermal Growth Factor (EGF).

Additionally, this proves that the anterior and posterior developments of the tongue are derived from embryonic tissues, where the anterior tongue is derived from the ectoderm and the posterior tongue is derived from the endoderm. Taste buds develop from the mesenchyme but require local signalling to properly differentiate. Some signalling factors for proper development of taste buds besides FGF are: Sonic Hedgehog (SHH), Bone Morphogenetic Proteins (BMPs), Epidermal Growth Factor (EGF).

As mentioned above, this article shows that the anterior and posterior developments of the tongue are derived from embryonic tissues, where the anterior tongue is derived front the ectoderm and the posterior tongue is derived from the endoderm. Secondly, FGF is required to regulate the growth of taste buds, while ''Spry'' genes limit the number of CVP. ''Fgf10''& ''Spry 1&2''work antagonistically through receptor tyrosine kinase (RTK)signalling.

However, the deletion of ''Spry2''led to the increase of CVPs it should be noted that they found that a significant decrease in number of fungiform papillae. Contrastingly, the absence of ''Fgf10'', while leading to the absence of CVPs lead to an increase in number and size of fungiform papillae. Therefore these genes have different effects on the anterior and posterior developing tongue and taste buds.<ref><pubmed>21655085</pubmed></ref>

==Current Research==
We have an evolving understanding of Embryonic Taste development, through the use of state-of-the-art technology and research techniques we are able to make brilliant discoveries that continue to connect the dots of this amazing natural process of human development.
The majority of research in taste development is involving mice, these mammals show similar embryonic pathways to humans and research is performed in ethical and humane methods.

[[File:Histology.jpg|Left|thumb|200px|Image shows histological stains of a mice tongue showing dysplasia]]

'''Synergistic relationships of Six Genes '''

In an animal study using mice by Suzuki Y, Ikeda K, Kawakami K.(2011) Firstly nominating "Six Genes" as a major component in gustatory development, stating that deficiencies in certain Six genes (specifically Six1 & Six4) leads to poor development. Their research also highlights evidence of cooperative relationships between Six genes for normal advance. This experiment involved breeding mice containing exclusively Six1 and Six4 genes and examining the expression of these genes in papillae under high powered microscope observation. Understanding the role of certain genes along with the intrinsic relationships they hold is crucial for the ability to identify possible causes and correction of any abnormalities <ref><pubmed>21978088</pubmed></ref>

'''Neural Crest responsibilities '''

Another Animal Study involving mice explores a new idea of Neural crest (NC) contribution in taste development, specifically the development of papillae and taste buds. Liu HX, Komatsu Y, Mishina Y, Mistretta CM. (2012) suggest that Neural crest cells travel to the location of the tongue in early embryonic stages, gain epithelium phenotypes, multiply and then differentiate to eventually form taste papillae. The experiment involved the comparison of 2 different types of Cre line mice, which both express Cre gene in neural crest protocol, the different distribution patterns where observed in specific regions that NC is responsible for.<ref><pubmed>22659543</pubmed></ref>

'''Augmentation of Endoderm'''

In an animal study conducted by Rothova M, Thompson H, Lickert H, Tucker AS.(2012) exploring the historically debated issue of endoderm contribution to tongue development showed promising evidence that position of taste buds are patterned by the border of ectoderm and endoderm derivative epithelium. This study was accomplished via microscopic examination of previously stained specimens. Concluding endoderm has direct influence on gustatory develoment <ref><pubmed>22581563</pubmed></ref>

'''Changes in Taste Cells over time'''

Research by
Ozdener H, Spielman AI, Rawson NE.(2012) developing a culture which allows taste cells to survive for up to 12 months, empowers researchers to study the processes of proliferation, differentiation and function. This experiment will provide a precidnet for future study of taste cells, as these cells are able to operate and grow normally. <ref><pubmed>22643728</pubmed></ref>

'''Shh key component of taste bud proginators'''

A tamoxifen treatment which supresses Sonic hedgehog (Shh) secretion in mice proving to reduce the number of cells visable within papillae, in contrast mice not treated with tamoxifen showed a mark increase of cells within papillae, these cells are assumed to become taste cells in later development.
Specific mice were bred to trace the destination of taste placode cells, the study concluded that Shh expressing placodes are taste bud proginators which in turn become taste cells within taste buds although do not have any prescuros relationship with pappilae. The results were obtain by examination of mice embryos using Bright-field or multichannel fluorescent images through the use of an "Axiocam CCD camera and Axioplan fluorescence microscope with Axiovision software" a study by Harlow, Yang, Williams, Barlow (2011)<ref><pubmed>PMC2674259</pubmed></ref>

'''WNT family exhibit various roles'''

The WNT gene family has a function of signally proteins for various reason such as development, In 2010 Liu, Staubach Grosse, Walton, Saims, Gumucio, Mistretta explored recent findings on the role of WNT's in tongue and papillae development, Concluding that WNT/β-catenin is essential for fungiform papillae differing to WNT5a which proved to be principle in tongue development. Intrinsic chemical mediators were considered by manipulating a tissue culture and then throughaly examined by scanning photomicrograph. <ref><pubmed>PMC2768563</pubmed></ref>

[http://www.surgicalneurologyint.com/article.asp?issn=2152-7806;year=2012;volume=3;issue=1;spage=23;epage=23;aulast=Manjila]
[[File:Abnormal of tongue.jpg|Left|thumb|200px|Image shows and example of tongue abnormalities, this is called "double tongue" each side has independent movement!]]

==Useful links==

==Glossary==

ectoderm- outer germ layer of embryo

endoderm - inner germ layer of embryo

epithelium - basic animal tissue that is composed of tightly packed cells, usually covering the outer portion of organs

exocystosis - movement of contents out of cell

ganglia - the accumulation of a nerve cell body

growth factor - a substance that stimulates the growth of cells

gustatory - anything that relates to the taste sense

hydrolysis - breakdown of a chemical when it reacts with water

mesoderm - middle germ layer of embryo

mesenchyme - multipotential cells

neural crest - a part of the ectoderm found on both sides of the neural tube

neuron - most simplistic unit of the nervous system

neurotransmitter - chemicals which allow the passing of signals from neuron to neuron via connecting part (synapse)

papillae - small rough surface projection

six genes - a family of genes

Sonic hedgehog (Shh) - signalling protein invloved in normal development

sulcus terminalis - describes a physical transition point separating the anterior 2/3 of the tongue from the posterior 1/3

tamoxifen - hormonal altering drug

==Image gallery==

== References ==
<references/>

==External Links==
{{External Links}}

http://www.webmd.com/oral-health/picture-of-the-tongue

http://www.tutorvista.com/content/biology/biology-iv/nervous-coordination/tongue-structure.php#parts-of-tongue

http://www.cf.ac.uk/biosi/staffinfo/jacob/teaching/sensory/taste.html

--[[User:Z8600021|Mark Hill]] 12:22, 15 August 2012 (EST) Please leave the content listed below the line at the bottom of your project page.

----

{{2012Projects}}

2012 Group Project 3

2012-09-30T04:45:19Z

Z3289738: /* Timeline of Developmental Processes of the Gustatory System */

=Taste Development=

== Introduction ==
**NEED TO ADD**

==History of Discoveries==

{| cellpadding=5 style="border:1px solid #BBB"
|- bgcolor="#faecc8"
|''' Date'''|| '''Significant Discovery'''

|- bgcolor="#faf6ed"
|'''350BC'''
|| Aristotle writes about the basic tastes, sweet and bitter. He also notes that it can be modified by salty and acidic. <ref name="PMID22717400"><pubmed>22717400</pubmed></ref>

|- bgcolor="#faecc8"
|'''1901'''
|| D. Hanig publishes a paper describing taste sensitivity in different regions of the tongue.
''Interesting fact:'' The modern concept of a 'tongue map' is a misinterpretation of this study. <ref name="PMID22717400"/>

|- bgcolor="#faf6ed"
|style=white-space:nowrap|'''1908'''
|Kikunae Ikeda, a professor of the Tokyo Imperial University, discovered and identified the fifth basic taste: umami (savouriness), made palatable by glutamate. <ref><pubmed>12438213</pubmed></ref>
[http://chemse.oxfordjournals.org/content/27/9/847.long New Seasonings]

|- bgcolor="#faecc8"
|style=white-space:nowrap|'''1931-32'''
| A chemist named Arthur Fox and his college noted that they had different sensitivities to the bitter tasting Phenylthiocarbamide (PTC).<ref>Blakeslee AF, Fox AL. Our different taste worlds. J Hered. 1932;23:97–107.</ref> Geneticists later confirm these findings, and discover that non-tasting is a recessive genetic trait. <ref><pubmed>17782493</pubmed></ref>
[http://www.ncbi.nlm.nih.gov/pubmed/17782493 Inherited taste deficiency]

|- bgcolor="#faf6ed"
|style=white-space:nowrap|'''1965'''
|Farbman's study of the developing taste but in rat fungiform papilla was significant in increasing our understanding of taste bud development. <ref><pubmed>14300090</pubmed></ref>
[http://www.sciencedirect.com/science/article/pii/0012160665900400 Electron microscope study of the developing taste bud in rat fungiform papilla.]

|- bgcolor="#faecc8"
|style=white-space:nowrap|'''1992'''
|McLaughlin SK et al. discovery a taste cell-specific G-protein within the taste buds called Gustucon. This protein is later used to mark bitter, umami and sweet cells. <ref><pubmed>1608467 </pubmed></ref>
[http://www.nature.com/nature/journal/v357/n6379/abs/357563a0.html Gustducin is a taste-cell-specific G protein closely related to the transducins]

|- bgcolor="#faf6ed"
|style=white-space:nowrap|'''1995'''
|Barlow et al. experimented with Axolotl salamanders and concluded that taste buds from this species arise exclusively from epithelial tissue, "oropharyngeal epithelium". <ref name="PMID17826760"><pubmed>17826760</pubmed></ref>
[http://www.ncbi.nlm.nih.gov/pubmed/17826760 Embryonic origin of gustatory cranial sensory neurons.]

|- bgcolor="#faecc8"
|style=white-space:nowrap|'''1996'''
| Witt M and Reutter K of the Technical University Dresden in Germany, carried out a transmission electron microscopy study to investigate the embryonic and fetal development of Human taste buds. Their results suggest an "at least dual function of embryonic/fetal taste buds", including non-gustatory, paracrine functions prior to the 14th week and gustatory after the 14th week. <ref name="PMID8955790"><pubmed>8955790</pubmed></ref>
[http://www.ncbi.nlm.nih.gov/pubmed/8955790 Embryonic and early fetal development of human taste buds: a transmission electron microscopical study]

|- bgcolor="#faf6ed"
|style=white-space:nowrap|'''2000'''
|Chandrashekar, J. et al. discover the first taste sonsors, the T2R bitter taste receptors. <ref><pubmed>10761935</pubmed></ref>
[http://www.sciencedirect.com/science/article/pii/S0092867400807060 T2Rs Function as Bitter Taste Receptors]

|- bgcolor="#faecc8"
|style=white-space:nowrap|'''2001'''
|Nelson, G. et al. discover the sweet receptor: a combination of T1R2 and T1R3. <ref><pubmed>11509186</pubmed></ref>
[http://www.ncbi.nlm.nih.gov/pubmed/11509186?dopt=Abstract&holding=npg Mammalian sweet taste receptors.]

|- bgcolor="#faf6ed"
|style=white-space:nowrap|'''2002'''
|Nelson G. et al. discover the amino acid (umami) taste receptor: a combination of T1R1 and T1R3 identified. <ref><pubmed>11894099</pubmed></ref>
[http://www.ncbi.nlm.nih.gov/pubmed/11894099?dopt=Abstract&holding=npg An amino-acid taste receptor]

|- bgcolor="#faecc8"
|style=white-space:nowrap|'''2005'''
|Dyer, J. et al. discover sweet taste receptors in the GI tract. <ref><pubmed>17855558</pubmed></ref>
[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1986582/ Sweet taste signaling in the gut]

|- bgcolor="#faf6ed"
|style=white-space:nowrap|'''2006'''
|Huang, A. L et al. discover cells for sour taste, identified by PKD2L1 (a polycystic kidney disease-like ion channel). <ref><pubmed>16929298</pubmed></ref>
[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1571047/ The Cells and Logic for Mammalian Sour Taste detection]

|- bgcolor="#faecc8"
|style=white-space:nowrap|'''2007'''
|Harlow DE, Barlow LA of the University of Colorado Denver Health Sciences Center provide evidence of the "embryonic origin of gustatory cranial sensory neurons". <ref name="PMID17826760"/>
[http://www.ncbi.nlm.nih.gov/pubmed/17826760 Embryonic origin of gustatory cranial sensory neurons.]

|- bgcolor="#faf6ed"
|style=white-space:nowrap|'''2009'''
|A study by Hevezi P et al, presents "the first comprehensive characterization of gene expression in primate taste buds", as opposed to previous studies which focused on rodents. <ref><pubmed>19636377</pubmed></ref>
[http://www.ncbi.nlm.nih.gov/pubmed/19636377 Genome-wide analysis of gene expression in primate taste buds reveals links to diverse processes]

|- bgcolor="#faecc8"
|style=white-space:nowrap|'''2010'''
|Chandrashekar, J. et al. identify epithelial sodium channel (ENaC) as the sodium-salt taste receptor. <ref><pubmed>20107438</pubmed></ref>
[http://www.ncbi.nlm.nih.gov/pubmed/20107438?dopt=Abstract&holding=npg The cells and peripheral representation of sodium taste in mice]
|}

==Gustatory System==

[[Image:Taste qualities.gif|thumb|The five basic tastes]]

Taste or more appropriately gustation, is a fundamental survival tool in animals as it directs the consumption of essential nutrients. The five tastes that exist within the human gustatory system: salty, sweet, sour, bitter and umami, all signify basic physiological requirements. Salty tastes denote the presence of Na+, an important ion involved in the transportation and retention of water across cell membranes. Sweetness is the recognition of carbohydrates, essential for maintaining optimal brain function and providing the basis for energy production in muscle tissue via ATP hydrolysis. Similarly umami codes for the presence of L-amino acids, especially L-glutamate which is an integral component of protein synthesis.

These different modalities not only function to maintain the proper intake of nutrients within the body but also, by way of aversion, prohibit the consumption of undesired or poisonous materials. The bitter modality for example is generally regarded as displeasing to the human palate. It represents a high acid content which may be a result of foods which have become rotten or are inherently poisonous to the body.<ref name=PMID20696704><pubmed>20696704</pubmed></ref>

Research has historically limited itself to investigating the mechanisms of these five taste qualities though it must be noted many other modalities may exist. Of particular conjecture is the existence of fatty acid recognition. In the past the detection of fat in food has been attributed to somatosensory inputs <ref name=PMID20696704/> from the tongue, that is, the oily feel and texture of fat rather than its actual ‘taste’ allows the brain to encode for its presence. Further research is therefore required to elicit the precise mechanisms of fat detection.

===Cell Biology===

The five taste qualities are not all detected by the same type of receptor cell located within the taste bud. Like rods and cones in the eye which detect different wavelengths of light, there are specific types of receptors for different tastes. For example, sweet, umami and bitter are recognised by Type II G-protein coupled receptors, whereas sour is related to Type III presynaptic cells. The cell type involved in salty taste transduction is unknown however it is known that sodium ions can enter the receptor cell membrane via ion channel permeation.

====Type II receptors====

When a bitter, sweet or umami ligand binds to a type II G-coupled receptor, a cascade of chemical reactions causes the release of Ca2+ which in turn mediates exocystosis of ATP. The function of this ATP is threefold:

# Stimulates gustatory nerve afferents which project to gustatory nuclei in the spinal cord
# Excites Type III presynaptic nerve fibres to release serotonin.
# Has a positive feedback effect on type II receptor cells, increasing the level of ATP production.

The role of serotonin is believed to be in the form of lateral inhibition i.e. when a bitter quality is recognised, adjacent receptors for sweetness are deactivated and thus the two tastes may be clearly differentiated. It also has a negative feedback effect on receptor cells, inhibiting umami, bitter and sweet taste transduction.

==Taste Map==
[[Image:Taste map.png|thumb|left|250px|Obsolete idea of the tongue map]]
The idea of a tongue map has disseminated through society for many years. This concept purports that different areas of the tongue are specialised to detect either sweet, salty, sour and bitter tastes. Recent research however has completely nullified such claims and suggests instead that different forms of taste are recognised all over the tongue as well as via the palate. Thus the term ''taste map'' has come to take on a new meaning and that is, the precise areas of taste modalities processing in areas of cortex and its subsequent neural inputs.

===Neural Pathways===

'''First order neurons''' - From the receptors located in the taste buds, gustatory nerve afferents project to the ipsilateral rostral 1/3 of the nucleus tractus solitarius (NTS), located in the medulla. This rostral 1/3 is commonly referred to as the ''gustatory nucleus''.

The ''gustatory nucleus'' receives input from cranial nerves VII (''Facial n.''), IX (''Hypglossal n.''), and X (''Vagus n.'') via special visceral afferent (SVA) nerve fibres. A summary of their functions is as follows:

* ''Facial nerve n''. - carries taste information from the anterior 2/3 of the tongue.
* ''Hypoglossal n.'' - carries taste information from the posterior 1/3 of the tongue.
* ''Vagus n''. - carries taste information from the palate

'''Second order neurons''' - From the NTS second order neurons carry taste information to the Ventral posteromedial (VPM) nucleus in the thalamus.<ref name=PMID21885776/>

Copious scientific conjecture surrounds how each taste modality is transmitted to the brain. The ‘labelled-line’ hypothesis suggests that there are taste specific neurons which exclusively carry that taste modality to cortical areas. In analogous terms it can be viewed like the pipelines leading toward a house. Each pipeline carries its own utility, there is one for gas, another for water and finally for electricity with each terminating in slightly different areas of the house. In the same way, on the tongues there are different receptors for each taste which concurrently have individual nerve tracts leading to the primary gustatory cortex.

Contrapuntally there is electrophysiological evidence that single nerve afferents carry multiple modalities. These studies show one nerve afferent may have both a strong and a weak activation in response to a multiple taste stimuli.

===Cortical Areas===

[[Image:Primary gustatory cortex.png|thumb|Primary gustatory cortex]]

The location of the taste perception centres has been observed via functional magnetic resonance imaging (fMRI) studies. The primary taste cortex has been identified as being located in the anterior insula/frontal operculum (I/fO)<ref name=PMID22245354><pubmed>22245354</pubmed></ref>, with the secondary taste cortex in the caudolateral orbitofrontal cortex.<ref name=PMID21305668><pubmed>21305668</pubmed></ref> Within the insula there are further subdivisions related to each taste modality. Two photon calcium imaging research has outlined certain ’hot-spots’ of activation which are clearly delineated in relation to each taste. For example, the bitter modality is represented on the insula cortex approximately 1mm posterior to the middle cerebral artery whereas the sweet modality is represented 2.5mm rostrodorsal to the bitter field with no apparent overlap.<ref name=PMID21885776><pubmed>21885776</pubmed></ref> These findings lend weight to the idea that there is only one receptor for each taste quality.

It is interesting to note the relationship between taste and the reward centres of the brain. There is evidence of neural input to the ventral tegmental area (the origin of the mesolimbic dopaminergic reward pathway) and nucleus accumbens (involved in the conversion of motivation into physical action).<ref name=PMID21885776/> Neural connections such as this provide the foundations in explaining concepts such as flavour learning and preference. It may also give some insight into chronic problems such as food addiction and craving. As of yet however the gustatory neural network is not well understood and more research is required to elucidate the relationship between pleasure and taste sensation

==Timeline of Developmental Processes of the Gustatory System==

{| cellpadding=5 style="border:1px solid #BBB"
|- bgcolor="#89CFF0"
|'''Postovulatory Week'''||'''Description'''||'''Image'''
|- bgcolor="#BCD4E6"
|'''Week 6''' ||
The surface of the developing tongue is covered by nearly flat epitheliuem (Figure 1). <ref name="PMID9455607"><pubmed>9455607</pubmed></ref> The first gustatory papillae of the tongue appears in the caudal midline near the foramen caecum and the first circumvallate papilla develop on the dorsal midline <ref name=PMID9455607/> .
||
image
|- bgcolor="#89CFF0"
| '''Weeks 6 to 7'''||
Nerve fibres approach the basal lamina of lingual epithelium <ref name=PMID8955790><pubmed>8955790</pubmed></ref>. At this stage the lingual epithelium consists of two to three cell layers and there is not yet any sign of cell specializations indicating early taste bud formation<ref name=PMID8955790/>.
||
Image
|- bgcolor="#BCD4E6"
| '''Week 7 '''||
A series of epithelial swellings in the anterior part and midline of the tongue indicate early forming fungiform papillae (figure 2) <ref name=PMID9455607/>.
||
Image
|- bgcolor="#89CFF0"
| ''' Week 8 ''' ||
The lingual epithelium shows first signs of taste bud development as nerve fibres penetrate epithelial basal lamina <ref name=PMID8955790/> and form synapses with taste bud progenitor cells. The synapses reach a maximum around the 12th to 13th week <ref name=PMID8955790/>. However, at this time these cells are still poorly differentiated, elongated epithelial cells <ref name=PMID8955790/> . The synapses demonstrate the neuronal connection between the taste bud primordium and the central nervous system <ref name=PMID8955790/>. Ciliated cells also appear around the 8th week, however the significance of these cells which are scattered randomly across the lingual surface remains unclear <ref name=PMID8955790/>.
||
Image
|- bgcolor="#BCD4E6"
|''' Weeks 8-9''' ||
“By this stage the top surface of circumvallate papillae usually contains a taste pit partly filled with microvilli of presumed underlying taste bud cells” (Figure 10) <ref name=PMID9455607/>
||
Image
|- bgcolor="#89CFF0"
|''' Weeks 10-11''' ||
At this stage, the lingual epithelium compromises of about four cell layers, and the first shallow grooves above the taste bud primordium are developed <ref name=PMID8955790/>.

Fungiform papillae appear on the lateral margins and the tip of the tongue <ref name=PMID9455607/>, containing taste bud primordial that display the first signs of a primitive pore formation <ref name=PMID8955790/>.

Untypically differentiated apical cellular processes extend onto the surface <ref name=PMID9455607/>

Some taste bud primordial contain cells that perforate the covering epithelial later with short, broad untypically differentiated apical cellular processes. (Figure 3,4) <ref name=PMID8955790/> <ref name=PMID9455607/>
||
Image
|- bgcolor="#BCD4E6"
|''' Week 12 ''' ||
Taste bud cells are more clearly differentiated into epithelial cell types II and III <ref name=PMID8955790/>.
||
Image
|- bgcolor="#89CFF0"
|''' Weeks 12-13 ''' ||
By this stage the taste bud primordial are all located on the top of dermal papillae (Fig 6a) <ref name=PMID8955790/>. There is also maximum synapses between cells and afferent nerve fibres, which intermingle with each other to form a plexus-like structure <ref name=PMID8955790/>.
||
Image
|- bgcolor="#BCD4E6"
|''' Weeks 14 -15 ''' ||
The shape of the taste buds primordial begins to resemble those of adult taste buds <ref name=PMID8955790/>. By the 14th week the taste pores develop as the taste pits are filled by microvilli <ref name=PMID8955790/>, indicating the possibility that the taste buds begin their gustatory function <ref name=PMID8955790/>, however they still lack an electron-dense mucous material (Fig.10) <ref name=PMID8955790/>. The tastebuds only achieve a fully developed function in week 15 of gestation with the development of type I cells to produce the mucous material in the taste pit <ref name=PMID8955790/>.
||
Image
|}

== Human Weekly Development - Two Prominent Studies ==
Martin Witt and Klaus Reutter of the University of Tubingen in Germany published two prominent studies regarding developing taste buds in humans. Their first study in 1996 was a transmission electron microscopical (TEM) study of the taste bud primordium and its morphological changes during the 8th-15th postovulatory week. Their next study in 1997 built on their previous findings by using Scanning Electron Microscopy (SEM) to observe the development of gustatory papillae during postovulatory weeks 6-15.

The findings of these two studies are summarized in the table below. The figures provided relate to the images on their respective research papers.

===Timeline of Developmental Processes of the Gustatory System===
{| cellpadding=5 style="border:1px solid #BBB"
|- bgcolor="#89CFF0"
|'''Postovulatory Week'''||'''Description'''||'''Image'''

|- bgcolor="#BCD4E6"
|'''Week 6''' ||
The surface of the developing tongue is covered by nearly flat epithelium (1997, Figure 1). The first gustatory papillae of the tongue appear in the caudal midline near the foramen caecum and the first circumvallate papilla develops on the dorsal midline. <ref name="PMID9455607"><pubmed>9455607</pubmed></ref>
||
image

|- bgcolor="#89CFF0"
| '''Weeks 6 to 7'''||
Nerve fibres approach the basal lamina of lingual epithelium. At this stage the lingual epithelium consists of two to three cell layers and there is not yet any sign of cell specializations indicating early taste bud formation. <ref name=PMID8955790/>
||
Image

|- bgcolor="#BCD4E6"
| '''Week 7 '''||
A series of irregular epithelial swellings in the anterior part and marginal parts of the tongue indicate early forming fungiform papillae. Furthermore, a V-like lane is observed anterior to the sulcus terminalis, which represents a smooth surface for developing circumvallate papillae (1997, Figure 2). Witt M et al observe that these circumvallate papillae are larger than the developing fungiform papillae of the same age, later noting that the fungiform papillae tend to increase in size over the 8-15th weeks of gestation, whilst the size of vallate papillae tend to remain constant during this period. <ref name=PMID9455607/>
||
Image

|- bgcolor="#89CFF0"
| ''' Week 8 ''' ||
* The taste bud primordium are still differentiated, elongated epithelial cells, resting on a slightly developed core of young dermal papilla.
* The lingual epithelium shows first signs of taste bud development as nerve fibres coming from the dermal papilla penetrate the epithelial basal lamina and form synapses with taste bud progenitor cells (1996, Figure 1). These synapses demonstrate the neuronal connection between the taste bud primordium and the central nervous system, reaching a maximum around the 12th to 13th week. However, it is important to note that at this time these cells are still poorly differentiated, elongated epithelial cells.
* Ciliated cells also appear around the 8th week, however the significance of these cells which are scattered randomly across the lingual surface remains unclear. <ref name=PMID8955790/>
||
Image

|- bgcolor="#BCD4E6"
|''' Week 9''' ||
By this stage, although a taste pore is not present, the surface of circumvallate papillae usually contains a taste pit partly filled with microvillus-like processes from the underlying taste bud cells (1997, Figure 10). <ref name=PMID9455607/>
||
Image

|- bgcolor="#89CFF0"
|''' Weeks 10-11''' ||
At this stage, the lingual epithelium compromises of about four cell layers, and the first shallow grooves above the taste bud primordium are developed. Fungiform papillae appear on the lateral margins and the tip of the tongue, containing taste bud primordial that display the first signs of a primitive pore formation (1996, Figure 6). <ref name=PMID8955790/>
||
Image

|- bgcolor="#BCD4E6"
|''' Week 12 ''' ||
Taste bud cells are more clearly differentiated into epithelial cell types II and III. <ref name=PMID8955790/>
||
Image

|- bgcolor="#89CFF0"
|''' Weeks 12-13 ''' ||
At this stage the taste bud primordial are all located on the top of dermal papillae. There is also maximum synapses between cells and afferent nerve fibres, which intermingle with each other to form a plexus-like structure (1996, Figure 6a). <ref name=PMID8955790/>
||
Image

|- bgcolor="#BCD4E6"
|''' Weeks 14 -15 ''' ||
The shape and size of the taste buds primordial begins to resemble those of adult taste buds (1996, Figure 9). By the 14th week the taste pores develop as the taste pits are filled by microvilli, and bubble like vesicles indicate the secretory activity of these cells (1996, Figure 10). However, the tastebuds only achieve a fully developed function in week 15 of gestation with the development of type I cells to produce the mucous material in the taste pit. <ref name=PMID8955790/>
||
Image
|}

==Adult Tongue and Taste Buds – Structure and Function==

'''Structure'''

The tongue is located on the floor of the oral cavity, It is a muscular structure with sensory units crowning. The tongue is divided into an anterior two thirds and a posterior one third. These regions are divided by a V-shaped groove at the back of the tongue (sulcus terminalis). The anterior two thirds of the tongue is covered by stratified squamous epithelium, It contains a roughened surface and has projections called papillae that vary in shape and number.

''''The Image Below is a very simplistic Diagram of the surface of the Tongue showing the locations of the different papillae and other important features'''

{|
| [[Image:Drawing of Tongue.png|500px]]

'''Papillae'''
[[File:Papillae.jpg|Left|thumb|200px|Close up of Human Tongue Papillae]]

There are 4 types of papillae on the tongue.
The most numerous papillae are the filiform papillae, which function to provide a surface that aids in holding food on the tongue during chewing but do not contain taste buds. The larger, less numerous fungiform papillae which contain taste buds, as do foliate papillae. Circumvallate papillae form a wide V at the sulcus terminalis also containing taste bus. There are no papillae or taste buds located on the posterior third of the tongue, having mucosal folds and the lingual tonsils instead.

'''Function'''

The tongue is for tasting, swallowing, and speech.
The functional unit of the taste bud is a taste cell, there are between 50 and 100 taste cells in each taste bud these taste cells represent all 5 different tastes. Historically is was believed that different areas of the tongue were responsible for different taste sensations although this has since been disregarded.[http://users.rcn.com/jkimball.ma.ultranet/BiologyPages/W/Welcome.html] The papillae contain taste buds which are connected to the oral cavity via a taste pore, the function of the taste bud is to transmit a chemical signal from the oral cavity to a taste cell, this chemical signal is the converted into an electrical impulse and delivered to the brain via nerve fibres for interpretation.

'''The Image Below is a very simplistic Hand drawn Diagram of a taste bud, in an extreme close up, cross section view of the the taste bud unit, not to scale'''

[[File:Taste_bud_1.jpg]]

==Abnormalities==

===Knocking out P2X Receptors===

[[File:Image of taste being evoked by visualising ATP release.jpeg|Left|thumb|200px|Evoking taste - ATP release in tongue]]

Gustatory abnormalities has not been widely researched and what has been researched has been through animal testing, most commonly we have found on mice.

In Huang, 2008 this team used the release of the neurotransmitter, ATP (adenosine triphosphate) as a quantitative measurement of gustatory sensation and taste. This was done by using a comparison of wild type (WT) and double knockout (DKO) mice. P2X receptors, P2X2 and P2X3 were knocked out in the DKO mice. The premise of this article was that knocking out P2X receptors reduces transmitter secretion of ATP in taste buds, therefore they cannot taste.

It should be noted that the taste buds in DKO are functional, but are not stimulated by the administration of tastants.

The transmission of release of ATP is secretion through gap junction hemichannels (pannexin 1 gap junction).

When both P2X2 and P2X3 are knocked out, no taste is elicited. However they found that if either P2X2 OR P2X3 was knocked out there was a taste response. So the inference made from this is that if one of the two receptors from the P2X family was knocked out there still can have taste response. The WT mice showed significant stimulation by tastants whereas DKO had little to no stimulation of ATP release.<ref><pubmed>21940456</pubmed></ref>

===FGF signalling and genes===

Sprouty, or ''Srpy'', genes have been related to regulating the development of circumvillate papillae (CVP). The CVP are large dome shaped papillae, which form a 'V' just in front of the terminal sulcus.

By knocking out ''Spry'' genes using mice which had ''Spry1'' and ''Spry2'' knocked out showed that the number of CVP doubled. However, when Fibroblast Growth Factor gene ("Fgf10") was absent, the number of CVP was significantly reduced, if not completely absent. The correlation between ''Spry1/2'' and ''Fgf10'' is that ''Spry1/2'' antagonises "Fgf10" to limit the size of the CVP progenitor placode. Exclusive expression of ''Fgf10'' in the mesenchyme is necessary for the formation of CVP.

'''This image shows the CVP stained with H&E and scanned by Scanning Electron Microscope (SEM)'''
[[File:CVP of WT(top) and DKO(bottom) mice with H&E and SEM.png]]

'''This image shows the location of the CVP and the increased number in DKO mice by SEM'''
[[File:Mouse circumvallate papilla 01.jpg|300px]]

Taste buds develop from the mesenchyme but require local signalling to properly differentiate. Some signalling factors for proper development of taste buds besides FGF are: Sonic Hedgehog (SHH), Bone Morphogenetic Proteins (BMPs), Epidermal Growth Factor (EGF).

Additionally, this proves that the anterior and posterior developments of the tongue are derived from embryonic tissues, where the anterior tongue is derived from the ectoderm and the posterior tongue is derived from the endoderm. Taste buds develop from the mesenchyme but require local signalling to properly differentiate. Some signalling factors for proper development of taste buds besides FGF are: Sonic Hedgehog (SHH), Bone Morphogenetic Proteins (BMPs), Epidermal Growth Factor (EGF).

As mentioned above, this article shows that the anterior and posterior developments of the tongue are derived from embryonic tissues, where the anterior tongue is derived front the ectoderm and the posterior tongue is derived from the endoderm. Secondly, FGF is required to regulate the growth of taste buds, while ''Spry'' genes limit the number of CVP. ''Fgf10''& ''Spry 1&2''work antagonistically through receptor tyrosine kinase (RTK)signalling.

However, the deletion of ''Spry2''led to the increase of CVPs it should be noted that they found that a significant decrease in number of fungiform papillae. Contrastingly, the absence of ''Fgf10'', while leading to the absence of CVPs lead to an increase in number and size of fungiform papillae. Therefore these genes have different effects on the anterior and posterior developing tongue and taste buds.<ref><pubmed>21655085</pubmed></ref>

==Current Research==
We have an evolving understanding of Embryonic Taste development, through the use of state-of-the-art technology and research techniques we are able to make brilliant discoveries that continue to connect the dots of this amazing natural process of human development.
The majority of research in taste development is involving mice, these mammals show similar embryonic pathways to humans and research is performed in ethical and humane methods.

[[File:Histology.jpg|Left|thumb|200px|Image shows histological stains of a mice tongue showing dysplasia]]

'''Synergistic relationships of Six Genes '''

In an animal study using mice by Suzuki Y, Ikeda K, Kawakami K.(2011) Firstly nominating "Six Genes" as a major component in gustatory development, stating that deficiencies in certain Six genes (specifically Six1 & Six4) leads to poor development. Their research also highlights evidence of cooperative relationships between Six genes for normal advance. This experiment involved breeding mice containing exclusively Six1 and Six4 genes and examining the expression of these genes in papillae under high powered microscope observation. Understanding the role of certain genes along with the intrinsic relationships they hold is crucial for the ability to identify possible causes and correction of any abnormalities <ref><pubmed>21978088</pubmed></ref>

'''Neural Crest responsibilities '''

Another Animal Study involving mice explores a new idea of Neural crest (NC) contribution in taste development, specifically the development of papillae and taste buds. Liu HX, Komatsu Y, Mishina Y, Mistretta CM. (2012) suggest that Neural crest cells travel to the location of the tongue in early embryonic stages, gain epithelium phenotypes, multiply and then differentiate to eventually form taste papillae. The experiment involved the comparison of 2 different types of Cre line mice, which both express Cre gene in neural crest protocol, the different distribution patterns where observed in specific regions that NC is responsible for.<ref><pubmed>22659543</pubmed></ref>

'''Augmentation of Endoderm'''

In an animal study conducted by Rothova M, Thompson H, Lickert H, Tucker AS.(2012) exploring the historically debated issue of endoderm contribution to tongue development showed promising evidence that position of taste buds are patterned by the border of ectoderm and endoderm derivative epithelium. This study was accomplished via microscopic examination of previously stained specimens. Concluding endoderm has direct influence on gustatory develoment <ref><pubmed>22581563</pubmed></ref>

'''Changes in Taste Cells over time'''

Research by
Ozdener H, Spielman AI, Rawson NE.(2012) developing a culture which allows taste cells to survive for up to 12 months, empowers researchers to study the processes of proliferation, differentiation and function. This experiment will provide a precidnet for future study of taste cells, as these cells are able to operate and grow normally. <ref><pubmed>22643728</pubmed></ref>

'''Shh key component of taste bud proginators'''

A tamoxifen treatment which supresses Sonic hedgehog (Shh) secretion in mice proving to reduce the number of cells visable within papillae, in contrast mice not treated with tamoxifen showed a mark increase of cells within papillae, these cells are assumed to become taste cells in later development.
Specific mice were bred to trace the destination of taste placode cells, the study concluded that Shh expressing placodes are taste bud proginators which in turn become taste cells within taste buds although do not have any prescuros relationship with pappilae. The results were obtain by examination of mice embryos using Bright-field or multichannel fluorescent images through the use of an "Axiocam CCD camera and Axioplan fluorescence microscope with Axiovision software" a study by Harlow, Yang, Williams, Barlow (2011)<ref><pubmed>PMC2674259</pubmed></ref>

'''WNT family exhibit various roles'''

The WNT gene family has a function of signally proteins for various reason such as development, In 2010 Liu, Staubach Grosse, Walton, Saims, Gumucio, Mistretta explored recent findings on the role of WNT's in tongue and papillae development, Concluding that WNT/β-catenin is essential for fungiform papillae differing to WNT5a which proved to be principle in tongue development. Intrinsic chemical mediators were considered by manipulating a tissue culture and then throughaly examined by scanning photomicrograph. <ref><pubmed>PMC2768563</pubmed></ref>

[http://www.surgicalneurologyint.com/article.asp?issn=2152-7806;year=2012;volume=3;issue=1;spage=23;epage=23;aulast=Manjila]
[[File:Abnormal of tongue.jpg|Left|thumb|200px|Image shows and example of tongue abnormalities, this is called "double tongue" each side has independent movement!]]

==Useful links==

==Glossary==

ectoderm- outer germ layer of embryo

endoderm - inner germ layer of embryo

epithelium - basic animal tissue that is composed of tightly packed cells, usually covering the outer portion of organs

exocystosis - movement of contents out of cell

ganglia - the accumulation of a nerve cell body

growth factor - a substance that stimulates the growth of cells

gustatory - anything that relates to the taste sense

hydrolysis - breakdown of a chemical when it reacts with water

mesoderm - middle germ layer of embryo

mesenchyme - multipotential cells

neural crest - a part of the ectoderm found on both sides of the neural tube

neuron - most simplistic unit of the nervous system

neurotransmitter - chemicals which allow the passing of signals from neuron to neuron via connecting part (synapse)

papillae - small rough surface projection

six genes - a family of genes

Sonic hedgehog (Shh) - signalling protein invloved in normal development

sulcus terminalis - describes a physical transition point separating the anterior 2/3 of the tongue from the posterior 1/3

tamoxifen - hormonal altering drug

==Image gallery==

== References ==
<references/>

==External Links==
{{External Links}}

http://www.webmd.com/oral-health/picture-of-the-tongue

http://www.tutorvista.com/content/biology/biology-iv/nervous-coordination/tongue-structure.php#parts-of-tongue

http://www.cf.ac.uk/biosi/staffinfo/jacob/teaching/sensory/taste.html

--[[User:Z8600021|Mark Hill]] 12:22, 15 August 2012 (EST) Please leave the content listed below the line at the bottom of your project page.

----

{{2012Projects}}

2012 Group Project 3

2012-09-29T04:26:15Z

Z3289738: /* Timeline of Developmental Processes of the Gustatory System */

=Taste Development=

== Introduction ==
**NEED TO ADD**

==History of Discoveries==

{| cellpadding=5 style="border:1px solid #BBB"
|- bgcolor="#faecc8"
|''' Date'''|| '''Significant Discovery'''

|- bgcolor="#faf6ed"
|'''350BC'''
|| Aristotle writes about the basic tastes, sweet and bitter. He also notes that it can be modified by salty and acidic. <ref name="PMID22717400"><pubmed>22717400</pubmed></ref>

|- bgcolor="#faecc8"
|'''1901'''
|| D. Hanig publishes a paper describing taste sensitivity in different regions of the tongue.
''Interesting fact:'' The modern concept of a 'tongue map' is a misinterpretation of this study. <ref name="PMID22717400"/>

|- bgcolor="#faf6ed"
|style=white-space:nowrap|'''1908'''
|Kikunae Ikeda, a professor of the Tokyo Imperial University, discovered and identified the fifth basic taste: umami (savouriness), made palatable by glutamate. <ref><pubmed>12438213</pubmed></ref>
[http://chemse.oxfordjournals.org/content/27/9/847.long New Seasonings]

|- bgcolor="#faecc8"
|style=white-space:nowrap|'''1931-32'''
| A chemist named Arthur Fox and his college noted that they had different sensitivities to the bitter tasting Phenylthiocarbamide (PTC).<ref>Blakeslee AF, Fox AL. Our different taste worlds. J Hered. 1932;23:97–107.</ref> Geneticists later confirm these findings, and discover that non-tasting is a recessive genetic trait. <ref><pubmed>17782493</pubmed></ref>
[http://www.ncbi.nlm.nih.gov/pubmed/17782493 Inherited taste deficiency]

|- bgcolor="#faf6ed"
|style=white-space:nowrap|'''1965'''
|Farbman's study of the developing taste but in rat fungiform papilla was significant in increasing our understanding of taste bud development. <ref><pubmed>14300090</pubmed></ref>
[http://www.sciencedirect.com/science/article/pii/0012160665900400 Electron microscope study of the developing taste bud in rat fungiform papilla.]

|- bgcolor="#faecc8"
|style=white-space:nowrap|'''1992'''
|McLaughlin SK et al. discovery a taste cell-specific G-protein within the taste buds called Gustucon. This protein is later used to mark bitter, umami and sweet cells. <ref><pubmed>1608467 </pubmed></ref>
[http://www.nature.com/nature/journal/v357/n6379/abs/357563a0.html Gustducin is a taste-cell-specific G protein closely related to the transducins]

|- bgcolor="#faf6ed"
|style=white-space:nowrap|'''1995'''
|Barlow et al. experimented with Axolotl salamanders and concluded that taste buds from this species arise exclusively from epithelial tissue, "oropharyngeal epithelium". <ref name="PMID17826760"><pubmed>17826760</pubmed></ref>
[http://www.ncbi.nlm.nih.gov/pubmed/17826760 Embryonic origin of gustatory cranial sensory neurons.]

|- bgcolor="#faecc8"
|style=white-space:nowrap|'''1996'''
| Witt M and Reutter K of the Technical University Dresden in Germany, carried out a transmission electron microscopy study to investigate the embryonic and fetal development of Human taste buds. Their results suggest an "at least dual function of embryonic/fetal taste buds", including non-gustatory, paracrine functions prior to the 14th week and gustatory after the 14th week. <ref name="PMID8955790"><pubmed>8955790</pubmed></ref>
[http://www.ncbi.nlm.nih.gov/pubmed/8955790 Embryonic and early fetal development of human taste buds: a transmission electron microscopical study]

|- bgcolor="#faf6ed"
|style=white-space:nowrap|'''2000'''
|Chandrashekar, J. et al. discover the first taste sonsors, the T2R bitter taste receptors. <ref><pubmed>10761935</pubmed></ref>
[http://www.sciencedirect.com/science/article/pii/S0092867400807060 T2Rs Function as Bitter Taste Receptors]

|- bgcolor="#faecc8"
|style=white-space:nowrap|'''2001'''
|Nelson, G. et al. discover the sweet receptor: a combination of T1R2 and T1R3. <ref><pubmed>11509186</pubmed></ref>
[http://www.ncbi.nlm.nih.gov/pubmed/11509186?dopt=Abstract&holding=npg Mammalian sweet taste receptors.]

|- bgcolor="#faf6ed"
|style=white-space:nowrap|'''2002'''
|Nelson G. et al. discover the amino acid (umami) taste receptor: a combination of T1R1 and T1R3 identified. <ref><pubmed>11894099</pubmed></ref>
[http://www.ncbi.nlm.nih.gov/pubmed/11894099?dopt=Abstract&holding=npg An amino-acid taste receptor]

|- bgcolor="#faecc8"
|style=white-space:nowrap|'''2005'''
|Dyer, J. et al. discover sweet taste receptors in the GI tract. <ref><pubmed>17855558</pubmed></ref>
[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1986582/ Sweet taste signaling in the gut]

|- bgcolor="#faf6ed"
|style=white-space:nowrap|'''2006'''
|Huang, A. L et al. discover cells for sour taste, identified by PKD2L1 (a polycystic kidney disease-like ion channel). <ref><pubmed>16929298</pubmed></ref>
[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1571047/ The Cells and Logic for Mammalian Sour Taste detection]

|- bgcolor="#faecc8"
|style=white-space:nowrap|'''2007'''
|Harlow DE, Barlow LA of the University of Colorado Denver Health Sciences Center provide evidence of the "embryonic origin of gustatory cranial sensory neurons". <ref name="PMID17826760"/>
[http://www.ncbi.nlm.nih.gov/pubmed/17826760 Embryonic origin of gustatory cranial sensory neurons.]

|- bgcolor="#faf6ed"
|style=white-space:nowrap|'''2009'''
|A study by Hevezi P et al, presents "the first comprehensive characterization of gene expression in primate taste buds", as opposed to previous studies which focused on rodents. <ref><pubmed>19636377</pubmed></ref>
[http://www.ncbi.nlm.nih.gov/pubmed/19636377 Genome-wide analysis of gene expression in primate taste buds reveals links to diverse processes]

|- bgcolor="#faecc8"
|style=white-space:nowrap|'''2010'''
|Chandrashekar, J. et al. identify epithelial sodium channel (ENaC) as the sodium-salt taste receptor. <ref><pubmed>20107438</pubmed></ref>
[http://www.ncbi.nlm.nih.gov/pubmed/20107438?dopt=Abstract&holding=npg The cells and peripheral representation of sodium taste in mice]
|}

==Gustatory System==

[[Image:Taste qualities.gif|thumb|The five basic tastes]]

Taste or more appropriately gustation, is a fundamental survival tool in animals as it directs the consumption of essential nutrients. The five tastes that exist within the human gustatory system: salty, sweet, sour, bitter and umami, all signify basic physiological requirements. Salty tastes denote the presence of Na+, an important ion involved in the transportation and retention of water across cell membranes. Sweetness is the recognition of carbohydrates, essential for maintaining optimal brain function and providing the basis for energy production in muscle tissue via ATP hydrolysis. Similarly umami codes for the presence of L-amino acids, especially L-glutamate which is an integral component of protein synthesis.

These different modalities not only function to maintain the proper intake of nutrients within the body but also, by way of aversion, prohibit the consumption of undesired or poisonous materials. The bitter modality for example is generally regarded as displeasing to the human palate. It represents a high acid content which may be a result of foods which have become rotten or are inherently poisonous to the body.<ref name=PMID20696704><pubmed>20696704</pubmed></ref>

Research has historically limited itself to investigating the mechanisms of these five taste qualities though it must be noted many other modalities may exist. Of particular conjecture is the existence of fatty acid recognition. In the past the detection of fat in food has been attributed to somatosensory inputs <ref name=PMID20696704/> from the tongue, that is, the oily feel and texture of fat rather than its actual ‘taste’ allows the brain to encode for its presence. Further research is therefore required to elicit the precise mechanisms of fat detection.

===Cell Biology===

The five taste qualities are not all detected by the same type of receptor cell located within the taste bud. Like rods and cones in the eye which detect different wavelengths of light, there are specific types of receptors for different tastes. For example, sweet, umami and bitter are recognised by Type II G-protein coupled receptors, whereas sour is related to Type III presynaptic cells. The cell type involved in salty taste transduction is unknown however it is known that sodium ions can enter the receptor cell membrane via ion channel permeation.

====Type II receptors====

When a bitter, sweet or umami ligand binds to a type II G-coupled receptor, a cascade of chemical reactions causes the release of Ca2+ which in turn mediates exocystosis of ATP. The function of this ATP is threefold:

# Stimulates gustatory nerve afferents which project to gustatory nuclei in the spinal cord
# Excites Type III presynaptic nerve fibres to release serotonin.
# Has a positive feedback effect on type II receptor cells, increasing the level of ATP production.

The role of serotonin is believed to be in the form of lateral inhibition i.e. when a bitter quality is recognised, adjacent receptors for sweetness are deactivated and thus the two tastes may be clearly differentiated. It also has a negative feedback effect on receptor cells, inhibiting umami, bitter and sweet taste transduction.

==Taste Map==
[[Image:Taste map.png|thumb|left|250px|Obsolete idea of the tongue map]]
The idea of a tongue map has disseminated through society for many years. This concept purports that different areas of the tongue are specialised to detect either sweet, salty, sour and bitter tastes. Recent research however has completely nullified such claims and suggests instead that different forms of taste are recognised all over the tongue as well as via the palate. Thus the term ''taste map'' has come to take on a new meaning and that is, the precise areas of taste modalities processing in areas of cortex and its subsequent neural inputs.

===Neural Pathways===

'''First order neurons''' - From the receptors located in the taste buds, gustatory nerve afferents project to the ipsilateral rostral 1/3 of the nucleus tractus solitarius (NTS), located in the medulla. This rostral 1/3 is commonly referred to as the ''gustatory nucleus''.

The ''gustatory nucleus'' receives input from cranial nerves VII (''Facial n.''), IX (''Hypglossal n.''), and X (''Vagus n.'') via special visceral afferent (SVA) nerve fibres. A summary of their functions is as follows:

* ''Facial nerve n''. - carries taste information from the anterior 2/3 of the tongue.
* ''Hypoglossal n.'' - carries taste information from the posterior 1/3 of the tongue.
* ''Vagus n''. - carries taste information from the palate

'''Second order neurons''' - From the NTS second order neurons carry taste information to the Ventral posteromedial (VPM) nucleus in the thalamus.<ref name=PMID21885776/>

Copious scientific conjecture surrounds how each taste modality is transmitted to the brain. The ‘labelled-line’ hypothesis suggests that there are taste specific neurons which exclusively carry that taste modality to cortical areas. In analogous terms it can be viewed like the pipelines leading toward a house. Each pipeline carries its own utility, there is one for gas, another for water and finally for electricity with each terminating in slightly different areas of the house. In the same way, on the tongues there are different receptors for each taste which concurrently have individual nerve tracts leading to the primary gustatory cortex.

Contrapuntally there is electrophysiological evidence that single nerve afferents carry multiple modalities. These studies show one nerve afferent may have both a strong and a weak activation in response to a multiple taste stimuli.

===Cortical Areas===

[[Image:Primary gustatory cortex.png|thumb|Primary gustatory cortex]]

The location of the taste perception centres has been observed via functional magnetic resonance imaging (fMRI) studies. The primary taste cortex has been identified as being located in the anterior insula/frontal operculum (I/fO)<ref name=PMID22245354><pubmed>22245354</pubmed></ref>, with the secondary taste cortex in the caudolateral orbitofrontal cortex.<ref name=PMID21305668><pubmed>21305668</pubmed></ref> Within the insula there are further subdivisions related to each taste modality. Two photon calcium imaging research has outlined certain ’hot-spots’ of activation which are clearly delineated in relation to each taste. For example, the bitter modality is represented on the insula cortex approximately 1mm posterior to the middle cerebral artery whereas the sweet modality is represented 2.5mm rostrodorsal to the bitter field with no apparent overlap.<ref name=PMID21885776><pubmed>21885776</pubmed></ref> These findings lend weight to the idea that there is only one receptor for each taste quality.

It is interesting to note the relationship between taste and the reward centres of the brain. There is evidence of neural input to the ventral tegmental area (the origin of the mesolimbic dopaminergic reward pathway) and nucleus accumbens (involved in the conversion of motivation into physical action).<ref name=PMID21885776/> Neural connections such as this provide the foundations in explaining concepts such as flavour learning and preference. It may also give some insight into chronic problems such as food addiction and craving. As of yet however the gustatory neural network is not well understood and more research is required to elucidate the relationship between pleasure and taste sensation

==Timeline of Developmental Processes of the Gustatory System==

{| cellpadding=5 style="border:1px solid #BBB"
|- bgcolor="#89CFF0"
|'''Postovulatory Week'''||'''Description'''||'''Image'''
|- bgcolor="#BCD4E6"
|'''Week 6''' ||
The surface of the developing tongue is covered by nearly flat epitheliuem (Figure 1). <ref name="PMID9455607"><pubmed>9455607</pubmed></ref> The first gustatory papillae of the tongue appears in the caudal midline near the foramen caecum and the first circumvallate papilla develop on the dorsal midline <ref name=PMID9455607/> .
||
image
|- bgcolor="#89CFF0"
| '''Weeks 6 to 7'''||
Nerve fibres approach the basal lamina of lingual epithelium <ref name=PMID8955790><pubmed>8955790</pubmed></ref>. At this stage the lingual epithelium consists of two to three cell layers and there is not yet any sign of cell specializations indicating early taste bud formation<ref name=PMID8955790/>.
||
Image
|- bgcolor="#BCD4E6"
| '''Week 7 '''||
A series of epithelial swellings in the anterior part and midline of the tongue indicate early forming fungiform papillae (figure 2) <ref name=PMID9455607/>.
||
Image
|- bgcolor="#89CFF0"
| ''' Week 8 ''' ||
The lingual epithelium shows first signs of taste bud development as nerve fibres penetrate epithelial basal lamina <ref name=PMID8955790/> and form synapses with taste bud progenitor cells. The synapses reach a maximum around the 12th to 13th week <ref name=PMID8955790/>. However, at this time these cells are still poorly differentiated, elongated epithelial cells <ref name=PMID8955790/> . The synapses demonstrate the neuronal connection between the taste bud primordium and the central nervous system <ref name=PMID8955790/>. Ciliated cells also appear around the 8th week, however the significance of these cells which are scattered randomly across the lingual surface remains unclear <ref name=PMID8955790/>.
||
Image
|- bgcolor="#BCD4E6"
|''' Weeks 8-9''' ||
“By this stage the top surface of circumvallate papillae usually contains a taste pit partly filled with microvilli of presumed underlying taste bud cells” (Figure 10) <ref name=PMID9455607/>
||
Image
|- bgcolor="#89CFF0"
|''' Weeks 10-11''' ||
At this stage, the lingual epithelium compromises of about four cell layers, and the first shallow grooves above the taste bud primordium are developed <ref name=PMID8955790/>.

Fungiform papillae appear on the lateral margins and the tip of the tongue <ref name=PMID9455607/>, containing taste bud primordial that display the first signs of a primitive pore formation <ref name=PMID8955790/>.

Untypically differentiated apical cellular processes extend onto the surface <ref name=PMID9455607/>

Some taste bud primordial contain cells that perforate the covering epithelial later with short, broad untypically differentiated apical cellular processes. (Figure 3,4) <ref name=PMID8955790/> <ref name=PMID9455607/>
||
Image
|- bgcolor="#BCD4E6"
|''' Week 12 ''' ||
Taste bud cells are more clearly differentiated into epithelial cell types II and III <ref name=PMID8955790/>.
||
Image
|- bgcolor="#89CFF0"
|''' Weeks 12-13 ''' ||
By this stage the taste bud primordial are all located on the top of dermal papillae (Fig 6a) <ref name=PMID8955790/>. There is also maximum synapses between cells and afferent nerve fibres, which intermingle with each other to form a plexus-like structure <ref name=PMID8955790/>.
||
Image
|- bgcolor="#BCD4E6"
|''' Weeks 14 -15 ''' ||
The shape of the taste buds primordial begins to resemble those of adult taste buds <ref name=PMID8955790/>. By the 14th week the taste pores develop as the taste pits are filled by microvilli <ref name=PMID8955790/>, indicating the possibility that the taste buds begin their gustatory function <ref name=PMID8955790/>, however they still lack an electron-dense mucous material (Fig.10) <ref name=PMID8955790/>. The tastebuds only achieve a fully developed function in week 15 of gestation with the development of type I cells to produce the mucous material in the taste pit <ref name=PMID8955790/>.
||
Image
|}

==Adult Tongue and Taste Buds – Structure and Function==

'''Structure'''

The tongue is located on the floor of the oral cavity, It is a muscular structure with sensory units crowning. The tongue is divided into an anterior two thirds and a posterior one third. These regions are divided by a V-shaped groove at the back of the tongue (sulcus terminalis). The anterior two thirds of the tongue is covered by stratified squamous epithelium, It contains a roughened surface and has projections called papillae that vary in shape and number.

''''The Image Below is a very simplistic Diagram of the surface of the Tongue showing the locations of the different papillae and other important features'''

{|
| [[Image:Drawing of Tongue.png|500px]]

'''Papillae'''
[[File:Papillae.jpg|Left|thumb|200px|Close up of Human Tongue Papillae]]

There are 4 types of papillae on the tongue.
The most numerous papillae are the filiform papillae, which function to provide a surface that aids in holding food on the tongue during chewing but do not contain taste buds. The larger, less numerous fungiform papillae which contain taste buds, as do foliate papillae. Circumvallate papillae form a wide V at the sulcus terminalis also containing taste bus. There are no papillae or taste buds located on the posterior third of the tongue, having mucosal folds and the lingual tonsils instead.

'''Function'''

The tongue is for tasting, swallowing, and speech.
The functional unit of the taste bud is a taste cell, there are between 50 and 100 taste cells in each taste bud these taste cells represent all 5 different tastes. Historically is was believed that different areas of the tongue were responsible for different taste sensations although this has since been disregarded.[http://users.rcn.com/jkimball.ma.ultranet/BiologyPages/W/Welcome.html] The papillae contain taste buds which are connected to the oral cavity via a taste pore, the function of the taste bud is to transmit a chemical signal from the oral cavity to a taste cell, this chemical signal is the converted into an electrical impulse and delivered to the brain via nerve fibres for interpretation.

'''The Image Below is a very simplistic Hand drawn Diagram of a taste bud, in an extreme close up, cross section view of the the taste bud unit, not to scale'''

[[File:Taste_bud_1.jpg]]

==Abnormalities==

===Knocking out P2X Receptors===

[[File:Image of taste being evoked by visualising ATP release.jpeg|Left|thumb|200px|Evoking taste - ATP release in tongue]]

Gustatory abnormalities has not been widely researched and what has been researched has been through animal testing, most commonly we have found on mice.

In Huang, 2008 this team used the release of the neurotransmitter, ATP (adenosine triphosphate) as a quantitative measurement of gustatory sensation and taste. This was done by using a comparison of wild type (WT) and double knockout (DKO) mice. P2X receptors, P2X2 and P2X3 were knocked out in the DKO mice. The premise of this article was that knocking out P2X receptors reduces transmitter secretion of ATP in taste buds, therefore they cannot taste.

It should be noted that the taste buds in DKO are functional, but are not stimulated by the administration of tastants.

The transmission of release of ATP is secretion through gap junction hemichannels (pannexin 1 gap junction).

When both P2X2 and P2X3 are knocked out, no taste is elicited. However they found that if either P2X2 OR P2X3 was knocked out there was a taste response. So the inference made from this is that if one of the two receptors from the P2X family was knocked out there still can have taste response. The WT mice showed significant stimulation by tastants whereas DKO had little to no stimulation of ATP release.<ref><pubmed>21940456</pubmed></ref>

===FGF signalling and genes===

Sprouty, or ''Srpy'', genes have been related to regulating the development of circumvillate papillae (CVP). The CVP are large dome shaped papillae, which form a 'V' just in front of the terminal sulcus.

By knocking out ''Spry'' genes using mice which had ''Spry1'' and ''Spry2'' knocked out showed that the number of CVP doubled. However, when Fibroblast Growth Factor gene ("Fgf10") was absent, the number of CVP was significantly reduced, if not completely absent. The correlation between ''Spry1/2'' and ''Fgf10'' is that ''Spry1/2'' antagonises "Fgf10" to limit the size of the CVP progenitor placode. Exclusive expression of ''Fgf10'' in the mesenchyme is necessary for the formation of CVP.

'''This image shows the CVP stained with H&E and scanned by Scanning Electron Microscope (SEM)'''
[[File:CVP of WT(top) and DKO(bottom) mice with H&E and SEM.png]]

'''This image shows the location of the CVP and the increased number in DKO mice by SEM'''
[[File:Mouse circumvallate papilla 01.jpg|300px]]

Taste buds develop from the mesenchyme but require local signalling to properly differentiate. Some signalling factors for proper development of taste buds besides FGF are: Sonic Hedgehog (SHH), Bone Morphogenetic Proteins (BMPs), Epidermal Growth Factor (EGF).

Additionally, this proves that the anterior and posterior developments of the tongue are derived from embryonic tissues, where the anterior tongue is derived from the ectoderm and the posterior tongue is derived from the endoderm. Taste buds develop from the mesenchyme but require local signalling to properly differentiate. Some signalling factors for proper development of taste buds besides FGF are: Sonic Hedgehog (SHH), Bone Morphogenetic Proteins (BMPs), Epidermal Growth Factor (EGF).

As mentioned above, this article shows that the anterior and posterior developments of the tongue are derived from embryonic tissues, where the anterior tongue is derived front the ectoderm and the posterior tongue is derived from the endoderm. Secondly, FGF is required to regulate the growth of taste buds, while ''Spry'' genes limit the number of CVP. ''Fgf10''& ''Spry 1&2''work antagonistically through receptor tyrosine kinase (RTK)signalling.

However, the deletion of ''Spry2''led to the increase of CVPs it should be noted that they found that a significant decrease in number of fungiform papillae. Contrastingly, the absence of ''Fgf10'', while leading to the absence of CVPs lead to an increase in number and size of fungiform papillae. Therefore these genes have different effects on the anterior and posterior developing tongue and taste buds.<ref><pubmed>21655085</pubmed></ref>

==Current Research==
We have an evolving understanding of Embryonic Taste development, through the use of state-of-the-art technology and research techniques we are able to make brilliant discoveries that continue to connect the dots of this amazing natural process of human development.
The majority of research in taste development is involving mice, these mammals show similar embryonic pathways to humans and research is performed in ethical and humane methods.

[[File:Histology.jpg|Left|thumb|200px|Image shows histological stains of a mice tongue showing dysplasia]]

'''Synergistic relationships of Six Genes '''

In an animal study using mice by Suzuki Y, Ikeda K, Kawakami K.(2011) Firstly nominating "Six Genes" as a major component in gustatory development, stating that deficiencies in certain Six genes (specifically Six1 & Six4) leads to poor development. Their research also highlights evidence of cooperative relationships between Six genes for normal advance. This experiment involved breeding mice containing exclusively Six1 and Six4 genes and examining the expression of these genes in papillae under high powered microscope observation. Understanding the role of certain genes along with the intrinsic relationships they hold is crucial for the ability to identify possible causes and correction of any abnormalities <ref><pubmed>21978088</pubmed></ref>

'''Neural Crest responsibilities '''

Another Animal Study involving mice explores a new idea of Neural crest (NC) contribution in taste development, specifically the development of papillae and taste buds. Liu HX, Komatsu Y, Mishina Y, Mistretta CM. (2012) suggest that Neural crest cells travel to the location of the tongue in early embryonic stages, gain epithelium phenotypes, multiply and then differentiate to eventually form taste papillae. The experiment involved the comparison of 2 different types of Cre line mice, which both express Cre gene in neural crest protocol, the different distribution patterns where observed in specific regions that NC is responsible for.<ref><pubmed>22659543</pubmed></ref>

'''Augmentation of Endoderm'''

In an animal study conducted by Rothova M, Thompson H, Lickert H, Tucker AS.(2012) exploring the historically debated issue of endoderm contribution to tongue development showed promising evidence that position of taste buds are patterned by the border of ectoderm and endoderm derivative epithelium. This study was accomplished via microscopic examination of previously stained specimens. Concluding endoderm has direct influence on gustatory develoment <ref><pubmed>22581563</pubmed></ref>

'''Changes in Taste Cells over time'''

Research by
Ozdener H, Spielman AI, Rawson NE.(2012) developing a culture which allows taste cells to survive for up to 12 months, empowers researchers to study the processes of proliferation, differentiation and function. This experiment will provide a precidnet for future study of taste cells, as these cells are able to operate and grow normally. <ref><pubmed>22643728</pubmed></ref>

'''Shh key component of taste bud proginators'''

A tamoxifen treatment which supresses Sonic hedgehog (Shh) secretion in mice proving to reduce the number of cells visable within papillae, in contrast mice not treated with tamoxifen showed a mark increase of cells within papillae, these cells are assumed to become taste cells in later development.
Specific mice were bred to trace the destination of taste placode cells, the study concluded that Shh expressing placodes are taste bud proginators which in turn become taste cells within taste buds although do not have any prescuros relationship with pappilae. The results were obtain by examination of mice embryos using Bright-field or multichannel fluorescent images through the use of an "Axiocam CCD camera and Axioplan fluorescence microscope with Axiovision software" a study by Harlow, Yang, Williams, Barlow (2011)<ref><pubmed>PMC2674259</pubmed></ref>

'''WNT family exhibit various roles'''

The WNT gene family has a function of signally proteins for various reason such as development, In 2010 Liu, Staubach Grosse, Walton, Saims, Gumucio, Mistretta explored recent findings on the role of WNT's in tongue and papillae development, Concluding that WNT/β-catenin is essential for fungiform papillae differing to WNT5a which proved to be principle in tongue development. Intrinsic chemical mediators were considered by manipulating a tissue culture and then throughaly examined by scanning photomicrograph. <ref><pubmed>PMC2768563</pubmed></ref>

[http://www.surgicalneurologyint.com/article.asp?issn=2152-7806;year=2012;volume=3;issue=1;spage=23;epage=23;aulast=Manjila]
[[File:Abnormal of tongue.jpg|Left|thumb|200px|Image shows and example of tongue abnormalities, this is called "double tongue" each side has independent movement!]]

==Useful links==

==Glossary==

ectoderm- outer germ layer of embryo

endoderm - inner germ layer of embryo

epithelium - basic animal tissue that is composed of tightly packed cells, usually covering the outer portion of organs

exocystosis - movement of contents out of cell

ganglia - the accumulation of a nerve cell body

growth factor - a substance that stimulates the growth of cells

gustatory - anything that relates to the taste sense

hydrolysis - breakdown of a chemical when it reacts with water

mesoderm - middle germ layer of embryo

mesenchyme - multipotential cells

neural crest - a part of the ectoderm found on both sides of the neural tube

neuron - most simplistic unit of the nervous system

neurotransmitter - chemicals which allow the passing of signals from neuron to neuron via connecting part (synapse)

papillae - small rough surface projection

six genes - a family of genes

Sonic hedgehog (Shh) - signalling protein invloved in normal development

sulcus terminalis - describes a physical transition point separating the anterior 2/3 of the tongue from the posterior 1/3

tamoxifen - hormonal altering drug

==Image gallery==

== References ==
<references/>

==External Links==
{{External Links}}

http://www.webmd.com/oral-health/picture-of-the-tongue

http://www.tutorvista.com/content/biology/biology-iv/nervous-coordination/tongue-structure.php#parts-of-tongue

http://www.cf.ac.uk/biosi/staffinfo/jacob/teaching/sensory/taste.html

--[[User:Z8600021|Mark Hill]] 12:22, 15 August 2012 (EST) Please leave the content listed below the line at the bottom of your project page.

----

{{2012Projects}}

2012 Group Project 3

2012-09-29T04:24:16Z

Z3289738: /* History of Discoveries */

=Taste Development=

== Introduction ==
**NEED TO ADD**

==History of Discoveries==

{| cellpadding=5 style="border:1px solid #BBB"
|- bgcolor="#faecc8"
|''' Date'''|| '''Significant Discovery'''

|- bgcolor="#faf6ed"
|'''350BC'''
|| Aristotle writes about the basic tastes, sweet and bitter. He also notes that it can be modified by salty and acidic. <ref name="PMID22717400"><pubmed>22717400</pubmed></ref>

|- bgcolor="#faecc8"
|'''1901'''
|| D. Hanig publishes a paper describing taste sensitivity in different regions of the tongue.
''Interesting fact:'' The modern concept of a 'tongue map' is a misinterpretation of this study. <ref name="PMID22717400"/>

|- bgcolor="#faf6ed"
|style=white-space:nowrap|'''1908'''
|Kikunae Ikeda, a professor of the Tokyo Imperial University, discovered and identified the fifth basic taste: umami (savouriness), made palatable by glutamate. <ref><pubmed>12438213</pubmed></ref>
[http://chemse.oxfordjournals.org/content/27/9/847.long New Seasonings]

|- bgcolor="#faecc8"
|style=white-space:nowrap|'''1931-32'''
| A chemist named Arthur Fox and his college noted that they had different sensitivities to the bitter tasting Phenylthiocarbamide (PTC).<ref>Blakeslee AF, Fox AL. Our different taste worlds. J Hered. 1932;23:97–107.</ref> Geneticists later confirm these findings, and discover that non-tasting is a recessive genetic trait. <ref><pubmed>17782493</pubmed></ref>
[http://www.ncbi.nlm.nih.gov/pubmed/17782493 Inherited taste deficiency]

|- bgcolor="#faf6ed"
|style=white-space:nowrap|'''1965'''
|Farbman's study of the developing taste but in rat fungiform papilla was significant in increasing our understanding of taste bud development. <ref><pubmed>14300090</pubmed></ref>
[http://www.sciencedirect.com/science/article/pii/0012160665900400 Electron microscope study of the developing taste bud in rat fungiform papilla.]

|- bgcolor="#faecc8"
|style=white-space:nowrap|'''1992'''
|McLaughlin SK et al. discovery a taste cell-specific G-protein within the taste buds called Gustucon. This protein is later used to mark bitter, umami and sweet cells. <ref><pubmed>1608467 </pubmed></ref>
[http://www.nature.com/nature/journal/v357/n6379/abs/357563a0.html Gustducin is a taste-cell-specific G protein closely related to the transducins]

|- bgcolor="#faf6ed"
|style=white-space:nowrap|'''1995'''
|Barlow et al. experimented with Axolotl salamanders and concluded that taste buds from this species arise exclusively from epithelial tissue, "oropharyngeal epithelium". <ref name="PMID17826760"><pubmed>17826760</pubmed></ref>
[http://www.ncbi.nlm.nih.gov/pubmed/17826760 Embryonic origin of gustatory cranial sensory neurons.]

|- bgcolor="#faecc8"
|style=white-space:nowrap|'''1996'''
| Witt M and Reutter K of the Technical University Dresden in Germany, carried out a transmission electron microscopy study to investigate the embryonic and fetal development of Human taste buds. Their results suggest an "at least dual function of embryonic/fetal taste buds", including non-gustatory, paracrine functions prior to the 14th week and gustatory after the 14th week. <ref name="PMID8955790"><pubmed>8955790</pubmed></ref>
[http://www.ncbi.nlm.nih.gov/pubmed/8955790 Embryonic and early fetal development of human taste buds: a transmission electron microscopical study]

|- bgcolor="#faf6ed"
|style=white-space:nowrap|'''2000'''
|Chandrashekar, J. et al. discover the first taste sonsors, the T2R bitter taste receptors. <ref><pubmed>10761935</pubmed></ref>
[http://www.sciencedirect.com/science/article/pii/S0092867400807060 T2Rs Function as Bitter Taste Receptors]

|- bgcolor="#faecc8"
|style=white-space:nowrap|'''2001'''
|Nelson, G. et al. discover the sweet receptor: a combination of T1R2 and T1R3. <ref><pubmed>11509186</pubmed></ref>
[http://www.ncbi.nlm.nih.gov/pubmed/11509186?dopt=Abstract&holding=npg Mammalian sweet taste receptors.]

|- bgcolor="#faf6ed"
|style=white-space:nowrap|'''2002'''
|Nelson G. et al. discover the amino acid (umami) taste receptor: a combination of T1R1 and T1R3 identified. <ref><pubmed>11894099</pubmed></ref>
[http://www.ncbi.nlm.nih.gov/pubmed/11894099?dopt=Abstract&holding=npg An amino-acid taste receptor]

|- bgcolor="#faecc8"
|style=white-space:nowrap|'''2005'''
|Dyer, J. et al. discover sweet taste receptors in the GI tract. <ref><pubmed>17855558</pubmed></ref>
[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1986582/ Sweet taste signaling in the gut]

|- bgcolor="#faf6ed"
|style=white-space:nowrap|'''2006'''
|Huang, A. L et al. discover cells for sour taste, identified by PKD2L1 (a polycystic kidney disease-like ion channel). <ref><pubmed>16929298</pubmed></ref>
[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1571047/ The Cells and Logic for Mammalian Sour Taste detection]

|- bgcolor="#faecc8"
|style=white-space:nowrap|'''2007'''
|Harlow DE, Barlow LA of the University of Colorado Denver Health Sciences Center provide evidence of the "embryonic origin of gustatory cranial sensory neurons". <ref name="PMID17826760"/>
[http://www.ncbi.nlm.nih.gov/pubmed/17826760 Embryonic origin of gustatory cranial sensory neurons.]

|- bgcolor="#faf6ed"
|style=white-space:nowrap|'''2009'''
|A study by Hevezi P et al, presents "the first comprehensive characterization of gene expression in primate taste buds", as opposed to previous studies which focused on rodents. <ref><pubmed>19636377</pubmed></ref>
[http://www.ncbi.nlm.nih.gov/pubmed/19636377 Genome-wide analysis of gene expression in primate taste buds reveals links to diverse processes]

|- bgcolor="#faecc8"
|style=white-space:nowrap|'''2010'''
|Chandrashekar, J. et al. identify epithelial sodium channel (ENaC) as the sodium-salt taste receptor. <ref><pubmed>20107438</pubmed></ref>
[http://www.ncbi.nlm.nih.gov/pubmed/20107438?dopt=Abstract&holding=npg The cells and peripheral representation of sodium taste in mice]
|}

==Gustatory System==

[[Image:Taste qualities.gif|thumb|The five basic tastes]]

Taste or more appropriately gustation, is a fundamental survival tool in animals as it directs the consumption of essential nutrients. The five tastes that exist within the human gustatory system: salty, sweet, sour, bitter and umami, all signify basic physiological requirements. Salty tastes denote the presence of Na+, an important ion involved in the transportation and retention of water across cell membranes. Sweetness is the recognition of carbohydrates, essential for maintaining optimal brain function and providing the basis for energy production in muscle tissue via ATP hydrolysis. Similarly umami codes for the presence of L-amino acids, especially L-glutamate which is an integral component of protein synthesis.

These different modalities not only function to maintain the proper intake of nutrients within the body but also, by way of aversion, prohibit the consumption of undesired or poisonous materials. The bitter modality for example is generally regarded as displeasing to the human palate. It represents a high acid content which may be a result of foods which have become rotten or are inherently poisonous to the body.<ref name=PMID20696704><pubmed>20696704</pubmed></ref>

Research has historically limited itself to investigating the mechanisms of these five taste qualities though it must be noted many other modalities may exist. Of particular conjecture is the existence of fatty acid recognition. In the past the detection of fat in food has been attributed to somatosensory inputs <ref name=PMID20696704/> from the tongue, that is, the oily feel and texture of fat rather than its actual ‘taste’ allows the brain to encode for its presence. Further research is therefore required to elicit the precise mechanisms of fat detection.

===Cell Biology===

The five taste qualities are not all detected by the same type of receptor cell located within the taste bud. Like rods and cones in the eye which detect different wavelengths of light, there are specific types of receptors for different tastes. For example, sweet, umami and bitter are recognised by Type II G-protein coupled receptors, whereas sour is related to Type III presynaptic cells. The cell type involved in salty taste transduction is unknown however it is known that sodium ions can enter the receptor cell membrane via ion channel permeation.

====Type II receptors====

When a bitter, sweet or umami ligand binds to a type II G-coupled receptor, a cascade of chemical reactions causes the release of Ca2+ which in turn mediates exocystosis of ATP. The function of this ATP is threefold:

# Stimulates gustatory nerve afferents which project to gustatory nuclei in the spinal cord
# Excites Type III presynaptic nerve fibres to release serotonin.
# Has a positive feedback effect on type II receptor cells, increasing the level of ATP production.

The role of serotonin is believed to be in the form of lateral inhibition i.e. when a bitter quality is recognised, adjacent receptors for sweetness are deactivated and thus the two tastes may be clearly differentiated. It also has a negative feedback effect on receptor cells, inhibiting umami, bitter and sweet taste transduction.

==Taste Map==
[[Image:Taste map.png|thumb|left|250px|Obsolete idea of the tongue map]]
The idea of a tongue map has disseminated through society for many years. This concept purports that different areas of the tongue are specialised to detect either sweet, salty, sour and bitter tastes. Recent research however has completely nullified such claims and suggests instead that different forms of taste are recognised all over the tongue as well as via the palate. Thus the term ''taste map'' has come to take on a new meaning and that is, the precise areas of taste modalities processing in areas of cortex and its subsequent neural inputs.

===Neural Pathways===

'''First order neurons''' - From the receptors located in the taste buds, gustatory nerve afferents project to the ipsilateral rostral 1/3 of the nucleus tractus solitarius (NTS), located in the medulla. This rostral 1/3 is commonly referred to as the ''gustatory nucleus''.

The ''gustatory nucleus'' receives input from cranial nerves VII (''Facial n.''), IX (''Hypglossal n.''), and X (''Vagus n.'') via special visceral afferent (SVA) nerve fibres. A summary of their functions is as follows:

* ''Facial nerve n''. - carries taste information from the anterior 2/3 of the tongue.
* ''Hypoglossal n.'' - carries taste information from the posterior 1/3 of the tongue.
* ''Vagus n''. - carries taste information from the palate

'''Second order neurons''' - From the NTS second order neurons carry taste information to the Ventral posteromedial (VPM) nucleus in the thalamus.<ref name=PMID21885776/>

Copious scientific conjecture surrounds how each taste modality is transmitted to the brain. The ‘labelled-line’ hypothesis suggests that there are taste specific neurons which exclusively carry that taste modality to cortical areas. In analogous terms it can be viewed like the pipelines leading toward a house. Each pipeline carries its own utility, there is one for gas, another for water and finally for electricity with each terminating in slightly different areas of the house. In the same way, on the tongues there are different receptors for each taste which concurrently have individual nerve tracts leading to the primary gustatory cortex.

Contrapuntally there is electrophysiological evidence that single nerve afferents carry multiple modalities. These studies show one nerve afferent may have both a strong and a weak activation in response to a multiple taste stimuli.

===Cortical Areas===

[[Image:Primary gustatory cortex.png|thumb|Primary gustatory cortex]]

The location of the taste perception centres has been observed via functional magnetic resonance imaging (fMRI) studies. The primary taste cortex has been identified as being located in the anterior insula/frontal operculum (I/fO)<ref name=PMID22245354><pubmed>22245354</pubmed></ref>, with the secondary taste cortex in the caudolateral orbitofrontal cortex.<ref name=PMID21305668><pubmed>21305668</pubmed></ref> Within the insula there are further subdivisions related to each taste modality. Two photon calcium imaging research has outlined certain ’hot-spots’ of activation which are clearly delineated in relation to each taste. For example, the bitter modality is represented on the insula cortex approximately 1mm posterior to the middle cerebral artery whereas the sweet modality is represented 2.5mm rostrodorsal to the bitter field with no apparent overlap.<ref name=PMID21885776><pubmed>21885776</pubmed></ref> These findings lend weight to the idea that there is only one receptor for each taste quality.

It is interesting to note the relationship between taste and the reward centres of the brain. There is evidence of neural input to the ventral tegmental area (the origin of the mesolimbic dopaminergic reward pathway) and nucleus accumbens (involved in the conversion of motivation into physical action).<ref name=PMID21885776/> Neural connections such as this provide the foundations in explaining concepts such as flavour learning and preference. It may also give some insight into chronic problems such as food addiction and craving. As of yet however the gustatory neural network is not well understood and more research is required to elucidate the relationship between pleasure and taste sensation

==Timeline of Developmental Processes of the Gustatory System==

{| cellpadding=5 style="border:1px solid #BBB"
|- bgcolor="#89CFF0"
|'''Postovulatory Week'''||'''Description'''||'''Image'''
|- bgcolor="#BCD4E6"
|'''Week 6''' ||
The surface of the developing tongue is covered by nearly flat epitheliuem (Figure 1) <ref name=PMID9455607/>. The first gustatory papillae of the tongue appears in the caudal midline near the foramen caecum and the first circumvallate papilla develop on the dorsal midline <ref name=PMID9455607/> .
||
image
|- bgcolor="#89CFF0"
| '''Weeks 6 to 7'''||
Nerve fibres approach the basal lamina of lingual epithelium <ref name=PMID8955790><pubmed>8955790</pubmed></ref>. At this stage the lingual epithelium consists of two to three cell layers and there is not yet any sign of cell specializations indicating early taste bud formation<ref name=PMID8955790/>.
||
Image
|- bgcolor="#BCD4E6"
| '''Week 7 '''||
A series of epithelial swellings in the anterior part and midline of the tongue indicate early forming fungiform papillae (figure 2) <ref name=PMID9455607/>.
||
Image
|- bgcolor="#89CFF0"
| ''' Week 8 ''' ||
The lingual epithelium shows first signs of taste bud development as nerve fibres penetrate epithelial basal lamina <ref name=PMID8955790/> and form synapses with taste bud progenitor cells. The synapses reach a maximum around the 12th to 13th week <ref name=PMID8955790/>. However, at this time these cells are still poorly differentiated, elongated epithelial cells <ref name=PMID8955790/> . The synapses demonstrate the neuronal connection between the taste bud primordium and the central nervous system <ref name=PMID8955790/>. Ciliated cells also appear around the 8th week, however the significance of these cells which are scattered randomly across the lingual surface remains unclear <ref name=PMID8955790/>.
||
Image
|- bgcolor="#BCD4E6"
|''' Weeks 8-9''' ||
“By this stage the top surface of circumvallate papillae usually contains a taste pit partly filled with microvilli of presumed underlying taste bud cells” (Figure 10) <ref name=PMID9455607/>
||
Image
|- bgcolor="#89CFF0"
|''' Weeks 10-11''' ||
At this stage, the lingual epithelium compromises of about four cell layers, and the first shallow grooves above the taste bud primordium are developed <ref name=PMID8955790/>.

Fungiform papillae appear on the lateral margins and the tip of the tongue <ref name=PMID9455607/>, containing taste bud primordial that display the first signs of a primitive pore formation <ref name=PMID8955790/>.

Untypically differentiated apical cellular processes extend onto the surface <ref name=PMID9455607/>

Some taste bud primordial contain cells that perforate the covering epithelial later with short, broad untypically differentiated apical cellular processes. (Figure 3,4) <ref name=PMID8955790/> <ref name=PMID9455607/>
||
Image
|- bgcolor="#BCD4E6"
|''' Week 12 ''' ||
Taste bud cells are more clearly differentiated into epithelial cell types II and III <ref name=PMID8955790/>.
||
Image
|- bgcolor="#89CFF0"
|''' Weeks 12-13 ''' ||
By this stage the taste bud primordial are all located on the top of dermal papillae (Fig 6a) <ref name=PMID8955790/>. There is also maximum synapses between cells and afferent nerve fibres, which intermingle with each other to form a plexus-like structure <ref name=PMID8955790/>.
||
Image
|- bgcolor="#BCD4E6"
|''' Weeks 14 -15 ''' ||
The shape of the taste buds primordial begins to resemble those of adult taste buds <ref name=PMID8955790/>. By the 14th week the taste pores develop as the taste pits are filled by microvilli <ref name=PMID8955790/>, indicating the possibility that the taste buds begin their gustatory function <ref name=PMID8955790/>, however they still lack an electron-dense mucous material (Fig.10) <ref name=PMID8955790/>. The tastebuds only achieve a fully developed function in week 15 of gestation with the development of type I cells to produce the mucous material in the taste pit <ref name=PMID8955790/>.
||
Image
|}

==Adult Tongue and Taste Buds – Structure and Function==

'''Structure'''

The tongue is located on the floor of the oral cavity, It is a muscular structure with sensory units crowning. The tongue is divided into an anterior two thirds and a posterior one third. These regions are divided by a V-shaped groove at the back of the tongue (sulcus terminalis). The anterior two thirds of the tongue is covered by stratified squamous epithelium, It contains a roughened surface and has projections called papillae that vary in shape and number.

''''The Image Below is a very simplistic Diagram of the surface of the Tongue showing the locations of the different papillae and other important features'''

{|
| [[Image:Drawing of Tongue.png|500px]]

'''Papillae'''
[[File:Papillae.jpg|Left|thumb|200px|Close up of Human Tongue Papillae]]

There are 4 types of papillae on the tongue.
The most numerous papillae are the filiform papillae, which function to provide a surface that aids in holding food on the tongue during chewing but do not contain taste buds. The larger, less numerous fungiform papillae which contain taste buds, as do foliate papillae. Circumvallate papillae form a wide V at the sulcus terminalis also containing taste bus. There are no papillae or taste buds located on the posterior third of the tongue, having mucosal folds and the lingual tonsils instead.

'''Function'''

The tongue is for tasting, swallowing, and speech.
The functional unit of the taste bud is a taste cell, there are between 50 and 100 taste cells in each taste bud these taste cells represent all 5 different tastes. Historically is was believed that different areas of the tongue were responsible for different taste sensations although this has since been disregarded.[http://users.rcn.com/jkimball.ma.ultranet/BiologyPages/W/Welcome.html] The papillae contain taste buds which are connected to the oral cavity via a taste pore, the function of the taste bud is to transmit a chemical signal from the oral cavity to a taste cell, this chemical signal is the converted into an electrical impulse and delivered to the brain via nerve fibres for interpretation.

'''The Image Below is a very simplistic Hand drawn Diagram of a taste bud, in an extreme close up, cross section view of the the taste bud unit, not to scale'''

[[File:Taste_bud_1.jpg]]

==Abnormalities==

===Knocking out P2X Receptors===

[[File:Image of taste being evoked by visualising ATP release.jpeg|Left|thumb|200px|Evoking taste - ATP release in tongue]]

Gustatory abnormalities has not been widely researched and what has been researched has been through animal testing, most commonly we have found on mice.

In Huang, 2008 this team used the release of the neurotransmitter, ATP (adenosine triphosphate) as a quantitative measurement of gustatory sensation and taste. This was done by using a comparison of wild type (WT) and double knockout (DKO) mice. P2X receptors, P2X2 and P2X3 were knocked out in the DKO mice. The premise of this article was that knocking out P2X receptors reduces transmitter secretion of ATP in taste buds, therefore they cannot taste.

It should be noted that the taste buds in DKO are functional, but are not stimulated by the administration of tastants.

The transmission of release of ATP is secretion through gap junction hemichannels (pannexin 1 gap junction).

When both P2X2 and P2X3 are knocked out, no taste is elicited. However they found that if either P2X2 OR P2X3 was knocked out there was a taste response. So the inference made from this is that if one of the two receptors from the P2X family was knocked out there still can have taste response. The WT mice showed significant stimulation by tastants whereas DKO had little to no stimulation of ATP release.<ref><pubmed>21940456</pubmed></ref>

===FGF signalling and genes===

Sprouty, or ''Srpy'', genes have been related to regulating the development of circumvillate papillae (CVP). The CVP are large dome shaped papillae, which form a 'V' just in front of the terminal sulcus.

By knocking out ''Spry'' genes using mice which had ''Spry1'' and ''Spry2'' knocked out showed that the number of CVP doubled. However, when Fibroblast Growth Factor gene ("Fgf10") was absent, the number of CVP was significantly reduced, if not completely absent. The correlation between ''Spry1/2'' and ''Fgf10'' is that ''Spry1/2'' antagonises "Fgf10" to limit the size of the CVP progenitor placode. Exclusive expression of ''Fgf10'' in the mesenchyme is necessary for the formation of CVP.

'''This image shows the CVP stained with H&E and scanned by Scanning Electron Microscope (SEM)'''
[[File:CVP of WT(top) and DKO(bottom) mice with H&E and SEM.png]]

'''This image shows the location of the CVP and the increased number in DKO mice by SEM'''
[[File:Mouse circumvallate papilla 01.jpg|300px]]

Taste buds develop from the mesenchyme but require local signalling to properly differentiate. Some signalling factors for proper development of taste buds besides FGF are: Sonic Hedgehog (SHH), Bone Morphogenetic Proteins (BMPs), Epidermal Growth Factor (EGF).

Additionally, this proves that the anterior and posterior developments of the tongue are derived from embryonic tissues, where the anterior tongue is derived from the ectoderm and the posterior tongue is derived from the endoderm. Taste buds develop from the mesenchyme but require local signalling to properly differentiate. Some signalling factors for proper development of taste buds besides FGF are: Sonic Hedgehog (SHH), Bone Morphogenetic Proteins (BMPs), Epidermal Growth Factor (EGF).

As mentioned above, this article shows that the anterior and posterior developments of the tongue are derived from embryonic tissues, where the anterior tongue is derived front the ectoderm and the posterior tongue is derived from the endoderm. Secondly, FGF is required to regulate the growth of taste buds, while ''Spry'' genes limit the number of CVP. ''Fgf10''& ''Spry 1&2''work antagonistically through receptor tyrosine kinase (RTK)signalling.

However, the deletion of ''Spry2''led to the increase of CVPs it should be noted that they found that a significant decrease in number of fungiform papillae. Contrastingly, the absence of ''Fgf10'', while leading to the absence of CVPs lead to an increase in number and size of fungiform papillae. Therefore these genes have different effects on the anterior and posterior developing tongue and taste buds.<ref><pubmed>21655085</pubmed></ref>

==Current Research==
We have an evolving understanding of Embryonic Taste development, through the use of state-of-the-art technology and research techniques we are able to make brilliant discoveries that continue to connect the dots of this amazing natural process of human development.
The majority of research in taste development is involving mice, these mammals show similar embryonic pathways to humans and research is performed in ethical and humane methods.

[[File:Histology.jpg|Left|thumb|200px|Image shows histological stains of a mice tongue showing dysplasia]]

'''Synergistic relationships of Six Genes '''

In an animal study using mice by Suzuki Y, Ikeda K, Kawakami K.(2011) Firstly nominating "Six Genes" as a major component in gustatory development, stating that deficiencies in certain Six genes (specifically Six1 & Six4) leads to poor development. Their research also highlights evidence of cooperative relationships between Six genes for normal advance. This experiment involved breeding mice containing exclusively Six1 and Six4 genes and examining the expression of these genes in papillae under high powered microscope observation. Understanding the role of certain genes along with the intrinsic relationships they hold is crucial for the ability to identify possible causes and correction of any abnormalities <ref><pubmed>21978088</pubmed></ref>

'''Neural Crest responsibilities '''

Another Animal Study involving mice explores a new idea of Neural crest (NC) contribution in taste development, specifically the development of papillae and taste buds. Liu HX, Komatsu Y, Mishina Y, Mistretta CM. (2012) suggest that Neural crest cells travel to the location of the tongue in early embryonic stages, gain epithelium phenotypes, multiply and then differentiate to eventually form taste papillae. The experiment involved the comparison of 2 different types of Cre line mice, which both express Cre gene in neural crest protocol, the different distribution patterns where observed in specific regions that NC is responsible for.<ref><pubmed>22659543</pubmed></ref>

'''Augmentation of Endoderm'''

In an animal study conducted by Rothova M, Thompson H, Lickert H, Tucker AS.(2012) exploring the historically debated issue of endoderm contribution to tongue development showed promising evidence that position of taste buds are patterned by the border of ectoderm and endoderm derivative epithelium. This study was accomplished via microscopic examination of previously stained specimens. Concluding endoderm has direct influence on gustatory develoment <ref><pubmed>22581563</pubmed></ref>

'''Changes in Taste Cells over time'''

Research by
Ozdener H, Spielman AI, Rawson NE.(2012) developing a culture which allows taste cells to survive for up to 12 months, empowers researchers to study the processes of proliferation, differentiation and function. This experiment will provide a precidnet for future study of taste cells, as these cells are able to operate and grow normally. <ref><pubmed>22643728</pubmed></ref>

'''Shh key component of taste bud proginators'''

A tamoxifen treatment which supresses Sonic hedgehog (Shh) secretion in mice proving to reduce the number of cells visable within papillae, in contrast mice not treated with tamoxifen showed a mark increase of cells within papillae, these cells are assumed to become taste cells in later development.
Specific mice were bred to trace the destination of taste placode cells, the study concluded that Shh expressing placodes are taste bud proginators which in turn become taste cells within taste buds although do not have any prescuros relationship with pappilae. The results were obtain by examination of mice embryos using Bright-field or multichannel fluorescent images through the use of an "Axiocam CCD camera and Axioplan fluorescence microscope with Axiovision software" a study by Harlow, Yang, Williams, Barlow (2011)<ref><pubmed>PMC2674259</pubmed></ref>

'''WNT family exhibit various roles'''

The WNT gene family has a function of signally proteins for various reason such as development, In 2010 Liu, Staubach Grosse, Walton, Saims, Gumucio, Mistretta explored recent findings on the role of WNT's in tongue and papillae development, Concluding that WNT/β-catenin is essential for fungiform papillae differing to WNT5a which proved to be principle in tongue development. Intrinsic chemical mediators were considered by manipulating a tissue culture and then throughaly examined by scanning photomicrograph. <ref><pubmed>PMC2768563</pubmed></ref>

[http://www.surgicalneurologyint.com/article.asp?issn=2152-7806;year=2012;volume=3;issue=1;spage=23;epage=23;aulast=Manjila]
[[File:Abnormal of tongue.jpg|Left|thumb|200px|Image shows and example of tongue abnormalities, this is called "double tongue" each side has independent movement!]]

==Useful links==

==Glossary==

ectoderm- outer germ layer of embryo

endoderm - inner germ layer of embryo

epithelium - basic animal tissue that is composed of tightly packed cells, usually covering the outer portion of organs

exocystosis - movement of contents out of cell

ganglia - the accumulation of a nerve cell body

growth factor - a substance that stimulates the growth of cells

gustatory - anything that relates to the taste sense

hydrolysis - breakdown of a chemical when it reacts with water

mesoderm - middle germ layer of embryo

mesenchyme - multipotential cells

neural crest - a part of the ectoderm found on both sides of the neural tube

neuron - most simplistic unit of the nervous system

neurotransmitter - chemicals which allow the passing of signals from neuron to neuron via connecting part (synapse)

papillae - small rough surface projection

six genes - a family of genes

Sonic hedgehog (Shh) - signalling protein invloved in normal development

sulcus terminalis - describes a physical transition point separating the anterior 2/3 of the tongue from the posterior 1/3

tamoxifen - hormonal altering drug

==Image gallery==

== References ==
<references/>

==External Links==
{{External Links}}

http://www.webmd.com/oral-health/picture-of-the-tongue

http://www.tutorvista.com/content/biology/biology-iv/nervous-coordination/tongue-structure.php#parts-of-tongue

http://www.cf.ac.uk/biosi/staffinfo/jacob/teaching/sensory/taste.html

--[[User:Z8600021|Mark Hill]] 12:22, 15 August 2012 (EST) Please leave the content listed below the line at the bottom of your project page.

----

{{2012Projects}}

2012 Group Project 3

2012-09-29T04:20:22Z

Z3289738: /* History of Discoveries */

=Taste Development=

== Introduction ==
**NEED TO ADD**

==History of Discoveries==

{| cellpadding=5 style="border:1px solid #BBB"
|- bgcolor="#faecc8"
|''' Date'''|| '''Significant Discovery'''

|- bgcolor="#faf6ed"
|'''350BC'''
|| Aristotle writes about the basic tastes, sweet and bitter. He also notes that it can be modified by salty and acidic. <ref name="PMID22717400"><pubmed>22717400</pubmed></ref>

|- bgcolor="#faecc8"
|'''1901'''
|| D. Hanig publishes a paper describing taste sensitivity in different regions of the tongue.
''Interesting fact:'' The modern concept of a 'tongue map' is a misinterpretation of this study. <ref><pubmed>22717400</pubmed></ref>

|- bgcolor="#faf6ed"
|style=white-space:nowrap|'''1908'''
|Kikunae Ikeda, a professor of the Tokyo Imperial University, discovered and identified the fifth basic taste: umami (savouriness), made palatable by glutamate. <ref><pubmed>12438213</pubmed></ref>
[http://chemse.oxfordjournals.org/content/27/9/847.long New Seasonings]

|- bgcolor="#faecc8"
|style=white-space:nowrap|'''1931-32'''
| A chemist named Arthur Fox and his college noted that they had different sensitivities to the bitter tasting Phenylthiocarbamide (PTC).<ref>Blakeslee AF, Fox AL. Our different taste worlds. J Hered. 1932;23:97–107.</ref> Geneticists later confirm these findings, and discover that non-tasting is a recessive genetic trait. <ref><pubmed>17782493</pubmed></ref>
[http://www.ncbi.nlm.nih.gov/pubmed/17782493 Inherited taste deficiency]

|- bgcolor="#faf6ed"
|style=white-space:nowrap|'''1965'''
|Farbman's study of the developing taste but in rat fungiform papilla was significant in increasing our understanding of taste bud development. <ref><pubmed>14300090</pubmed></ref>
[http://www.sciencedirect.com/science/article/pii/0012160665900400 Electron microscope study of the developing taste bud in rat fungiform papilla.]

|- bgcolor="#faecc8"
|style=white-space:nowrap|'''1992'''
|McLaughlin SK et al. discovery a taste cell-specific G-protein within the taste buds called Gustucon. This protein is later used to mark bitter, umami and sweet cells. <ref><pubmed>1608467 </pubmed></ref>
[http://www.nature.com/nature/journal/v357/n6379/abs/357563a0.html Gustducin is a taste-cell-specific G protein closely related to the transducins]

|- bgcolor="#faf6ed"
|style=white-space:nowrap|'''1995'''
|Barlow et al. experimented with Axolotl salamanders and concluded that taste buds from this species arise exclusively from epithelial tissue, "oropharyngeal epithelium". <ref name="PMID17826760"><pubmed>17826760</pubmed></ref>
[http://www.ncbi.nlm.nih.gov/pubmed/17826760 Embryonic origin of gustatory cranial sensory neurons.]

|- bgcolor="#faecc8"
|style=white-space:nowrap|'''1996'''
| Witt M and Reutter K of the Technical University Dresden in Germany, carried out a transmission electron microscopy study to investigate the embryonic and fetal development of Human taste buds. Their results suggest an "at least dual function of embryonic/fetal taste buds", including non-gustatory, paracrine functions prior to the 14th week and gustatory after the 14th week. <ref name="PMID8955790"><pubmed>8955790</pubmed></ref>
[http://www.ncbi.nlm.nih.gov/pubmed/8955790 Embryonic and early fetal development of human taste buds: a transmission electron microscopical study]

|- bgcolor="#faf6ed"
|style=white-space:nowrap|'''2000'''
|Chandrashekar, J. et al. discover the first taste sonsors, the T2R bitter taste receptors. <ref><pubmed>10761935</pubmed></ref>
[http://www.sciencedirect.com/science/article/pii/S0092867400807060 T2Rs Function as Bitter Taste Receptors]

|- bgcolor="#faecc8"
|style=white-space:nowrap|'''2001'''
|Nelson, G. et al. discover the sweet receptor: a combination of T1R2 and T1R3. <ref><pubmed>11509186</pubmed></ref>
[http://www.ncbi.nlm.nih.gov/pubmed/11509186?dopt=Abstract&holding=npg Mammalian sweet taste receptors.]

|- bgcolor="#faf6ed"
|style=white-space:nowrap|'''2002'''
|Nelson G. et al. discover the amino acid (umami) taste receptor: a combination of T1R1 and T1R3 identified. <ref><pubmed>11894099</pubmed></ref>
[http://www.ncbi.nlm.nih.gov/pubmed/11894099?dopt=Abstract&holding=npg An amino-acid taste receptor]

|- bgcolor="#faecc8"
|style=white-space:nowrap|'''2005'''
|Dyer, J. et al. discover sweet taste receptors in the GI tract. <ref><pubmed>17855558</pubmed></ref>
[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1986582/ Sweet taste signaling in the gut]

|- bgcolor="#faf6ed"
|style=white-space:nowrap|'''2006'''
|Huang, A. L et al. discover cells for sour taste, identified by PKD2L1 (a polycystic kidney disease-like ion channel). <ref><pubmed>16929298</pubmed></ref>
[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1571047/ The Cells and Logic for Mammalian Sour Taste detection]

|- bgcolor="#faecc8"
|style=white-space:nowrap|'''2007'''
|Harlow DE, Barlow LA of the University of Colorado Denver Health Sciences Center provide evidence of the "embryonic origin of gustatory cranial sensory neurons". <ref><pubmed>17826760</pubmed></ref>
[http://www.ncbi.nlm.nih.gov/pubmed/17826760 Embryonic origin of gustatory cranial sensory neurons.]

|- bgcolor="#faf6ed"
|style=white-space:nowrap|'''2009'''
|A study by Hevezi P et al, presents "the first comprehensive characterization of gene expression in primate taste buds", as opposed to previous studies which focused on rodents. <ref><pubmed>19636377</pubmed></ref>
[http://www.ncbi.nlm.nih.gov/pubmed/19636377 Genome-wide analysis of gene expression in primate taste buds reveals links to diverse processes]

|- bgcolor="#faecc8"
|style=white-space:nowrap|'''2010'''
|Chandrashekar, J. et al. identify epithelial sodium channel (ENaC) as the sodium-salt taste receptor. <ref><pubmed>20107438</pubmed></ref>
[http://www.ncbi.nlm.nih.gov/pubmed/20107438?dopt=Abstract&holding=npg The cells and peripheral representation of sodium taste in mice]
|}

==Gustatory System==

[[Image:Taste qualities.gif|thumb|The five basic tastes]]

Taste or more appropriately gustation, is a fundamental survival tool in animals as it directs the consumption of essential nutrients. The five tastes that exist within the human gustatory system: salty, sweet, sour, bitter and umami, all signify basic physiological requirements. Salty tastes denote the presence of Na+, an important ion involved in the transportation and retention of water across cell membranes. Sweetness is the recognition of carbohydrates, essential for maintaining optimal brain function and providing the basis for energy production in muscle tissue via ATP hydrolysis. Similarly umami codes for the presence of L-amino acids, especially L-glutamate which is an integral component of protein synthesis.

These different modalities not only function to maintain the proper intake of nutrients within the body but also, by way of aversion, prohibit the consumption of undesired or poisonous materials. The bitter modality for example is generally regarded as displeasing to the human palate. It represents a high acid content which may be a result of foods which have become rotten or are inherently poisonous to the body.<ref name=PMID20696704><pubmed>20696704</pubmed></ref>

Research has historically limited itself to investigating the mechanisms of these five taste qualities though it must be noted many other modalities may exist. Of particular conjecture is the existence of fatty acid recognition. In the past the detection of fat in food has been attributed to somatosensory inputs <ref name=PMID20696704/> from the tongue, that is, the oily feel and texture of fat rather than its actual ‘taste’ allows the brain to encode for its presence. Further research is therefore required to elicit the precise mechanisms of fat detection.

===Cell Biology===

The five taste qualities are not all detected by the same type of receptor cell located within the taste bud. Like rods and cones in the eye which detect different wavelengths of light, there are specific types of receptors for different tastes. For example, sweet, umami and bitter are recognised by Type II G-protein coupled receptors, whereas sour is related to Type III presynaptic cells. The cell type involved in salty taste transduction is unknown however it is known that sodium ions can enter the receptor cell membrane via ion channel permeation.

====Type II receptors====

When a bitter, sweet or umami ligand binds to a type II G-coupled receptor, a cascade of chemical reactions causes the release of Ca2+ which in turn mediates exocystosis of ATP. The function of this ATP is threefold:

# Stimulates gustatory nerve afferents which project to gustatory nuclei in the spinal cord
# Excites Type III presynaptic nerve fibres to release serotonin.
# Has a positive feedback effect on type II receptor cells, increasing the level of ATP production.

The role of serotonin is believed to be in the form of lateral inhibition i.e. when a bitter quality is recognised, adjacent receptors for sweetness are deactivated and thus the two tastes may be clearly differentiated. It also has a negative feedback effect on receptor cells, inhibiting umami, bitter and sweet taste transduction.

==Taste Map==
[[Image:Taste map.png|thumb|left|250px|Obsolete idea of the tongue map]]
The idea of a tongue map has disseminated through society for many years. This concept purports that different areas of the tongue are specialised to detect either sweet, salty, sour and bitter tastes. Recent research however has completely nullified such claims and suggests instead that different forms of taste are recognised all over the tongue as well as via the palate. Thus the term ''taste map'' has come to take on a new meaning and that is, the precise areas of taste modalities processing in areas of cortex and its subsequent neural inputs.

===Neural Pathways===

'''First order neurons''' - From the receptors located in the taste buds, gustatory nerve afferents project to the ipsilateral rostral 1/3 of the nucleus tractus solitarius (NTS), located in the medulla. This rostral 1/3 is commonly referred to as the ''gustatory nucleus''.

The ''gustatory nucleus'' receives input from cranial nerves VII (''Facial n.''), IX (''Hypglossal n.''), and X (''Vagus n.'') via special visceral afferent (SVA) nerve fibres. A summary of their functions is as follows:

* ''Facial nerve n''. - carries taste information from the anterior 2/3 of the tongue.
* ''Hypoglossal n.'' - carries taste information from the posterior 1/3 of the tongue.
* ''Vagus n''. - carries taste information from the palate

'''Second order neurons''' - From the NTS second order neurons carry taste information to the Ventral posteromedial (VPM) nucleus in the thalamus.<ref name=PMID21885776/>

Copious scientific conjecture surrounds how each taste modality is transmitted to the brain. The ‘labelled-line’ hypothesis suggests that there are taste specific neurons which exclusively carry that taste modality to cortical areas. In analogous terms it can be viewed like the pipelines leading toward a house. Each pipeline carries its own utility, there is one for gas, another for water and finally for electricity with each terminating in slightly different areas of the house. In the same way, on the tongues there are different receptors for each taste which concurrently have individual nerve tracts leading to the primary gustatory cortex.

Contrapuntally there is electrophysiological evidence that single nerve afferents carry multiple modalities. These studies show one nerve afferent may have both a strong and a weak activation in response to a multiple taste stimuli.

===Cortical Areas===

[[Image:Primary gustatory cortex.png|thumb|Primary gustatory cortex]]

The location of the taste perception centres has been observed via functional magnetic resonance imaging (fMRI) studies. The primary taste cortex has been identified as being located in the anterior insula/frontal operculum (I/fO)<ref name=PMID22245354><pubmed>22245354</pubmed></ref>, with the secondary taste cortex in the caudolateral orbitofrontal cortex.<ref name=PMID21305668><pubmed>21305668</pubmed></ref> Within the insula there are further subdivisions related to each taste modality. Two photon calcium imaging research has outlined certain ’hot-spots’ of activation which are clearly delineated in relation to each taste. For example, the bitter modality is represented on the insula cortex approximately 1mm posterior to the middle cerebral artery whereas the sweet modality is represented 2.5mm rostrodorsal to the bitter field with no apparent overlap.<ref name=PMID21885776><pubmed>21885776</pubmed></ref> These findings lend weight to the idea that there is only one receptor for each taste quality.

It is interesting to note the relationship between taste and the reward centres of the brain. There is evidence of neural input to the ventral tegmental area (the origin of the mesolimbic dopaminergic reward pathway) and nucleus accumbens (involved in the conversion of motivation into physical action).<ref name=PMID21885776/> Neural connections such as this provide the foundations in explaining concepts such as flavour learning and preference. It may also give some insight into chronic problems such as food addiction and craving. As of yet however the gustatory neural network is not well understood and more research is required to elucidate the relationship between pleasure and taste sensation

==Timeline of Developmental Processes of the Gustatory System==

{| cellpadding=5 style="border:1px solid #BBB"
|- bgcolor="#89CFF0"
|'''Postovulatory Week'''||'''Description'''||'''Image'''
|- bgcolor="#BCD4E6"
|'''Week 6''' ||
The surface of the developing tongue is covered by nearly flat epitheliuem (Figure 1) <ref name=PMID9455607/>. The first gustatory papillae of the tongue appears in the caudal midline near the foramen caecum and the first circumvallate papilla develop on the dorsal midline <ref name=PMID9455607/> .
||
image
|- bgcolor="#89CFF0"
| '''Weeks 6 to 7'''||
Nerve fibres approach the basal lamina of lingual epithelium <ref name=PMID8955790><pubmed>8955790</pubmed></ref>. At this stage the lingual epithelium consists of two to three cell layers and there is not yet any sign of cell specializations indicating early taste bud formation<ref name=PMID8955790/>.
||
Image
|- bgcolor="#BCD4E6"
| '''Week 7 '''||
A series of epithelial swellings in the anterior part and midline of the tongue indicate early forming fungiform papillae (figure 2) <ref name=PMID9455607/>.
||
Image
|- bgcolor="#89CFF0"
| ''' Week 8 ''' ||
The lingual epithelium shows first signs of taste bud development as nerve fibres penetrate epithelial basal lamina <ref name=PMID8955790/> and form synapses with taste bud progenitor cells. The synapses reach a maximum around the 12th to 13th week <ref name=PMID8955790/>. However, at this time these cells are still poorly differentiated, elongated epithelial cells <ref name=PMID8955790/> . The synapses demonstrate the neuronal connection between the taste bud primordium and the central nervous system <ref name=PMID8955790/>. Ciliated cells also appear around the 8th week, however the significance of these cells which are scattered randomly across the lingual surface remains unclear <ref name=PMID8955790/>.
||
Image
|- bgcolor="#BCD4E6"
|''' Weeks 8-9''' ||
“By this stage the top surface of circumvallate papillae usually contains a taste pit partly filled with microvilli of presumed underlying taste bud cells” (Figure 10) <ref name=PMID9455607/>
||
Image
|- bgcolor="#89CFF0"
|''' Weeks 10-11''' ||
At this stage, the lingual epithelium compromises of about four cell layers, and the first shallow grooves above the taste bud primordium are developed <ref name=PMID8955790/>.

Fungiform papillae appear on the lateral margins and the tip of the tongue <ref name=PMID9455607/>, containing taste bud primordial that display the first signs of a primitive pore formation <ref name=PMID8955790/>.

Untypically differentiated apical cellular processes extend onto the surface <ref name=PMID9455607/>

Some taste bud primordial contain cells that perforate the covering epithelial later with short, broad untypically differentiated apical cellular processes. (Figure 3,4) <ref name=PMID8955790/> <ref name=PMID9455607/>
||
Image
|- bgcolor="#BCD4E6"
|''' Week 12 ''' ||
Taste bud cells are more clearly differentiated into epithelial cell types II and III <ref name=PMID8955790/>.
||
Image
|- bgcolor="#89CFF0"
|''' Weeks 12-13 ''' ||
By this stage the taste bud primordial are all located on the top of dermal papillae (Fig 6a) <ref name=PMID8955790/>. There is also maximum synapses between cells and afferent nerve fibres, which intermingle with each other to form a plexus-like structure <ref name=PMID8955790/>.
||
Image
|- bgcolor="#BCD4E6"
|''' Weeks 14 -15 ''' ||
The shape of the taste buds primordial begins to resemble those of adult taste buds <ref name=PMID8955790/>. By the 14th week the taste pores develop as the taste pits are filled by microvilli <ref name=PMID8955790/>, indicating the possibility that the taste buds begin their gustatory function <ref name=PMID8955790/>, however they still lack an electron-dense mucous material (Fig.10) <ref name=PMID8955790/>. The tastebuds only achieve a fully developed function in week 15 of gestation with the development of type I cells to produce the mucous material in the taste pit <ref name=PMID8955790/>.
||
Image
|}

==Adult Tongue and Taste Buds – Structure and Function==

'''Structure'''

The tongue is located on the floor of the oral cavity, It is a muscular structure with sensory units crowning. The tongue is divided into an anterior two thirds and a posterior one third. These regions are divided by a V-shaped groove at the back of the tongue (sulcus terminalis). The anterior two thirds of the tongue is covered by stratified squamous epithelium, It contains a roughened surface and has projections called papillae that vary in shape and number.

''''The Image Below is a very simplistic Diagram of the surface of the Tongue showing the locations of the different papillae and other important features'''

{|
| [[Image:Drawing of Tongue.png|500px]]

'''Papillae'''
[[File:Papillae.jpg|Left|thumb|200px|Close up of Human Tongue Papillae]]

There are 4 types of papillae on the tongue.
The most numerous papillae are the filiform papillae, which function to provide a surface that aids in holding food on the tongue during chewing but do not contain taste buds. The larger, less numerous fungiform papillae which contain taste buds, as do foliate papillae. Circumvallate papillae form a wide V at the sulcus terminalis also containing taste bus. There are no papillae or taste buds located on the posterior third of the tongue, having mucosal folds and the lingual tonsils instead.

'''Function'''

The tongue is for tasting, swallowing, and speech.
The functional unit of the taste bud is a taste cell, there are between 50 and 100 taste cells in each taste bud these taste cells represent all 5 different tastes. Historically is was believed that different areas of the tongue were responsible for different taste sensations although this has since been disregarded.[http://users.rcn.com/jkimball.ma.ultranet/BiologyPages/W/Welcome.html] The papillae contain taste buds which are connected to the oral cavity via a taste pore, the function of the taste bud is to transmit a chemical signal from the oral cavity to a taste cell, this chemical signal is the converted into an electrical impulse and delivered to the brain via nerve fibres for interpretation.

'''The Image Below is a very simplistic Hand drawn Diagram of a taste bud, in an extreme close up, cross section view of the the taste bud unit, not to scale'''

[[File:Taste_bud_1.jpg]]

==Abnormalities==

===Knocking out P2X Receptors===

[[File:Image of taste being evoked by visualising ATP release.jpeg|Left|thumb|200px|Evoking taste - ATP release in tongue]]

Gustatory abnormalities has not been widely researched and what has been researched has been through animal testing, most commonly we have found on mice.

In Huang, 2008 this team used the release of the neurotransmitter, ATP (adenosine triphosphate) as a quantitative measurement of gustatory sensation and taste. This was done by using a comparison of wild type (WT) and double knockout (DKO) mice. P2X receptors, P2X2 and P2X3 were knocked out in the DKO mice. The premise of this article was that knocking out P2X receptors reduces transmitter secretion of ATP in taste buds, therefore they cannot taste.

It should be noted that the taste buds in DKO are functional, but are not stimulated by the administration of tastants.

The transmission of release of ATP is secretion through gap junction hemichannels (pannexin 1 gap junction).

When both P2X2 and P2X3 are knocked out, no taste is elicited. However they found that if either P2X2 OR P2X3 was knocked out there was a taste response. So the inference made from this is that if one of the two receptors from the P2X family was knocked out there still can have taste response. The WT mice showed significant stimulation by tastants whereas DKO had little to no stimulation of ATP release.<ref><pubmed>21940456</pubmed></ref>

===FGF signalling and genes===

Sprouty, or ''Srpy'', genes have been related to regulating the development of circumvillate papillae (CVP). The CVP are large dome shaped papillae, which form a 'V' just in front of the terminal sulcus.

By knocking out ''Spry'' genes using mice which had ''Spry1'' and ''Spry2'' knocked out showed that the number of CVP doubled. However, when Fibroblast Growth Factor gene ("Fgf10") was absent, the number of CVP was significantly reduced, if not completely absent. The correlation between ''Spry1/2'' and ''Fgf10'' is that ''Spry1/2'' antagonises "Fgf10" to limit the size of the CVP progenitor placode. Exclusive expression of ''Fgf10'' in the mesenchyme is necessary for the formation of CVP.

'''This image shows the CVP stained with H&E and scanned by Scanning Electron Microscope (SEM)'''
[[File:CVP of WT(top) and DKO(bottom) mice with H&E and SEM.png]]

'''This image shows the location of the CVP and the increased number in DKO mice by SEM'''
[[File:Mouse circumvallate papilla 01.jpg|300px]]

Taste buds develop from the mesenchyme but require local signalling to properly differentiate. Some signalling factors for proper development of taste buds besides FGF are: Sonic Hedgehog (SHH), Bone Morphogenetic Proteins (BMPs), Epidermal Growth Factor (EGF).

Additionally, this proves that the anterior and posterior developments of the tongue are derived from embryonic tissues, where the anterior tongue is derived from the ectoderm and the posterior tongue is derived from the endoderm. Taste buds develop from the mesenchyme but require local signalling to properly differentiate. Some signalling factors for proper development of taste buds besides FGF are: Sonic Hedgehog (SHH), Bone Morphogenetic Proteins (BMPs), Epidermal Growth Factor (EGF).

As mentioned above, this article shows that the anterior and posterior developments of the tongue are derived from embryonic tissues, where the anterior tongue is derived front the ectoderm and the posterior tongue is derived from the endoderm. Secondly, FGF is required to regulate the growth of taste buds, while ''Spry'' genes limit the number of CVP. ''Fgf10''& ''Spry 1&2''work antagonistically through receptor tyrosine kinase (RTK)signalling.

However, the deletion of ''Spry2''led to the increase of CVPs it should be noted that they found that a significant decrease in number of fungiform papillae. Contrastingly, the absence of ''Fgf10'', while leading to the absence of CVPs lead to an increase in number and size of fungiform papillae. Therefore these genes have different effects on the anterior and posterior developing tongue and taste buds.<ref><pubmed>21655085</pubmed></ref>

==Current Research==
We have an evolving understanding of Embryonic Taste development, through the use of state-of-the-art technology and research techniques we are able to make brilliant discoveries that continue to connect the dots of this amazing natural process of human development.
The majority of research in taste development is involving mice, these mammals show similar embryonic pathways to humans and research is performed in ethical and humane methods.

[[File:Histology.jpg|Left|thumb|200px|Image shows histological stains of a mice tongue showing dysplasia]]

'''Synergistic relationships of Six Genes '''

In an animal study using mice by Suzuki Y, Ikeda K, Kawakami K.(2011) Firstly nominating "Six Genes" as a major component in gustatory development, stating that deficiencies in certain Six genes (specifically Six1 & Six4) leads to poor development. Their research also highlights evidence of cooperative relationships between Six genes for normal advance. This experiment involved breeding mice containing exclusively Six1 and Six4 genes and examining the expression of these genes in papillae under high powered microscope observation. Understanding the role of certain genes along with the intrinsic relationships they hold is crucial for the ability to identify possible causes and correction of any abnormalities <ref><pubmed>21978088</pubmed></ref>

'''Neural Crest responsibilities '''

Another Animal Study involving mice explores a new idea of Neural crest (NC) contribution in taste development, specifically the development of papillae and taste buds. Liu HX, Komatsu Y, Mishina Y, Mistretta CM. (2012) suggest that Neural crest cells travel to the location of the tongue in early embryonic stages, gain epithelium phenotypes, multiply and then differentiate to eventually form taste papillae. The experiment involved the comparison of 2 different types of Cre line mice, which both express Cre gene in neural crest protocol, the different distribution patterns where observed in specific regions that NC is responsible for.<ref><pubmed>22659543</pubmed></ref>

'''Augmentation of Endoderm'''

In an animal study conducted by Rothova M, Thompson H, Lickert H, Tucker AS.(2012) exploring the historically debated issue of endoderm contribution to tongue development showed promising evidence that position of taste buds are patterned by the border of ectoderm and endoderm derivative epithelium. This study was accomplished via microscopic examination of previously stained specimens. Concluding endoderm has direct influence on gustatory develoment <ref><pubmed>22581563</pubmed></ref>

'''Changes in Taste Cells over time'''

Research by
Ozdener H, Spielman AI, Rawson NE.(2012) developing a culture which allows taste cells to survive for up to 12 months, empowers researchers to study the processes of proliferation, differentiation and function. This experiment will provide a precidnet for future study of taste cells, as these cells are able to operate and grow normally. <ref><pubmed>22643728</pubmed></ref>

'''Shh key component of taste bud proginators'''

A tamoxifen treatment which supresses Sonic hedgehog (Shh) secretion in mice proving to reduce the number of cells visable within papillae, in contrast mice not treated with tamoxifen showed a mark increase of cells within papillae, these cells are assumed to become taste cells in later development.
Specific mice were bred to trace the destination of taste placode cells, the study concluded that Shh expressing placodes are taste bud proginators which in turn become taste cells within taste buds although do not have any prescuros relationship with pappilae. The results were obtain by examination of mice embryos using Bright-field or multichannel fluorescent images through the use of an "Axiocam CCD camera and Axioplan fluorescence microscope with Axiovision software" a study by Harlow, Yang, Williams, Barlow (2011)<ref><pubmed>PMC2674259</pubmed></ref>

'''WNT family exhibit various roles'''

The WNT gene family has a function of signally proteins for various reason such as development, In 2010 Liu, Staubach Grosse, Walton, Saims, Gumucio, Mistretta explored recent findings on the role of WNT's in tongue and papillae development, Concluding that WNT/β-catenin is essential for fungiform papillae differing to WNT5a which proved to be principle in tongue development. Intrinsic chemical mediators were considered by manipulating a tissue culture and then throughaly examined by scanning photomicrograph. <ref><pubmed>PMC2768563</pubmed></ref>

[http://www.surgicalneurologyint.com/article.asp?issn=2152-7806;year=2012;volume=3;issue=1;spage=23;epage=23;aulast=Manjila]
[[File:Abnormal of tongue.jpg|Left|thumb|200px|Image shows and example of tongue abnormalities, this is called "double tongue" each side has independent movement!]]

==Useful links==

==Glossary==

ectoderm- outer germ layer of embryo

endoderm - inner germ layer of embryo

epithelium - basic animal tissue that is composed of tightly packed cells, usually covering the outer portion of organs

exocystosis - movement of contents out of cell

ganglia - the accumulation of a nerve cell body

growth factor - a substance that stimulates the growth of cells

gustatory - anything that relates to the taste sense

hydrolysis - breakdown of a chemical when it reacts with water

mesoderm - middle germ layer of embryo

mesenchyme - multipotential cells

neural crest - a part of the ectoderm found on both sides of the neural tube

neuron - most simplistic unit of the nervous system

neurotransmitter - chemicals which allow the passing of signals from neuron to neuron via connecting part (synapse)

papillae - small rough surface projection

six genes - a family of genes

Sonic hedgehog (Shh) - signalling protein invloved in normal development

sulcus terminalis - describes a physical transition point separating the anterior 2/3 of the tongue from the posterior 1/3

tamoxifen - hormonal altering drug

==Image gallery==

== References ==
<references/>

==External Links==
{{External Links}}

http://www.webmd.com/oral-health/picture-of-the-tongue

http://www.tutorvista.com/content/biology/biology-iv/nervous-coordination/tongue-structure.php#parts-of-tongue

http://www.cf.ac.uk/biosi/staffinfo/jacob/teaching/sensory/taste.html

--[[User:Z8600021|Mark Hill]] 12:22, 15 August 2012 (EST) Please leave the content listed below the line at the bottom of your project page.

----

{{2012Projects}}

2012 Group Project 3

2012-09-29T04:09:44Z

Z3289738: /* History of Discoveries */

=Taste Development=

== Introduction ==
**NEED TO ADD**

==History of Discoveries==

{| cellpadding=5 style="border:1px solid #BBB"
|- bgcolor="#faecc8"
|''' Date'''|| '''Significant Discovery'''

|- bgcolor="#faf6ed"
|'''350BC'''
|| Aristotle writes about the basic tastes, sweet and bitter. He also notes that it can be modified by salty and acidic. <ref><pubmed>22717400</pubmed></ref>

|- bgcolor="#faecc8"
|'''1901'''
|| D. Hanig publishes a paper describing taste sensitivity in different regions of the tongue.
''Interesting fact:'' The modern concept of a 'tongue map' is a misinterpretation of this study. <ref><pubmed>22717400</pubmed></ref>

|- bgcolor="#faf6ed"
|style=white-space:nowrap|'''1908'''
|Kikunae Ikeda, a professor of the Tokyo Imperial University, discovered and identified the fifth basic taste: umami (savouriness), made palatable by glutamate. <ref><pubmed>12438213</pubmed></ref>
[http://chemse.oxfordjournals.org/content/27/9/847.long New Seasonings]

|- bgcolor="#faecc8"
|style=white-space:nowrap|'''1931-32'''
| A chemist named Arthur Fox and his college noted that they had different sensitivities to the bitter tasting Phenylthiocarbamide (PTC).<ref>Blakeslee AF, Fox AL. Our different taste worlds. J Hered. 1932;23:97–107.</ref> Geneticists later confirm these findings, and discover that non-tasting is a recessive genetic trait. <ref><pubmed>17782493</pubmed></ref>
[http://www.ncbi.nlm.nih.gov/pubmed/17782493 Inherited taste deficiency]

|- bgcolor="#faf6ed"
|style=white-space:nowrap|'''1965'''
|Farbman's study of the developing taste but in rat fungiform papilla was significant in increasing our understanding of taste bud development. <ref><pubmed>14300090</pubmed></ref>
[http://www.sciencedirect.com/science/article/pii/0012160665900400 Electron microscope study of the developing taste bud in rat fungiform papilla.]

|- bgcolor="#faecc8"
|style=white-space:nowrap|'''1992'''
|McLaughlin SK et al. discovery a taste cell-specific G-protein within the taste buds called Gustucon. This protein is later used to mark bitter, umami and sweet cells. <ref><pubmed>1608467 </pubmed></ref>
[http://www.nature.com/nature/journal/v357/n6379/abs/357563a0.html Gustducin is a taste-cell-specific G protein closely related to the transducins]

|- bgcolor="#faf6ed"
|style=white-space:nowrap|'''1995'''
|Barlow et al. experimented with Axolotl salamanders and concluded that taste buds from this species arise exclusively from epithelial tissue, "oropharyngeal epithelium". <ref><pubmed>17826760</pubmed></ref>
[http://www.ncbi.nlm.nih.gov/pubmed/17826760 Embryonic origin of gustatory cranial sensory neurons.]

|- bgcolor="#faecc8"
|style=white-space:nowrap|'''1996'''
| Witt M and Reutter K of the Technical University Dresden in Germany, carried out a transmission electron microscopy study to investigate the embryonic and fetal development of Human taste buds. Their results suggest an "at least dual function of embryonic/fetal taste buds", including non-gustatory, paracrine functions prior to the 14th week and gustatory after the 14th week. <ref><pubmed>8955790</pubmed></ref>
[http://www.ncbi.nlm.nih.gov/pubmed/8955790 Embryonic and early fetal development of human taste buds: a transmission electron microscopical study]

|- bgcolor="#faf6ed"
|style=white-space:nowrap|'''2000'''
|Chandrashekar, J. et al. discover the first taste sonsors, the T2R bitter taste receptors. <ref><pubmed>10761935</pubmed></ref>
[http://www.sciencedirect.com/science/article/pii/S0092867400807060 T2Rs Function as Bitter Taste Receptors]

|- bgcolor="#faecc8"
|style=white-space:nowrap|'''2001'''
|Nelson, G. et al. discover the sweet receptor: a combination of T1R2 and T1R3. <ref><pubmed>11509186</pubmed></ref>
[http://www.ncbi.nlm.nih.gov/pubmed/11509186?dopt=Abstract&holding=npg Mammalian sweet taste receptors.]

|- bgcolor="#faf6ed"
|style=white-space:nowrap|'''2002'''
|Nelson G. et al. discover the amino acid (umami) taste receptor: a combination of T1R1 and T1R3 identified. <ref><pubmed>11894099</pubmed></ref>
[http://www.ncbi.nlm.nih.gov/pubmed/11894099?dopt=Abstract&holding=npg An amino-acid taste receptor]

|- bgcolor="#faecc8"
|style=white-space:nowrap|'''2005'''
|Dyer, J. et al. discover sweet taste receptors in the GI tract. <ref><pubmed>17855558</pubmed></ref>
[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1986582/ Sweet taste signaling in the gut]

|- bgcolor="#faf6ed"
|style=white-space:nowrap|'''2006'''
|Huang, A. L et al. discover cells for sour taste, identified by PKD2L1 (a polycystic kidney disease-like ion channel). <ref><pubmed>16929298</pubmed></ref>
[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1571047/ The Cells and Logic for Mammalian Sour Taste detection]

|- bgcolor="#faecc8"
|style=white-space:nowrap|'''2007'''
|Harlow DE, Barlow LA of the University of Colorado Denver Health Sciences Center provide evidence of the "embryonic origin of gustatory cranial sensory neurons". <ref><pubmed>17826760</pubmed></ref>
[http://www.ncbi.nlm.nih.gov/pubmed/17826760 Embryonic origin of gustatory cranial sensory neurons.]

|- bgcolor="#faf6ed"
|style=white-space:nowrap|'''2009'''
|A study by Hevezi P et al, presents "the first comprehensive characterization of gene expression in primate taste buds", as opposed to previous studies which focused on rodents. <ref><pubmed>19636377</pubmed></ref>
[http://www.ncbi.nlm.nih.gov/pubmed/19636377 Genome-wide analysis of gene expression in primate taste buds reveals links to diverse processes]

|- bgcolor="#faecc8"
|style=white-space:nowrap|'''2010'''
|Chandrashekar, J. et al. identify epithelial sodium channel (ENaC) as the sodium-salt taste receptor. <ref><pubmed>20107438</pubmed></ref>
[http://www.ncbi.nlm.nih.gov/pubmed/20107438?dopt=Abstract&holding=npg The cells and peripheral representation of sodium taste in mice]
|}

==Gustatory System==

[[Image:Taste qualities.gif|thumb|The five basic tastes]]

Taste or more appropriately gustation, is a fundamental survival tool in animals as it directs the consumption of essential nutrients. The five tastes that exist within the human gustatory system: salty, sweet, sour, bitter and umami, all signify basic physiological requirements. Salty tastes denote the presence of Na+, an important ion involved in the transportation and retention of water across cell membranes. Sweetness is the recognition of carbohydrates, essential for maintaining optimal brain function and providing the basis for energy production in muscle tissue via ATP hydrolysis. Similarly umami codes for the presence of L-amino acids, especially L-glutamate which is an integral component of protein synthesis.

These different modalities not only function to maintain the proper intake of nutrients within the body but also, by way of aversion, prohibit the consumption of undesired or poisonous materials. The bitter modality for example is generally regarded as displeasing to the human palate. It represents a high acid content which may be a result of foods which have become rotten or are inherently poisonous to the body.<ref name=PMID20696704><pubmed>20696704</pubmed></ref>

Research has historically limited itself to investigating the mechanisms of these five taste qualities though it must be noted many other modalities may exist. Of particular conjecture is the existence of fatty acid recognition. In the past the detection of fat in food has been attributed to somatosensory inputs <ref name=PMID20696704/> from the tongue, that is, the oily feel and texture of fat rather than its actual ‘taste’ allows the brain to encode for its presence. Further research is therefore required to elicit the precise mechanisms of fat detection.

===Cell Biology===

The five taste qualities are not all detected by the same type of receptor cell located within the taste bud. Like rods and cones in the eye which detect different wavelengths of light, there are specific types of receptors for different tastes. For example, sweet, umami and bitter are recognised by Type II G-protein coupled receptors, whereas sour is related to Type III presynaptic cells. The cell type involved in salty taste transduction is unknown however it is known that sodium ions can enter the receptor cell membrane via ion channel permeation.

====Type II receptors====

When a bitter, sweet or umami ligand binds to a type II G-coupled receptor, a cascade of chemical reactions causes the release of Ca2+ which in turn mediates exocystosis of ATP. The function of this ATP is threefold:

# Stimulates gustatory nerve afferents which project to gustatory nuclei in the spinal cord
# Excites Type III presynaptic nerve fibres to release serotonin.
# Has a positive feedback effect on type II receptor cells, increasing the level of ATP production.

The role of serotonin is believed to be in the form of lateral inhibition i.e. when a bitter quality is recognised, adjacent receptors for sweetness are deactivated and thus the two tastes may be clearly differentiated. It also has a negative feedback effect on receptor cells, inhibiting umami, bitter and sweet taste transduction.

==Taste Map==
[[Image:Taste map.png|thumb|left|250px|Obsolete idea of the tongue map]]
The idea of a tongue map has disseminated through society for many years. This concept purports that different areas of the tongue are specialised to detect either sweet, salty, sour and bitter tastes. Recent research however has completely nullified such claims and suggests instead that different forms of taste are recognised all over the tongue as well as via the palate. Thus the term ''taste map'' has come to take on a new meaning and that is, the precise areas of taste modalities processing in areas of cortex and its subsequent neural inputs.

===Neural Pathways===

'''First order neurons''' - From the receptors located in the taste buds, gustatory nerve afferents project to the ipsilateral rostral 1/3 of the nucleus tractus solitarius (NTS), located in the medulla. This rostral 1/3 is commonly referred to as the ''gustatory nucleus''.

The ''gustatory nucleus'' receives input from cranial nerves VII (''Facial n.''), IX (''Hypglossal n.''), and X (''Vagus n.'') via special visceral afferent (SVA) nerve fibres. A summary of their functions is as follows:

* ''Facial nerve n''. - carries taste information from the anterior 2/3 of the tongue.
* ''Hypoglossal n.'' - carries taste information from the posterior 1/3 of the tongue.
* ''Vagus n''. - carries taste information from the palate

'''Second order neurons''' - From the NTS second order neurons carry taste information to the Ventral posteromedial (VPM) nucleus in the thalamus.<ref name=PMID21885776/>

Copious scientific conjecture surrounds how each taste modality is transmitted to the brain. The ‘labelled-line’ hypothesis suggests that there are taste specific neurons which exclusively carry that taste modality to cortical areas. In analogous terms it can be viewed like the pipelines leading toward a house. Each pipeline carries its own utility, there is one for gas, another for water and finally for electricity with each terminating in slightly different areas of the house. In the same way, on the tongues there are different receptors for each taste which concurrently have individual nerve tracts leading to the primary gustatory cortex.

Contrapuntally there is electrophysiological evidence that single nerve afferents carry multiple modalities. These studies show one nerve afferent may have both a strong and a weak activation in response to a multiple taste stimuli.

===Cortical Areas===

[[Image:Primary gustatory cortex.png|thumb|Primary gustatory cortex]]

The location of the taste perception centres has been observed via functional magnetic resonance imaging (fMRI) studies. The primary taste cortex has been identified as being located in the anterior insula/frontal operculum (I/fO)<ref name=PMID22245354><pubmed>22245354</pubmed></ref>, with the secondary taste cortex in the caudolateral orbitofrontal cortex.<ref name=PMID21305668><pubmed>21305668</pubmed></ref> Within the insula there are further subdivisions related to each taste modality. Two photon calcium imaging research has outlined certain ’hot-spots’ of activation which are clearly delineated in relation to each taste. For example, the bitter modality is represented on the insula cortex approximately 1mm posterior to the middle cerebral artery whereas the sweet modality is represented 2.5mm rostrodorsal to the bitter field with no apparent overlap.<ref name=PMID21885776><pubmed>21885776</pubmed></ref> These findings lend weight to the idea that there is only one receptor for each taste quality.

It is interesting to note the relationship between taste and the reward centres of the brain. There is evidence of neural input to the ventral tegmental area (the origin of the mesolimbic dopaminergic reward pathway) and nucleus accumbens (involved in the conversion of motivation into physical action).<ref name=PMID21885776/> Neural connections such as this provide the foundations in explaining concepts such as flavour learning and preference. It may also give some insight into chronic problems such as food addiction and craving. As of yet however the gustatory neural network is not well understood and more research is required to elucidate the relationship between pleasure and taste sensation

==Timeline of Developmental Processes of the Gustatory System==

{| cellpadding=5 style="border:1px solid #BBB"
|- bgcolor="#89CFF0"
|'''Postovulatory Week'''||'''Description'''||'''Image'''
|- bgcolor="#BCD4E6"
|'''Week 6''' ||
The surface of the developing tongue is covered by nearly flat epitheliuem (Figure 1) <ref name=PMID9455607/>. The first gustatory papillae of the tongue appears in the caudal midline near the foramen caecum and the first circumvallate papilla develop on the dorsal midline <ref name=PMID9455607/> .
||
image
|- bgcolor="#89CFF0"
| '''Weeks 6 to 7'''||
Nerve fibres approach the basal lamina of lingual epithelium <ref name=PMID8955790><pubmed>8955790</pubmed></ref>. At this stage the lingual epithelium consists of two to three cell layers and there is not yet any sign of cell specializations indicating early taste bud formation<ref name=PMID8955790/>.
||
Image
|- bgcolor="#BCD4E6"
| '''Week 7 '''||
A series of epithelial swellings in the anterior part and midline of the tongue indicate early forming fungiform papillae (figure 2) <ref name=PMID9455607/>.
||
Image
|- bgcolor="#89CFF0"
| ''' Week 8 ''' ||
The lingual epithelium shows first signs of taste bud development as nerve fibres penetrate epithelial basal lamina <ref name=PMID8955790/> and form synapses with taste bud progenitor cells. The synapses reach a maximum around the 12th to 13th week <ref name=PMID8955790/>. However, at this time these cells are still poorly differentiated, elongated epithelial cells <ref name=PMID8955790/> . The synapses demonstrate the neuronal connection between the taste bud primordium and the central nervous system <ref name=PMID8955790/>. Ciliated cells also appear around the 8th week, however the significance of these cells which are scattered randomly across the lingual surface remains unclear <ref name=PMID8955790/>.
||
Image
|- bgcolor="#BCD4E6"
|''' Weeks 8-9''' ||
“By this stage the top surface of circumvallate papillae usually contains a taste pit partly filled with microvilli of presumed underlying taste bud cells” (Figure 10) <ref name=PMID9455607/>
||
Image
|- bgcolor="#89CFF0"
|''' Weeks 10-11''' ||
At this stage, the lingual epithelium compromises of about four cell layers, and the first shallow grooves above the taste bud primordium are developed <ref name=PMID8955790/>.

Fungiform papillae appear on the lateral margins and the tip of the tongue <ref name=PMID9455607/>, containing taste bud primordial that display the first signs of a primitive pore formation <ref name=PMID8955790/>.

Untypically differentiated apical cellular processes extend onto the surface <ref name=PMID9455607/>

Some taste bud primordial contain cells that perforate the covering epithelial later with short, broad untypically differentiated apical cellular processes. (Figure 3,4) <ref name=PMID8955790/> <ref name=PMID9455607/>
||
Image
|- bgcolor="#BCD4E6"
|''' Week 12 ''' ||
Taste bud cells are more clearly differentiated into epithelial cell types II and III <ref name=PMID8955790/>.
||
Image
|- bgcolor="#89CFF0"
|''' Weeks 12-13 ''' ||
By this stage the taste bud primordial are all located on the top of dermal papillae (Fig 6a) <ref name=PMID8955790/>. There is also maximum synapses between cells and afferent nerve fibres, which intermingle with each other to form a plexus-like structure <ref name=PMID8955790/>.
||
Image
|- bgcolor="#BCD4E6"
|''' Weeks 14 -15 ''' ||
The shape of the taste buds primordial begins to resemble those of adult taste buds <ref name=PMID8955790/>. By the 14th week the taste pores develop as the taste pits are filled by microvilli <ref name=PMID8955790/>, indicating the possibility that the taste buds begin their gustatory function <ref name=PMID8955790/>, however they still lack an electron-dense mucous material (Fig.10) <ref name=PMID8955790/>. The tastebuds only achieve a fully developed function in week 15 of gestation with the development of type I cells to produce the mucous material in the taste pit <ref name=PMID8955790/>.
||
Image
|}

==Adult Tongue and Taste Buds – Structure and Function==

'''Structure'''

The tongue is located on the floor of the oral cavity, It is a muscular structure with sensory units crowning. The tongue is divided into an anterior two thirds and a posterior one third. These regions are divided by a V-shaped groove at the back of the tongue (sulcus terminalis). The anterior two thirds of the tongue is covered by stratified squamous epithelium, It contains a roughened surface and has projections called papillae that vary in shape and number.

''''The Image Below is a very simplistic Diagram of the surface of the Tongue showing the locations of the different papillae and other important features'''

{|
| [[Image:Drawing of Tongue.png|500px]]

'''Papillae'''
[[File:Papillae.jpg|Left|thumb|200px|Close up of Human Tongue Papillae]]

There are 4 types of papillae on the tongue.
The most numerous papillae are the filiform papillae, which function to provide a surface that aids in holding food on the tongue during chewing but do not contain taste buds. The larger, less numerous fungiform papillae which contain taste buds, as do foliate papillae. Circumvallate papillae form a wide V at the sulcus terminalis also containing taste bus. There are no papillae or taste buds located on the posterior third of the tongue, having mucosal folds and the lingual tonsils instead.

'''Function'''

The tongue is for tasting, swallowing, and speech.
The functional unit of the taste bud is a taste cell, there are between 50 and 100 taste cells in each taste bud these taste cells represent all 5 different tastes. Historically is was believed that different areas of the tongue were responsible for different taste sensations although this has since been disregarded.[http://users.rcn.com/jkimball.ma.ultranet/BiologyPages/W/Welcome.html] The papillae contain taste buds which are connected to the oral cavity via a taste pore, the function of the taste bud is to transmit a chemical signal from the oral cavity to a taste cell, this chemical signal is the converted into an electrical impulse and delivered to the brain via nerve fibres for interpretation.

'''The Image Below is a very simplistic Hand drawn Diagram of a taste bud, in an extreme close up, cross section view of the the taste bud unit, not to scale'''

[[File:Taste_bud_1.jpg]]

==Abnormalities==

===Knocking out P2X Receptors===

[[File:Image of taste being evoked by visualising ATP release.jpeg|Left|thumb|200px|Evoking taste - ATP release in tongue]]

Gustatory abnormalities has not been widely researched and what has been researched has been through animal testing, most commonly we have found on mice.

In Huang, 2008 this team used the release of the neurotransmitter, ATP (adenosine triphosphate) as a quantitative measurement of gustatory sensation and taste. This was done by using a comparison of wild type (WT) and double knockout (DKO) mice. P2X receptors, P2X2 and P2X3 were knocked out in the DKO mice. The premise of this article was that knocking out P2X receptors reduces transmitter secretion of ATP in taste buds, therefore they cannot taste.

It should be noted that the taste buds in DKO are functional, but are not stimulated by the administration of tastants.

The transmission of release of ATP is secretion through gap junction hemichannels (pannexin 1 gap junction).

When both P2X2 and P2X3 are knocked out, no taste is elicited. However they found that if either P2X2 OR P2X3 was knocked out there was a taste response. So the inference made from this is that if one of the two receptors from the P2X family was knocked out there still can have taste response. The WT mice showed significant stimulation by tastants whereas DKO had little to no stimulation of ATP release.<ref><pubmed>21940456</pubmed></ref>

===FGF signalling and genes===

Sprouty, or ''Srpy'', genes have been related to regulating the development of circumvillate papillae (CVP). The CVP are large dome shaped papillae, which form a 'V' just in front of the terminal sulcus.

By knocking out ''Spry'' genes using mice which had ''Spry1'' and ''Spry2'' knocked out showed that the number of CVP doubled. However, when Fibroblast Growth Factor gene ("Fgf10") was absent, the number of CVP was significantly reduced, if not completely absent. The correlation between ''Spry1/2'' and ''Fgf10'' is that ''Spry1/2'' antagonises "Fgf10" to limit the size of the CVP progenitor placode. Exclusive expression of ''Fgf10'' in the mesenchyme is necessary for the formation of CVP.

'''This image shows the CVP stained with H&E and scanned by Scanning Electron Microscope (SEM)'''
[[File:CVP of WT(top) and DKO(bottom) mice with H&E and SEM.png]]

'''This image shows the location of the CVP and the increased number in DKO mice by SEM'''
[[File:Mouse circumvallate papilla 01.jpg|300px]]

Taste buds develop from the mesenchyme but require local signalling to properly differentiate. Some signalling factors for proper development of taste buds besides FGF are: Sonic Hedgehog (SHH), Bone Morphogenetic Proteins (BMPs), Epidermal Growth Factor (EGF).

Additionally, this proves that the anterior and posterior developments of the tongue are derived from embryonic tissues, where the anterior tongue is derived from the ectoderm and the posterior tongue is derived from the endoderm. Taste buds develop from the mesenchyme but require local signalling to properly differentiate. Some signalling factors for proper development of taste buds besides FGF are: Sonic Hedgehog (SHH), Bone Morphogenetic Proteins (BMPs), Epidermal Growth Factor (EGF).

As mentioned above, this article shows that the anterior and posterior developments of the tongue are derived from embryonic tissues, where the anterior tongue is derived front the ectoderm and the posterior tongue is derived from the endoderm. Secondly, FGF is required to regulate the growth of taste buds, while ''Spry'' genes limit the number of CVP. ''Fgf10''& ''Spry 1&2''work antagonistically through receptor tyrosine kinase (RTK)signalling.

However, the deletion of ''Spry2''led to the increase of CVPs it should be noted that they found that a significant decrease in number of fungiform papillae. Contrastingly, the absence of ''Fgf10'', while leading to the absence of CVPs lead to an increase in number and size of fungiform papillae. Therefore these genes have different effects on the anterior and posterior developing tongue and taste buds.<ref><pubmed>21655085</pubmed></ref>

==Current Research==
We have an evolving understanding of Embryonic Taste development, through the use of state-of-the-art technology and research techniques we are able to make brilliant discoveries that continue to connect the dots of this amazing natural process of human development.
The majority of research in taste development is involving mice, these mammals show similar embryonic pathways to humans and research is performed in ethical and humane methods.

[[File:Histology.jpg|Left|thumb|200px|Image shows histological stains of a mice tongue showing dysplasia]]

'''Synergistic relationships of Six Genes '''

In an animal study using mice by Suzuki Y, Ikeda K, Kawakami K.(2011) Firstly nominating "Six Genes" as a major component in gustatory development, stating that deficiencies in certain Six genes (specifically Six1 & Six4) leads to poor development. Their research also highlights evidence of cooperative relationships between Six genes for normal advance. This experiment involved breeding mice containing exclusively Six1 and Six4 genes and examining the expression of these genes in papillae under high powered microscope observation. Understanding the role of certain genes along with the intrinsic relationships they hold is crucial for the ability to identify possible causes and correction of any abnormalities <ref><pubmed>21978088</pubmed></ref>

'''Neural Crest responsibilities '''

Another Animal Study involving mice explores a new idea of Neural crest (NC) contribution in taste development, specifically the development of papillae and taste buds. Liu HX, Komatsu Y, Mishina Y, Mistretta CM. (2012) suggest that Neural crest cells travel to the location of the tongue in early embryonic stages, gain epithelium phenotypes, multiply and then differentiate to eventually form taste papillae. The experiment involved the comparison of 2 different types of Cre line mice, which both express Cre gene in neural crest protocol, the different distribution patterns where observed in specific regions that NC is responsible for.<ref><pubmed>22659543</pubmed></ref>

'''Augmentation of Endoderm'''

In an animal study conducted by Rothova M, Thompson H, Lickert H, Tucker AS.(2012) exploring the historically debated issue of endoderm contribution to tongue development showed promising evidence that position of taste buds are patterned by the border of ectoderm and endoderm derivative epithelium. This study was accomplished via microscopic examination of previously stained specimens. Concluding endoderm has direct influence on gustatory develoment <ref><pubmed>22581563</pubmed></ref>

'''Changes in Taste Cells over time'''

Research by
Ozdener H, Spielman AI, Rawson NE.(2012) developing a culture which allows taste cells to survive for up to 12 months, empowers researchers to study the processes of proliferation, differentiation and function. This experiment will provide a precidnet for future study of taste cells, as these cells are able to operate and grow normally. <ref><pubmed>22643728</pubmed></ref>

'''Shh key component of taste bud proginators'''

A tamoxifen treatment which supresses Sonic hedgehog (Shh) secretion in mice proving to reduce the number of cells visable within papillae, in contrast mice not treated with tamoxifen showed a mark increase of cells within papillae, these cells are assumed to become taste cells in later development.
Specific mice were bred to trace the destination of taste placode cells, the study concluded that Shh expressing placodes are taste bud proginators which in turn become taste cells within taste buds although do not have any prescuros relationship with pappilae. The results were obtain by examination of mice embryos using Bright-field or multichannel fluorescent images through the use of an "Axiocam CCD camera and Axioplan fluorescence microscope with Axiovision software" a study by Harlow, Yang, Williams, Barlow (2011)<ref><pubmed>PMC2674259</pubmed></ref>

'''WNT family exhibit various roles'''

The WNT gene family has a function of signally proteins for various reason such as development, In 2010 Liu, Staubach Grosse, Walton, Saims, Gumucio, Mistretta explored recent findings on the role of WNT's in tongue and papillae development, Concluding that WNT/β-catenin is essential for fungiform papillae differing to WNT5a which proved to be principle in tongue development. Intrinsic chemical mediators were considered by manipulating a tissue culture and then throughaly examined by scanning photomicrograph. <ref><pubmed>PMC2768563</pubmed></ref>

[http://www.surgicalneurologyint.com/article.asp?issn=2152-7806;year=2012;volume=3;issue=1;spage=23;epage=23;aulast=Manjila]
[[File:Abnormal of tongue.jpg|Left|thumb|200px|Image shows and example of tongue abnormalities, this is called "double tongue" each side has independent movement!]]

==Useful links==

==Glossary==

ectoderm- outer germ layer of embryo

endoderm - inner germ layer of embryo

epithelium - basic animal tissue that is composed of tightly packed cells, usually covering the outer portion of organs

exocystosis - movement of contents out of cell

ganglia - the accumulation of a nerve cell body

growth factor - a substance that stimulates the growth of cells

gustatory - anything that relates to the taste sense

hydrolysis - breakdown of a chemical when it reacts with water

mesoderm - middle germ layer of embryo

mesenchyme - multipotential cells

neural crest - a part of the ectoderm found on both sides of the neural tube

neuron - most simplistic unit of the nervous system

neurotransmitter - chemicals which allow the passing of signals from neuron to neuron via connecting part (synapse)

papillae - small rough surface projection

six genes - a family of genes

Sonic hedgehog (Shh) - signalling protein invloved in normal development

sulcus terminalis - describes a physical transition point separating the anterior 2/3 of the tongue from the posterior 1/3

tamoxifen - hormonal altering drug

==Image gallery==

== References ==
<references/>

==External Links==
{{External Links}}

http://www.webmd.com/oral-health/picture-of-the-tongue

http://www.tutorvista.com/content/biology/biology-iv/nervous-coordination/tongue-structure.php#parts-of-tongue

http://www.cf.ac.uk/biosi/staffinfo/jacob/teaching/sensory/taste.html

--[[User:Z8600021|Mark Hill]] 12:22, 15 August 2012 (EST) Please leave the content listed below the line at the bottom of your project page.

----

{{2012Projects}}

2012 Group Project 3

2012-09-29T04:04:49Z

Z3289738: /* History of Discoveries */

=Taste Development=

== Introduction ==
**NEED TO ADD**

==History of Discoveries==

{| cellpadding=5 style="border:1px solid #BBB"
|- bgcolor="#faecc8"
|''' Date'''|| '''Significant Discovery'''

|- bgcolor="#faf6ed"
|'''350BC'''
|| Aristotle writes about the basic tastes, sweet and bitter. He also notes that it can be modified by salty and acidic. <ref><pubmed>22717400</pubmed></ref>

|- bgcolor="#faecc8"
|'''1901'''
|| D. Hanig publishes a paper describing taste sensitivity in different regions of the tongue.
''Interesting fact:'' The modern concept of a 'tongue map' is a misinterpretation of this study. <ref><pubmed>22717400</pubmed></ref>

|- bgcolor="#faf6ed"
|style=white-space:nowrap|'''1908'''
|Kikunae Ikeda, a professor of the Tokyo Imperial University, discovered and identified the fifth basic taste: umami (savouriness), made palatable by glutamate. <ref><pubmed>12438213</pubmed></ref> [http://chemse.oxfordjournals.org/content/27/9/847.long New Seasonings]

|- bgcolor="#faf6ed"
|style=white-space:nowrap|'''1931-32'''
| A chemist named Arthur Fox and his college noted that they had different sensitivities to the bitter tasting Phenylthiocarbamide (PTC).<ref>Blakeslee AF, Fox AL. Our different taste worlds. J Hered. 1932;23:97–107.</ref> [ Genetisists later confirm these findings, and discover that non-tasting is a recessive genetic trait. <ref><pubmed>17782493</pubmed></ref> [http://www.ncbi.nlm.nih.gov/pubmed/17782493 Inherited taste deficiency]

|- bgcolor="#faecc8"
|style=white-space:nowrap|'''1965'''
|Farbman's study of the developing taste but in rat fungiform papilla was significant in increasing our understanding of taste bud development. <ref><pubmed>14300090</pubmed></ref> [http://www.sciencedirect.com/science/article/pii/0012160665900400 Electron microscope study of the developing taste bud in rat fungiform papilla.]

|- bgcolor="#faf6ed"
|style=white-space:nowrap|'''1992'''
|McLaughlin SK et al. discovery a taste cell-specific G-protein within the taste buds called Gustucon. This protein is later used to mark bitter, umami and sweet cells. <ref><pubmed>1608467 </pubmed></ref> [http://www.nature.com/nature/journal/v357/n6379/abs/357563a0.html Gustducin is a taste-cell-specific G protein closely related to the transducins]

|- bgcolor="#faecc8"
|style=white-space:nowrap|'''1995'''
|Barlow et al. experimented with Axolotl salamanders and concluded that taste buds from this species arise exclusively from epithelial tissue, "oropharyngeal epithelium". <ref><pubmed>17826760</pubmed></ref> [http://www.ncbi.nlm.nih.gov/pubmed/17826760 Embryonic origin of gustatory cranial sensory neurons.]

|- bgcolor="#faf6ed"
|style=white-space:nowrap|'''1996'''
| Witt M and Reutter K of the Technical University Dresden in Germany, carried out a transmission electron microscopy study to investigate the embryonic and fetal development of Human taste buds. Their results suggest an "at least dual function of embryonic/fetal taste buds", including non-gustatory, paracrine functions prior to the 14th week and gustatory after the 14th week. <ref><pubmed>8955790</pubmed></ref> [http://www.ncbi.nlm.nih.gov/pubmed/8955790 Embryonic and early fetal development of human taste buds: a transmission electron microscopical study]

|- bgcolor="#faecc8"
|style=white-space:nowrap|'''2000'''
|Chandrashekar, J. et al. discover the first taste sonsors, the T2R bitter taste receptors. <ref><pubmed>10761935</pubmed></ref> [http://www.sciencedirect.com/science/article/pii/S0092867400807060 T2Rs Function as Bitter Taste Receptors]

|- bgcolor="#faf6ed"
|style=white-space:nowrap|'''2001'''
|Nelson, G. et al. discover the sweet receptor: a combination of T1R2 and T1R3. <ref><pubmed>11509186</pubmed></ref> [http://www.ncbi.nlm.nih.gov/pubmed/11509186?dopt=Abstract&holding=npg Mammalian sweet taste receptors.]

|- bgcolor="#faecc8"
|style=white-space:nowrap|'''2002'''
|Nelson G. et al. discover the amino acid (umami) taste receptor: a combination of T1R1 and T1R3 identified. <ref><pubmed>11894099</pubmed></ref> [http://www.ncbi.nlm.nih.gov/pubmed/11894099?dopt=Abstract&holding=npg An amino-acid taste receptor]

|- bgcolor="#faf6ed"
|style=white-space:nowrap|'''2005'''
|Dyer, J. et al. discover sweet taste receptors in the GI tract. <ref><pubmed>17855558</pubmed></ref> [http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1986582/ Sweet taste signaling in the gut]

|- bgcolor="#faecc8"
|style=white-space:nowrap|'''2006'''
|Huang, A. L et al. discover cells for sour taste, identified by PKD2L1 (a polycystic kidney disease-like ion channel). <ref><pubmed>16929298</pubmed></ref> [http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1571047/ The Cells and Logic for Mammalian Sour Taste detection]

|- bgcolor="#faf6ed"
|style=white-space:nowrap|'''2007'''
|Harlow DE, Barlow LA of the University of Colorado Denver Health Sciences Center provide evidence of the "embryonic origin of gustatory cranial sensory neurons". <ref><pubmed>17826760</pubmed></ref> [http://www.ncbi.nlm.nih.gov/pubmed/17826760 Embryonic origin of gustatory cranial sensory neurons.]

|- bgcolor="#faecc8"
|style=white-space:nowrap|'''2009'''
|A study by Hevezi P et al, presents "the first comprehensive characterization of gene expression in primate taste buds", as opposed to previous studies which focused on rodents. <ref><pubmed>19636377</pubmed></ref> [http://www.ncbi.nlm.nih.gov/pubmed/19636377 Genome-wide analysis of gene expression in primate taste buds reveals links to diverse processes]

|- bgcolor="#faf6ed"
|style=white-space:nowrap|'''2010'''
|Chandrashekar, J. et al. identify epithelial sodium channel (ENaC) as the sodium-salt taste receptor. <ref><pubmed>20107438</pubmed></ref> [http://www.ncbi.nlm.nih.gov/pubmed/20107438?dopt=Abstract&holding=npg The cells and peripheral representation of sodium taste in mice]
|}

==Gustatory System==

[[Image:Taste qualities.gif|thumb|The five basic tastes]]

Taste or more appropriately gustation, is a fundamental survival tool in animals as it directs the consumption of essential nutrients. The five tastes that exist within the human gustatory system: salty, sweet, sour, bitter and umami, all signify basic physiological requirements. Salty tastes denote the presence of Na+, an important ion involved in the transportation and retention of water across cell membranes. Sweetness is the recognition of carbohydrates, essential for maintaining optimal brain function and providing the basis for energy production in muscle tissue via ATP hydrolysis. Similarly umami codes for the presence of L-amino acids, especially L-glutamate which is an integral component of protein synthesis.

These different modalities not only function to maintain the proper intake of nutrients within the body but also, by way of aversion, prohibit the consumption of undesired or poisonous materials. The bitter modality for example is generally regarded as displeasing to the human palate. It represents a high acid content which may be a result of foods which have become rotten or are inherently poisonous to the body.<ref name=PMID20696704><pubmed>20696704</pubmed></ref>

Research has historically limited itself to investigating the mechanisms of these five taste qualities though it must be noted many other modalities may exist. Of particular conjecture is the existence of fatty acid recognition. In the past the detection of fat in food has been attributed to somatosensory inputs <ref name=PMID20696704/> from the tongue, that is, the oily feel and texture of fat rather than its actual ‘taste’ allows the brain to encode for its presence. Further research is therefore required to elicit the precise mechanisms of fat detection.

===Cell Biology===

The five taste qualities are not all detected by the same type of receptor cell located within the taste bud. Like rods and cones in the eye which detect different wavelengths of light, there are specific types of receptors for different tastes. For example, sweet, umami and bitter are recognised by Type II G-protein coupled receptors, whereas sour is related to Type III presynaptic cells. The cell type involved in salty taste transduction is unknown however it is known that sodium ions can enter the receptor cell membrane via ion channel permeation.

====Type II receptors====

When a bitter, sweet or umami ligand binds to a type II G-coupled receptor, a cascade of chemical reactions causes the release of Ca2+ which in turn mediates exocystosis of ATP. The function of this ATP is threefold:

# Stimulates gustatory nerve afferents which project to gustatory nuclei in the spinal cord
# Excites Type III presynaptic nerve fibres to release serotonin.
# Has a positive feedback effect on type II receptor cells, increasing the level of ATP production.

The role of serotonin is believed to be in the form of lateral inhibition i.e. when a bitter quality is recognised, adjacent receptors for sweetness are deactivated and thus the two tastes may be clearly differentiated. It also has a negative feedback effect on receptor cells, inhibiting umami, bitter and sweet taste transduction.

==Taste Map==
[[Image:Taste map.png|thumb|left|250px|Obsolete idea of the tongue map]]
The idea of a tongue map has disseminated through society for many years. This concept purports that different areas of the tongue are specialised to detect either sweet, salty, sour and bitter tastes. Recent research however has completely nullified such claims and suggests instead that different forms of taste are recognised all over the tongue as well as via the palate. Thus the term ''taste map'' has come to take on a new meaning and that is, the precise areas of taste modalities processing in areas of cortex and its subsequent neural inputs.

===Neural Pathways===

'''First order neurons''' - From the receptors located in the taste buds, gustatory nerve afferents project to the ipsilateral rostral 1/3 of the nucleus tractus solitarius (NTS), located in the medulla. This rostral 1/3 is commonly referred to as the ''gustatory nucleus''.

The ''gustatory nucleus'' receives input from cranial nerves VII (''Facial n.''), IX (''Hypglossal n.''), and X (''Vagus n.'') via special visceral afferent (SVA) nerve fibres. A summary of their functions is as follows:

* ''Facial nerve n''. - carries taste information from the anterior 2/3 of the tongue.
* ''Hypoglossal n.'' - carries taste information from the posterior 1/3 of the tongue.
* ''Vagus n''. - carries taste information from the palate

'''Second order neurons''' - From the NTS second order neurons carry taste information to the Ventral posteromedial (VPM) nucleus in the thalamus.<ref name=PMID21885776/>

Copious scientific conjecture surrounds how each taste modality is transmitted to the brain. The ‘labelled-line’ hypothesis suggests that there are taste specific neurons which exclusively carry that taste modality to cortical areas. In analogous terms it can be viewed like the pipelines leading toward a house. Each pipeline carries its own utility, there is one for gas, another for water and finally for electricity with each terminating in slightly different areas of the house. In the same way, on the tongues there are different receptors for each taste which concurrently have individual nerve tracts leading to the primary gustatory cortex.

Contrapuntally there is electrophysiological evidence that single nerve afferents carry multiple modalities. These studies show one nerve afferent may have both a strong and a weak activation in response to a multiple taste stimuli.

===Cortical Areas===

[[Image:Primary gustatory cortex.png|thumb|Primary gustatory cortex]]

The location of the taste perception centres has been observed via functional magnetic resonance imaging (fMRI) studies. The primary taste cortex has been identified as being located in the anterior insula/frontal operculum (I/fO)<ref name=PMID22245354><pubmed>22245354</pubmed></ref>, with the secondary taste cortex in the caudolateral orbitofrontal cortex.<ref name=PMID21305668><pubmed>21305668</pubmed></ref> Within the insula there are further subdivisions related to each taste modality. Two photon calcium imaging research has outlined certain ’hot-spots’ of activation which are clearly delineated in relation to each taste. For example, the bitter modality is represented on the insula cortex approximately 1mm posterior to the middle cerebral artery whereas the sweet modality is represented 2.5mm rostrodorsal to the bitter field with no apparent overlap.<ref name=PMID21885776><pubmed>21885776</pubmed></ref> These findings lend weight to the idea that there is only one receptor for each taste quality.

It is interesting to note the relationship between taste and the reward centres of the brain. There is evidence of neural input to the ventral tegmental area (the origin of the mesolimbic dopaminergic reward pathway) and nucleus accumbens (involved in the conversion of motivation into physical action).<ref name=PMID21885776/> Neural connections such as this provide the foundations in explaining concepts such as flavour learning and preference. It may also give some insight into chronic problems such as food addiction and craving. As of yet however the gustatory neural network is not well understood and more research is required to elucidate the relationship between pleasure and taste sensation

==Timeline of Developmental Processes of the Gustatory System==

{| cellpadding=5 style="border:1px solid #BBB"
|- bgcolor="#89CFF0"
|'''Postovulatory Week'''||'''Description'''||'''Image'''
|- bgcolor="#BCD4E6"
|'''Week 6''' ||
The surface of the developing tongue is covered by nearly flat epitheliuem (Figure 1) <ref name=PMID9455607/>. The first gustatory papillae of the tongue appears in the caudal midline near the foramen caecum and the first circumvallate papilla develop on the dorsal midline <ref name=PMID9455607/> .
||
image
|- bgcolor="#89CFF0"
| '''Weeks 6 to 7'''||
Nerve fibres approach the basal lamina of lingual epithelium <ref name=PMID8955790><pubmed>8955790</pubmed></ref>. At this stage the lingual epithelium consists of two to three cell layers and there is not yet any sign of cell specializations indicating early taste bud formation<ref name=PMID8955790/>.
||
Image
|- bgcolor="#BCD4E6"
| '''Week 7 '''||
A series of epithelial swellings in the anterior part and midline of the tongue indicate early forming fungiform papillae (figure 2) <ref name=PMID9455607/>.
||
Image
|- bgcolor="#89CFF0"
| ''' Week 8 ''' ||
The lingual epithelium shows first signs of taste bud development as nerve fibres penetrate epithelial basal lamina <ref name=PMID8955790/> and form synapses with taste bud progenitor cells. The synapses reach a maximum around the 12th to 13th week <ref name=PMID8955790/>. However, at this time these cells are still poorly differentiated, elongated epithelial cells <ref name=PMID8955790/> . The synapses demonstrate the neuronal connection between the taste bud primordium and the central nervous system <ref name=PMID8955790/>. Ciliated cells also appear around the 8th week, however the significance of these cells which are scattered randomly across the lingual surface remains unclear <ref name=PMID8955790/>.
||
Image
|- bgcolor="#BCD4E6"
|''' Weeks 8-9''' ||
“By this stage the top surface of circumvallate papillae usually contains a taste pit partly filled with microvilli of presumed underlying taste bud cells” (Figure 10) <ref name=PMID9455607/>
||
Image
|- bgcolor="#89CFF0"
|''' Weeks 10-11''' ||
At this stage, the lingual epithelium compromises of about four cell layers, and the first shallow grooves above the taste bud primordium are developed <ref name=PMID8955790/>.

Fungiform papillae appear on the lateral margins and the tip of the tongue <ref name=PMID9455607/>, containing taste bud primordial that display the first signs of a primitive pore formation <ref name=PMID8955790/>.

Untypically differentiated apical cellular processes extend onto the surface <ref name=PMID9455607/>

Some taste bud primordial contain cells that perforate the covering epithelial later with short, broad untypically differentiated apical cellular processes. (Figure 3,4) <ref name=PMID8955790/> <ref name=PMID9455607/>
||
Image
|- bgcolor="#BCD4E6"
|''' Week 12 ''' ||
Taste bud cells are more clearly differentiated into epithelial cell types II and III <ref name=PMID8955790/>.
||
Image
|- bgcolor="#89CFF0"
|''' Weeks 12-13 ''' ||
By this stage the taste bud primordial are all located on the top of dermal papillae (Fig 6a) <ref name=PMID8955790/>. There is also maximum synapses between cells and afferent nerve fibres, which intermingle with each other to form a plexus-like structure <ref name=PMID8955790/>.
||
Image
|- bgcolor="#BCD4E6"
|''' Weeks 14 -15 ''' ||
The shape of the taste buds primordial begins to resemble those of adult taste buds <ref name=PMID8955790/>. By the 14th week the taste pores develop as the taste pits are filled by microvilli <ref name=PMID8955790/>, indicating the possibility that the taste buds begin their gustatory function <ref name=PMID8955790/>, however they still lack an electron-dense mucous material (Fig.10) <ref name=PMID8955790/>. The tastebuds only achieve a fully developed function in week 15 of gestation with the development of type I cells to produce the mucous material in the taste pit <ref name=PMID8955790/>.
||
Image
|}

==Adult Tongue and Taste Buds – Structure and Function==

'''Structure'''

The tongue is located on the floor of the oral cavity, It is a muscular structure with sensory units crowning. The tongue is divided into an anterior two thirds and a posterior one third. These regions are divided by a V-shaped groove at the back of the tongue (sulcus terminalis). The anterior two thirds of the tongue is covered by stratified squamous epithelium, It contains a roughened surface and has projections called papillae that vary in shape and number.

''''The Image Below is a very simplistic Diagram of the surface of the Tongue showing the locations of the different papillae and other important features'''

{|
| [[Image:Drawing of Tongue.png|500px]]

'''Papillae'''
[[File:Papillae.jpg|Left|thumb|200px|Close up of Human Tongue Papillae]]

There are 4 types of papillae on the tongue.
The most numerous papillae are the filiform papillae, which function to provide a surface that aids in holding food on the tongue during chewing but do not contain taste buds. The larger, less numerous fungiform papillae which contain taste buds, as do foliate papillae. Circumvallate papillae form a wide V at the sulcus terminalis also containing taste bus. There are no papillae or taste buds located on the posterior third of the tongue, having mucosal folds and the lingual tonsils instead.

'''Function'''

The tongue is for tasting, swallowing, and speech.
The functional unit of the taste bud is a taste cell, there are between 50 and 100 taste cells in each taste bud these taste cells represent all 5 different tastes. Historically is was believed that different areas of the tongue were responsible for different taste sensations although this has since been disregarded.[http://users.rcn.com/jkimball.ma.ultranet/BiologyPages/W/Welcome.html] The papillae contain taste buds which are connected to the oral cavity via a taste pore, the function of the taste bud is to transmit a chemical signal from the oral cavity to a taste cell, this chemical signal is the converted into an electrical impulse and delivered to the brain via nerve fibres for interpretation.

'''The Image Below is a very simplistic Hand drawn Diagram of a taste bud, in an extreme close up, cross section view of the the taste bud unit, not to scale'''

[[File:Taste_bud_1.jpg]]

==Abnormalities==

===Knocking out P2X Receptors===

[[File:Image of taste being evoked by visualising ATP release.jpeg|Left|thumb|200px|Evoking taste - ATP release in tongue]]

Gustatory abnormalities has not been widely researched and what has been researched has been through animal testing, most commonly we have found on mice.

In Huang, 2008 this team used the release of the neurotransmitter, ATP (adenosine triphosphate) as a quantitative measurement of gustatory sensation and taste. This was done by using a comparison of wild type (WT) and double knockout (DKO) mice. P2X receptors, P2X2 and P2X3 were knocked out in the DKO mice. The premise of this article was that knocking out P2X receptors reduces transmitter secretion of ATP in taste buds, therefore they cannot taste.

It should be noted that the taste buds in DKO are functional, but are not stimulated by the administration of tastants.

The transmission of release of ATP is secretion through gap junction hemichannels (pannexin 1 gap junction).

When both P2X2 and P2X3 are knocked out, no taste is elicited. However they found that if either P2X2 OR P2X3 was knocked out there was a taste response. So the inference made from this is that if one of the two receptors from the P2X family was knocked out there still can have taste response. The WT mice showed significant stimulation by tastants whereas DKO had little to no stimulation of ATP release.<ref><pubmed>21940456</pubmed></ref>

===FGF signalling and genes===

Sprouty, or ''Srpy'', genes have been related to regulating the development of circumvillate papillae (CVP). The CVP are large dome shaped papillae, which form a 'V' just in front of the terminal sulcus.

By knocking out ''Spry'' genes using mice which had ''Spry1'' and ''Spry2'' knocked out showed that the number of CVP doubled. However, when Fibroblast Growth Factor gene ("Fgf10") was absent, the number of CVP was significantly reduced, if not completely absent. The correlation between ''Spry1/2'' and ''Fgf10'' is that ''Spry1/2'' antagonises "Fgf10" to limit the size of the CVP progenitor placode. Exclusive expression of ''Fgf10'' in the mesenchyme is necessary for the formation of CVP.

'''This image shows the CVP stained with H&E and scanned by Scanning Electron Microscope (SEM)'''
[[File:CVP of WT(top) and DKO(bottom) mice with H&E and SEM.png]]

'''This image shows the location of the CVP and the increased number in DKO mice by SEM'''
[[File:Mouse circumvallate papilla 01.jpg|300px]]

Taste buds develop from the mesenchyme but require local signalling to properly differentiate. Some signalling factors for proper development of taste buds besides FGF are: Sonic Hedgehog (SHH), Bone Morphogenetic Proteins (BMPs), Epidermal Growth Factor (EGF).

Additionally, this proves that the anterior and posterior developments of the tongue are derived from embryonic tissues, where the anterior tongue is derived from the ectoderm and the posterior tongue is derived from the endoderm. Taste buds develop from the mesenchyme but require local signalling to properly differentiate. Some signalling factors for proper development of taste buds besides FGF are: Sonic Hedgehog (SHH), Bone Morphogenetic Proteins (BMPs), Epidermal Growth Factor (EGF).

As mentioned above, this article shows that the anterior and posterior developments of the tongue are derived from embryonic tissues, where the anterior tongue is derived front the ectoderm and the posterior tongue is derived from the endoderm. Secondly, FGF is required to regulate the growth of taste buds, while ''Spry'' genes limit the number of CVP. ''Fgf10''& ''Spry 1&2''work antagonistically through receptor tyrosine kinase (RTK)signalling.

However, the deletion of ''Spry2''led to the increase of CVPs it should be noted that they found that a significant decrease in number of fungiform papillae. Contrastingly, the absence of ''Fgf10'', while leading to the absence of CVPs lead to an increase in number and size of fungiform papillae. Therefore these genes have different effects on the anterior and posterior developing tongue and taste buds.<ref><pubmed>21655085</pubmed></ref>

==Current Research==
We have an evolving understanding of Embryonic Taste development, through the use of state-of-the-art technology and research techniques we are able to make brilliant discoveries that continue to connect the dots of this amazing natural process of human development.
The majority of research in taste development is involving mice, these mammals show similar embryonic pathways to humans and research is performed in ethical and humane methods.

[[File:Histology.jpg|Left|thumb|200px|Image shows histological stains of a mice tongue showing dysplasia]]

'''Synergistic relationships of Six Genes '''

In an animal study using mice by Suzuki Y, Ikeda K, Kawakami K.(2011) Firstly nominating "Six Genes" as a major component in gustatory development, stating that deficiencies in certain Six genes (specifically Six1 & Six4) leads to poor development. Their research also highlights evidence of cooperative relationships between Six genes for normal advance. This experiment involved breeding mice containing exclusively Six1 and Six4 genes and examining the expression of these genes in papillae under high powered microscope observation. Understanding the role of certain genes along with the intrinsic relationships they hold is crucial for the ability to identify possible causes and correction of any abnormalities <ref><pubmed>21978088</pubmed></ref>

'''Neural Crest responsibilities '''

Another Animal Study involving mice explores a new idea of Neural crest (NC) contribution in taste development, specifically the development of papillae and taste buds. Liu HX, Komatsu Y, Mishina Y, Mistretta CM. (2012) suggest that Neural crest cells travel to the location of the tongue in early embryonic stages, gain epithelium phenotypes, multiply and then differentiate to eventually form taste papillae. The experiment involved the comparison of 2 different types of Cre line mice, which both express Cre gene in neural crest protocol, the different distribution patterns where observed in specific regions that NC is responsible for.<ref><pubmed>22659543</pubmed></ref>

'''Augmentation of Endoderm'''

In an animal study conducted by Rothova M, Thompson H, Lickert H, Tucker AS.(2012) exploring the historically debated issue of endoderm contribution to tongue development showed promising evidence that position of taste buds are patterned by the border of ectoderm and endoderm derivative epithelium. This study was accomplished via microscopic examination of previously stained specimens. Concluding endoderm has direct influence on gustatory develoment <ref><pubmed>22581563</pubmed></ref>

'''Changes in Taste Cells over time'''

Research by
Ozdener H, Spielman AI, Rawson NE.(2012) developing a culture which allows taste cells to survive for up to 12 months, empowers researchers to study the processes of proliferation, differentiation and function. This experiment will provide a precidnet for future study of taste cells, as these cells are able to operate and grow normally. <ref><pubmed>22643728</pubmed></ref>

'''Shh key component of taste bud proginators'''

A tamoxifen treatment which supresses Sonic hedgehog (Shh) secretion in mice proving to reduce the number of cells visable within papillae, in contrast mice not treated with tamoxifen showed a mark increase of cells within papillae, these cells are assumed to become taste cells in later development.
Specific mice were bred to trace the destination of taste placode cells, the study concluded that Shh expressing placodes are taste bud proginators which in turn become taste cells within taste buds although do not have any prescuros relationship with pappilae. The results were obtain by examination of mice embryos using Bright-field or multichannel fluorescent images through the use of an "Axiocam CCD camera and Axioplan fluorescence microscope with Axiovision software" a study by Harlow, Yang, Williams, Barlow (2011)<ref><pubmed>PMC2674259</pubmed></ref>

'''WNT family exhibit various roles'''

The WNT gene family has a function of signally proteins for various reason such as development, In 2010 Liu, Staubach Grosse, Walton, Saims, Gumucio, Mistretta explored recent findings on the role of WNT's in tongue and papillae development, Concluding that WNT/β-catenin is essential for fungiform papillae differing to WNT5a which proved to be principle in tongue development. Intrinsic chemical mediators were considered by manipulating a tissue culture and then throughaly examined by scanning photomicrograph. <ref><pubmed>PMC2768563</pubmed></ref>

[http://www.surgicalneurologyint.com/article.asp?issn=2152-7806;year=2012;volume=3;issue=1;spage=23;epage=23;aulast=Manjila]
[[File:Abnormal of tongue.jpg|Left|thumb|200px|Image shows and example of tongue abnormalities, this is called "double tongue" each side has independent movement!]]

==Useful links==

==Glossary==

ectoderm- outer germ layer of embryo

endoderm - inner germ layer of embryo

epithelium - basic animal tissue that is composed of tightly packed cells, usually covering the outer portion of organs

exocystosis - movement of contents out of cell

ganglia - the accumulation of a nerve cell body

growth factor - a substance that stimulates the growth of cells

gustatory - anything that relates to the taste sense

hydrolysis - breakdown of a chemical when it reacts with water

mesoderm - middle germ layer of embryo

mesenchyme - multipotential cells

neural crest - a part of the ectoderm found on both sides of the neural tube

neuron - most simplistic unit of the nervous system

neurotransmitter - chemicals which allow the passing of signals from neuron to neuron via connecting part (synapse)

papillae - small rough surface projection

six genes - a family of genes

Sonic hedgehog (Shh) - signalling protein invloved in normal development

sulcus terminalis - describes a physical transition point separating the anterior 2/3 of the tongue from the posterior 1/3

tamoxifen - hormonal altering drug

==Image gallery==

== References ==
<references/>

==External Links==
{{External Links}}

http://www.webmd.com/oral-health/picture-of-the-tongue

http://www.tutorvista.com/content/biology/biology-iv/nervous-coordination/tongue-structure.php#parts-of-tongue

http://www.cf.ac.uk/biosi/staffinfo/jacob/teaching/sensory/taste.html

--[[User:Z8600021|Mark Hill]] 12:22, 15 August 2012 (EST) Please leave the content listed below the line at the bottom of your project page.

----

{{2012Projects}}

2012 Group Project 3

2012-09-29T03:54:36Z

Z3289738: /* History of Discoveries */

=Taste Development=

== Introduction ==
**NEED TO ADD**

==History of Discoveries==

{| cellpadding=5 style="border:1px solid #BBB"
|- bgcolor="#faecc8"
|''' Date'''|| '''Significant Discovery'''

|- bgcolor="#faf6ed"
|'''350BC'''
|| Aristotle writes about the basic tastes, sweet and bitter. He also notes that it can be modified by salty and acidic. <ref><pubmed>22717400</pubmed></ref>

|- bgcolor="#faecc8"
|'''1901'''
|| D. Hanig publishes a paper describing taste sensitivity in different regions of the tongue.
''Interesting fact:'' The modern concept of a 'tongue map' is a misinterpretation of this study. <ref><pubmed>22717400</pubmed></ref>

|- bgcolor="#faf6ed"
|style=white-space:nowrap|'''1908'''
|Kikunae Ikeda, a professor of the Tokyo Imperial University, discovered and identified the fifth basic taste: umami (savouriness), made palatable by glutamate. <ref><pubmed>12438213</pubmed></ref>

|- bgcolor="#faecc8"
|style=white-space:nowrap|'''1931'''
|Bitter taste sensitivity found to vary among humans. <ref><pubmed>22717400</pubmed></ref>

|- bgcolor="#faf6ed"
|style=white-space:nowrap|'''1931-32'''
| A chemist named Arthur Fox and his college noted that they had different sensitivities to the bitter tasting Phenylthiocarbamide (PTC). Genetisists later confirm these findings, and discover that non-tasting is a recessive genetic trait. <ref><pubmed>17782493</pubmed></ref> <ref>Blakeslee AF, Fox AL. Our different taste worlds. J Hered. 1932;23:97–107.</ref>

|- bgcolor="#faecc8"
|style=white-space:nowrap|'''1965'''
|Farbman's study of the developing taste but in rat fungiform papilla was significant in increasing our understanding of taste bud development. <ref><pubmed>14300090</pubmed></ref> [http://www.sciencedirect.com/science/article/pii/0012160665900400 Electron microscope study of the developing taste bud in rat fungiform papilla.]

|- bgcolor="#faf6ed"
|style=white-space:nowrap|'''1992'''
|McLaughlin SK et al. discovery a taste cell-specific G-protein within the taste buds called Gustucon. This protein is later used to mark bitter, umami and sweet cells. <ref><pubmed>1608467 </pubmed></ref> [http://www.nature.com/nature/journal/v357/n6379/abs/357563a0.html Gustducin is a taste-cell-specific G protein closely related to the transducins]

|- bgcolor="#faecc8"
|style=white-space:nowrap|'''1995'''
|Barlow et al. experimented with Axolotl salamanders and concluded that taste buds from this species arise exclusively from epithelial tissue, "oropharyngeal epithelium". <ref><pubmed>17826760</pubmed></ref> [http://www.ncbi.nlm.nih.gov/pubmed/17826760 Embryonic origin of gustatory cranial sensory neurons.]

|- bgcolor="#faf6ed"
|style=white-space:nowrap|'''1996'''
| Witt M and Reutter K of the Technical University Dresden in Germany, carried out a transmission electron microscopy study to investigate the embryonic and fetal development of Human taste buds. Their results suggest an "at least dual function of embryonic/fetal taste buds", including non-gustatory, paracrine functions prior to the 14th week and gustatory after the 14th week. <ref><pubmed>8955790</pubmed></ref> [http://www.ncbi.nlm.nih.gov/pubmed/8955790 Embryonic and early fetal development of human taste buds: a transmission electron microscopical study]

|- bgcolor="#faecc8"
|style=white-space:nowrap|'''2000'''
|Chandrashekar, J. et al. discover the first taste sonsors, the T2R bitter taste receptors. <ref><pubmed>10761935</pubmed></ref>

|- bgcolor="#faf6ed"
|style=white-space:nowrap|'''2001'''
|Nelson, G. et al. discover the sweet receptor: a combination of T1R2 and T1R3. <ref><pubmed>11509186</pubmed></ref> [http://www.ncbi.nlm.nih.gov/pubmed/11509186?dopt=Abstract&holding=npg Mammalian sweet taste receptors.]

|- bgcolor="#faecc8"
|style=white-space:nowrap|'''2002'''
|Nelson G. et al. discover the amino acid (umami) taste receptor: a combination of T1R1 and T1R3 identified. <ref><pubmed>11894099</pubmed></ref> [http://www.ncbi.nlm.nih.gov/pubmed/11894099?dopt=Abstract&holding=npg An amino-acid taste receptor]

|- bgcolor="#faf6ed"
|style=white-space:nowrap|'''2005'''
|Dyer, J. et al. discover sweet taste receptors in the GI tract. <ref><pubmed>17855558</pubmed></ref> [http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1986582/ Sweet taste signaling in the gut]

|- bgcolor="#faecc8"
|style=white-space:nowrap|'''2006'''
|Huang, A. L et al. discover cells for sour taste, identified by PKD2L1 (a polycystic kidney disease-like ion channel). <ref><pubmed>16929298</pubmed></ref> [http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1571047/ The Cells and Logic for Mammalian Sour Taste detection]

|- bgcolor="#faf6ed"
|style=white-space:nowrap|'''2007'''
|Harlow DE, Barlow LA of the University of Colorado Denver Health Sciences Center provide evidence of the "embryonic origin of gustatory cranial sensory neurons". <ref><pubmed>17826760</pubmed></ref> [http://www.ncbi.nlm.nih.gov/pubmed/17826760 Embryonic origin of gustatory cranial sensory neurons.]

|- bgcolor="#faecc8"
|style=white-space:nowrap|'''2009'''
|A study by Hevezi P et al, presents "the first comprehensive characterization of gene expression in primate taste buds", as opposed to previous studies which focused on rodents. <ref><pubmed>19636377</pubmed></ref> [http://www.ncbi.nlm.nih.gov/pubmed/19636377 Genome-wide analysis of gene expression in primate taste buds reveals links to diverse processes]

|- bgcolor="#faf6ed"
|style=white-space:nowrap|'''2010'''
|Chandrashekar, J. et al. identify epithelial sodium channel (ENaC) as the sodium-salt taste receptor. <ref><pubmed>20107438</pubmed></ref> [http://www.ncbi.nlm.nih.gov/pubmed/20107438?dopt=Abstract&holding=npg The cells and peripheral representation of sodium taste in mice]
|}

==Gustatory System==

[[Image:Taste qualities.gif|thumb|The five basic tastes]]

Taste or more appropriately gustation, is a fundamental survival tool in animals as it directs the consumption of essential nutrients. The five tastes that exist within the human gustatory system: salty, sweet, sour, bitter and umami, all signify basic physiological requirements. Salty tastes denote the presence of Na+, an important ion involved in the transportation and retention of water across cell membranes. Sweetness is the recognition of carbohydrates, essential for maintaining optimal brain function and providing the basis for energy production in muscle tissue via ATP hydrolysis. Similarly umami codes for the presence of L-amino acids, especially L-glutamate which is an integral component of protein synthesis.

These different modalities not only function to maintain the proper intake of nutrients within the body but also, by way of aversion, prohibit the consumption of undesired or poisonous materials. The bitter modality for example is generally regarded as displeasing to the human palate. It represents a high acid content which may be a result of foods which have become rotten or are inherently poisonous to the body.<ref name=PMID20696704><pubmed>20696704</pubmed></ref>

Research has historically limited itself to investigating the mechanisms of these five taste qualities though it must be noted many other modalities may exist. Of particular conjecture is the existence of fatty acid recognition. In the past the detection of fat in food has been attributed to somatosensory inputs <ref name=PMID20696704/> from the tongue, that is, the oily feel and texture of fat rather than its actual ‘taste’ allows the brain to encode for its presence. Further research is therefore required to elicit the precise mechanisms of fat detection.

===Cell Biology===

The five taste qualities are not all detected by the same type of receptor cell located within the taste bud. Like rods and cones in the eye which detect different wavelengths of light, there are specific types of receptors for different tastes. For example, sweet, umami and bitter are recognised by Type II G-protein coupled receptors, whereas sour is related to Type III presynaptic cells. The cell type involved in salty taste transduction is unknown however it is known that sodium ions can enter the receptor cell membrane via ion channel permeation.

====Type II receptors====

When a bitter, sweet or umami ligand binds to a type II G-coupled receptor, a cascade of chemical reactions causes the release of Ca2+ which in turn mediates exocystosis of ATP. The function of this ATP is threefold:

# Stimulates gustatory nerve afferents which project to gustatory nuclei in the spinal cord
# Excites Type III presynaptic nerve fibres to release serotonin.
# Has a positive feedback effect on type II receptor cells, increasing the level of ATP production.

The role of serotonin is believed to be in the form of lateral inhibition i.e. when a bitter quality is recognised, adjacent receptors for sweetness are deactivated and thus the two tastes may be clearly differentiated. It also has a negative feedback effect on receptor cells, inhibiting umami, bitter and sweet taste transduction.

==Taste Map==
[[Image:Taste map.png|thumb|left|250px|Obsolete idea of the tongue map]]
The idea of a tongue map has disseminated through society for many years. This concept purports that different areas of the tongue are specialised to detect either sweet, salty, sour and bitter tastes. Recent research however has completely nullified such claims and suggests instead that different forms of taste are recognised all over the tongue as well as via the palate. Thus the term ''taste map'' has come to take on a new meaning and that is, the precise areas of taste modalities processing in areas of cortex and its subsequent neural inputs.

===Neural Pathways===

'''First order neurons''' - From the receptors located in the taste buds, gustatory nerve afferents project to the ipsilateral rostral 1/3 of the nucleus tractus solitarius (NTS), located in the medulla. This rostral 1/3 is commonly referred to as the ''gustatory nucleus''.

The ''gustatory nucleus'' receives input from cranial nerves VII (''Facial n.''), IX (''Hypglossal n.''), and X (''Vagus n.'') via special visceral afferent (SVA) nerve fibres. A summary of their functions is as follows:

* ''Facial nerve n''. - carries taste information from the anterior 2/3 of the tongue.
* ''Hypoglossal n.'' - carries taste information from the posterior 1/3 of the tongue.
* ''Vagus n''. - carries taste information from the palate

'''Second order neurons''' - From the NTS second order neurons carry taste information to the Ventral posteromedial (VPM) nucleus in the thalamus.<ref name=PMID21885776/>

Copious scientific conjecture surrounds how each taste modality is transmitted to the brain. The ‘labelled-line’ hypothesis suggests that there are taste specific neurons which exclusively carry that taste modality to cortical areas. In analogous terms it can be viewed like the pipelines leading toward a house. Each pipeline carries its own utility, there is one for gas, another for water and finally for electricity with each terminating in slightly different areas of the house. In the same way, on the tongues there are different receptors for each taste which concurrently have individual nerve tracts leading to the primary gustatory cortex.

Contrapuntally there is electrophysiological evidence that single nerve afferents carry multiple modalities. These studies show one nerve afferent may have both a strong and a weak activation in response to a multiple taste stimuli.

===Cortical Areas===

[[Image:Primary gustatory cortex.png|thumb|Primary gustatory cortex]]

The location of the taste perception centres has been observed via functional magnetic resonance imaging (fMRI) studies. The primary taste cortex has been identified as being located in the anterior insula/frontal operculum (I/fO)<ref name=PMID22245354><pubmed>22245354</pubmed></ref>, with the secondary taste cortex in the caudolateral orbitofrontal cortex.<ref name=PMID21305668><pubmed>21305668</pubmed></ref> Within the insula there are further subdivisions related to each taste modality. Two photon calcium imaging research has outlined certain ’hot-spots’ of activation which are clearly delineated in relation to each taste. For example, the bitter modality is represented on the insula cortex approximately 1mm posterior to the middle cerebral artery whereas the sweet modality is represented 2.5mm rostrodorsal to the bitter field with no apparent overlap.<ref name=PMID21885776><pubmed>21885776</pubmed></ref> These findings lend weight to the idea that there is only one receptor for each taste quality.

It is interesting to note the relationship between taste and the reward centres of the brain. There is evidence of neural input to the ventral tegmental area (the origin of the mesolimbic dopaminergic reward pathway) and nucleus accumbens (involved in the conversion of motivation into physical action).<ref name=PMID21885776/> Neural connections such as this provide the foundations in explaining concepts such as flavour learning and preference. It may also give some insight into chronic problems such as food addiction and craving. As of yet however the gustatory neural network is not well understood and more research is required to elucidate the relationship between pleasure and taste sensation

==Timeline of Developmental Processes of the Gustatory System==

{| cellpadding=5 style="border:1px solid #BBB"
|- bgcolor="#89CFF0"
|'''Postovulatory Week'''||'''Description'''||'''Image'''
|- bgcolor="#BCD4E6"
|'''Week 6''' ||
The surface of the developing tongue is covered by nearly flat epitheliuem (Figure 1) <ref name=PMID9455607/>. The first gustatory papillae of the tongue appears in the caudal midline near the foramen caecum and the first circumvallate papilla develop on the dorsal midline <ref name=PMID9455607/> .
||
image
|- bgcolor="#89CFF0"
| '''Weeks 6 to 7'''||
Nerve fibres approach the basal lamina of lingual epithelium <ref name=PMID8955790><pubmed>8955790</pubmed></ref>. At this stage the lingual epithelium consists of two to three cell layers and there is not yet any sign of cell specializations indicating early taste bud formation<ref name=PMID8955790/>.
||
Image
|- bgcolor="#BCD4E6"
| '''Week 7 '''||
A series of epithelial swellings in the anterior part and midline of the tongue indicate early forming fungiform papillae (figure 2) <ref name=PMID9455607/>.
||
Image
|- bgcolor="#89CFF0"
| ''' Week 8 ''' ||
The lingual epithelium shows first signs of taste bud development as nerve fibres penetrate epithelial basal lamina <ref name=PMID8955790/> and form synapses with taste bud progenitor cells. The synapses reach a maximum around the 12th to 13th week <ref name=PMID8955790/>. However, at this time these cells are still poorly differentiated, elongated epithelial cells <ref name=PMID8955790/> . The synapses demonstrate the neuronal connection between the taste bud primordium and the central nervous system <ref name=PMID8955790/>. Ciliated cells also appear around the 8th week, however the significance of these cells which are scattered randomly across the lingual surface remains unclear <ref name=PMID8955790/>.
||
Image
|- bgcolor="#BCD4E6"
|''' Weeks 8-9''' ||
“By this stage the top surface of circumvallate papillae usually contains a taste pit partly filled with microvilli of presumed underlying taste bud cells” (Figure 10) <ref name=PMID9455607/>
||
Image
|- bgcolor="#89CFF0"
|''' Weeks 10-11''' ||
At this stage, the lingual epithelium compromises of about four cell layers, and the first shallow grooves above the taste bud primordium are developed <ref name=PMID8955790/>.

Fungiform papillae appear on the lateral margins and the tip of the tongue <ref name=PMID9455607/>, containing taste bud primordial that display the first signs of a primitive pore formation <ref name=PMID8955790/>.

Untypically differentiated apical cellular processes extend onto the surface <ref name=PMID9455607/>

Some taste bud primordial contain cells that perforate the covering epithelial later with short, broad untypically differentiated apical cellular processes. (Figure 3,4) <ref name=PMID8955790/> <ref name=PMID9455607/>
||
Image
|- bgcolor="#BCD4E6"
|''' Week 12 ''' ||
Taste bud cells are more clearly differentiated into epithelial cell types II and III <ref name=PMID8955790/>.
||
Image
|- bgcolor="#89CFF0"
|''' Weeks 12-13 ''' ||
By this stage the taste bud primordial are all located on the top of dermal papillae (Fig 6a) <ref name=PMID8955790/>. There is also maximum synapses between cells and afferent nerve fibres, which intermingle with each other to form a plexus-like structure <ref name=PMID8955790/>.
||
Image
|- bgcolor="#BCD4E6"
|''' Weeks 14 -15 ''' ||
The shape of the taste buds primordial begins to resemble those of adult taste buds <ref name=PMID8955790/>. By the 14th week the taste pores develop as the taste pits are filled by microvilli <ref name=PMID8955790/>, indicating the possibility that the taste buds begin their gustatory function <ref name=PMID8955790/>, however they still lack an electron-dense mucous material (Fig.10) <ref name=PMID8955790/>. The tastebuds only achieve a fully developed function in week 15 of gestation with the development of type I cells to produce the mucous material in the taste pit <ref name=PMID8955790/>.
||
Image
|}

==Adult Tongue and Taste Buds – Structure and Function==

'''Structure'''

The tongue is located on the floor of the oral cavity, It is a muscular structure with sensory units crowning. The tongue is divided into an anterior two thirds and a posterior one third. These regions are divided by a V-shaped groove at the back of the tongue (sulcus terminalis). The anterior two thirds of the tongue is covered by stratified squamous epithelium, It contains a roughened surface and has projections called papillae that vary in shape and number.

''''The Image Below is a very simplistic Diagram of the surface of the Tongue showing the locations of the different papillae and other important features'''

{|
| [[Image:Drawing of Tongue.png|500px]]

'''Papillae'''
[[File:Papillae.jpg|Left|thumb|200px|Close up of Human Tongue Papillae]]

There are 4 types of papillae on the tongue.
The most numerous papillae are the filiform papillae, which function to provide a surface that aids in holding food on the tongue during chewing but do not contain taste buds. The larger, less numerous fungiform papillae which contain taste buds, as do foliate papillae. Circumvallate papillae form a wide V at the sulcus terminalis also containing taste bus. There are no papillae or taste buds located on the posterior third of the tongue, having mucosal folds and the lingual tonsils instead.

'''Function'''

The tongue is for tasting, swallowing, and speech.
The functional unit of the taste bud is a taste cell, there are between 50 and 100 taste cells in each taste bud these taste cells represent all 5 different tastes. Historically is was believed that different areas of the tongue were responsible for different taste sensations although this has since been disregarded.[http://users.rcn.com/jkimball.ma.ultranet/BiologyPages/W/Welcome.html] The papillae contain taste buds which are connected to the oral cavity via a taste pore, the function of the taste bud is to transmit a chemical signal from the oral cavity to a taste cell, this chemical signal is the converted into an electrical impulse and delivered to the brain via nerve fibres for interpretation.

'''The Image Below is a very simplistic Hand drawn Diagram of a taste bud, in an extreme close up, cross section view of the the taste bud unit, not to scale'''

[[File:Taste_bud_1.jpg]]

==Abnormalities==

===Knocking out P2X Receptors===

[[File:Image of taste being evoked by visualising ATP release.jpeg|Left|thumb|200px|Evoking taste - ATP release in tongue]]

Gustatory abnormalities has not been widely researched and what has been researched has been through animal testing, most commonly we have found on mice.

In Huang, 2008 this team used the release of the neurotransmitter, ATP (adenosine triphosphate) as a quantitative measurement of gustatory sensation and taste. This was done by using a comparison of wild type (WT) and double knockout (DKO) mice. P2X receptors, P2X2 and P2X3 were knocked out in the DKO mice. The premise of this article was that knocking out P2X receptors reduces transmitter secretion of ATP in taste buds, therefore they cannot taste.

It should be noted that the taste buds in DKO are functional, but are not stimulated by the administration of tastants.

The transmission of release of ATP is secretion through gap junction hemichannels (pannexin 1 gap junction).

When both P2X2 and P2X3 are knocked out, no taste is elicited. However they found that if either P2X2 OR P2X3 was knocked out there was a taste response. So the inference made from this is that if one of the two receptors from the P2X family was knocked out there still can have taste response. The WT mice showed significant stimulation by tastants whereas DKO had little to no stimulation of ATP release.<ref><pubmed>21940456</pubmed></ref>

===FGF signalling and genes===

Sprouty, or ''Srpy'', genes have been related to regulating the development of circumvillate papillae (CVP). The CVP are large dome shaped papillae, which form a 'V' just in front of the terminal sulcus.

By knocking out ''Spry'' genes using mice which had ''Spry1'' and ''Spry2'' knocked out showed that the number of CVP doubled. However, when Fibroblast Growth Factor gene ("Fgf10") was absent, the number of CVP was significantly reduced, if not completely absent. The correlation between ''Spry1/2'' and ''Fgf10'' is that ''Spry1/2'' antagonises "Fgf10" to limit the size of the CVP progenitor placode. Exclusive expression of ''Fgf10'' in the mesenchyme is necessary for the formation of CVP.

'''This image shows the CVP stained with H&E and scanned by Scanning Electron Microscope (SEM)'''
[[File:CVP of WT(top) and DKO(bottom) mice with H&E and SEM.png]]

'''This image shows the location of the CVP and the increased number in DKO mice by SEM'''
[[File:Mouse circumvallate papilla 01.jpg|300px]]

Taste buds develop from the mesenchyme but require local signalling to properly differentiate. Some signalling factors for proper development of taste buds besides FGF are: Sonic Hedgehog (SHH), Bone Morphogenetic Proteins (BMPs), Epidermal Growth Factor (EGF).

Additionally, this proves that the anterior and posterior developments of the tongue are derived from embryonic tissues, where the anterior tongue is derived from the ectoderm and the posterior tongue is derived from the endoderm. Taste buds develop from the mesenchyme but require local signalling to properly differentiate. Some signalling factors for proper development of taste buds besides FGF are: Sonic Hedgehog (SHH), Bone Morphogenetic Proteins (BMPs), Epidermal Growth Factor (EGF).

As mentioned above, this article shows that the anterior and posterior developments of the tongue are derived from embryonic tissues, where the anterior tongue is derived front the ectoderm and the posterior tongue is derived from the endoderm. Secondly, FGF is required to regulate the growth of taste buds, while ''Spry'' genes limit the number of CVP. ''Fgf10''& ''Spry 1&2''work antagonistically through receptor tyrosine kinase (RTK)signalling.

However, the deletion of ''Spry2''led to the increase of CVPs it should be noted that they found that a significant decrease in number of fungiform papillae. Contrastingly, the absence of ''Fgf10'', while leading to the absence of CVPs lead to an increase in number and size of fungiform papillae. Therefore these genes have different effects on the anterior and posterior developing tongue and taste buds.<ref><pubmed>21655085</pubmed></ref>

==Current Research==
We have an evolving understanding of Embryonic Taste development, through the use of state-of-the-art technology and research techniques we are able to make brilliant discoveries that continue to connect the dots of this amazing natural process of human development.
The majority of research in taste development is involving mice, these mammals show similar embryonic pathways to humans and research is performed in ethical and humane methods.

[[File:Histology.jpg|Left|thumb|200px|Image shows histological stains of a mice tongue showing dysplasia]]

'''Synergistic relationships of Six Genes '''

In an animal study using mice by Suzuki Y, Ikeda K, Kawakami K.(2011) Firstly nominating "Six Genes" as a major component in gustatory development, stating that deficiencies in certain Six genes (specifically Six1 & Six4) leads to poor development. Their research also highlights evidence of cooperative relationships between Six genes for normal advance. This experiment involved breeding mice containing exclusively Six1 and Six4 genes and examining the expression of these genes in papillae under high powered microscope observation. Understanding the role of certain genes along with the intrinsic relationships they hold is crucial for the ability to identify possible causes and correction of any abnormalities <ref><pubmed>21978088</pubmed></ref>

'''Neural Crest responsibilities '''

Another Animal Study involving mice explores a new idea of Neural crest (NC) contribution in taste development, specifically the development of papillae and taste buds. Liu HX, Komatsu Y, Mishina Y, Mistretta CM. (2012) suggest that Neural crest cells travel to the location of the tongue in early embryonic stages, gain epithelium phenotypes, multiply and then differentiate to eventually form taste papillae. The experiment involved the comparison of 2 different types of Cre line mice, which both express Cre gene in neural crest protocol, the different distribution patterns where observed in specific regions that NC is responsible for.<ref><pubmed>22659543</pubmed></ref>

'''Augmentation of Endoderm'''

In an animal study conducted by Rothova M, Thompson H, Lickert H, Tucker AS.(2012) exploring the historically debated issue of endoderm contribution to tongue development showed promising evidence that position of taste buds are patterned by the border of ectoderm and endoderm derivative epithelium. This study was accomplished via microscopic examination of previously stained specimens. Concluding endoderm has direct influence on gustatory develoment <ref><pubmed>22581563</pubmed></ref>

'''Changes in Taste Cells over time'''

Research by
Ozdener H, Spielman AI, Rawson NE.(2012) developing a culture which allows taste cells to survive for up to 12 months, empowers researchers to study the processes of proliferation, differentiation and function. This experiment will provide a precidnet for future study of taste cells, as these cells are able to operate and grow normally. <ref><pubmed>22643728</pubmed></ref>

'''Shh key component of taste bud proginators'''

A tamoxifen treatment which supresses Sonic hedgehog (Shh) secretion in mice proving to reduce the number of cells visable within papillae, in contrast mice not treated with tamoxifen showed a mark increase of cells within papillae, these cells are assumed to become taste cells in later development.
Specific mice were bred to trace the destination of taste placode cells, the study concluded that Shh expressing placodes are taste bud proginators which in turn become taste cells within taste buds although do not have any prescuros relationship with pappilae. The results were obtain by examination of mice embryos using Bright-field or multichannel fluorescent images through the use of an "Axiocam CCD camera and Axioplan fluorescence microscope with Axiovision software" a study by Harlow, Yang, Williams, Barlow (2011)<ref><pubmed>PMC2674259</pubmed></ref>

'''WNT family exhibit various roles'''

The WNT gene family has a function of signally proteins for various reason such as development, In 2010 Liu, Staubach Grosse, Walton, Saims, Gumucio, Mistretta explored recent findings on the role of WNT's in tongue and papillae development, Concluding that WNT/β-catenin is essential for fungiform papillae differing to WNT5a which proved to be principle in tongue development. Intrinsic chemical mediators were considered by manipulating a tissue culture and then throughaly examined by scanning photomicrograph. <ref><pubmed>PMC2768563</pubmed></ref>

[http://www.surgicalneurologyint.com/article.asp?issn=2152-7806;year=2012;volume=3;issue=1;spage=23;epage=23;aulast=Manjila]
[[File:Abnormal of tongue.jpg|Left|thumb|200px|Image shows and example of tongue abnormalities, this is called "double tongue" each side has independent movement!]]

==Useful links==

==Glossary==

ectoderm- outer germ layer of embryo

endoderm - inner germ layer of embryo

epithelium - basic animal tissue that is composed of tightly packed cells, usually covering the outer portion of organs

exocystosis - movement of contents out of cell

ganglia - the accumulation of a nerve cell body

growth factor - a substance that stimulates the growth of cells

gustatory - anything that relates to the taste sense

hydrolysis - breakdown of a chemical when it reacts with water

mesoderm - middle germ layer of embryo

mesenchyme - multipotential cells

neural crest - a part of the ectoderm found on both sides of the neural tube

neuron - most simplistic unit of the nervous system

neurotransmitter - chemicals which allow the passing of signals from neuron to neuron via connecting part (synapse)

papillae - small rough surface projection

six genes - a family of genes

Sonic hedgehog (Shh) - signalling protein invloved in normal development

sulcus terminalis - describes a physical transition point separating the anterior 2/3 of the tongue from the posterior 1/3

tamoxifen - hormonal altering drug

==Image gallery==

== References ==
<references/>

==External Links==
{{External Links}}

http://www.webmd.com/oral-health/picture-of-the-tongue

http://www.tutorvista.com/content/biology/biology-iv/nervous-coordination/tongue-structure.php#parts-of-tongue

http://www.cf.ac.uk/biosi/staffinfo/jacob/teaching/sensory/taste.html

--[[User:Z8600021|Mark Hill]] 12:22, 15 August 2012 (EST) Please leave the content listed below the line at the bottom of your project page.

----

{{2012Projects}}

2012 Group Project 3

2012-09-29T03:53:58Z

Z3289738: /* History of Discoveries */

=Taste Development=

== Introduction ==
**NEED TO ADD**

==History of Discoveries==

{| cellpadding=5 style="border:1px solid #BBB"
|- bgcolor="#faecc8"
|''' Date'''|| '''Significant Discovery'''

|- bgcolor="#faf6ed"
|'''350BC'''
|| Aristotle writes about the basic tastes, sweet and bitter. He also notes that it can be modified by salty and acidic. <ref><pubmed>22717400</pubmed></ref>

|- bgcolor="#faecc8"
|'''1901'''
|| D. Hanig publishes a paper describing taste sensitivity in different regions of the tongue.
''Interesting fact:'' The modern concept of a 'tongue map' is a misinterpretation of this study. <ref><pubmed>22717400</pubmed></ref>

|- bgcolor="#faf6ed"
|style=white-space:nowrap|'''1908'''
|Kikunae Ikeda, a professor of the Tokyo Imperial University, discovered and identified the fifth basic taste: umami (savouriness), made palatable by glutamate. <ref><pubmed>12438213</pubmed></ref>

|- bgcolor="#faecc8"
|style=white-space:nowrap|'''1931'''
|Bitter taste sensitivity found to vary among humans. <ref><pubmed>22717400</pubmed></ref>

|- bgcolor="#faf6ed"
|style=white-space:nowrap|'''1931-32'''
| A chemist named Arthur Fox and his college noted that they had different sensitivities to the bitter tasting Phenylthiocarbamide (PTC). Genetisists later confirm these findings, and discover that non-tasting is a recessive genetic trait. <ref><pubmed>17782493</pubmed></ref> <ref>Blakeslee AF, Fox AL. Our different taste worlds. J Hered. 1932;23:97–107.</ref>

|- bgcolor="#faecc8"
|style=white-space:nowrap|'''1965'''
|Farbman's study of the developing taste but in rat fungiform papilla was significant in increasing our understanding of taste bud development. <ref><pubmed>14300090</pubmed></ref> [http://www.sciencedirect.com/science/article/pii/0012160665900400 Electron microscope study of the developing taste bud in rat fungiform papilla.]

|- bgcolor="#faf6ed"
|style=white-space:nowrap|'''1992'''
|McLaughlin SK et al. discovery a taste cell-specific G-protein within the taste buds called Gustucon. This protein is later used to mark bitter, umami and sweet cells. <ref><pubmed>1608467 </pubmed></ref> [http://www.nature.com/nature/journal/v357/n6379/abs/357563a0.html Gustducin is a taste-cell-specific G protein closely related to the transducins]

|- bgcolor="#faecc8"
|style=white-space:nowrap|'''1995'''
|Barlow et al. experimented with Axolotl salamanders and concluded that taste buds from this species arise exclusively from epithelial tissue, "oropharyngeal epithelium". <ref><pubmed>17826760</pubmed></ref> [http://www.ncbi.nlm.nih.gov/pubmed/17826760 Embryonic origin of gustatory cranial sensory neurons.]

|- bgcolor="#faf6ed"
|style=white-space:nowrap|'''1996'''
| Witt M and Reutter K of the Technical University Dresden in Germany, carried out a transmission electron microscopy study to investigate the embryonic and fetal development of Human taste buds. Their results suggest an "at least dual function of embryonic/fetal taste buds", including non-gustatory, paracrine functions prior to the 14th week and gustatory after the 14th week. <ref><pubmed>8955790</pubmed></ref> [http://www.ncbi.nlm.nih.gov/pubmed/8955790 Embryonic and early fetal development of human taste buds: a transmission electron microscopical study]

|- bgcolor="#faecc8"
|style=white-space:nowrap|'''2000'''
|Chandrashekar, J. et al. discover the first taste sonsors, the T2R bitter taste receptors. <ref><pubmed>10761935</pubmed></ref>

|- bgcolor="#faf6ed"
|style=white-space:nowrap|'''2001'''
|Nelson, G. et al. discover the sweet receptor: a combination of T1R2 and T1R3. <ref><pubmed>11509186</pubmed></ref> [http://www.ncbi.nlm.nih.gov/pubmed/11509186?dopt=Abstract&holding=npg Mammalian sweet taste receptors.]

|- bgcolor="#faecc8"
|style=white-space:nowrap|'''2002'''
|Nelson G. et al. discover the amino acid (umami) taste receptor: a combination of T1R1 and T1R3 identified. <ref><pubmed>11894099</pubmed></ref> [http://www.ncbi.nlm.nih.gov/pubmed/11894099?dopt=Abstract&holding=npg An amino-acid taste receptor]

|- bgcolor="#faf6ed"
|style=white-space:nowrap|'''2005'''
|Dyer, J. et al. discover sweet taste receptors in the GI tract. <ref><pubmed>17855558</pubmed></ref> [http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1986582/ Sweet taste signaling in the gut]

|- bgcolor="#faecc8"
|style=white-space:nowrap|'''2006'''
|Huang, A. L et al. discover cells for sour taste, identified by PKD2L1 (a polycystic kidney disease-like ion channel). <ref><pubmed>16929298</pubmed></ref> [http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1571047/ The Cells and Logic for Mammalian Sour Taste detection]

|- bgcolor="#faf6ed"
|style=white-space:nowrap|'''2007'''
|Harlow DE, Barlow LA of the University of Colorado Denver Health Sciences Center provide evidence of the "embryonic origin of gustatory cranial sensory neurons". <ref><pubmed>17826760</pubmed></ref> [http://www.ncbi.nlm.nih.gov/pubmed/17826760 Embryonic origin of gustatory cranial sensory neurons.]

|- bgcolor="#faecc8"
|style=white-space:nowrap|'''2009'''
|A study by Hevezi P et al, presents "the first comprehensive characterization of gene expression in primate taste buds", as opposed to previous studies which focused on rodents. <ref><pubmed>19636377</pubmed></ref> [http://www.ncbi.nlm.nih.gov/pubmed/19636377 Genome-wide analysis of gene expression in primate taste buds reveals links to diverse processes]

|- bgcolor="#faf6ed"
|style=white-space:nowrap|'''2010'''
|Chandrashekar, J. et al. identify epithelial sodium channel (ENaC) as the sodium-salt taste receptor. <ref><pubmed>20107438</pubmed></ref> [http://www.ncbi.nlm.nih.gov/pubmed/20107438?dopt=Abstract&holding=npg The cells and peripheral representation of sodium taste in mice]
|}

*[http://www.nature.com/nature/journal/v486/n7403_supp/fig_tab/486S2a_F1.html Gustatory system: The finer points of taste] <ref><pubmed>22717400</pubmed></ref>

==Gustatory System==

[[Image:Taste qualities.gif|thumb|The five basic tastes]]

Taste or more appropriately gustation, is a fundamental survival tool in animals as it directs the consumption of essential nutrients. The five tastes that exist within the human gustatory system: salty, sweet, sour, bitter and umami, all signify basic physiological requirements. Salty tastes denote the presence of Na+, an important ion involved in the transportation and retention of water across cell membranes. Sweetness is the recognition of carbohydrates, essential for maintaining optimal brain function and providing the basis for energy production in muscle tissue via ATP hydrolysis. Similarly umami codes for the presence of L-amino acids, especially L-glutamate which is an integral component of protein synthesis.

These different modalities not only function to maintain the proper intake of nutrients within the body but also, by way of aversion, prohibit the consumption of undesired or poisonous materials. The bitter modality for example is generally regarded as displeasing to the human palate. It represents a high acid content which may be a result of foods which have become rotten or are inherently poisonous to the body.<ref name=PMID20696704><pubmed>20696704</pubmed></ref>

Research has historically limited itself to investigating the mechanisms of these five taste qualities though it must be noted many other modalities may exist. Of particular conjecture is the existence of fatty acid recognition. In the past the detection of fat in food has been attributed to somatosensory inputs <ref name=PMID20696704/> from the tongue, that is, the oily feel and texture of fat rather than its actual ‘taste’ allows the brain to encode for its presence. Further research is therefore required to elicit the precise mechanisms of fat detection.

===Cell Biology===

The five taste qualities are not all detected by the same type of receptor cell located within the taste bud. Like rods and cones in the eye which detect different wavelengths of light, there are specific types of receptors for different tastes. For example, sweet, umami and bitter are recognised by Type II G-protein coupled receptors, whereas sour is related to Type III presynaptic cells. The cell type involved in salty taste transduction is unknown however it is known that sodium ions can enter the receptor cell membrane via ion channel permeation.

====Type II receptors====

When a bitter, sweet or umami ligand binds to a type II G-coupled receptor, a cascade of chemical reactions causes the release of Ca2+ which in turn mediates exocystosis of ATP. The function of this ATP is threefold:

# Stimulates gustatory nerve afferents which project to gustatory nuclei in the spinal cord
# Excites Type III presynaptic nerve fibres to release serotonin.
# Has a positive feedback effect on type II receptor cells, increasing the level of ATP production.

The role of serotonin is believed to be in the form of lateral inhibition i.e. when a bitter quality is recognised, adjacent receptors for sweetness are deactivated and thus the two tastes may be clearly differentiated. It also has a negative feedback effect on receptor cells, inhibiting umami, bitter and sweet taste transduction.

==Taste Map==
[[Image:Taste map.png|thumb|left|250px|Obsolete idea of the tongue map]]
The idea of a tongue map has disseminated through society for many years. This concept purports that different areas of the tongue are specialised to detect either sweet, salty, sour and bitter tastes. Recent research however has completely nullified such claims and suggests instead that different forms of taste are recognised all over the tongue as well as via the palate. Thus the term ''taste map'' has come to take on a new meaning and that is, the precise areas of taste modalities processing in areas of cortex and its subsequent neural inputs.

===Neural Pathways===

'''First order neurons''' - From the receptors located in the taste buds, gustatory nerve afferents project to the ipsilateral rostral 1/3 of the nucleus tractus solitarius (NTS), located in the medulla. This rostral 1/3 is commonly referred to as the ''gustatory nucleus''.

The ''gustatory nucleus'' receives input from cranial nerves VII (''Facial n.''), IX (''Hypglossal n.''), and X (''Vagus n.'') via special visceral afferent (SVA) nerve fibres. A summary of their functions is as follows:

* ''Facial nerve n''. - carries taste information from the anterior 2/3 of the tongue.
* ''Hypoglossal n.'' - carries taste information from the posterior 1/3 of the tongue.
* ''Vagus n''. - carries taste information from the palate

'''Second order neurons''' - From the NTS second order neurons carry taste information to the Ventral posteromedial (VPM) nucleus in the thalamus.<ref name=PMID21885776/>

Copious scientific conjecture surrounds how each taste modality is transmitted to the brain. The ‘labelled-line’ hypothesis suggests that there are taste specific neurons which exclusively carry that taste modality to cortical areas. In analogous terms it can be viewed like the pipelines leading toward a house. Each pipeline carries its own utility, there is one for gas, another for water and finally for electricity with each terminating in slightly different areas of the house. In the same way, on the tongues there are different receptors for each taste which concurrently have individual nerve tracts leading to the primary gustatory cortex.

Contrapuntally there is electrophysiological evidence that single nerve afferents carry multiple modalities. These studies show one nerve afferent may have both a strong and a weak activation in response to a multiple taste stimuli.

===Cortical Areas===

[[Image:Primary gustatory cortex.png|thumb|Primary gustatory cortex]]

The location of the taste perception centres has been observed via functional magnetic resonance imaging (fMRI) studies. The primary taste cortex has been identified as being located in the anterior insula/frontal operculum (I/fO)<ref name=PMID22245354><pubmed>22245354</pubmed></ref>, with the secondary taste cortex in the caudolateral orbitofrontal cortex.<ref name=PMID21305668><pubmed>21305668</pubmed></ref> Within the insula there are further subdivisions related to each taste modality. Two photon calcium imaging research has outlined certain ’hot-spots’ of activation which are clearly delineated in relation to each taste. For example, the bitter modality is represented on the insula cortex approximately 1mm posterior to the middle cerebral artery whereas the sweet modality is represented 2.5mm rostrodorsal to the bitter field with no apparent overlap.<ref name=PMID21885776><pubmed>21885776</pubmed></ref> These findings lend weight to the idea that there is only one receptor for each taste quality.

It is interesting to note the relationship between taste and the reward centres of the brain. There is evidence of neural input to the ventral tegmental area (the origin of the mesolimbic dopaminergic reward pathway) and nucleus accumbens (involved in the conversion of motivation into physical action).<ref name=PMID21885776/> Neural connections such as this provide the foundations in explaining concepts such as flavour learning and preference. It may also give some insight into chronic problems such as food addiction and craving. As of yet however the gustatory neural network is not well understood and more research is required to elucidate the relationship between pleasure and taste sensation

==Timeline of Developmental Processes of the Gustatory System==

{| cellpadding=5 style="border:1px solid #BBB"
|- bgcolor="#89CFF0"
|'''Postovulatory Week'''||'''Description'''||'''Image'''
|- bgcolor="#BCD4E6"
|'''Week 6''' ||
The surface of the developing tongue is covered by nearly flat epitheliuem (Figure 1) <ref name=PMID9455607/>. The first gustatory papillae of the tongue appears in the caudal midline near the foramen caecum and the first circumvallate papilla develop on the dorsal midline <ref name=PMID9455607/> .
||
image
|- bgcolor="#89CFF0"
| '''Weeks 6 to 7'''||
Nerve fibres approach the basal lamina of lingual epithelium <ref name=PMID8955790><pubmed>8955790</pubmed></ref>. At this stage the lingual epithelium consists of two to three cell layers and there is not yet any sign of cell specializations indicating early taste bud formation<ref name=PMID8955790/>.
||
Image
|- bgcolor="#BCD4E6"
| '''Week 7 '''||
A series of epithelial swellings in the anterior part and midline of the tongue indicate early forming fungiform papillae (figure 2) <ref name=PMID9455607/>.
||
Image
|- bgcolor="#89CFF0"
| ''' Week 8 ''' ||
The lingual epithelium shows first signs of taste bud development as nerve fibres penetrate epithelial basal lamina <ref name=PMID8955790/> and form synapses with taste bud progenitor cells. The synapses reach a maximum around the 12th to 13th week <ref name=PMID8955790/>. However, at this time these cells are still poorly differentiated, elongated epithelial cells <ref name=PMID8955790/> . The synapses demonstrate the neuronal connection between the taste bud primordium and the central nervous system <ref name=PMID8955790/>. Ciliated cells also appear around the 8th week, however the significance of these cells which are scattered randomly across the lingual surface remains unclear <ref name=PMID8955790/>.
||
Image
|- bgcolor="#BCD4E6"
|''' Weeks 8-9''' ||
“By this stage the top surface of circumvallate papillae usually contains a taste pit partly filled with microvilli of presumed underlying taste bud cells” (Figure 10) <ref name=PMID9455607/>
||
Image
|- bgcolor="#89CFF0"
|''' Weeks 10-11''' ||
At this stage, the lingual epithelium compromises of about four cell layers, and the first shallow grooves above the taste bud primordium are developed <ref name=PMID8955790/>.

Fungiform papillae appear on the lateral margins and the tip of the tongue <ref name=PMID9455607/>, containing taste bud primordial that display the first signs of a primitive pore formation <ref name=PMID8955790/>.

Untypically differentiated apical cellular processes extend onto the surface <ref name=PMID9455607/>

Some taste bud primordial contain cells that perforate the covering epithelial later with short, broad untypically differentiated apical cellular processes. (Figure 3,4) <ref name=PMID8955790/> <ref name=PMID9455607/>
||
Image
|- bgcolor="#BCD4E6"
|''' Week 12 ''' ||
Taste bud cells are more clearly differentiated into epithelial cell types II and III <ref name=PMID8955790/>.
||
Image
|- bgcolor="#89CFF0"
|''' Weeks 12-13 ''' ||
By this stage the taste bud primordial are all located on the top of dermal papillae (Fig 6a) <ref name=PMID8955790/>. There is also maximum synapses between cells and afferent nerve fibres, which intermingle with each other to form a plexus-like structure <ref name=PMID8955790/>.
||
Image
|- bgcolor="#BCD4E6"
|''' Weeks 14 -15 ''' ||
The shape of the taste buds primordial begins to resemble those of adult taste buds <ref name=PMID8955790/>. By the 14th week the taste pores develop as the taste pits are filled by microvilli <ref name=PMID8955790/>, indicating the possibility that the taste buds begin their gustatory function <ref name=PMID8955790/>, however they still lack an electron-dense mucous material (Fig.10) <ref name=PMID8955790/>. The tastebuds only achieve a fully developed function in week 15 of gestation with the development of type I cells to produce the mucous material in the taste pit <ref name=PMID8955790/>.
||
Image
|}

==Adult Tongue and Taste Buds – Structure and Function==

'''Structure'''

The tongue is located on the floor of the oral cavity, It is a muscular structure with sensory units crowning. The tongue is divided into an anterior two thirds and a posterior one third. These regions are divided by a V-shaped groove at the back of the tongue (sulcus terminalis). The anterior two thirds of the tongue is covered by stratified squamous epithelium, It contains a roughened surface and has projections called papillae that vary in shape and number.

''''The Image Below is a very simplistic Diagram of the surface of the Tongue showing the locations of the different papillae and other important features'''

{|
| [[Image:Drawing of Tongue.png|500px]]

'''Papillae'''
[[File:Papillae.jpg|Left|thumb|200px|Close up of Human Tongue Papillae]]

There are 4 types of papillae on the tongue.
The most numerous papillae are the filiform papillae, which function to provide a surface that aids in holding food on the tongue during chewing but do not contain taste buds. The larger, less numerous fungiform papillae which contain taste buds, as do foliate papillae. Circumvallate papillae form a wide V at the sulcus terminalis also containing taste bus. There are no papillae or taste buds located on the posterior third of the tongue, having mucosal folds and the lingual tonsils instead.

'''Function'''

The tongue is for tasting, swallowing, and speech.
The functional unit of the taste bud is a taste cell, there are between 50 and 100 taste cells in each taste bud these taste cells represent all 5 different tastes. Historically is was believed that different areas of the tongue were responsible for different taste sensations although this has since been disregarded.[http://users.rcn.com/jkimball.ma.ultranet/BiologyPages/W/Welcome.html] The papillae contain taste buds which are connected to the oral cavity via a taste pore, the function of the taste bud is to transmit a chemical signal from the oral cavity to a taste cell, this chemical signal is the converted into an electrical impulse and delivered to the brain via nerve fibres for interpretation.

'''The Image Below is a very simplistic Hand drawn Diagram of a taste bud, in an extreme close up, cross section view of the the taste bud unit, not to scale'''

[[File:Taste_bud_1.jpg]]

==Abnormalities==

===Knocking out P2X Receptors===

[[File:Image of taste being evoked by visualising ATP release.jpeg|Left|thumb|200px|Evoking taste - ATP release in tongue]]

Gustatory abnormalities has not been widely researched and what has been researched has been through animal testing, most commonly we have found on mice.

In Huang, 2008 this team used the release of the neurotransmitter, ATP (adenosine triphosphate) as a quantitative measurement of gustatory sensation and taste. This was done by using a comparison of wild type (WT) and double knockout (DKO) mice. P2X receptors, P2X2 and P2X3 were knocked out in the DKO mice. The premise of this article was that knocking out P2X receptors reduces transmitter secretion of ATP in taste buds, therefore they cannot taste.

It should be noted that the taste buds in DKO are functional, but are not stimulated by the administration of tastants.

The transmission of release of ATP is secretion through gap junction hemichannels (pannexin 1 gap junction).

When both P2X2 and P2X3 are knocked out, no taste is elicited. However they found that if either P2X2 OR P2X3 was knocked out there was a taste response. So the inference made from this is that if one of the two receptors from the P2X family was knocked out there still can have taste response. The WT mice showed significant stimulation by tastants whereas DKO had little to no stimulation of ATP release.<ref><pubmed>21940456</pubmed></ref>

===FGF signalling and genes===

Sprouty, or ''Srpy'', genes have been related to regulating the development of circumvillate papillae (CVP). The CVP are large dome shaped papillae, which form a 'V' just in front of the terminal sulcus.

By knocking out ''Spry'' genes using mice which had ''Spry1'' and ''Spry2'' knocked out showed that the number of CVP doubled. However, when Fibroblast Growth Factor gene ("Fgf10") was absent, the number of CVP was significantly reduced, if not completely absent. The correlation between ''Spry1/2'' and ''Fgf10'' is that ''Spry1/2'' antagonises "Fgf10" to limit the size of the CVP progenitor placode. Exclusive expression of ''Fgf10'' in the mesenchyme is necessary for the formation of CVP.

'''This image shows the CVP stained with H&E and scanned by Scanning Electron Microscope (SEM)'''
[[File:CVP of WT(top) and DKO(bottom) mice with H&E and SEM.png]]

'''This image shows the location of the CVP and the increased number in DKO mice by SEM'''
[[File:Mouse circumvallate papilla 01.jpg|300px]]

Taste buds develop from the mesenchyme but require local signalling to properly differentiate. Some signalling factors for proper development of taste buds besides FGF are: Sonic Hedgehog (SHH), Bone Morphogenetic Proteins (BMPs), Epidermal Growth Factor (EGF).

Additionally, this proves that the anterior and posterior developments of the tongue are derived from embryonic tissues, where the anterior tongue is derived from the ectoderm and the posterior tongue is derived from the endoderm. Taste buds develop from the mesenchyme but require local signalling to properly differentiate. Some signalling factors for proper development of taste buds besides FGF are: Sonic Hedgehog (SHH), Bone Morphogenetic Proteins (BMPs), Epidermal Growth Factor (EGF).

As mentioned above, this article shows that the anterior and posterior developments of the tongue are derived from embryonic tissues, where the anterior tongue is derived front the ectoderm and the posterior tongue is derived from the endoderm. Secondly, FGF is required to regulate the growth of taste buds, while ''Spry'' genes limit the number of CVP. ''Fgf10''& ''Spry 1&2''work antagonistically through receptor tyrosine kinase (RTK)signalling.

However, the deletion of ''Spry2''led to the increase of CVPs it should be noted that they found that a significant decrease in number of fungiform papillae. Contrastingly, the absence of ''Fgf10'', while leading to the absence of CVPs lead to an increase in number and size of fungiform papillae. Therefore these genes have different effects on the anterior and posterior developing tongue and taste buds.<ref><pubmed>21655085</pubmed></ref>

==Current Research==
We have an evolving understanding of Embryonic Taste development, through the use of state-of-the-art technology and research techniques we are able to make brilliant discoveries that continue to connect the dots of this amazing natural process of human development.
The majority of research in taste development is involving mice, these mammals show similar embryonic pathways to humans and research is performed in ethical and humane methods.

[[File:Histology.jpg|Left|thumb|200px|Image shows histological stains of a mice tongue showing dysplasia]]

'''Synergistic relationships of Six Genes '''

In an animal study using mice by Suzuki Y, Ikeda K, Kawakami K.(2011) Firstly nominating "Six Genes" as a major component in gustatory development, stating that deficiencies in certain Six genes (specifically Six1 & Six4) leads to poor development. Their research also highlights evidence of cooperative relationships between Six genes for normal advance. This experiment involved breeding mice containing exclusively Six1 and Six4 genes and examining the expression of these genes in papillae under high powered microscope observation. Understanding the role of certain genes along with the intrinsic relationships they hold is crucial for the ability to identify possible causes and correction of any abnormalities <ref><pubmed>21978088</pubmed></ref>

'''Neural Crest responsibilities '''

Another Animal Study involving mice explores a new idea of Neural crest (NC) contribution in taste development, specifically the development of papillae and taste buds. Liu HX, Komatsu Y, Mishina Y, Mistretta CM. (2012) suggest that Neural crest cells travel to the location of the tongue in early embryonic stages, gain epithelium phenotypes, multiply and then differentiate to eventually form taste papillae. The experiment involved the comparison of 2 different types of Cre line mice, which both express Cre gene in neural crest protocol, the different distribution patterns where observed in specific regions that NC is responsible for.<ref><pubmed>22659543</pubmed></ref>

'''Augmentation of Endoderm'''

In an animal study conducted by Rothova M, Thompson H, Lickert H, Tucker AS.(2012) exploring the historically debated issue of endoderm contribution to tongue development showed promising evidence that position of taste buds are patterned by the border of ectoderm and endoderm derivative epithelium. This study was accomplished via microscopic examination of previously stained specimens. Concluding endoderm has direct influence on gustatory develoment <ref><pubmed>22581563</pubmed></ref>

'''Changes in Taste Cells over time'''

Research by
Ozdener H, Spielman AI, Rawson NE.(2012) developing a culture which allows taste cells to survive for up to 12 months, empowers researchers to study the processes of proliferation, differentiation and function. This experiment will provide a precidnet for future study of taste cells, as these cells are able to operate and grow normally. <ref><pubmed>22643728</pubmed></ref>

'''Shh key component of taste bud proginators'''

A tamoxifen treatment which supresses Sonic hedgehog (Shh) secretion in mice proving to reduce the number of cells visable within papillae, in contrast mice not treated with tamoxifen showed a mark increase of cells within papillae, these cells are assumed to become taste cells in later development.
Specific mice were bred to trace the destination of taste placode cells, the study concluded that Shh expressing placodes are taste bud proginators which in turn become taste cells within taste buds although do not have any prescuros relationship with pappilae. The results were obtain by examination of mice embryos using Bright-field or multichannel fluorescent images through the use of an "Axiocam CCD camera and Axioplan fluorescence microscope with Axiovision software" a study by Harlow, Yang, Williams, Barlow (2011)<ref><pubmed>PMC2674259</pubmed></ref>

'''WNT family exhibit various roles'''

The WNT gene family has a function of signally proteins for various reason such as development, In 2010 Liu, Staubach Grosse, Walton, Saims, Gumucio, Mistretta explored recent findings on the role of WNT's in tongue and papillae development, Concluding that WNT/β-catenin is essential for fungiform papillae differing to WNT5a which proved to be principle in tongue development. Intrinsic chemical mediators were considered by manipulating a tissue culture and then throughaly examined by scanning photomicrograph. <ref><pubmed>PMC2768563</pubmed></ref>

[http://www.surgicalneurologyint.com/article.asp?issn=2152-7806;year=2012;volume=3;issue=1;spage=23;epage=23;aulast=Manjila]
[[File:Abnormal of tongue.jpg|Left|thumb|200px|Image shows and example of tongue abnormalities, this is called "double tongue" each side has independent movement!]]

==Useful links==

==Glossary==

ectoderm- outer germ layer of embryo

endoderm - inner germ layer of embryo

epithelium - basic animal tissue that is composed of tightly packed cells, usually covering the outer portion of organs

exocystosis - movement of contents out of cell

ganglia - the accumulation of a nerve cell body

growth factor - a substance that stimulates the growth of cells

gustatory - anything that relates to the taste sense

hydrolysis - breakdown of a chemical when it reacts with water

mesoderm - middle germ layer of embryo

mesenchyme - multipotential cells

neural crest - a part of the ectoderm found on both sides of the neural tube

neuron - most simplistic unit of the nervous system

neurotransmitter - chemicals which allow the passing of signals from neuron to neuron via connecting part (synapse)

papillae - small rough surface projection

six genes - a family of genes

Sonic hedgehog (Shh) - signalling protein invloved in normal development

sulcus terminalis - describes a physical transition point separating the anterior 2/3 of the tongue from the posterior 1/3

tamoxifen - hormonal altering drug

==Image gallery==

== References ==
<references/>

==External Links==
{{External Links}}

http://www.webmd.com/oral-health/picture-of-the-tongue

http://www.tutorvista.com/content/biology/biology-iv/nervous-coordination/tongue-structure.php#parts-of-tongue

http://www.cf.ac.uk/biosi/staffinfo/jacob/teaching/sensory/taste.html

--[[User:Z8600021|Mark Hill]] 12:22, 15 August 2012 (EST) Please leave the content listed below the line at the bottom of your project page.

----

{{2012Projects}}

2012 Group Project 3

2012-09-29T03:50:42Z

Z3289738: /* History of Discoveries */

=Taste Development=

== Introduction ==
**NEED TO ADD**

==History of Discoveries==

{| cellpadding=5 style="border:1px solid #BBB"
|- bgcolor="#faecc8"
|''' Date'''|| '''Significant Discovery'''

|- bgcolor="#faf6ed"
|'''350BC'''
|| Aristotle writes about the basic tastes, sweet and bitter. He also notes that it can be modified by salty and acidic. <ref><pubmed>22717400</pubmed></ref>

|- bgcolor="#faecc8"
|'''1901'''
|| D. Hanig publishes a paper describing taste sensitivity in different regions of the tongue.
''Interesting fact:'' The modern concept of a 'tongue map' is a misinterpretation of this study. <ref><pubmed>22717400</pubmed></ref>

|- bgcolor="#faf6ed"
|style=white-space:nowrap|'''1908'''
|Kikunae Ikeda, a professor of the Tokyo Imperial University, discovered and identified the fifth basic taste: umami (savouriness), made palatable by glutamate. <ref><pubmed>12438213</pubmed></ref>

|- bgcolor="#faecc8"
|style=white-space:nowrap|'''1931'''
|Bitter taste sensitivity found to vary among humans <ref><pubmed>22717400</pubmed></ref>

|- bgcolor="#faf6ed"
|style=white-space:nowrap|'''1931-32'''
| A chemist named Arthur Fox and his college noted that they had different sensitivities to the bitter tasting Phenylthiocarbamide (PTC). Genetisists later confirm these findings, and discover that non-tasting is a recessive genetic trait. <ref><pubmed>17782493</pubmed></ref> <ref>Blakeslee AF, Fox AL. Our different taste worlds. J Hered. 1932;23:97–107.</ref>

|- bgcolor="#faecc8"
|style=white-space:nowrap|'''1965'''
|Farbman's study of the developing taste but in rat fungiform papilla was significant in increasing our understanding of taste bud development. <ref><pubmed>14300090</pubmed></ref> [http://www.sciencedirect.com/science/article/pii/0012160665900400 Electron microscope study of the developing taste bud in rat fungiform papilla.]

|- bgcolor="#faf6ed"
|style=white-space:nowrap|'''1992'''
|McLaughlin SK et al. discovery a taste cell-specific G-protein within the taste buds called Gustucon. This protein is later used to mark bitter, umami and sweet cells. <ref><pubmed>1608467 </pubmed></ref> [http://www.nature.com/nature/journal/v357/n6379/abs/357563a0.html Gustducin is a taste-cell-specific G protein closely related to the transducins]

|- bgcolor="#faecc8"
|style=white-space:nowrap|'''1995'''
|Barlow et al. experimented with Axolotl salamanders and concluded that taste buds from this species arise exclusively from epithelial tissue, "oropharyngeal epithelium". <ref><pubmed>17826760</pubmed></ref> http://www.ncbi.nlm.nih.gov/pubmed/17826760 Embryonic origin of gustatory cranial sensory neurons.]

|- bgcolor="#faf6ed"
|style=white-space:nowrap|'''1996'''
| Witt M and Reutter K of the Technical University Dresden in Germany, carried out a transmission electron microscopy study to investigate the embryonic and fetal development of Human taste buds. Their results suggest an "at least dual function of embryonic/fetal taste buds", including non-gustatory, paracrine functions prior to the 14th week and gustatory after the 14th week. <ref><pubmed>8955790</pubmed></ref> [http://www.ncbi.nlm.nih.gov/pubmed/8955790 Embryonic and early fetal development of human taste buds: a transmission electron microscopical study]

|- bgcolor="#faecc8"
|style=white-space:nowrap|'''2000'''
|Chandrashekar, J. et al. discover the first taste sonsors, the T2R bitter taste receptors. <ref><pubmed>10761935</pubmed></ref>

|- bgcolor="#faf6ed"
|style=white-space:nowrap|'''2001'''
|Nelson, G. et al. discover the sweet receptor: a combination of T1R2 and T1R3. <ref><pubmed>11509186</pubmed></ref>[http://www.ncbi.nlm.nih.gov/pubmed/11509186?dopt=Abstract&holding=npg Mammalian sweet taste receptors.]

|- bgcolor="#faecc8"
|style=white-space:nowrap|'''2002'''
|Nelson G. et al. discover the amino acid (umami) taste receptor: a combination of T1R1 and T1R3 identified. <ref><pubmed>11894099</pubmed></ref> [http://www.ncbi.nlm.nih.gov/pubmed/11894099?dopt=Abstract&holding=npg An amino-acid taste receptor]

|- bgcolor="#faf6ed"
|style=white-space:nowrap|'''2005'''
|Dyer, J. et al. discover sweet taste receptors in the GI tract. <ref><pubmed>17855558</pubmed></ref> [http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1986582/ Sweet taste signaling in the gut]

|- bgcolor="#faecc8"
|style=white-space:nowrap|'''2006'''
|Huang, A. L et al. discover cells for sour taste, identified by PKD2L1 (a polycystic kidney disease-like ion channel) <ref><pubmed>16929298</pubmed></ref> [http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1571047/ The Cells and Logic for Mammalian Sour Taste detection]

|- bgcolor="#faf6ed"
|style=white-space:nowrap|'''2007'''
|Harlow DE, Barlow LA of the University of Colorado Denver Health Sciences Center provide evidence of the "embryonic origin of gustatory cranial sensory neurons" <ref><pubmed>17826760</pubmed></ref> [http://www.ncbi.nlm.nih.gov/pubmed/17826760 Embryonic origin of gustatory cranial sensory neurons.]

|- bgcolor="#faecc8"
|style=white-space:nowrap|'''2009'''
|A study by Hevezi P et al, presents "the first comprehensive characterization of gene expression in primate taste buds", as opposed to previous studies which focused on rodents. <ref><pubmed>19636377</pubmed></ref> [http://www.ncbi.nlm.nih.gov/pubmed/19636377 Genome-wide analysis of gene expression in primate taste buds reveals links to diverse processes]

|- bgcolor="#faf6ed"
|style=white-space:nowrap|'''2010'''
|Chandrashekar, J. et al. identify epithelial sodium channel (ENaC) as the sodium-salt taste receptor <ref><pubmed>20107438</pubmed></ref> [http://www.ncbi.nlm.nih.gov/pubmed/20107438?dopt=Abstract&holding=npg The cells and peripheral representation of sodium taste in mice]
|}

*[http://www.nature.com/nature/journal/v486/n7403_supp/fig_tab/486S2a_F1.html Gustatory system: The finer points of taste] <ref><pubmed>22717400</pubmed></ref>

==Gustatory System==

[[Image:Taste qualities.gif|thumb|The five basic tastes]]

Taste or more appropriately gustation, is a fundamental survival tool in animals as it directs the consumption of essential nutrients. The five tastes that exist within the human gustatory system: salty, sweet, sour, bitter and umami, all signify basic physiological requirements. Salty tastes denote the presence of Na+, an important ion involved in the transportation and retention of water across cell membranes. Sweetness is the recognition of carbohydrates, essential for maintaining optimal brain function and providing the basis for energy production in muscle tissue via ATP hydrolysis. Similarly umami codes for the presence of L-amino acids, especially L-glutamate which is an integral component of protein synthesis.

These different modalities not only function to maintain the proper intake of nutrients within the body but also, by way of aversion, prohibit the consumption of undesired or poisonous materials. The bitter modality for example is generally regarded as displeasing to the human palate. It represents a high acid content which may be a result of foods which have become rotten or are inherently poisonous to the body.<ref name=PMID20696704><pubmed>20696704</pubmed></ref>

Research has historically limited itself to investigating the mechanisms of these five taste qualities though it must be noted many other modalities may exist. Of particular conjecture is the existence of fatty acid recognition. In the past the detection of fat in food has been attributed to somatosensory inputs <ref name=PMID20696704/> from the tongue, that is, the oily feel and texture of fat rather than its actual ‘taste’ allows the brain to encode for its presence. Further research is therefore required to elicit the precise mechanisms of fat detection.

===Cell Biology===

The five taste qualities are not all detected by the same type of receptor cell located within the taste bud. Like rods and cones in the eye which detect different wavelengths of light, there are specific types of receptors for different tastes. For example, sweet, umami and bitter are recognised by Type II G-protein coupled receptors, whereas sour is related to Type III presynaptic cells. The cell type involved in salty taste transduction is unknown however it is known that sodium ions can enter the receptor cell membrane via ion channel permeation.

====Type II receptors====

When a bitter, sweet or umami ligand binds to a type II G-coupled receptor, a cascade of chemical reactions causes the release of Ca2+ which in turn mediates exocystosis of ATP. The function of this ATP is threefold:

# Stimulates gustatory nerve afferents which project to gustatory nuclei in the spinal cord
# Excites Type III presynaptic nerve fibres to release serotonin.
# Has a positive feedback effect on type II receptor cells, increasing the level of ATP production.

The role of serotonin is believed to be in the form of lateral inhibition i.e. when a bitter quality is recognised, adjacent receptors for sweetness are deactivated and thus the two tastes may be clearly differentiated. It also has a negative feedback effect on receptor cells, inhibiting umami, bitter and sweet taste transduction.

==Taste Map==
[[Image:Taste map.png|thumb|left|250px|Obsolete idea of the tongue map]]
The idea of a tongue map has disseminated through society for many years. This concept purports that different areas of the tongue are specialised to detect either sweet, salty, sour and bitter tastes. Recent research however has completely nullified such claims and suggests instead that different forms of taste are recognised all over the tongue as well as via the palate. Thus the term ''taste map'' has come to take on a new meaning and that is, the precise areas of taste modalities processing in areas of cortex and its subsequent neural inputs.

===Neural Pathways===

'''First order neurons''' - From the receptors located in the taste buds, gustatory nerve afferents project to the ipsilateral rostral 1/3 of the nucleus tractus solitarius (NTS), located in the medulla. This rostral 1/3 is commonly referred to as the ''gustatory nucleus''.

The ''gustatory nucleus'' receives input from cranial nerves VII (''Facial n.''), IX (''Hypglossal n.''), and X (''Vagus n.'') via special visceral afferent (SVA) nerve fibres. A summary of their functions is as follows:

* ''Facial nerve n''. - carries taste information from the anterior 2/3 of the tongue.
* ''Hypoglossal n.'' - carries taste information from the posterior 1/3 of the tongue.
* ''Vagus n''. - carries taste information from the palate

'''Second order neurons''' - From the NTS second order neurons carry taste information to the Ventral posteromedial (VPM) nucleus in the thalamus.<ref name=PMID21885776/>

Copious scientific conjecture surrounds how each taste modality is transmitted to the brain. The ‘labelled-line’ hypothesis suggests that there are taste specific neurons which exclusively carry that taste modality to cortical areas. In analogous terms it can be viewed like the pipelines leading toward a house. Each pipeline carries its own utility, there is one for gas, another for water and finally for electricity with each terminating in slightly different areas of the house. In the same way, on the tongues there are different receptors for each taste which concurrently have individual nerve tracts leading to the primary gustatory cortex.

Contrapuntally there is electrophysiological evidence that single nerve afferents carry multiple modalities. These studies show one nerve afferent may have both a strong and a weak activation in response to a multiple taste stimuli.

===Cortical Areas===

[[Image:Primary gustatory cortex.png|thumb|Primary gustatory cortex]]

The location of the taste perception centres has been observed via functional magnetic resonance imaging (fMRI) studies. The primary taste cortex has been identified as being located in the anterior insula/frontal operculum (I/fO)<ref name=PMID22245354><pubmed>22245354</pubmed></ref>, with the secondary taste cortex in the caudolateral orbitofrontal cortex.<ref name=PMID21305668><pubmed>21305668</pubmed></ref> Within the insula there are further subdivisions related to each taste modality. Two photon calcium imaging research has outlined certain ’hot-spots’ of activation which are clearly delineated in relation to each taste. For example, the bitter modality is represented on the insula cortex approximately 1mm posterior to the middle cerebral artery whereas the sweet modality is represented 2.5mm rostrodorsal to the bitter field with no apparent overlap.<ref name=PMID21885776><pubmed>21885776</pubmed></ref> These findings lend weight to the idea that there is only one receptor for each taste quality.

It is interesting to note the relationship between taste and the reward centres of the brain. There is evidence of neural input to the ventral tegmental area (the origin of the mesolimbic dopaminergic reward pathway) and nucleus accumbens (involved in the conversion of motivation into physical action).<ref name=PMID21885776/> Neural connections such as this provide the foundations in explaining concepts such as flavour learning and preference. It may also give some insight into chronic problems such as food addiction and craving. As of yet however the gustatory neural network is not well understood and more research is required to elucidate the relationship between pleasure and taste sensation

==Timeline of Developmental Processes of the Gustatory System==

{| cellpadding=5 style="border:1px solid #BBB"
|- bgcolor="#89CFF0"
|'''Postovulatory Week'''||'''Description'''||'''Image'''
|- bgcolor="#BCD4E6"
|'''Week 6''' ||
The surface of the developing tongue is covered by nearly flat epitheliuem (Figure 1) <ref name=PMID9455607/>. The first gustatory papillae of the tongue appears in the caudal midline near the foramen caecum and the first circumvallate papilla develop on the dorsal midline <ref name=PMID9455607/> .
||
image
|- bgcolor="#89CFF0"
| '''Weeks 6 to 7'''||
Nerve fibres approach the basal lamina of lingual epithelium <ref name=PMID8955790><pubmed>8955790</pubmed></ref>. At this stage the lingual epithelium consists of two to three cell layers and there is not yet any sign of cell specializations indicating early taste bud formation<ref name=PMID8955790/>.
||
Image
|- bgcolor="#BCD4E6"
| '''Week 7 '''||
A series of epithelial swellings in the anterior part and midline of the tongue indicate early forming fungiform papillae (figure 2) <ref name=PMID9455607/>.
||
Image
|- bgcolor="#89CFF0"
| ''' Week 8 ''' ||
The lingual epithelium shows first signs of taste bud development as nerve fibres penetrate epithelial basal lamina <ref name=PMID8955790/> and form synapses with taste bud progenitor cells. The synapses reach a maximum around the 12th to 13th week <ref name=PMID8955790/>. However, at this time these cells are still poorly differentiated, elongated epithelial cells <ref name=PMID8955790/> . The synapses demonstrate the neuronal connection between the taste bud primordium and the central nervous system <ref name=PMID8955790/>. Ciliated cells also appear around the 8th week, however the significance of these cells which are scattered randomly across the lingual surface remains unclear <ref name=PMID8955790/>.
||
Image
|- bgcolor="#BCD4E6"
|''' Weeks 8-9''' ||
“By this stage the top surface of circumvallate papillae usually contains a taste pit partly filled with microvilli of presumed underlying taste bud cells” (Figure 10) <ref name=PMID9455607/>
||
Image
|- bgcolor="#89CFF0"
|''' Weeks 10-11''' ||
At this stage, the lingual epithelium compromises of about four cell layers, and the first shallow grooves above the taste bud primordium are developed <ref name=PMID8955790/>.

Fungiform papillae appear on the lateral margins and the tip of the tongue <ref name=PMID9455607/>, containing taste bud primordial that display the first signs of a primitive pore formation <ref name=PMID8955790/>.

Untypically differentiated apical cellular processes extend onto the surface <ref name=PMID9455607/>

Some taste bud primordial contain cells that perforate the covering epithelial later with short, broad untypically differentiated apical cellular processes. (Figure 3,4) <ref name=PMID8955790/> <ref name=PMID9455607/>
||
Image
|- bgcolor="#BCD4E6"
|''' Week 12 ''' ||
Taste bud cells are more clearly differentiated into epithelial cell types II and III <ref name=PMID8955790/>.
||
Image
|- bgcolor="#89CFF0"
|''' Weeks 12-13 ''' ||
By this stage the taste bud primordial are all located on the top of dermal papillae (Fig 6a) <ref name=PMID8955790/>. There is also maximum synapses between cells and afferent nerve fibres, which intermingle with each other to form a plexus-like structure <ref name=PMID8955790/>.
||
Image
|- bgcolor="#BCD4E6"
|''' Weeks 14 -15 ''' ||
The shape of the taste buds primordial begins to resemble those of adult taste buds <ref name=PMID8955790/>. By the 14th week the taste pores develop as the taste pits are filled by microvilli <ref name=PMID8955790/>, indicating the possibility that the taste buds begin their gustatory function <ref name=PMID8955790/>, however they still lack an electron-dense mucous material (Fig.10) <ref name=PMID8955790/>. The tastebuds only achieve a fully developed function in week 15 of gestation with the development of type I cells to produce the mucous material in the taste pit <ref name=PMID8955790/>.
||
Image
|}

==Adult Tongue and Taste Buds – Structure and Function==

'''Structure'''

The tongue is located on the floor of the oral cavity, It is a muscular structure with sensory units crowning. The tongue is divided into an anterior two thirds and a posterior one third. These regions are divided by a V-shaped groove at the back of the tongue (sulcus terminalis). The anterior two thirds of the tongue is covered by stratified squamous epithelium, It contains a roughened surface and has projections called papillae that vary in shape and number.

''''The Image Below is a very simplistic Diagram of the surface of the Tongue showing the locations of the different papillae and other important features'''

{|
| [[Image:Drawing of Tongue.png|500px]]

'''Papillae'''
[[File:Papillae.jpg|Left|thumb|200px|Close up of Human Tongue Papillae]]

There are 4 types of papillae on the tongue.
The most numerous papillae are the filiform papillae, which function to provide a surface that aids in holding food on the tongue during chewing but do not contain taste buds. The larger, less numerous fungiform papillae which contain taste buds, as do foliate papillae. Circumvallate papillae form a wide V at the sulcus terminalis also containing taste bus. There are no papillae or taste buds located on the posterior third of the tongue, having mucosal folds and the lingual tonsils instead.

'''Function'''

The tongue is for tasting, swallowing, and speech.
The functional unit of the taste bud is a taste cell, there are between 50 and 100 taste cells in each taste bud these taste cells represent all 5 different tastes. Historically is was believed that different areas of the tongue were responsible for different taste sensations although this has since been disregarded.[http://users.rcn.com/jkimball.ma.ultranet/BiologyPages/W/Welcome.html] The papillae contain taste buds which are connected to the oral cavity via a taste pore, the function of the taste bud is to transmit a chemical signal from the oral cavity to a taste cell, this chemical signal is the converted into an electrical impulse and delivered to the brain via nerve fibres for interpretation.

'''The Image Below is a very simplistic Hand drawn Diagram of a taste bud, in an extreme close up, cross section view of the the taste bud unit, not to scale'''

[[File:Taste_bud_1.jpg]]

==Abnormalities==

===Knocking out P2X Receptors===

[[File:Image of taste being evoked by visualising ATP release.jpeg|Left|thumb|200px|Evoking taste - ATP release in tongue]]

Gustatory abnormalities has not been widely researched and what has been researched has been through animal testing, most commonly we have found on mice.

In Huang, 2008 this team used the release of the neurotransmitter, ATP (adenosine triphosphate) as a quantitative measurement of gustatory sensation and taste. This was done by using a comparison of wild type (WT) and double knockout (DKO) mice. P2X receptors, P2X2 and P2X3 were knocked out in the DKO mice. The premise of this article was that knocking out P2X receptors reduces transmitter secretion of ATP in taste buds, therefore they cannot taste.

It should be noted that the taste buds in DKO are functional, but are not stimulated by the administration of tastants.

The transmission of release of ATP is secretion through gap junction hemichannels (pannexin 1 gap junction).

When both P2X2 and P2X3 are knocked out, no taste is elicited. However they found that if either P2X2 OR P2X3 was knocked out there was a taste response. So the inference made from this is that if one of the two receptors from the P2X family was knocked out there still can have taste response. The WT mice showed significant stimulation by tastants whereas DKO had little to no stimulation of ATP release.<ref><pubmed>21940456</pubmed></ref>

===FGF signalling and genes===

Sprouty, or ''Srpy'', genes have been related to regulating the development of circumvillate papillae (CVP). The CVP are large dome shaped papillae, which form a 'V' just in front of the terminal sulcus.

By knocking out ''Spry'' genes using mice which had ''Spry1'' and ''Spry2'' knocked out showed that the number of CVP doubled. However, when Fibroblast Growth Factor gene ("Fgf10") was absent, the number of CVP was significantly reduced, if not completely absent. The correlation between ''Spry1/2'' and ''Fgf10'' is that ''Spry1/2'' antagonises "Fgf10" to limit the size of the CVP progenitor placode. Exclusive expression of ''Fgf10'' in the mesenchyme is necessary for the formation of CVP.

'''This image shows the CVP stained with H&E and scanned by Scanning Electron Microscope (SEM)'''
[[File:CVP of WT(top) and DKO(bottom) mice with H&E and SEM.png]]

'''This image shows the location of the CVP and the increased number in DKO mice by SEM'''
[[File:Mouse circumvallate papilla 01.jpg|300px]]

Taste buds develop from the mesenchyme but require local signalling to properly differentiate. Some signalling factors for proper development of taste buds besides FGF are: Sonic Hedgehog (SHH), Bone Morphogenetic Proteins (BMPs), Epidermal Growth Factor (EGF).

Additionally, this proves that the anterior and posterior developments of the tongue are derived from embryonic tissues, where the anterior tongue is derived from the ectoderm and the posterior tongue is derived from the endoderm. Taste buds develop from the mesenchyme but require local signalling to properly differentiate. Some signalling factors for proper development of taste buds besides FGF are: Sonic Hedgehog (SHH), Bone Morphogenetic Proteins (BMPs), Epidermal Growth Factor (EGF).

As mentioned above, this article shows that the anterior and posterior developments of the tongue are derived from embryonic tissues, where the anterior tongue is derived front the ectoderm and the posterior tongue is derived from the endoderm. Secondly, FGF is required to regulate the growth of taste buds, while ''Spry'' genes limit the number of CVP. ''Fgf10''& ''Spry 1&2''work antagonistically through receptor tyrosine kinase (RTK)signalling.

However, the deletion of ''Spry2''led to the increase of CVPs it should be noted that they found that a significant decrease in number of fungiform papillae. Contrastingly, the absence of ''Fgf10'', while leading to the absence of CVPs lead to an increase in number and size of fungiform papillae. Therefore these genes have different effects on the anterior and posterior developing tongue and taste buds.<ref><pubmed>21655085</pubmed></ref>

==Current Research==
We have an evolving understanding of Embryonic Taste development, through the use of state-of-the-art technology and research techniques we are able to make brilliant discoveries that continue to connect the dots of this amazing natural process of human development.
The majority of research in taste development is involving mice, these mammals show similar embryonic pathways to humans and research is performed in ethical and humane methods.

[[File:Histology.jpg|Left|thumb|200px|Image shows histological stains of a mice tongue showing dysplasia]]

'''Synergistic relationships of Six Genes '''

In an animal study using mice by Suzuki Y, Ikeda K, Kawakami K.(2011) Firstly nominating "Six Genes" as a major component in gustatory development, stating that deficiencies in certain Six genes (specifically Six1 & Six4) leads to poor development. Their research also highlights evidence of cooperative relationships between Six genes for normal advance. This experiment involved breeding mice containing exclusively Six1 and Six4 genes and examining the expression of these genes in papillae under high powered microscope observation. Understanding the role of certain genes along with the intrinsic relationships they hold is crucial for the ability to identify possible causes and correction of any abnormalities <ref><pubmed>21978088</pubmed></ref>

'''Neural Crest responsibilities '''

Another Animal Study involving mice explores a new idea of Neural crest (NC) contribution in taste development, specifically the development of papillae and taste buds. Liu HX, Komatsu Y, Mishina Y, Mistretta CM. (2012) suggest that Neural crest cells travel to the location of the tongue in early embryonic stages, gain epithelium phenotypes, multiply and then differentiate to eventually form taste papillae. The experiment involved the comparison of 2 different types of Cre line mice, which both express Cre gene in neural crest protocol, the different distribution patterns where observed in specific regions that NC is responsible for.<ref><pubmed>22659543</pubmed></ref>

'''Augmentation of Endoderm'''

In an animal study conducted by Rothova M, Thompson H, Lickert H, Tucker AS.(2012) exploring the historically debated issue of endoderm contribution to tongue development showed promising evidence that position of taste buds are patterned by the border of ectoderm and endoderm derivative epithelium. This study was accomplished via microscopic examination of previously stained specimens. Concluding endoderm has direct influence on gustatory develoment <ref><pubmed>22581563</pubmed></ref>

'''Changes in Taste Cells over time'''

Research by
Ozdener H, Spielman AI, Rawson NE.(2012) developing a culture which allows taste cells to survive for up to 12 months, empowers researchers to study the processes of proliferation, differentiation and function. This experiment will provide a precidnet for future study of taste cells, as these cells are able to operate and grow normally. <ref><pubmed>22643728</pubmed></ref>

'''Shh key component of taste bud proginators'''

A tamoxifen treatment which supresses Sonic hedgehog (Shh) secretion in mice proving to reduce the number of cells visable within papillae, in contrast mice not treated with tamoxifen showed a mark increase of cells within papillae, these cells are assumed to become taste cells in later development.
Specific mice were bred to trace the destination of taste placode cells, the study concluded that Shh expressing placodes are taste bud proginators which in turn become taste cells within taste buds although do not have any prescuros relationship with pappilae. The results were obtain by examination of mice embryos using Bright-field or multichannel fluorescent images through the use of an "Axiocam CCD camera and Axioplan fluorescence microscope with Axiovision software" a study by Harlow, Yang, Williams, Barlow (2011)<ref><pubmed>PMC2674259</pubmed></ref>

'''WNT family exhibit various roles'''

The WNT gene family has a function of signally proteins for various reason such as development, In 2010 Liu, Staubach Grosse, Walton, Saims, Gumucio, Mistretta explored recent findings on the role of WNT's in tongue and papillae development, Concluding that WNT/β-catenin is essential for fungiform papillae differing to WNT5a which proved to be principle in tongue development. Intrinsic chemical mediators were considered by manipulating a tissue culture and then throughaly examined by scanning photomicrograph. <ref><pubmed>PMC2768563</pubmed></ref>

[http://www.surgicalneurologyint.com/article.asp?issn=2152-7806;year=2012;volume=3;issue=1;spage=23;epage=23;aulast=Manjila]
[[File:Abnormal of tongue.jpg|Left|thumb|200px|Image shows and example of tongue abnormalities, this is called "double tongue" each side has independent movement!]]

==Useful links==

==Glossary==

ectoderm- outer germ layer of embryo

endoderm - inner germ layer of embryo

epithelium - basic animal tissue that is composed of tightly packed cells, usually covering the outer portion of organs

exocystosis - movement of contents out of cell

ganglia - the accumulation of a nerve cell body

growth factor - a substance that stimulates the growth of cells

gustatory - anything that relates to the taste sense

hydrolysis - breakdown of a chemical when it reacts with water

mesoderm - middle germ layer of embryo

mesenchyme - multipotential cells

neural crest - a part of the ectoderm found on both sides of the neural tube

neuron - most simplistic unit of the nervous system

neurotransmitter - chemicals which allow the passing of signals from neuron to neuron via connecting part (synapse)

papillae - small rough surface projection

six genes - a family of genes

Sonic hedgehog (Shh) - signalling protein invloved in normal development

sulcus terminalis - describes a physical transition point separating the anterior 2/3 of the tongue from the posterior 1/3

tamoxifen - hormonal altering drug

==Image gallery==

== References ==
<references/>

==External Links==
{{External Links}}

http://www.webmd.com/oral-health/picture-of-the-tongue

http://www.tutorvista.com/content/biology/biology-iv/nervous-coordination/tongue-structure.php#parts-of-tongue

http://www.cf.ac.uk/biosi/staffinfo/jacob/teaching/sensory/taste.html

--[[User:Z8600021|Mark Hill]] 12:22, 15 August 2012 (EST) Please leave the content listed below the line at the bottom of your project page.

----

{{2012Projects}}

2012 Group Project 3

2012-09-28T03:19:03Z

Z3289738: /* History of Discoveries */

=Taste Development=

== Introduction ==
**NEED TO ADD**

==History of Discoveries==

{| cellpadding=5 style="border:1px solid #BBB"
|- bgcolor="#faecc8"
|''' Date'''|| '''Significant Discovery'''
|- bgcolor="#faf6ed"
|'''350BC'''
|| Aristotle writes about the basic tastes, sweet and bitter. He also notes that it can be modified by salty and acidic. <ref><pubmed>22717400</pubmed></ref>
|- bgcolor="#faecc8"
|'''1901'''
|| D. Hanig publishes a paper describing taste sensitivity in different regions of the tongue.
''Interesting fact:'' The modern concept of a 'tongue map' is a misinterpretation of this study. <ref><pubmed>22717400</pubmed></ref>

|- bgcolor="#faf6ed"
|style=white-space:nowrap|'''1908'''
|Kikunae Ikeda, a professor of the Tokyo Imperial University, discovered and identified the fifth basic taste: umami (savouriness), made palatable by glutamate. <ref><pubmed>12438213</pubmed></ref>

|- bgcolor="#faecc8"
|style=white-space:nowrap|'''1931'''
|Bitter taste sensitivity found to vary among humans <ref><pubmed>22717400</pubmed></ref>

|- bgcolor="#faf6ed"
|style=white-space:nowrap|'''1931-32'''
| A chemist named Arthur Fox and his college noted that they had different sensitivities to the bitter tasting Phenylthiocarbamide (PTC). Genetisists later confirm these findings, and discover that non-tasting is a recessive genetic trait. <ref><pubmed>17782493</pubmed></ref> <ref>Blakeslee AF, Fox AL. Our different taste worlds. J Hered. 1932;23:97–107.</ref>

|- bgcolor="#faf6ed"
|style=white-space:nowrap|'''1965'''
|Farbman's study of the developing taste but in rat fungiform papilla was significant in increasing our understanding of taste bud development. <ref><pubmed>14300090</pubmed></ref> [http://www.sciencedirect.com/science/article/pii/0012160665900400 Electron microscope study of the developing taste bud in rat fungiform papilla.]

|- bgcolor="#faf6ed"
|style=white-space:nowrap|'''1992'''
|McLaughlin SK et al. discovery a taste cell-specific G-protein within the taste buds called Gustucon. This protein is later used to mark bitter, umami and sweet cells. <ref><pubmed>1608467 </pubmed></ref> [http://www.nature.com/nature/journal/v357/n6379/abs/357563a0.html Gustducin is a taste-cell-specific G protein closely related to the transducins]

|- bgcolor="#faf6ed"
|style=white-space:nowrap|'''1995'''
|Barlow et al. experimented with Axolotl salamanders and concluded that taste buds from this species arise exclusively from epithelial tissue, "oropharyngeal epithelium". <ref><pubmed>17826760</pubmed></ref> http://www.ncbi.nlm.nih.gov/pubmed/17826760 Embryonic origin of gustatory cranial sensory neurons.]

|- bgcolor="#faecc8"
|style=white-space:nowrap|'''1996'''
| Witt M and Reutter K of the Technical University Dresden in Germany, carried out a transmission electron microscopy study to investigate the embryonic and fetal development of Human taste buds. Their results suggest an "at least dual function of embryonic/fetal taste buds", including non-gustatory, paracrine functions prior to the 14th week and gustatory after the 14th week. <ref><pubmed>8955790</pubmed></ref> [http://www.ncbi.nlm.nih.gov/pubmed/8955790 Embryonic and early fetal development of human taste buds: a transmission electron microscopical study]

|- bgcolor="#faf6ed"
|style=white-space:nowrap|'''2000'''
|Chandrashekar, J. et al. discover the first taste sonsors, the T2R bitter taste receptors. <ref><pubmed>10761935</pubmed></ref>

|- bgcolor="#faecc8"
|style=white-space:nowrap|'''2001'''
|Nelson, G. et al. discover the sweet receptor: a combination of T1R2 and T1R3. <ref><pubmed>11509186</pubmed></ref>[http://www.ncbi.nlm.nih.gov/pubmed/11509186?dopt=Abstract&holding=npg Mammalian sweet taste receptors.]

|- bgcolor="#faf6ed"
|style=white-space:nowrap|'''2002'''
|Nelson G. et al. discover the amino acid (umami) taste receptor: a combination of T1R1 and T1R3 identified. <ref><pubmed>11894099</pubmed></ref> [http://www.ncbi.nlm.nih.gov/pubmed/11894099?dopt=Abstract&holding=npg An amino-acid taste receptor]

|- bgcolor="#faecc8"
|style=white-space:nowrap|'''2005'''
|Dyer, J. et al. discover sweet taste receptors in the GI tract. <ref><pubmed>17855558</pubmed></ref> [http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1986582/ Sweet taste signaling in the gut]

|- bgcolor="#faf6ed"
|style=white-space:nowrap|'''2006'''
|Huang, A. L et al. discover cells for sour taste, identified by PKD2L1 (a polycystic kidney disease-like ion channel) <ref><pubmed>16929298</pubmed></ref> [http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1571047/ The Cells and Logic for Mammalian Sour Taste detection]

|- bgcolor="#faecc8"
|style=white-space:nowrap|'''2007'''
|Harlow DE, Barlow LA of the University of Colorado Denver Health Sciences Center provide evidence of the "embryonic origin of gustatory cranial sensory neurons" <ref><pubmed>17826760</pubmed></ref> [http://www.ncbi.nlm.nih.gov/pubmed/17826760 Embryonic origin of gustatory cranial sensory neurons.]

|- bgcolor="#faf6ed"
|style=white-space:nowrap|'''2009'''
|A study by Hevezi P et al, presents "the first comprehensive characterization of gene expression in primate taste buds", as opposed to previous studies which focused on rodents. <ref><pubmed>19636377</pubmed></ref> [http://www.ncbi.nlm.nih.gov/pubmed/19636377 Genome-wide analysis of gene expression in primate taste buds reveals links to diverse processes]

|- bgcolor="#faecc8"
|style=white-space:nowrap|'''2010'''
|Chandrashekar, J. et al. identify epithelial sodium channel (ENaC) as the sodium-salt taste receptor <ref><pubmed>20107438</pubmed></ref> [http://www.ncbi.nlm.nih.gov/pubmed/20107438?dopt=Abstract&holding=npg The cells and peripheral representation of sodium taste in mice]
|}

*[http://www.nature.com/nature/journal/v486/n7403_supp/fig_tab/486S2a_F1.html Gustatory system: The finer points of taste] <ref><pubmed>22717400</pubmed></ref>

==Gustatory System==

[[Image:Taste qualities.gif|thumb|The five basic tastes]]

Taste or more appropriately gustation, is a fundamental survival tool in animals as it directs the consumption of essential nutrients. The five tastes that exist within the human gustatory system: salty, sweet, sour, bitter and umami, all signify basic physiological requirements. Salty tastes denote the presence of Na+, an important ion involved in the transportation and retention of water across cell membranes. Sweetness is the recognition of carbohydrates, essential for maintaining optimal brain function and providing the basis for energy production in muscle tissue via ATP hydrolysis. Similarly umami codes for the presence of L-amino acids, especially L-glutamate which is an integral component of protein synthesis.

These different modalities not only function to maintain the proper intake of nutrients within the body but also, by way of aversion, prohibit the consumption of undesired or poisonous materials. The bitter modality for example is generally regarded as displeasing to the human palate. It represents a high acid content which may be a result of foods which have become rotten or are inherently poisonous to the body.<ref name=PMID20696704><pubmed>20696704</pubmed></ref>

Research has historically limited itself to investigating the mechanisms of these five taste qualities though it must be noted many other modalities may exist. Of particular conjecture is the existence of fatty acid recognition. In the past the detection of fat in food has been attributed to somatosensory inputs <ref name=PMID20696704/> from the tongue, that is, the oily feel and texture of fat rather than its actual ‘taste’ allows the brain to encode for its presence. Further research is therefore required to elicit the precise mechanisms of fat detection.

===Cell Biology===

The five taste qualities are not all detected by the same type of receptor cell located within the taste bud. Like rods and cones in the eye which detect different wavelengths of light, there are specific types of receptors for different tastes. For example, sweet, umami and bitter are recognised by Type II G-protein coupled receptors, whereas sour is related to Type III presynaptic cells. The cell type involved in salty taste transduction is unknown however it is known that sodium ions can enter the receptor cell membrane via ion channel permeation.

====Type II receptors====

When a bitter, sweet or umami ligand binds to a type II G-coupled receptor, a cascade of chemical reactions causes the release of Ca2+ which in turn mediates exocystosis of ATP. The function of this ATP is threefold:

# Stimulates gustatory nerve afferents which project to gustatory nuclei in the spinal cord
# Excites Type III presynaptic nerve fibres to release serotonin.
# Has a positive feedback effect on type II receptor cells, increasing the level of ATP production.

The role of serotonin is believed to be in the form of lateral inhibition i.e. when a bitter quality is recognised, adjacent receptors for sweetness are deactivated and thus the two tastes may be clearly differentiated. It also has a negative feedback effect on receptor cells, inhibiting umami, bitter and sweet taste transduction.

==Taste Map==
[[Image:Taste map.png|thumb|left|250px|Obsolete idea of the tongue map]]
The idea of a tongue map has disseminated through society for many years. This concept purports that different areas of the tongue are specialised to detect either sweet, salty, sour and bitter tastes. Recent research however has completely nullified such claims and suggests instead that different forms of taste are recognised all over the tongue as well as via the palate. Thus the term ''taste map'' has come to take on a new meaning and that is, the precise areas of taste modalities processing in areas of cortex and its subsequent neural inputs.

===Neural Pathways===

'''First order neurons''' - From the receptors located in the taste buds, gustatory nerve afferents project to the ipsilateral rostral 1/3 of the nucleus tractus solitarius (NTS), located in the medulla. This rostral 1/3 is commonly referred to as the ''gustatory nucleus''.

The ''gustatory nucleus'' receives input from cranial nerves VII (''Facial n.''), IX (''Hypglossal n.''), and X (''Vagus n.'') via special visceral afferent (SVA) nerve fibres. A summary of their functions is as follows:

* ''Facial nerve n''. - carries taste information from the anterior 2/3 of the tongue.
* ''Hypoglossal n.'' - carries taste information from the posterior 1/3 of the tongue.
* ''Vagus n''. - carries taste information from the palate

'''Second order neurons''' - From the NTS second order neurons carry taste information to the Ventral posteromedial (VPM) nucleus in the thalamus.<ref name=PMID21885776/>

Copious scientific conjecture surrounds how each taste modality is transmitted to the brain. The ‘labelled-line’ hypothesis suggests that there are taste specific neurons which exclusively carry that taste modality to cortical areas. In analogous terms it can be viewed like the pipelines leading toward a house. Each pipeline carries its own utility, there is one for gas, another for water and finally for electricity with each terminating in slightly different areas of the house. In the same way, on the tongues there are different receptors for each taste which concurrently have individual nerve tracts leading to the primary gustatory cortex.

Contrapuntally there is electrophysiological evidence that single nerve afferents carry multiple modalities. These studies show one nerve afferent may have both a strong and a weak activation in response to a multiple taste stimuli.

===Cortical Areas===

[[Image:Primary gustatory cortex.png|thumb|Primary gustatory cortex]]

The location of the taste perception centres has been observed via functional magnetic resonance imaging (fMRI) studies. The primary taste cortex has been identified as being located in the anterior insula/frontal operculum (I/fO)<ref name=PMID22245354><pubmed>22245354</pubmed></ref>, with the secondary taste cortex in the caudolateral orbitofrontal cortex.<ref name=PMID21305668><pubmed>21305668</pubmed></ref> Within the insula there are further subdivisions related to each taste modality. Two photon calcium imaging research has outlined certain ’hot-spots’ of activation which are clearly delineated in relation to each taste. For example, the bitter modality is represented on the insula cortex approximately 1mm posterior to the middle cerebral artery whereas the sweet modality is represented 2.5mm rostrodorsal to the bitter field with no apparent overlap.<ref name=PMID21885776><pubmed>21885776</pubmed></ref> These findings lend weight to the idea that there is only one receptor for each taste quality.

It is interesting to note the relationship between taste and the reward centres of the brain. There is evidence of neural input to the ventral tegmental area (the origin of the mesolimbic dopaminergic reward pathway) and nucleus accumbens (involved in the conversion of motivation into physical action).<ref name=PMID21885776/> Neural connections such as this provide the foundations in explaining concepts such as flavour learning and preference. It may also give some insight into chronic problems such as food addiction and craving. As of yet however the gustatory neural network is not well understood and more research is required to elucidate the relationship between pleasure and taste sensation

==Timeline of Developmental Processes of the Gustatory System==

{| cellpadding=5 style="border:1px solid #BBB"
|- bgcolor="#89CFF0"
|'''Postovulatory Week'''||'''Description'''||'''Image'''
|- bgcolor="#BCD4E6"
|'''Week 6''' ||
The surface of the developing tongue is covered by nearly flat epitheliuem (Figure 1) <ref name=PMID9455607/>. The first gustatory papillae of the tongue appears in the caudal midline near the foramen caecum and the first circumvallate papilla develop on the dorsal midline <ref name=PMID9455607/> .
||
image
|- bgcolor="#89CFF0"
| '''Weeks 6 to 7'''||
Nerve fibres approach the basal lamina of lingual epithelium <ref name=PMID8955790><pubmed>8955790</pubmed></ref>. At this stage the lingual epithelium consists of two to three cell layers and there is not yet any sign of cell specializations indicating early taste bud formation<ref name=PMID8955790/>.
||
Image
|- bgcolor="#BCD4E6"
| '''Week 7 '''||
A series of epithelial swellings in the anterior part and midline of the tongue indicate early forming fungiform papillae (figure 2) <ref name=PMID9455607/>.
||
Image
|- bgcolor="#89CFF0"
| ''' Week 8 ''' ||
The lingual epithelium shows first signs of taste bud development as nerve fibres penetrate epithelial basal lamina <ref name=PMID8955790/> and form synapses with taste bud progenitor cells. The synapses reach a maximum around the 12th to 13th week <ref name=PMID8955790/>. However, at this time these cells are still poorly differentiated, elongated epithelial cells <ref name=PMID8955790/> . The synapses demonstrate the neuronal connection between the taste bud primordium and the central nervous system <ref name=PMID8955790/>. Ciliated cells also appear around the 8th week, however the significance of these cells which are scattered randomly across the lingual surface remains unclear <ref name=PMID8955790/>.
||
Image
|- bgcolor="#BCD4E6"
|''' Weeks 8-9''' ||
“By this stage the top surface of circumvallate papillae usually contains a taste pit partly filled with microvilli of presumed underlying taste bud cells” (Figure 10) <ref name=PMID9455607/>
||
Image
|- bgcolor="#89CFF0"
|''' Weeks 10-11''' ||
At this stage, the lingual epithelium compromises of about four cell layers, and the first shallow grooves above the taste bud primordium are developed <ref name=PMID8955790/>.

Fungiform papillae appear on the lateral margins and the tip of the tongue <ref name=PMID9455607/>, containing taste bud primordial that display the first signs of a primitive pore formation <ref name=PMID8955790/>.

Untypically differentiated apical cellular processes extend onto the surface <ref name=PMID9455607/>

Some taste bud primordial contain cells that perforate the covering epithelial later with short, broad untypically differentiated apical cellular processes. (Figure 3,4) <ref name=PMID8955790/> <ref name=PMID9455607/>
||
Image
|- bgcolor="#BCD4E6"
|''' Week 12 ''' ||
Taste bud cells are more clearly differentiated into epithelial cell types II and III <ref name=PMID8955790/>.
||
Image
|- bgcolor="#89CFF0"
|''' Weeks 12-13 ''' ||
By this stage the taste bud primordial are all located on the top of dermal papillae (Fig 6a) <ref name=PMID8955790/>. There is also maximum synapses between cells and afferent nerve fibres, which intermingle with each other to form a plexus-like structure <ref name=PMID8955790/>.
||
Image
|- bgcolor="#BCD4E6"
|''' Weeks 14 -15 ''' ||
The shape of the taste buds primordial begins to resemble those of adult taste buds <ref name=PMID8955790/>. By the 14th week the taste pores develop as the taste pits are filled by microvilli <ref name=PMID8955790/>, indicating the possibility that the taste buds begin their gustatory function <ref name=PMID8955790/>, however they still lack an electron-dense mucous material (Fig.10) <ref name=PMID8955790/>. The tastebuds only achieve a fully developed function in week 15 of gestation with the development of type I cells to produce the mucous material in the taste pit <ref name=PMID8955790/>.
||
Image
|}

==Adult Tongue and Taste Buds – Structure and Function==

'''Structure'''

The tongue is located on the floor of the oral cavity, It is a muscular structure with sensory units crowning. The tongue is divided into an anterior two thirds and a posterior one third. These regions are divided by a V-shaped groove at the back of the tongue (sulcus terminalis). The anterior two thirds of the tongue is covered by stratified squamous epithelium, It contains a roughened surface and has projections called papillae that vary in shape and number.

''''The Image Below is a very simplistic Diagram of the surface of the Tongue showing the locations of the different papillae and other important features'''

{|
| [[Image:Drawing of Tongue.png|500px]]

'''Papillae'''
[[File:Papillae.jpg|Left|thumb|200px|Close up of Human Tongue Papillae]]

There are 4 types of papillae on the tongue.
The most numerous papillae are the filiform papillae, which function to provide a surface that aids in holding food on the tongue during chewing but do not contain taste buds. The larger, less numerous fungiform papillae which contain taste buds, as do foliate papillae. Circumvallate papillae form a wide V at the sulcus terminalis also containing taste bus. There are no papillae or taste buds located on the posterior third of the tongue, having mucosal folds and the lingual tonsils instead.

'''Function'''

The tongue is for tasting, swallowing, and speech.
The functional unit of the taste bud is a taste cell, there are between 50 and 100 taste cells in each taste bud these taste cells represent all 5 different tastes. Historically is was believed that different areas of the tongue were responsible for different taste sensations although this has since been disregarded.[http://users.rcn.com/jkimball.ma.ultranet/BiologyPages/W/Welcome.html] The papillae contain taste buds which are connected to the oral cavity via a taste pore, the function of the taste bud is to transmit a chemical signal from the oral cavity to a taste cell, this chemical signal is the converted into an electrical impulse and delivered to the brain via nerve fibres for interpretation.

'''The Image Below is a very simplistic Hand drawn Diagram of a taste bud, in an extreme close up, cross section view of the the taste bud unit, not to scale'''

[[File:Taste_bud_1.jpg]]

==Abnormalities==

===Knocking out P2X Receptors===

[[File:Image of taste being evoked by visualising ATP release.jpeg|Left|thumb|200px|Evoking taste - ATP release in tongue]]

Gustatory abnormalities has not been widely researched and what has been researched has been through animal testing, most commonly we have found on mice.

In Huang, 2008 this team used the release of the neurotransmitter, ATP (adenosine triphosphate) as a quantitative measurement of gustatory sensation and taste. This was done by using a comparison of wild type (WT) and double knockout (DKO) mice. P2X receptors, P2X2 and P2X3 were knocked out in the DKO mice. The premise of this article was that knocking out P2X receptors reduces transmitter secretion of ATP in taste buds, therefore they cannot taste.

It should be noted that the taste buds in DKO are functional, but are not stimulated by the administration of tastants.

The transmission of release of ATP is secretion through gap junction hemichannels (pannexin 1 gap junction).

When both P2X2 and P2X3 are knocked out, no taste is elicited. However they found that if either P2X2 OR P2X3 was knocked out there was a taste response. So the inference made from this is that if one of the two receptors from the P2X family was knocked out there still can have taste response. The WT mice showed significant stimulation by tastants whereas DKO had little to no stimulation of ATP release.<ref><pubmed>21940456</pubmed></ref>

===FGF signalling and genes===

Sprouty, or ''Srpy'', genes have been related to regulating the development of circumvillate papillae (CVP). The CVP are large dome shaped papillae, which form a 'V' just in front of the terminal sulcus.

By knocking out ''Spry'' genes using mice which had ''Spry1'' and ''Spry2'' knocked out showed that the number of CVP doubled. However, when Fibroblast Growth Factor gene ("Fgf10") was absent, the number of CVP was significantly reduced, if not completely absent. The correlation between ''Spry1/2'' and ''Fgf10'' is that ''Spry1/2'' antagonises "Fgf10" to limit the size of the CVP progenitor placode. Exclusive expression of ''Fgf10'' in the mesenchyme is necessary for the formation of CVP.

'''This image shows the CVP stained with H&E and scanned by Scanning Electron Microscope (SEM)'''
[[File:CVP of WT(top) and DKO(bottom) mice with H&E and SEM.png]]

'''This image shows the location of the CVP and the increased number in DKO mice by SEM'''
[[File:Mouse circumvallate papilla 01.jpg|300px]]

Taste buds develop from the mesenchyme but require local signalling to properly differentiate. Some signalling factors for proper development of taste buds besides FGF are: Sonic Hedgehog (SHH), Bone Morphogenetic Proteins (BMPs), Epidermal Growth Factor (EGF).

Additionally, this proves that the anterior and posterior developments of the tongue are derived from embryonic tissues, where the anterior tongue is derived from the ectoderm and the posterior tongue is derived from the endoderm. Taste buds develop from the mesenchyme but require local signalling to properly differentiate. Some signalling factors for proper development of taste buds besides FGF are: Sonic Hedgehog (SHH), Bone Morphogenetic Proteins (BMPs), Epidermal Growth Factor (EGF).

As mentioned above, this article shows that the anterior and posterior developments of the tongue are derived from embryonic tissues, where the anterior tongue is derived front the ectoderm and the posterior tongue is derived from the endoderm. Secondly, FGF is required to regulate the growth of taste buds, while ''Spry'' genes limit the number of CVP. ''Fgf10''& ''Spry 1&2''work antagonistically through receptor tyrosine kinase (RTK)signalling.

However, the deletion of ''Spry2''led to the increase of CVPs it should be noted that they found that a significant decrease in number of fungiform papillae. Contrastingly, the absence of ''Fgf10'', while leading to the absence of CVPs lead to an increase in number and size of fungiform papillae. Therefore these genes have different effects on the anterior and posterior developing tongue and taste buds.<ref><pubmed>21655085</pubmed></ref>

==Current Research==
We have an evolving understanding of Embryonic Taste development, through the use of state-of-the-art technology and research techniques we are able to make brilliant discoveries that continue to connect the dots of this amazing natural process of human development.
The majority of research in taste development is involving mice, these mammals show similar embryonic pathways to humans and research is performed in ethical and humane methods.

[[File:Histology.jpg|Left|thumb|200px|Image shows histological stains of a mice tongue showing dysplasia]]

'''Synergistic relationships of Six Genes '''

In an animal study using mice by Suzuki Y, Ikeda K, Kawakami K.(2011) Firstly nominating "Six Genes" as a major component in gustatory development, stating that deficiencies in certain Six genes (specifically Six1 & Six4) leads to poor development. Their research also highlights evidence of cooperative relationships between Six genes for normal advance. This experiment involved breeding mice containing exclusively Six1 and Six4 genes and examining the expression of these genes in papillae under high powered microscope observation. Understanding the role of certain genes along with the intrinsic relationships they hold is crucial for the ability to identify possible causes and correction of any abnormalities <ref><pubmed>21978088</pubmed></ref>

'''Neural Crest responsibilities '''

Another Animal Study involving mice explores a new idea of Neural crest (NC) contribution in taste development, specifically the development of papillae and taste buds. Liu HX, Komatsu Y, Mishina Y, Mistretta CM. (2012) suggest that Neural crest cells travel to the location of the tongue in early embryonic stages, gain epithelium phenotypes, multiply and then differentiate to eventually form taste papillae. The experiment involved the comparison of 2 different types of Cre line mice, which both express Cre gene in neural crest protocol, the different distribution patterns where observed in specific regions that NC is responsible for.<ref><pubmed>22659543</pubmed></ref>

'''Augmentation of Endoderm'''

In an animal study conducted by Rothova M, Thompson H, Lickert H, Tucker AS.(2012) exploring the historically debated issue of endoderm contribution to tongue development showed promising evidence that position of taste buds are patterned by the border of ectoderm and endoderm derivative epithelium. This study was accomplished via microscopic examination of previously stained specimens. Concluding endoderm has direct influence on gustatory develoment <ref><pubmed>22581563</pubmed></ref>

'''Changes in Taste Cells over time'''

Research by
Ozdener H, Spielman AI, Rawson NE.(2012) developing a culture which allows taste cells to survive for up to 12 months, empowers researchers to study the processes of proliferation, differentiation and function. This experiment will provide a precidnet for future study of taste cells, as these cells are able to operate and grow normally. <ref><pubmed>22643728</pubmed></ref>

'''Shh key component of taste bud proginators'''

A tamoxifen treatment which supresses Sonic hedgehog (Shh) secretion in mice proving to reduce the number of cells visable within papillae, in contrast mice not treated with tamoxifen showed a mark increase of cells within papillae, these cells are assumed to become taste cells in later development.
Specific mice were bred to trace the destination of taste placode cells, the study concluded that Shh expressing placodes are taste bud proginators which in turn become taste cells within taste buds although do not have any prescuros relationship with pappilae. The results were obtain by examination of mice embryos using Bright-field or multichannel fluorescent images through the use of an "Axiocam CCD camera and Axioplan fluorescence microscope with Axiovision software" a study by Harlow, Yang, Williams, Barlow (2011)<ref><pubmed>PMC2674259</pubmed></ref>

'''WNT family exhibit various roles'''

The WNT gene family has a function of signally proteins for various reason such as development, In 2010 Liu, Staubach Grosse, Walton, Saims, Gumucio, Mistretta explored recent findings on the role of WNT's in tongue and papillae development, Concluding that WNT/β-catenin is essential for fungiform papillae differing to WNT5a which proved to be principle in tongue development. Intrinsic chemical mediators were considered by manipulating a tissue culture and then throughaly examined by scanning photomicrograph. <ref><pubmed>PMC2768563</pubmed></ref>

[http://www.surgicalneurologyint.com/article.asp?issn=2152-7806;year=2012;volume=3;issue=1;spage=23;epage=23;aulast=Manjila]
[[File:Abnormal of tongue.jpg|Left|thumb|200px|Image shows and example of tongue abnormalities, this is called "double tongue" each side has independent movement!]]

==Useful links==

==Glossary==

ectoderm- outer germ layer of embryo

endoderm - inner germ layer of embryo

epithelium - basic animal tissue that is composed of tightly packed cells, usually covering the outer portion of organs

exocystosis - movement of contents out of cell

ganglia - the accumulation of a nerve cell body

growth factor - a substance that stimulates the growth of cells

gustatory - anything that relates to the taste sense

hydrolysis - breakdown of a chemical when it reacts with water

mesoderm - middle germ layer of embryo

mesenchyme - multipotential cells

neural crest - a part of the ectoderm found on both sides of the neural tube

neuron - most simplistic unit of the nervous system

neurotransmitter - chemicals which allow the passing of signals from neuron to neuron via connecting part (synapse)

papillae - small rough surface projection

six genes - a family of genes

Sonic hedgehog (Shh) - signalling protein invloved in normal development

sulcus terminalis - describes a physical transition point separating the anterior 2/3 of the tongue from the posterior 1/3

tamoxifen - hormonal altering drug

==Image gallery==

== References ==
<references/>

==External Links==
{{External Links}}

--[[User:Z8600021|Mark Hill]] 12:22, 15 August 2012 (EST) Please leave the content listed below the line at the bottom of your project page.

----

{{2012Projects}}

2012 Group Project 3

2012-09-26T04:52:21Z

Z3289738: /* History of Discoveries */

=Taste Development=

== Introduction ==
**NEED TO ADD**

==History of Discoveries==

{| cellpadding=5 style="border:1px solid #BBB"
|- bgcolor="#faecc8"
|''' Date'''|| '''Significant Discovery'''
|- bgcolor="#faf6ed"
|'''350BC'''
|| Aristotle writes about the basic tastes, sweet and bitter. He also notes that it can be modified by salty and acidic. <ref><pubmed>22717400</pubmed></ref>
|- bgcolor="#faecc8"
|'''1901'''
|| D. Hanig publishes a paper describing taste sensitivity in different regions of the tongue.
''Interesting fact:'' The modern concept of a 'tongue map' is a misinterpretation of this study. <ref><pubmed>22717400</pubmed></ref>

|- bgcolor="#faf6ed"
|style=white-space:nowrap|'''1908'''
|Kikunae Ikeda, a professor of the Tokyo Imperial University, discovered and identified the fifth basic taste: umami (savouriness), made palatable by glutamate. <ref><pubmed>12438213</pubmed></ref>

|- bgcolor="#faecc8"
|style=white-space:nowrap|'''1931'''
|Bitter taste sensitivity found to vary among humans <ref><pubmed>22717400</pubmed></ref>

|- bgcolor="#faf6ed"
|style=white-space:nowrap|'''1931-32'''
| A chemist named Arthur Fox and his college noted that they had different sensitivities to the bitter tasting Phenylthiocarbamide (PTC). Genetisists later confirm these findings, and discover that non-tasting is a recessive genetic trait. <ref><pubmed>17782493</pubmed></ref> <ref>Blakeslee AF, Fox AL. Our different taste worlds. J Hered. 1932;23:97–107.</ref>

|- bgcolor="#faf6ed"
|style=white-space:nowrap|'''1992'''
|McLaughlin SK et al. discovery a taste cell-specific G-protein within the taste buds called Gustucon. This protein is later used to mark bitter, umami and sweet cells. <ref><pubmed>1608467 </pubmed></ref> [http://www.nature.com/nature/journal/v357/n6379/abs/357563a0.html Gustducin is a taste-cell-specific G protein closely related to the transducins]

|- bgcolor="#faecc8"
|style=white-space:nowrap|'''1996'''
| Witt M and Reutter K of the Technical University Dresden in Germany, carried out a transmission electron microscopy study to investigate the embryonic and fetal development of Human taste buds. Their results suggest an "at least dual function of embryonic/fetal taste buds", including non-gustatory, paracrine functions prior to the 14th week and gustatory after the 14th week. <ref><pubmed>8955790</pubmed></ref> [http://www.ncbi.nlm.nih.gov/pubmed/8955790 Embryonic and early fetal development of human taste buds: a transmission electron microscopical study]

|- bgcolor="#faf6ed"
|style=white-space:nowrap|'''2000'''
|Chandrashekar, J. et al. discover the first taste sonsors, the T2R bitter taste receptors. <ref><pubmed>10761935</pubmed></ref>

|- bgcolor="#faecc8"
|style=white-space:nowrap|'''2001'''
|Nelson, G. et al. discover the sweet receptor: a combination of T1R2 and T1R3. <ref><pubmed>11509186</pubmed></ref>[http://www.ncbi.nlm.nih.gov/pubmed/11509186?dopt=Abstract&holding=npg Mammalian sweet taste receptors.]

|- bgcolor="#faf6ed"
|style=white-space:nowrap|'''2002'''
|Nelson G. et al. discover the amino acid (umami) taste receptor: a combination of T1R1 and T1R3 identified. <ref><pubmed>11894099</pubmed></ref> [http://www.ncbi.nlm.nih.gov/pubmed/11894099?dopt=Abstract&holding=npg An amino-acid taste receptor]

|- bgcolor="#faecc8"
|style=white-space:nowrap|'''2005'''
|Dyer, J. et al. discover sweet taste receptors in the GI tract. <ref><pubmed>17855558</pubmed></ref> [http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1986582/ Sweet taste signaling in the gut]

|- bgcolor="#faf6ed"
|style=white-space:nowrap|'''2006'''
|Huang, A. L et al. discover cells for sour taste, identified by PKD2L1 (a polycystic kidney disease-like ion channel) <ref><pubmed>16929298</pubmed></ref> [http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1571047/ The Cells and Logic for Mammalian Sour Taste detection]

|- bgcolor="#faecc8"
|style=white-space:nowrap|'''2007'''
|Harlow DE, Barlow LA of the University of Colorado Denver Health Sciences Center provide evidence of the "embryonic origin of gustatory cranial sensory neurons" <ref><pubmed>17826760</pubmed></ref> [http://www.ncbi.nlm.nih.gov/pubmed/17826760 Embryonic origin of gustatory cranial sensory neurons.]

|- bgcolor="#faf6ed"
|style=white-space:nowrap|'''2009'''
|A study by Hevezi P et al, presents "the first comprehensive characterization of gene expression in primate taste buds", as opposed to previous studies which focused on rodents. <ref><pubmed>19636377</pubmed></ref> [http://www.ncbi.nlm.nih.gov/pubmed/19636377 Genome-wide analysis of gene expression in primate taste buds reveals links to diverse processes]

|- bgcolor="#faecc8"
|style=white-space:nowrap|'''2010'''
|Chandrashekar, J. et al. identify epithelial sodium channel (ENaC) as the sodium-salt taste receptor <ref><pubmed>20107438</pubmed></ref> [http://www.ncbi.nlm.nih.gov/pubmed/20107438?dopt=Abstract&holding=npg The cells and peripheral representation of sodium taste in mice]
|}

*[http://www.nature.com/nature/journal/v486/n7403_supp/fig_tab/486S2a_F1.html Gustatory system: The finer points of taste] <ref><pubmed>22717400</pubmed></ref>

==Gustatory System==

[[Image:Taste qualities.gif|thumb|The five basic tastes]]

Taste or more appropriately gustation, is a fundamental survival tool in animals as it directs the consumption of essential nutrients. The five tastes that exist within the human gustatory system: salty, sweet, sour, bitter and umami, all signify basic physiological requirements. Salty tastes denote the presence of Na+, an important ion involved in the transportation and retention of water across cell membranes. Sweetness is the recognition of carbohydrates, essential for maintaining optimal brain function and providing the basis for energy production in muscle tissue via ATP hydrolysis. Similarly umami codes for the presence of L-amino acids, especially L-glutamate which is an integral component of protein synthesis.

These different modalities not only function to maintain the proper intake of nutrients within the body but also, by way of aversion, prohibit the consumption of undesired or poisonous materials. The bitter modality for example is generally regarded as displeasing to the human palate. It represents a high acid content which may be a result of foods which have become rotten or are inherently poisonous to the body.<ref name=PMID20696704><pubmed>20696704</pubmed></ref>

Research has historically limited itself to investigating the mechanisms of these five taste qualities though it must be noted many other modalities may exist. Of particular conjecture is the existence of fatty acid recognition. In the past the detection of fat in food has been attributed to somatosensory inputs <ref name=PMID20696704/> from the tongue, that is, the oily feel and texture of fat rather than its actual ‘taste’ allows the brain to encode for its presence. Further research is therefore required to elicit the precise mechanisms of fat detection.

===Cell Biology===

The five taste qualities are not all detected by the same type of receptor cell located within the taste bud. Like rods and cones in the eye which detect different wavelengths of light, there are specific types of receptors for different tastes. For example, sweet, umami and bitter are recognised by Type II G-protein coupled receptors, whereas sour is related to Type III presynaptic cells. The cell type involved in salty taste transduction is unknown however it is known that sodium ions can enter the receptor cell membrane via ion channel permeation.

====Type II receptors====

When a bitter, sweet or umami ligand binds to a type II G-coupled receptor, a cascade of chemical reactions causes the release of Ca2+ which in turn mediates exocystosis of ATP. The function of this ATP is threefold:

# Stimulates gustatory nerve afferents which project to gustatory nuclei in the spinal cord
# Excites Type III presynaptic nerve fibres to release serotonin.
# Has a positive feedback effect on type II receptor cells, increasing the level of ATP production.

The role of serotonin is believed to be in the form of lateral inhibition i.e. when a bitter quality is recognised, adjacent receptors for sweetness are deactivated and thus the two tastes may be clearly differentiated. It also has a negative feedback effect on receptor cells, inhibiting umami, bitter and sweet taste transduction.

==Taste Map==
[[Image:Taste map.png|thumb|left|250px|Obsolete idea of the tongue map]]
The idea of a tongue map has disseminated through society for many years. This concept purports that different areas of the tongue are specialised to detect either sweet, salty, sour and bitter tastes. Recent research however has completely nullified such claims and suggests instead that different forms of taste are recognised all over the tongue as well as via the palate. Thus the term ''taste map'' has come to take on a new meaning and that is, the precise areas of taste modalities processing in areas of cortex and its subsequent neural inputs.

===Neural Pathways===

'''First order neurons''' - From the receptors located in the taste buds, gustatory nerve afferents project to the ipsilateral rostral 1/3 of the nucleus tractus solitarius (NTS), located in the medulla. This rostral 1/3 is commonly referred to as the ''gustatory nucleus''.

The ''gustatory nucleus'' receives input from cranial nerves VII (''Facial n.''), IX (''Hypglossal n.''), and X (''Vagus n.'') via special visceral afferent (SVA) nerve fibres. A summary of their functions is as follows:

* ''Facial nerve n''. - carries taste information from the anterior 2/3 of the tongue.
* ''Hypoglossal n.'' - carries taste information from the posterior 1/3 of the tongue.
* ''Vagus n''. - carries taste information from the palate

'''Second order neurons''' - From the NTS second order neurons carry taste information to the Ventral posteromedial (VPM) nucleus in the thalamus.<ref name=PMID21885776/>

Copious scientific conjecture surrounds how each taste modality is transmitted to the brain. The ‘labelled-line’ hypothesis suggests that there are taste specific neurons which exclusively carry that taste modality to cortical areas. In analogous terms it can be viewed like the pipelines leading toward a house. Each pipeline carries its own utility, there is one for gas, another for water and finally for electricity with each terminating in slightly different areas of the house. In the same way, on the tongues there are different receptors for each taste which concurrently have individual nerve tracts leading to the primary gustatory cortex.

Contrapuntally there is electrophysiological evidence that single nerve afferents carry multiple modalities. These studies show one nerve afferent may have both a strong and a weak activation in response to a multiple taste stimuli.

===Cortical Areas===

[[Image:Primary gustatory cortex.png|thumb|Primary gustatory cortex]]

The location of the taste perception centres has been observed via functional magnetic resonance imaging (fMRI) studies. The primary taste cortex has been identified as being located in the anterior insula/frontal operculum (I/fO)<ref name=PMID22245354><pubmed>22245354</pubmed></ref>, with the secondary taste cortex in the caudolateral orbitofrontal cortex.<ref name=PMID21305668><pubmed>21305668</pubmed></ref> Within the insula there are further subdivisions related to each taste modality. Two photon calcium imaging research has outlined certain ’hot-spots’ of activation which are clearly delineated in relation to each taste. For example, the bitter modality is represented on the insula cortex approximately 1mm posterior to the middle cerebral artery whereas the sweet modality is represented 2.5mm rostrodorsal to the bitter field with no apparent overlap.<ref name=PMID21885776><pubmed>21885776</pubmed></ref> These findings lend weight to the idea that there is only one receptor for each taste quality.

It is interesting to note the relationship between taste and the reward centres of the brain. There is evidence of neural input to the ventral tegmental area (the origin of the mesolimbic dopaminergic reward pathway) and nucleus accumbens (involved in the conversion of motivation into physical action).<ref name=PMID21885776/> Neural connections such as this provide the foundations in explaining concepts such as flavour learning and preference. It may also give some insight into chronic problems such as food addiction and craving. As of yet however the gustatory neural network is not well understood and more research is required to elucidate the relationship between pleasure and taste sensation

==Timeline of Developmental Processes of the Gustatory System==

{| cellpadding=5 style="border:1px solid #BBB"
|- bgcolor="#89CFF0"
|'''Postovulatory Week'''||'''Description'''||'''Image'''
|- bgcolor="#BCD4E6"
|'''Week 6''' ||
The surface of the developing tongue is covered by nearly flat epitheliuem (Figure 1) <ref name=PMID9455607/>. The first gustatory papillae of the tongue appears in the caudal midline near the foramen caecum and the first circumvallate papilla develop on the dorsal midline <ref name=PMID9455607/> .
||
image
|- bgcolor="#89CFF0"
| '''Weeks 6 to 7'''||
Nerve fibres approach the basal lamina of lingual epithelium <ref name=PMID8955790><pubmed>8955790</pubmed></ref>. At this stage the lingual epithelium consists of two to three cell layers and there is not yet any sign of cell specializations indicating early taste bud formation<ref name=PMID8955790/>.
||
Image
|- bgcolor="#BCD4E6"
| '''Week 7 '''||
A series of epithelial swellings in the anterior part and midline of the tongue indicate early forming fungiform papillae (figure 2) <ref name=PMID9455607/>.
||
Image
|- bgcolor="#89CFF0"
| ''' Week 8 ''' ||
The lingual epithelium shows first signs of taste bud development as nerve fibres penetrate epithelial basal lamina <ref name=PMID8955790/> and form synapses with taste bud progenitor cells. The synapses reach a maximum around the 12th to 13th week <ref name=PMID8955790/>. However, at this time these cells are still poorly differentiated, elongated epithelial cells <ref name=PMID8955790/> . The synapses demonstrate the neuronal connection between the taste bud primordium and the central nervous system <ref name=PMID8955790/>. Ciliated cells also appear around the 8th week, however the significance of these cells which are scattered randomly across the lingual surface remains unclear <ref name=PMID8955790/>.
||
Image
|- bgcolor="#BCD4E6"
|''' Weeks 8-9''' ||
“By this stage the top surface of circumvallate papillae usually contains a taste pit partly filled with microvilli of presumed underlying taste bud cells” (Figure 10) <ref name=PMID9455607/>
||
Image
|- bgcolor="#89CFF0"
|''' Weeks 10-11''' ||
At this stage, the lingual epithelium compromises of about four cell layers, and the first shallow grooves above the taste bud primordium are developed <ref name=PMID8955790/>.

Fungiform papillae appear on the lateral margins and the tip of the tongue <ref name=PMID9455607/>, containing taste bud primordial that display the first signs of a primitive pore formation <ref name=PMID8955790/>.

Untypically differentiated apical cellular processes extend onto the surface <ref name=PMID9455607/>

Some taste bud primordial contain cells that perforate the covering epithelial later with short, broad untypically differentiated apical cellular processes. (Figure 3,4) <ref name=PMID8955790/> <ref name=PMID9455607/>
||
Image
|- bgcolor="#BCD4E6"
|''' Week 12 ''' ||
Taste bud cells are more clearly differentiated into epithelial cell types II and III <ref name=PMID8955790/>.
||
Image
|- bgcolor="#89CFF0"
|''' Weeks 12-13 ''' ||
By this stage the taste bud primordial are all located on the top of dermal papillae (Fig 6a) <ref name=PMID8955790/>. There is also maximum synapses between cells and afferent nerve fibres, which intermingle with each other to form a plexus-like structure <ref name=PMID8955790/>.
||
Image
|- bgcolor="#BCD4E6"
|''' Weeks 14 -15 ''' ||
The shape of the taste buds primordial begins to resemble those of adult taste buds <ref name=PMID8955790/>. By the 14th week the taste pores develop as the taste pits are filled by microvilli <ref name=PMID8955790/>, indicating the possibility that the taste buds begin their gustatory function <ref name=PMID8955790/>, however they still lack an electron-dense mucous material (Fig.10) <ref name=PMID8955790/>. The tastebuds only achieve a fully developed function in week 15 of gestation with the development of type I cells to produce the mucous material in the taste pit <ref name=PMID8955790/>.
||
Image
|}

==Adult Tongue and Taste Buds – Structure and Function==

'''Structure'''

The tongue is located on the floor of the oral cavity, It is a muscular structure with sensory units crowning. The tongue is divided into an anterior two thirds and a posterior one third. These regions are divided by a V-shaped groove at the back of the tongue (sulcus terminalis). The anterior two thirds of the tongue is covered by stratified squamous epithelium, It contains a roughened surface and has projections called papillae that vary in shape and number.

''''The Image Below is a very simplistic Diagram of the surface of the Tongue showing the locations of the different papillae and other important features'''

{|
| [[Image:Drawing of Tongue.png|500px]]

'''Papillae'''
[[File:Papillae.jpg|Left|thumb|200px|Close up of Human Tongue Papillae]]

There are 4 types of papillae on the tongue.
The most numerous papillae are the filiform papillae, which function to provide a surface that aids in holding food on the tongue during chewing but do not contain taste buds. The larger, less numerous fungiform papillae which contain taste buds, as do foliate papillae. Circumvallate papillae form a wide V at the sulcus terminalis also containing taste bus. There are no papillae or taste buds located on the posterior third of the tongue, having mucosal folds and the lingual tonsils instead.

'''Function'''

The tongue is for tasting, swallowing, and speech.
The functional unit of the taste bud is a taste cell, there are between 50 and 100 taste cells in each taste bud these taste cells represent all 5 different tastes. Historically is was believed that different areas of the tongue were responsible for different taste sensations although this has since been disregarded.[http://users.rcn.com/jkimball.ma.ultranet/BiologyPages/W/Welcome.html] The papillae contain taste buds which are connected to the oral cavity via a taste pore, the function of the taste bud is to transmit a chemical signal from the oral cavity to a taste cell, this chemical signal is the converted into an electrical impulse and delivered to the brain via nerve fibres for interpretation.

'''The Image Below is a very simplistic Hand drawn Diagram of a taste bud, in an extreme close up, cross section view of the the taste bud unit, not to scale'''

[[File:Taste_bud_1.jpg]]

==Abnormalities==

===Knocking out P2X Receptors===

[[File:Image of taste being evoked by visualising ATP release.jpeg|Left|thumb|200px|Evoking taste - ATP release in tongue]]

Gustatory abnormalities has not been widely researched and what has been researched has been through animal testing, most commonly we have found on mice.

In Huang, 2008 this team used the release of the neurotransmitter, ATP (adenosine triphosphate) as a quantitative measurement of gustatory sensation and taste. This was done by using a comparison of wild type (WT) and double knockout (DKO) mice. P2X receptors, P2X2 and P2X3 were knocked out in the DKO mice. The premise of this article was that knocking out P2X receptors reduces transmitter secretion of ATP in taste buds, therefore they cannot taste.

It should be noted that the taste buds in DKO are functional, but are not stimulated by the administration of tastants.

The transmission of release of ATP is secretion through gap junction hemichannels (pannexin 1 gap junction).

When both P2X2 and P2X3 are knocked out, no taste is elicited. However they found that if either P2X2 OR P2X3 was knocked out there was a taste response. So the inference made from this is that if one of the two receptors from the P2X family was knocked out there still can have taste response. The WT mice showed significant stimulation by tastants whereas DKO had little to no stimulation of ATP release.<ref><pubmed>21940456</pubmed></ref>

===FGF signalling and genes===

Sprouty, or ''Srpy'', genes have been related to regulating the development of circumvillate papillae (CVP). The CVP are large dome shaped papillae, which form a 'V' just in front of the terminal sulcus.

By knocking out ''Spry'' genes using mice which had ''Spry1'' and ''Spry2'' knocked out showed that the number of CVP doubled. However, when Fibroblast Growth Factor gene ("Fgf10") was absent, the number of CVP was significantly reduced, if not completely absent. The correlation between ''Spry1/2'' and ''Fgf10'' is that ''Spry1/2'' antagonises "Fgf10" to limit the size of the CVP progenitor placode. Exclusive expression of ''Fgf10'' in the mesenchyme is necessary for the formation of CVP.

'''This image shows the CVP stained with H&E and scanned by Scanning Electron Microscope (SEM)'''
[[File:CVP of WT(top) and DKO(bottom) mice with H&E and SEM.png]]

'''This image shows the location of the CVP and the increased number in DKO mice by SEM'''
[[File:Mouse circumvallate papilla 01.jpg|300px]]

Taste buds develop from the mesenchyme but require local signalling to properly differentiate. Some signalling factors for proper development of taste buds besides FGF are: Sonic Hedgehog (SHH), Bone Morphogenetic Proteins (BMPs), Epidermal Growth Factor (EGF).

Additionally, this proves that the anterior and posterior developments of the tongue are derived from embryonic tissues, where the anterior tongue is derived from the ectoderm and the posterior tongue is derived from the endoderm. Taste buds develop from the mesenchyme but require local signalling to properly differentiate. Some signalling factors for proper development of taste buds besides FGF are: Sonic Hedgehog (SHH), Bone Morphogenetic Proteins (BMPs), Epidermal Growth Factor (EGF).

As mentioned above, this article shows that the anterior and posterior developments of the tongue are derived from embryonic tissues, where the anterior tongue is derived front the ectoderm and the posterior tongue is derived from the endoderm. Secondly, FGF is required to regulate the growth of taste buds, while ''Spry'' genes limit the number of CVP. ''Fgf10''& ''Spry 1&2''work antagonistically through receptor tyrosine kinase (RTK)signalling.

However, the deletion of ''Spry2''led to the increase of CVPs it should be noted that they found that a significant decrease in number of fungiform papillae. Contrastingly, the absence of ''Fgf10'', while leading to the absence of CVPs lead to an increase in number and size of fungiform papillae. Therefore these genes have different effects on the anterior and posterior developing tongue and taste buds.<ref><pubmed>21655085</pubmed></ref>

==Current Research==
We have an evolving understanding of Embryonic Taste development, through the use of state-of-the-art technology and research techniques we are able to make brilliant discoveries that continue to connect the dots of this amazing natural process of human development.
The majority of research in taste development is involving mice, these mammals show similar embryonic pathways to humans and research is performed in ethical and humane methods.

[[File:Histology.jpg|Left|thumb|200px|Image shows histological stains of a mice tongue showing dysplasia]]

'''Synergistic relationships of Six Genes '''

In an animal study using mice by Suzuki Y, Ikeda K, Kawakami K.(2011) Firstly nominating "Six Genes" as a major component in gustatory development, stating that deficiencies in certain Six genes (specifically Six1 & Six4) leads to poor development. Their research also highlights evidence of cooperative relationships between Six genes for normal advance. This experiment involved breeding mice containing exclusively Six1 and Six4 genes and examining the expression of these genes in papillae under high powered microscope observation. Understanding the role of certain genes along with the intrinsic relationships they hold is crucial for the ability to identify possible causes and correction of any abnormalities <ref><pubmed>21978088</pubmed></ref>

'''Neural Crest responsibilities '''

Another Animal Study involving mice explores a new idea of Neural crest (NC) contribution in taste development, specifically the development of papillae and taste buds. Liu HX, Komatsu Y, Mishina Y, Mistretta CM. (2012) suggest that Neural crest cells travel to the location of the tongue in early embryonic stages, gain epithelium phenotypes, multiply and then differentiate to eventually form taste papillae. The experiment involved the comparison of 2 different types of Cre line mice, which both express Cre gene in neural crest protocol, the different distribution patterns where observed in specific regions that NC is responsible for.<ref><pubmed>22659543</pubmed></ref>

'''Augmentation of Endoderm'''

In an animal study conducted by Rothova M, Thompson H, Lickert H, Tucker AS.(2012) exploring the historically debated issue of endoderm contribution to tongue development showed promising evidence that position of taste buds are patterned by the border of ectoderm and endoderm derivative epithelium. This study was accomplished via microscopic examination of previously stained specimens. Concluding endoderm has direct influence on gustatory develoment <ref><pubmed>22581563</pubmed></ref>

'''Changes in Taste Cells over time'''

Research by
Ozdener H, Spielman AI, Rawson NE.(2012) developing a culture which allows taste cells to survive for up to 12 months, empowers researchers to study the processes of proliferation, differentiation and function. This experiment will provide a precidnet for future study of taste cells, as these cells are able to operate and grow normally. <ref><pubmed>22643728</pubmed></ref>

'''Shh key component of taste bud proginators'''

A tamoxifen treatment which supresses Sonic hedgehog (Shh) secretion in mice proving to reduce the number of cells visable within papillae, in contrast mice not treated with tamoxifen showed a mark increase of cells within papillae, these cells are assumed to become taste cells in later development.
Specific mice were bred to trace the destination of taste placode cells, the study concluded that Shh expressing placodes are taste bud proginators which in turn become taste cells within taste buds although do not have any prescuros relationship with pappilae. The results were obtain by examination of mice embryos using Bright-field or multichannel fluorescent images through the use of an "Axiocam CCD camera and Axioplan fluorescence microscope with Axiovision software" a study by Harlow, Yang, Williams, Barlow (2011)<ref><pubmed>PMC2674259</pubmed></ref>

'''WNT family exhibit various roles'''

The WNT gene family has a function of signally proteins for various reason such as development, In 2010 Liu, Staubach Grosse, Walton, Saims, Gumucio, Mistretta explored recent findings on the role of WNT's in tongue and papillae development, Concluding that WNT/β-catenin is essential for fungiform papillae differing to WNT5a which proved to be principle in tongue development. Intrinsic chemical mediators were considered by manipulating a tissue culture and then throughaly examined by scanning photomicrograph. <ref><pubmed>PMC2768563</pubmed></ref>

[http://www.surgicalneurologyint.com/article.asp?issn=2152-7806;year=2012;volume=3;issue=1;spage=23;epage=23;aulast=Manjila]
[[File:Abnormal of tongue.jpg|Left|thumb|200px|Image shows and example of tongue abnormalities, this is called "double tongue" each side has independent movement!]]

==Useful links==

==Glossary==

ectoderm- outer germ layer of embryo

endoderm - inner germ layer of embryo

epithelium - basic animal tissue that is composed of tightly packed cells, usually covering the outer portion of organs

exocystosis - movement of contents out of cell

ganglia - the accumulation of a nerve cell body

growth factor - a substance that stimulates the growth of cells

gustatory - anything that relates to the taste sense

hydrolysis - breakdown of a chemical when it reacts with water

mesoderm - middle germ layer of embryo

mesenchyme - multipotential cells

neural crest - a part of the ectoderm found on both sides of the neural tube

neuron - most simplistic unit of the nervous system

neurotransmitter - chemicals which allow the passing of signals from neuron to neuron via connecting part (synapse)

papillae - small rough surface projection

six genes - a family of genes

Sonic hedgehog (Shh) - signalling protein invloved in normal development

sulcus terminalis - describes a physical transition point separating the anterior 2/3 of the tongue from the posterior 1/3

tamoxifen - hormonal altering drug

==Image gallery==

== References ==
<references/>

==External Links==
{{External Links}}

--[[User:Z8600021|Mark Hill]] 12:22, 15 August 2012 (EST) Please leave the content listed below the line at the bottom of your project page.

----

{{2012Projects}}

2012 Group Project 3

2012-09-26T04:50:15Z

Z3289738: /* History of Discoveries */

=Taste Development=

== Introduction ==
**NEED TO ADD**

==History of Discoveries==

{| cellpadding=5 style="border:1px solid #BBB"
|- bgcolor="#faecc8"
|''' Date'''|| '''Significant Discovery'''
|- bgcolor="#faf6ed"
|'''350BC'''
|| Aristotle writes about the basic tastes, sweet and bitter. He also notes that it can be modified by salty and acidic. <ref><pubmed>22717400</pubmed></ref>
|- bgcolor="#faecc8"
|'''1901'''
|| D. Hanig publishes a paper describing taste sensitivity in different regions of the tongue.
''Interesting fact:'' The modern concept of a 'tongue map' is a misinterpretation of this study. <ref><pubmed>22717400</pubmed></ref>

|- bgcolor="#faf6ed"
|style=white-space:nowrap|'''1908'''
|Kikunae Ikeda, a professor of the Tokyo Imperial University, discovered and identified the fifth basic taste: umami (savouriness), made palatable by glutamate. <ref><pubmed>12438213</pubmed></ref>

|- bgcolor="#faecc8"
|style=white-space:nowrap|'''1931'''
|Bitter taste sensitivity found to vary among humans <ref><pubmed>22717400</pubmed></ref>

|- bgcolor="#faf6ed"
|style=white-space:nowrap|'''1931-32'''
| A chemist named Arthur Fox and his college noted that they had different sensitivities to the bitter tasting Phenylthiocarbamide (PTC). Genetisists later confirm these findings, and discover that non-tasting is a recessive genetic trait. <ref><pubmed>17782493</pubmed></ref> <ref>Blakeslee AF, Fox AL. Our different taste worlds. J Hered. 1932;23:97–107.</ref>

|- bgcolor="#faf6ed"
|style=white-space:nowrap|'''1992'''
|McLaughlin SK et al. discovery a taste cell-specific G-protein within the taste buds called Gustucon. This protein is later used to mark bitter, umami and sweet cells. <ref><pubmed>1608467 </pubmed></ref> [http://www.nature.com/nature/journal/v357/n6379/abs/357563a0.html Gustducin is a taste-cell-specific G protein closely related to the transducins]

|- bgcolor="#faecc8"
|style=white-space:nowrap|'''1996'''
| Witt M and Reutter K of the Technical University Dresden in Germany, carried out a transmission electron microscopy study to investigate the embryonic and fetal development of Human taste buds. Their results suggest an "at least dual function of embryonic/fetal taste buds", including non-gustatory, paracrine functions prior to the 14th week and gustatory after the 14th week. <ref><pubmed>8955790</pubmed></ref> [http://www.ncbi.nlm.nih.gov/pubmed/8955790 Embryonic and early fetal development of human taste buds: a transmission electron microscopical study]

|- bgcolor="#faf6ed"
|style=white-space:nowrap|'''2000'''
|Chandrashekar, J. et al. discover the first taste sonsors, the T2R bitter taste receptors. <ref><pubmed>10761935</pubmed></ref>

|- bgcolor="#faecc8"
|style=white-space:nowrap|'''2001'''
|Nelson, G. et al. discover the sweet receptor: a combination of T1R2 and T1R3. <ref><pubmed>11509186</pubmed></ref>[http://www.ncbi.nlm.nih.gov/pubmed/11509186?dopt=Abstract&holding=npg Mammalian sweet taste receptors.]

|- bgcolor="#faf6ed"
|style=white-space:nowrap|'''2002'''
|Nelson G. et al. discover the amino acid (umami) taste receptor: a combination of T1R1 and T1R3 identified. <ref><pubmed>11894099</pubmed></ref> [http://www.ncbi.nlm.nih.gov/pubmed/11894099?dopt=Abstract&holding=npg An amino-acid taste receptor]

|- bgcolor="#faecc8"
|style=white-space:nowrap|'''2005'''
|Dyer, J. et al. discover sweet taste receptors in the GI tract. <ref><pubmed>17855558</pubmed></ref> [http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1986582/ Sweet taste signaling in the gut]

|- bgcolor="#faf6ed"
|style=white-space:nowrap|'''2006'''
|Huang, A. L et al. discover cells for sour taste, identified by PKD2L1 (a polycystic kidney disease-like ion channel) <ref><pubmed>16929298</pubmed></ref> [http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1571047/ The Cells and Logic for Mammalian Sour Taste detection]

|- bgcolor="#faecc8"
|style=white-space:nowrap|'''2007'''
|Harlow DE, Barlow LA of the University of Colorado Denver Health Sciences Center provide evidence of the '''embryonic origin of gustatory cranial sensory neurons''' <ref><pubmed>17826760</pubmed></ref> [http://www.ncbi.nlm.nih.gov/pubmed/17826760 Embryonic origin of gustatory cranial sensory neurons.]

|- bgcolor="#faf6ed"
|style=white-space:nowrap|'''2009'''
|A study by Hevezi P et al, presents "the first comprehensive characterization of gene expression in primate taste buds", as opposed to previous studies which focused on rodents. <pubmed>19636377</pubmed></ref> [http://www.ncbi.nlm.nih.gov/pubmed/19636377 Genome-wide analysis of gene expression in primate taste buds reveals links to diverse processes]

|- bgcolor="#faecc8"
|style=white-space:nowrap|'''2010'''
|Chandrashekar, J. et al. identify epithelial sodium channel (ENaC) as the sodium-salt taste receptor <pubmed>20107438</pubmed></ref> [http://www.ncbi.nlm.nih.gov/pubmed/20107438?dopt=Abstract&holding=npg The cells and peripheral representation of sodium taste in mice]
|}

*[http://www.nature.com/nature/journal/v486/n7403_supp/fig_tab/486S2a_F1.html Gustatory system: The finer points of taste] <ref><pubmed>22717400</pubmed></ref>

==Gustatory System==

[[Image:Taste qualities.gif|thumb|The five basic tastes]]

Taste or more appropriately gustation, is a fundamental survival tool in animals as it directs the consumption of essential nutrients. The five tastes that exist within the human gustatory system: salty, sweet, sour, bitter and umami, all signify basic physiological requirements. Salty tastes denote the presence of Na+, an important ion involved in the transportation and retention of water across cell membranes. Sweetness is the recognition of carbohydrates, essential for maintaining optimal brain function and providing the basis for energy production in muscle tissue via ATP hydrolysis. Similarly umami codes for the presence of L-amino acids, especially L-glutamate which is an integral component of protein synthesis.

These different modalities not only function to maintain the proper intake of nutrients within the body but also, by way of aversion, prohibit the consumption of undesired or poisonous materials. The bitter modality for example is generally regarded as displeasing to the human palate. It represents a high acid content which may be a result of foods which have become rotten or are inherently poisonous to the body.<ref name=PMID20696704><pubmed>20696704</pubmed></ref>

Research has historically limited itself to investigating the mechanisms of these five taste qualities though it must be noted many other modalities may exist. Of particular conjecture is the existence of fatty acid recognition. In the past the detection of fat in food has been attributed to somatosensory inputs <ref name=PMID20696704/> from the tongue, that is, the oily feel and texture of fat rather than its actual ‘taste’ allows the brain to encode for its presence. Further research is therefore required to elicit the precise mechanisms of fat detection.

===Cell Biology===

The five taste qualities are not all detected by the same type of receptor cell located within the taste bud. Like rods and cones in the eye which detect different wavelengths of light, there are specific types of receptors for different tastes. For example, sweet, umami and bitter are recognised by Type II G-protein coupled receptors, whereas sour is related to Type III presynaptic cells. The cell type involved in salty taste transduction is unknown however it is known that sodium ions can enter the receptor cell membrane via ion channel permeation.

====Type II receptors====

When a bitter, sweet or umami ligand binds to a type II G-coupled receptor, a cascade of chemical reactions causes the release of Ca2+ which in turn mediates exocystosis of ATP. The function of this ATP is threefold:

# Stimulates gustatory nerve afferents which project to gustatory nuclei in the spinal cord
# Excites Type III presynaptic nerve fibres to release serotonin.
# Has a positive feedback effect on type II receptor cells, increasing the level of ATP production.

The role of serotonin is believed to be in the form of lateral inhibition i.e. when a bitter quality is recognised, adjacent receptors for sweetness are deactivated and thus the two tastes may be clearly differentiated. It also has a negative feedback effect on receptor cells, inhibiting umami, bitter and sweet taste transduction.

==Taste Map==
[[Image:Taste map.png|thumb|left|250px|Obsolete idea of the tongue map]]
The idea of a tongue map has disseminated through society for many years. This concept purports that different areas of the tongue are specialised to detect either sweet, salty, sour and bitter tastes. Recent research however has completely nullified such claims and suggests instead that different forms of taste are recognised all over the tongue as well as via the palate. Thus the term ''taste map'' has come to take on a new meaning and that is, the precise areas of taste modalities processing in areas of cortex and its subsequent neural inputs.

===Neural Pathways===

'''First order neurons''' - From the receptors located in the taste buds, gustatory nerve afferents project to the ipsilateral rostral 1/3 of the nucleus tractus solitarius (NTS), located in the medulla. This rostral 1/3 is commonly referred to as the ''gustatory nucleus''.

The ''gustatory nucleus'' receives input from cranial nerves VII (''Facial n.''), IX (''Hypglossal n.''), and X (''Vagus n.'') via special visceral afferent (SVA) nerve fibres. A summary of their functions is as follows:

* ''Facial nerve n''. - carries taste information from the anterior 2/3 of the tongue.
* ''Hypoglossal n.'' - carries taste information from the posterior 1/3 of the tongue.
* ''Vagus n''. - carries taste information from the palate

'''Second order neurons''' - From the NTS second order neurons carry taste information to the Ventral posteromedial (VPM) nucleus in the thalamus.<ref name=PMID21885776/>

Copious scientific conjecture surrounds how each taste modality is transmitted to the brain. The ‘labelled-line’ hypothesis suggests that there are taste specific neurons which exclusively carry that taste modality to cortical areas. In analogous terms it can be viewed like the pipelines leading toward a house. Each pipeline carries its own utility, there is one for gas, another for water and finally for electricity with each terminating in slightly different areas of the house. In the same way, on the tongues there are different receptors for each taste which concurrently have individual nerve tracts leading to the primary gustatory cortex.

Contrapuntally there is electrophysiological evidence that single nerve afferents carry multiple modalities. These studies show one nerve afferent may have both a strong and a weak activation in response to a multiple taste stimuli.

===Cortical Areas===

[[Image:Primary gustatory cortex.png|thumb|Primary gustatory cortex]]

The location of the taste perception centres has been observed via functional magnetic resonance imaging (fMRI) studies. The primary taste cortex has been identified as being located in the anterior insula/frontal operculum (I/fO)<ref name=PMID22245354><pubmed>22245354</pubmed></ref>, with the secondary taste cortex in the caudolateral orbitofrontal cortex.<ref name=PMID21305668><pubmed>21305668</pubmed></ref> Within the insula there are further subdivisions related to each taste modality. Two photon calcium imaging research has outlined certain ’hot-spots’ of activation which are clearly delineated in relation to each taste. For example, the bitter modality is represented on the insula cortex approximately 1mm posterior to the middle cerebral artery whereas the sweet modality is represented 2.5mm rostrodorsal to the bitter field with no apparent overlap.<ref name=PMID21885776><pubmed>21885776</pubmed></ref> These findings lend weight to the idea that there is only one receptor for each taste quality.

It is interesting to note the relationship between taste and the reward centres of the brain. There is evidence of neural input to the ventral tegmental area (the origin of the mesolimbic dopaminergic reward pathway) and nucleus accumbens (involved in the conversion of motivation into physical action).<ref name=PMID21885776/> Neural connections such as this provide the foundations in explaining concepts such as flavour learning and preference. It may also give some insight into chronic problems such as food addiction and craving. As of yet however the gustatory neural network is not well understood and more research is required to elucidate the relationship between pleasure and taste sensation

==Timeline of Developmental Processes of the Gustatory System==

{| cellpadding=5 style="border:1px solid #BBB"
|- bgcolor="#89CFF0"
|'''Postovulatory Week'''||'''Description'''||'''Image'''
|- bgcolor="#BCD4E6"
|'''Week 6''' ||
The surface of the developing tongue is covered by nearly flat epitheliuem (Figure 1) <ref name=PMID9455607/>. The first gustatory papillae of the tongue appears in the caudal midline near the foramen caecum and the first circumvallate papilla develop on the dorsal midline <ref name=PMID9455607/> .
||
image
|- bgcolor="#89CFF0"
| '''Weeks 6 to 7'''||
Nerve fibres approach the basal lamina of lingual epithelium <ref name=PMID8955790><pubmed>8955790</pubmed></ref>. At this stage the lingual epithelium consists of two to three cell layers and there is not yet any sign of cell specializations indicating early taste bud formation<ref name=PMID8955790/>.
||
Image
|- bgcolor="#BCD4E6"
| '''Week 7 '''||
A series of epithelial swellings in the anterior part and midline of the tongue indicate early forming fungiform papillae (figure 2) <ref name=PMID9455607/>.
||
Image
|- bgcolor="#89CFF0"
| ''' Week 8 ''' ||
The lingual epithelium shows first signs of taste bud development as nerve fibres penetrate epithelial basal lamina <ref name=PMID8955790/> and form synapses with taste bud progenitor cells. The synapses reach a maximum around the 12th to 13th week <ref name=PMID8955790/>. However, at this time these cells are still poorly differentiated, elongated epithelial cells <ref name=PMID8955790/> . The synapses demonstrate the neuronal connection between the taste bud primordium and the central nervous system <ref name=PMID8955790/>. Ciliated cells also appear around the 8th week, however the significance of these cells which are scattered randomly across the lingual surface remains unclear <ref name=PMID8955790/>.
||
Image
|- bgcolor="#BCD4E6"
|''' Weeks 8-9''' ||
“By this stage the top surface of circumvallate papillae usually contains a taste pit partly filled with microvilli of presumed underlying taste bud cells” (Figure 10) <ref name=PMID9455607/>
||
Image
|- bgcolor="#89CFF0"
|''' Weeks 10-11''' ||
At this stage, the lingual epithelium compromises of about four cell layers, and the first shallow grooves above the taste bud primordium are developed <ref name=PMID8955790/>.

Fungiform papillae appear on the lateral margins and the tip of the tongue <ref name=PMID9455607/>, containing taste bud primordial that display the first signs of a primitive pore formation <ref name=PMID8955790/>.

Untypically differentiated apical cellular processes extend onto the surface <ref name=PMID9455607/>

Some taste bud primordial contain cells that perforate the covering epithelial later with short, broad untypically differentiated apical cellular processes. (Figure 3,4) <ref name=PMID8955790/> <ref name=PMID9455607/>
||
Image
|- bgcolor="#BCD4E6"
|''' Week 12 ''' ||
Taste bud cells are more clearly differentiated into epithelial cell types II and III <ref name=PMID8955790/>.
||
Image
|- bgcolor="#89CFF0"
|''' Weeks 12-13 ''' ||
By this stage the taste bud primordial are all located on the top of dermal papillae (Fig 6a) <ref name=PMID8955790/>. There is also maximum synapses between cells and afferent nerve fibres, which intermingle with each other to form a plexus-like structure <ref name=PMID8955790/>.
||
Image
|- bgcolor="#BCD4E6"
|''' Weeks 14 -15 ''' ||
The shape of the taste buds primordial begins to resemble those of adult taste buds <ref name=PMID8955790/>. By the 14th week the taste pores develop as the taste pits are filled by microvilli <ref name=PMID8955790/>, indicating the possibility that the taste buds begin their gustatory function <ref name=PMID8955790/>, however they still lack an electron-dense mucous material (Fig.10) <ref name=PMID8955790/>. The tastebuds only achieve a fully developed function in week 15 of gestation with the development of type I cells to produce the mucous material in the taste pit <ref name=PMID8955790/>.
||
Image
|}

==Adult Tongue and Taste Buds – Structure and Function==

'''Structure'''

The tongue is located on the floor of the oral cavity, It is a muscular structure with sensory units crowning. The tongue is divided into an anterior two thirds and a posterior one third. These regions are divided by a V-shaped groove at the back of the tongue (sulcus terminalis). The anterior two thirds of the tongue is covered by stratified squamous epithelium, It contains a roughened surface and has projections called papillae that vary in shape and number.

''''The Image Below is a very simplistic Diagram of the surface of the Tongue showing the locations of the different papillae and other important features'''

{|
| [[Image:Drawing of Tongue.png|500px]]

'''Papillae'''
[[File:Papillae.jpg|Left|thumb|200px|Close up of Human Tongue Papillae]]

There are 4 types of papillae on the tongue.
The most numerous papillae are the filiform papillae, which function to provide a surface that aids in holding food on the tongue during chewing but do not contain taste buds. The larger, less numerous fungiform papillae which contain taste buds, as do foliate papillae. Circumvallate papillae form a wide V at the sulcus terminalis also containing taste bus. There are no papillae or taste buds located on the posterior third of the tongue, having mucosal folds and the lingual tonsils instead.

'''Function'''

The tongue is for tasting, swallowing, and speech.
The functional unit of the taste bud is a taste cell, there are between 50 and 100 taste cells in each taste bud these taste cells represent all 5 different tastes. Historically is was believed that different areas of the tongue were responsible for different taste sensations although this has since been disregarded.[http://users.rcn.com/jkimball.ma.ultranet/BiologyPages/W/Welcome.html] The papillae contain taste buds which are connected to the oral cavity via a taste pore, the function of the taste bud is to transmit a chemical signal from the oral cavity to a taste cell, this chemical signal is the converted into an electrical impulse and delivered to the brain via nerve fibres for interpretation.

'''The Image Below is a very simplistic Hand drawn Diagram of a taste bud, in an extreme close up, cross section view of the the taste bud unit, not to scale'''

[[File:Taste_bud_1.jpg]]

==Abnormalities==

===Knocking out P2X Receptors===

[[File:Image of taste being evoked by visualising ATP release.jpeg|Left|thumb|200px|Evoking taste - ATP release in tongue]]

Gustatory abnormalities has not been widely researched and what has been researched has been through animal testing, most commonly we have found on mice.

In Huang, 2008 this team used the release of the neurotransmitter, ATP (adenosine triphosphate) as a quantitative measurement of gustatory sensation and taste. This was done by using a comparison of wild type (WT) and double knockout (DKO) mice. P2X receptors, P2X2 and P2X3 were knocked out in the DKO mice. The premise of this article was that knocking out P2X receptors reduces transmitter secretion of ATP in taste buds, therefore they cannot taste.

It should be noted that the taste buds in DKO are functional, but are not stimulated by the administration of tastants.

The transmission of release of ATP is secretion through gap junction hemichannels (pannexin 1 gap junction).

When both P2X2 and P2X3 are knocked out, no taste is elicited. However they found that if either P2X2 OR P2X3 was knocked out there was a taste response. So the inference made from this is that if one of the two receptors from the P2X family was knocked out there still can have taste response. The WT mice showed significant stimulation by tastants whereas DKO had little to no stimulation of ATP release.<ref><pubmed>21940456</pubmed></ref>

===FGF signalling and genes===

Sprouty, or ''Srpy'', genes have been related to regulating the development of circumvillate papillae (CVP). The CVP are large dome shaped papillae, which form a 'V' just in front of the terminal sulcus.

By knocking out ''Spry'' genes using mice which had ''Spry1'' and ''Spry2'' knocked out showed that the number of CVP doubled. However, when Fibroblast Growth Factor gene ("Fgf10") was absent, the number of CVP was significantly reduced, if not completely absent. The correlation between ''Spry1/2'' and ''Fgf10'' is that ''Spry1/2'' antagonises "Fgf10" to limit the size of the CVP progenitor placode. Exclusive expression of ''Fgf10'' in the mesenchyme is necessary for the formation of CVP.

'''This image shows the CVP stained with H&E and scanned by Scanning Electron Microscope (SEM)'''
[[File:CVP of WT(top) and DKO(bottom) mice with H&E and SEM.png]]

'''This image shows the location of the CVP and the increased number in DKO mice by SEM'''
[[File:Mouse circumvallate papilla 01.jpg|300px]]

Taste buds develop from the mesenchyme but require local signalling to properly differentiate. Some signalling factors for proper development of taste buds besides FGF are: Sonic Hedgehog (SHH), Bone Morphogenetic Proteins (BMPs), Epidermal Growth Factor (EGF).

Additionally, this proves that the anterior and posterior developments of the tongue are derived from embryonic tissues, where the anterior tongue is derived from the ectoderm and the posterior tongue is derived from the endoderm. Taste buds develop from the mesenchyme but require local signalling to properly differentiate. Some signalling factors for proper development of taste buds besides FGF are: Sonic Hedgehog (SHH), Bone Morphogenetic Proteins (BMPs), Epidermal Growth Factor (EGF).

As mentioned above, this article shows that the anterior and posterior developments of the tongue are derived from embryonic tissues, where the anterior tongue is derived front the ectoderm and the posterior tongue is derived from the endoderm. Secondly, FGF is required to regulate the growth of taste buds, while ''Spry'' genes limit the number of CVP. ''Fgf10''& ''Spry 1&2''work antagonistically through receptor tyrosine kinase (RTK)signalling.

However, the deletion of ''Spry2''led to the increase of CVPs it should be noted that they found that a significant decrease in number of fungiform papillae. Contrastingly, the absence of ''Fgf10'', while leading to the absence of CVPs lead to an increase in number and size of fungiform papillae. Therefore these genes have different effects on the anterior and posterior developing tongue and taste buds.<ref><pubmed>21655085</pubmed></ref>

==Current Research==
We have an evolving understanding of Embryonic Taste development, through the use of state-of-the-art technology and research techniques we are able to make brilliant discoveries that continue to connect the dots of this amazing natural process of human development.
The majority of research in taste development is involving mice, these mammals show similar embryonic pathways to humans and research is performed in ethical and humane methods.

[[File:Histology.jpg|Left|thumb|200px|Image shows histological stains of a mice tongue showing dysplasia]]

'''Synergistic relationships of Six Genes '''

In an animal study using mice by Suzuki Y, Ikeda K, Kawakami K.(2011) Firstly nominating "Six Genes" as a major component in gustatory development, stating that deficiencies in certain Six genes (specifically Six1 & Six4) leads to poor development. Their research also highlights evidence of cooperative relationships between Six genes for normal advance. This experiment involved breeding mice containing exclusively Six1 and Six4 genes and examining the expression of these genes in papillae under high powered microscope observation. Understanding the role of certain genes along with the intrinsic relationships they hold is crucial for the ability to identify possible causes and correction of any abnormalities <ref><pubmed>21978088</pubmed></ref>

'''Neural Crest responsibilities '''

Another Animal Study involving mice explores a new idea of Neural crest (NC) contribution in taste development, specifically the development of papillae and taste buds. Liu HX, Komatsu Y, Mishina Y, Mistretta CM. (2012) suggest that Neural crest cells travel to the location of the tongue in early embryonic stages, gain epithelium phenotypes, multiply and then differentiate to eventually form taste papillae. The experiment involved the comparison of 2 different types of Cre line mice, which both express Cre gene in neural crest protocol, the different distribution patterns where observed in specific regions that NC is responsible for.<ref><pubmed>22659543</pubmed></ref>

'''Augmentation of Endoderm'''

In an animal study conducted by Rothova M, Thompson H, Lickert H, Tucker AS.(2012) exploring the historically debated issue of endoderm contribution to tongue development showed promising evidence that position of taste buds are patterned by the border of ectoderm and endoderm derivative epithelium. This study was accomplished via microscopic examination of previously stained specimens. Concluding endoderm has direct influence on gustatory develoment <ref><pubmed>22581563</pubmed></ref>

'''Changes in Taste Cells over time'''

Research by
Ozdener H, Spielman AI, Rawson NE.(2012) developing a culture which allows taste cells to survive for up to 12 months, empowers researchers to study the processes of proliferation, differentiation and function. This experiment will provide a precidnet for future study of taste cells, as these cells are able to operate and grow normally. <ref><pubmed>22643728</pubmed></ref>

'''Shh key component of taste bud proginators'''

A tamoxifen treatment which supresses Sonic hedgehog (Shh) secretion in mice proving to reduce the number of cells visable within papillae, in contrast mice not treated with tamoxifen showed a mark increase of cells within papillae, these cells are assumed to become taste cells in later development.
Specific mice were bred to trace the destination of taste placode cells, the study concluded that Shh expressing placodes are taste bud proginators which in turn become taste cells within taste buds although do not have any prescuros relationship with pappilae. The results were obtain by examination of mice embryos using Bright-field or multichannel fluorescent images through the use of an "Axiocam CCD camera and Axioplan fluorescence microscope with Axiovision software" a study by Harlow, Yang, Williams, Barlow (2011)<ref><pubmed>PMC2674259</pubmed></ref>

'''WNT family exhibit various roles'''

The WNT gene family has a function of signally proteins for various reason such as development, In 2010 Liu, Staubach Grosse, Walton, Saims, Gumucio, Mistretta explored recent findings on the role of WNT's in tongue and papillae development, Concluding that WNT/β-catenin is essential for fungiform papillae differing to WNT5a which proved to be principle in tongue development. Intrinsic chemical mediators were considered by manipulating a tissue culture and then throughaly examined by scanning photomicrograph. <ref><pubmed>PMC2768563</pubmed></ref>

[http://www.surgicalneurologyint.com/article.asp?issn=2152-7806;year=2012;volume=3;issue=1;spage=23;epage=23;aulast=Manjila]
[[File:Abnormal of tongue.jpg|Left|thumb|200px|Image shows and example of tongue abnormalities, this is called "double tongue" each side has independent movement!]]

==Useful links==

==Glossary==

ectoderm- outer germ layer of embryo

endoderm - inner germ layer of embryo

epithelium - basic animal tissue that is composed of tightly packed cells, usually covering the outer portion of organs

exocystosis - movement of contents out of cell

ganglia - the accumulation of a nerve cell body

growth factor - a substance that stimulates the growth of cells

gustatory - anything that relates to the taste sense

hydrolysis - breakdown of a chemical when it reacts with water

mesoderm - middle germ layer of embryo

mesenchyme - multipotential cells

neural crest - a part of the ectoderm found on both sides of the neural tube

neuron - most simplistic unit of the nervous system

neurotransmitter - chemicals which allow the passing of signals from neuron to neuron via connecting part (synapse)

papillae - small rough surface projection

six genes - a family of genes

Sonic hedgehog (Shh) - signalling protein invloved in normal development

sulcus terminalis - describes a physical transition point separating the anterior 2/3 of the tongue from the posterior 1/3

tamoxifen - hormonal altering drug

==Image gallery==

== References ==
<references/>

==External Links==
{{External Links}}

--[[User:Z8600021|Mark Hill]] 12:22, 15 August 2012 (EST) Please leave the content listed below the line at the bottom of your project page.

----

{{2012Projects}}

2012 Group Project 3

2012-09-26T04:48:53Z

Z3289738: /* History of Discoveries */

=Taste Development=

== Introduction ==
**NEED TO ADD**

==History of Discoveries==

{| cellpadding=5 style="border:1px solid #BBB"
|- bgcolor="#faecc8"
|''' Date'''|| '''Significant Discovery'''
|- bgcolor="#faf6ed"
|'''350BC'''
|| Aristotle writes about the basic tastes, sweet and bitter. He also notes that it can be modified by salty and acidic. <ref><pubmed>22717400</pubmed></ref>
|- bgcolor="#faecc8"
|'''1901'''
|| D. Hanig publishes a paper describing taste sensitivity in different regions of the tongue.
''Interesting fact:'' The modern concept of a 'tongue map' is a misinterpretation of this study. <ref><pubmed>22717400</pubmed></ref>

|- bgcolor="#faf6ed"
|style=white-space:nowrap|'''1908'''
|Kikunae Ikeda, a professor of the Tokyo Imperial University, discovered and identified the fifth basic taste: umami (savouriness), made palatable by glutamate. <ref><pubmed>12438213</pubmed></ref>

|- bgcolor="#faecc8"
|style=white-space:nowrap|'''1931'''
|Bitter taste sensitivity found to vary among humans <ref><pubmed>22717400</pubmed></ref>

|- bgcolor="#faf6ed"
|style=white-space:nowrap|'''1931-32'''
| A chemist named Arthur Fox and his college noted that they had different sensitivities to the bitter tasting Phenylthiocarbamide (PTC). Genetisists later confirm these findings, and discover that non-tasting is a recessive genetic trait. <ref><pubmed>17782493</pubmed></ref> <ref>Blakeslee AF, Fox AL. Our different taste worlds. J Hered. 1932;23:97–107.</ref>

|- bgcolor="#faf6ed"
|style=white-space:nowrap|'''1992'''
|McLaughlin SK et al. discovery a taste cell-specific G-protein within the taste buds called Gustucon. This protein is later used to mark bitter, umami and sweet cells. <ref><pubmed>1608467 </pubmed></ref> [http://www.nature.com/nature/journal/v357/n6379/abs/357563a0.html Gustducin is a taste-cell-specific G protein closely related to the transducins]

|- bgcolor="#faecc8"
|style=white-space:nowrap|'''1996'''
| Witt M and Reutter K of the Technical University Dresden in Germany, carried out a transmission electron microscopy study to investigate the embryonic and fetal development of Human taste buds. Their results suggest an "at least dual function of embryonic/fetal taste buds", including non-gustatory, paracrine functions prior to the 14th week and gustatory after the 14th week. <ref><pubmed>8955790</pubmed></ref> [http://www.ncbi.nlm.nih.gov/pubmed/8955790 Embryonic and early fetal development of human taste buds: a transmission electron microscopical study]

|- bgcolor="#faf6ed"
|style=white-space:nowrap|'''2000'''
|Chandrashekar, J. et al. discover the first taste sonsors, the T2R bitter taste receptors. <ref><pubmed>10761935</pubmed></ref>

|- bgcolor="#faecc8"
|style=white-space:nowrap|'''2001'''
|Nelson, G. et al. discover the sweet receptor: a combination of T1R2 and T1R3. <ref><pubmed>11509186</pubmed></ref>[http://www.ncbi.nlm.nih.gov/pubmed/11509186?dopt=Abstract&holding=npg Mammalian sweet taste receptors.]

|- bgcolor="#faf6ed"
|style=white-space:nowrap|'''2002'''
|Nelson G. et al. discover the amino acid (umami) taste receptor: a combination of T1R1 and T1R3 identified. <ref><pubmed>11894099</pubmed></ref> [http://www.ncbi.nlm.nih.gov/pubmed/11894099?dopt=Abstract&holding=npg An amino-acid taste receptor]

|- bgcolor="#faecc8"
|style=white-space:nowrap|'''2005'''
|Dyer, J. et al. discover sweet taste receptors in the GI tract. <ref><pubmed>17855558</pubmed></ref> [http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1986582/ Sweet taste signaling in the gut]

|- bgcolor="#faf6ed"
|style=white-space:nowrap|'''2006'''
|Huang, A. L et al. discover cells for sour taste, identified by PKD2L1 (a polycystic kidney disease-like ion channel) <ref><pubmed>16929298</pubmed></ref> [http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1571047/ The Cells and Logic for Mammalian Sour Taste detection]

|- bgcolor="#faecc8"
|style=white-space:nowrap|'''2007'''
|Harlow DE, Barlow LA of the University of Colorado Denver Health Sciences Center provide evidence of the '''embryonic origin of gustatory cranial sensory neurons''' <ref><pubmed>17826760</pubmed></ref> [http://www.ncbi.nlm.nih.gov/pubmed/17826760 Embryonic origin of gustatory cranial sensory neurons.]

|- bgcolor="#faf6ed"
|style=white-space:nowrap|'''2009'''
|A study by Hevezi P et al, presents "the first comprehensive characterization of gene expression in primate taste buds", as opposed to previous studies which focused on rodents. PMID <pubmed>19636377</pubmed></ref> [http://www.ncbi.nlm.nih.gov/pubmed/19636377 Genome-wide analysis of gene expression in primate taste buds reveals links to diverse processes]

|- bgcolor="#faecc8"
|style=white-space:nowrap|'''2010'''
|Chandrashekar, J. et al. identify epithelial sodium channel (ENaC) as the sodium-salt taste receptor <pubmed>20107438</pubmed></ref> [http://www.ncbi.nlm.nih.gov/pubmed/20107438?dopt=Abstract&holding=npg The cells and peripheral representation of sodium taste in mice]
|}

*[http://www.nature.com/nature/journal/v486/n7403_supp/fig_tab/486S2a_F1.html Gustatory system: The finer points of taste] <ref><pubmed>22717400</pubmed></ref>

==Gustatory System==

[[Image:Taste qualities.gif|thumb|The five basic tastes]]

Taste or more appropriately gustation, is a fundamental survival tool in animals as it directs the consumption of essential nutrients. The five tastes that exist within the human gustatory system: salty, sweet, sour, bitter and umami, all signify basic physiological requirements. Salty tastes denote the presence of Na+, an important ion involved in the transportation and retention of water across cell membranes. Sweetness is the recognition of carbohydrates, essential for maintaining optimal brain function and providing the basis for energy production in muscle tissue via ATP hydrolysis. Similarly umami codes for the presence of L-amino acids, especially L-glutamate which is an integral component of protein synthesis.

These different modalities not only function to maintain the proper intake of nutrients within the body but also, by way of aversion, prohibit the consumption of undesired or poisonous materials. The bitter modality for example is generally regarded as displeasing to the human palate. It represents a high acid content which may be a result of foods which have become rotten or are inherently poisonous to the body.<ref name=PMID20696704><pubmed>20696704</pubmed></ref>

Research has historically limited itself to investigating the mechanisms of these five taste qualities though it must be noted many other modalities may exist. Of particular conjecture is the existence of fatty acid recognition. In the past the detection of fat in food has been attributed to somatosensory inputs <ref name=PMID20696704/> from the tongue, that is, the oily feel and texture of fat rather than its actual ‘taste’ allows the brain to encode for its presence. Further research is therefore required to elicit the precise mechanisms of fat detection.

===Cell Biology===

The five taste qualities are not all detected by the same type of receptor cell located within the taste bud. Like rods and cones in the eye which detect different wavelengths of light, there are specific types of receptors for different tastes. For example, sweet, umami and bitter are recognised by Type II G-protein coupled receptors, whereas sour is related to Type III presynaptic cells. The cell type involved in salty taste transduction is unknown however it is known that sodium ions can enter the receptor cell membrane via ion channel permeation.

====Type II receptors====

When a bitter, sweet or umami ligand binds to a type II G-coupled receptor, a cascade of chemical reactions causes the release of Ca2+ which in turn mediates exocystosis of ATP. The function of this ATP is threefold:

# Stimulates gustatory nerve afferents which project to gustatory nuclei in the spinal cord
# Excites Type III presynaptic nerve fibres to release serotonin.
# Has a positive feedback effect on type II receptor cells, increasing the level of ATP production.

The role of serotonin is believed to be in the form of lateral inhibition i.e. when a bitter quality is recognised, adjacent receptors for sweetness are deactivated and thus the two tastes may be clearly differentiated. It also has a negative feedback effect on receptor cells, inhibiting umami, bitter and sweet taste transduction.

==Taste Map==
[[Image:Taste map.png|thumb|left|250px|Obsolete idea of the tongue map]]
The idea of a tongue map has disseminated through society for many years. This concept purports that different areas of the tongue are specialised to detect either sweet, salty, sour and bitter tastes. Recent research however has completely nullified such claims and suggests instead that different forms of taste are recognised all over the tongue as well as via the palate. Thus the term ''taste map'' has come to take on a new meaning and that is, the precise areas of taste modalities processing in areas of cortex and its subsequent neural inputs.

===Neural Pathways===

'''First order neurons''' - From the receptors located in the taste buds, gustatory nerve afferents project to the ipsilateral rostral 1/3 of the nucleus tractus solitarius (NTS), located in the medulla. This rostral 1/3 is commonly referred to as the ''gustatory nucleus''.

The ''gustatory nucleus'' receives input from cranial nerves VII (''Facial n.''), IX (''Hypglossal n.''), and X (''Vagus n.'') via special visceral afferent (SVA) nerve fibres. A summary of their functions is as follows:

* ''Facial nerve n''. - carries taste information from the anterior 2/3 of the tongue.
* ''Hypoglossal n.'' - carries taste information from the posterior 1/3 of the tongue.
* ''Vagus n''. - carries taste information from the palate

'''Second order neurons''' - From the NTS second order neurons carry taste information to the Ventral posteromedial (VPM) nucleus in the thalamus.<ref name=PMID21885776/>

Copious scientific conjecture surrounds how each taste modality is transmitted to the brain. The ‘labelled-line’ hypothesis suggests that there are taste specific neurons which exclusively carry that taste modality to cortical areas. In analogous terms it can be viewed like the pipelines leading toward a house. Each pipeline carries its own utility, there is one for gas, another for water and finally for electricity with each terminating in slightly different areas of the house. In the same way, on the tongues there are different receptors for each taste which concurrently have individual nerve tracts leading to the primary gustatory cortex.

Contrapuntally there is electrophysiological evidence that single nerve afferents carry multiple modalities. These studies show one nerve afferent may have both a strong and a weak activation in response to a multiple taste stimuli.

===Cortical Areas===

[[Image:Primary gustatory cortex.png|thumb|Primary gustatory cortex]]

The location of the taste perception centres has been observed via functional magnetic resonance imaging (fMRI) studies. The primary taste cortex has been identified as being located in the anterior insula/frontal operculum (I/fO)<ref name=PMID22245354><pubmed>22245354</pubmed></ref>, with the secondary taste cortex in the caudolateral orbitofrontal cortex.<ref name=PMID21305668><pubmed>21305668</pubmed></ref> Within the insula there are further subdivisions related to each taste modality. Two photon calcium imaging research has outlined certain ’hot-spots’ of activation which are clearly delineated in relation to each taste. For example, the bitter modality is represented on the insula cortex approximately 1mm posterior to the middle cerebral artery whereas the sweet modality is represented 2.5mm rostrodorsal to the bitter field with no apparent overlap.<ref name=PMID21885776><pubmed>21885776</pubmed></ref> These findings lend weight to the idea that there is only one receptor for each taste quality.

It is interesting to note the relationship between taste and the reward centres of the brain. There is evidence of neural input to the ventral tegmental area (the origin of the mesolimbic dopaminergic reward pathway) and nucleus accumbens (involved in the conversion of motivation into physical action).<ref name=PMID21885776/> Neural connections such as this provide the foundations in explaining concepts such as flavour learning and preference. It may also give some insight into chronic problems such as food addiction and craving. As of yet however the gustatory neural network is not well understood and more research is required to elucidate the relationship between pleasure and taste sensation

==Timeline of Developmental Processes of the Gustatory System==

{| cellpadding=5 style="border:1px solid #BBB"
|- bgcolor="#89CFF0"
|'''Postovulatory Week'''||'''Description'''||'''Image'''
|- bgcolor="#BCD4E6"
|'''Week 6''' ||
The surface of the developing tongue is covered by nearly flat epitheliuem (Figure 1) <ref name=PMID9455607/>. The first gustatory papillae of the tongue appears in the caudal midline near the foramen caecum and the first circumvallate papilla develop on the dorsal midline <ref name=PMID9455607/> .
||
image
|- bgcolor="#89CFF0"
| '''Weeks 6 to 7'''||
Nerve fibres approach the basal lamina of lingual epithelium <ref name=PMID8955790><pubmed>8955790</pubmed></ref>. At this stage the lingual epithelium consists of two to three cell layers and there is not yet any sign of cell specializations indicating early taste bud formation<ref name=PMID8955790/>.
||
Image
|- bgcolor="#BCD4E6"
| '''Week 7 '''||
A series of epithelial swellings in the anterior part and midline of the tongue indicate early forming fungiform papillae (figure 2) <ref name=PMID9455607/>.
||
Image
|- bgcolor="#89CFF0"
| ''' Week 8 ''' ||
The lingual epithelium shows first signs of taste bud development as nerve fibres penetrate epithelial basal lamina <ref name=PMID8955790/> and form synapses with taste bud progenitor cells. The synapses reach a maximum around the 12th to 13th week <ref name=PMID8955790/>. However, at this time these cells are still poorly differentiated, elongated epithelial cells <ref name=PMID8955790/> . The synapses demonstrate the neuronal connection between the taste bud primordium and the central nervous system <ref name=PMID8955790/>. Ciliated cells also appear around the 8th week, however the significance of these cells which are scattered randomly across the lingual surface remains unclear <ref name=PMID8955790/>.
||
Image
|- bgcolor="#BCD4E6"
|''' Weeks 8-9''' ||
“By this stage the top surface of circumvallate papillae usually contains a taste pit partly filled with microvilli of presumed underlying taste bud cells” (Figure 10) <ref name=PMID9455607/>
||
Image
|- bgcolor="#89CFF0"
|''' Weeks 10-11''' ||
At this stage, the lingual epithelium compromises of about four cell layers, and the first shallow grooves above the taste bud primordium are developed <ref name=PMID8955790/>.

Fungiform papillae appear on the lateral margins and the tip of the tongue <ref name=PMID9455607/>, containing taste bud primordial that display the first signs of a primitive pore formation <ref name=PMID8955790/>.

Untypically differentiated apical cellular processes extend onto the surface <ref name=PMID9455607/>

Some taste bud primordial contain cells that perforate the covering epithelial later with short, broad untypically differentiated apical cellular processes. (Figure 3,4) <ref name=PMID8955790/> <ref name=PMID9455607/>
||
Image
|- bgcolor="#BCD4E6"
|''' Week 12 ''' ||
Taste bud cells are more clearly differentiated into epithelial cell types II and III <ref name=PMID8955790/>.
||
Image
|- bgcolor="#89CFF0"
|''' Weeks 12-13 ''' ||
By this stage the taste bud primordial are all located on the top of dermal papillae (Fig 6a) <ref name=PMID8955790/>. There is also maximum synapses between cells and afferent nerve fibres, which intermingle with each other to form a plexus-like structure <ref name=PMID8955790/>.
||
Image
|- bgcolor="#BCD4E6"
|''' Weeks 14 -15 ''' ||
The shape of the taste buds primordial begins to resemble those of adult taste buds <ref name=PMID8955790/>. By the 14th week the taste pores develop as the taste pits are filled by microvilli <ref name=PMID8955790/>, indicating the possibility that the taste buds begin their gustatory function <ref name=PMID8955790/>, however they still lack an electron-dense mucous material (Fig.10) <ref name=PMID8955790/>. The tastebuds only achieve a fully developed function in week 15 of gestation with the development of type I cells to produce the mucous material in the taste pit <ref name=PMID8955790/>.
||
Image
|}

==Adult Tongue and Taste Buds – Structure and Function==

'''Structure'''

The tongue is located on the floor of the oral cavity, It is a muscular structure with sensory units crowning. The tongue is divided into an anterior two thirds and a posterior one third. These regions are divided by a V-shaped groove at the back of the tongue (sulcus terminalis). The anterior two thirds of the tongue is covered by stratified squamous epithelium, It contains a roughened surface and has projections called papillae that vary in shape and number.

''''The Image Below is a very simplistic Diagram of the surface of the Tongue showing the locations of the different papillae and other important features'''

{|
| [[Image:Drawing of Tongue.png|500px]]

'''Papillae'''
[[File:Papillae.jpg|Left|thumb|200px|Close up of Human Tongue Papillae]]

There are 4 types of papillae on the tongue.
The most numerous papillae are the filiform papillae, which function to provide a surface that aids in holding food on the tongue during chewing but do not contain taste buds. The larger, less numerous fungiform papillae which contain taste buds, as do foliate papillae. Circumvallate papillae form a wide V at the sulcus terminalis also containing taste bus. There are no papillae or taste buds located on the posterior third of the tongue, having mucosal folds and the lingual tonsils instead.

'''Function'''

The tongue is for tasting, swallowing, and speech.
The functional unit of the taste bud is a taste cell, there are between 50 and 100 taste cells in each taste bud these taste cells represent all 5 different tastes. Historically is was believed that different areas of the tongue were responsible for different taste sensations although this has since been disregarded.[http://users.rcn.com/jkimball.ma.ultranet/BiologyPages/W/Welcome.html] The papillae contain taste buds which are connected to the oral cavity via a taste pore, the function of the taste bud is to transmit a chemical signal from the oral cavity to a taste cell, this chemical signal is the converted into an electrical impulse and delivered to the brain via nerve fibres for interpretation.

'''The Image Below is a very simplistic Hand drawn Diagram of a taste bud, in an extreme close up, cross section view of the the taste bud unit, not to scale'''

[[File:Taste_bud_1.jpg]]

==Abnormalities==

===Knocking out P2X Receptors===

[[File:Image of taste being evoked by visualising ATP release.jpeg|Left|thumb|200px|Evoking taste - ATP release in tongue]]

Gustatory abnormalities has not been widely researched and what has been researched has been through animal testing, most commonly we have found on mice.

In Huang, 2008 this team used the release of the neurotransmitter, ATP (adenosine triphosphate) as a quantitative measurement of gustatory sensation and taste. This was done by using a comparison of wild type (WT) and double knockout (DKO) mice. P2X receptors, P2X2 and P2X3 were knocked out in the DKO mice. The premise of this article was that knocking out P2X receptors reduces transmitter secretion of ATP in taste buds, therefore they cannot taste.

It should be noted that the taste buds in DKO are functional, but are not stimulated by the administration of tastants.

The transmission of release of ATP is secretion through gap junction hemichannels (pannexin 1 gap junction).

When both P2X2 and P2X3 are knocked out, no taste is elicited. However they found that if either P2X2 OR P2X3 was knocked out there was a taste response. So the inference made from this is that if one of the two receptors from the P2X family was knocked out there still can have taste response. The WT mice showed significant stimulation by tastants whereas DKO had little to no stimulation of ATP release.<ref><pubmed>21940456</pubmed></ref>

===FGF signalling and genes===

Sprouty, or ''Srpy'', genes have been related to regulating the development of circumvillate papillae (CVP). The CVP are large dome shaped papillae, which form a 'V' just in front of the terminal sulcus.

By knocking out ''Spry'' genes using mice which had ''Spry1'' and ''Spry2'' knocked out showed that the number of CVP doubled. However, when Fibroblast Growth Factor gene ("Fgf10") was absent, the number of CVP was significantly reduced, if not completely absent. The correlation between ''Spry1/2'' and ''Fgf10'' is that ''Spry1/2'' antagonises "Fgf10" to limit the size of the CVP progenitor placode. Exclusive expression of ''Fgf10'' in the mesenchyme is necessary for the formation of CVP.

'''This image shows the CVP stained with H&E and scanned by Scanning Electron Microscope (SEM)'''
[[File:CVP of WT(top) and DKO(bottom) mice with H&E and SEM.png]]

'''This image shows the location of the CVP and the increased number in DKO mice by SEM'''
[[File:Mouse circumvallate papilla 01.jpg|300px]]

Taste buds develop from the mesenchyme but require local signalling to properly differentiate. Some signalling factors for proper development of taste buds besides FGF are: Sonic Hedgehog (SHH), Bone Morphogenetic Proteins (BMPs), Epidermal Growth Factor (EGF).

Additionally, this proves that the anterior and posterior developments of the tongue are derived from embryonic tissues, where the anterior tongue is derived from the ectoderm and the posterior tongue is derived from the endoderm. Taste buds develop from the mesenchyme but require local signalling to properly differentiate. Some signalling factors for proper development of taste buds besides FGF are: Sonic Hedgehog (SHH), Bone Morphogenetic Proteins (BMPs), Epidermal Growth Factor (EGF).

As mentioned above, this article shows that the anterior and posterior developments of the tongue are derived from embryonic tissues, where the anterior tongue is derived front the ectoderm and the posterior tongue is derived from the endoderm. Secondly, FGF is required to regulate the growth of taste buds, while ''Spry'' genes limit the number of CVP. ''Fgf10''& ''Spry 1&2''work antagonistically through receptor tyrosine kinase (RTK)signalling.

However, the deletion of ''Spry2''led to the increase of CVPs it should be noted that they found that a significant decrease in number of fungiform papillae. Contrastingly, the absence of ''Fgf10'', while leading to the absence of CVPs lead to an increase in number and size of fungiform papillae. Therefore these genes have different effects on the anterior and posterior developing tongue and taste buds.<ref><pubmed>21655085</pubmed></ref>

==Current Research==
We have an evolving understanding of Embryonic Taste development, through the use of state-of-the-art technology and research techniques we are able to make brilliant discoveries that continue to connect the dots of this amazing natural process of human development.
The majority of research in taste development is involving mice, these mammals show similar embryonic pathways to humans and research is performed in ethical and humane methods.

[[File:Histology.jpg|Left|thumb|200px|Image shows histological stains of a mice tongue showing dysplasia]]

'''Synergistic relationships of Six Genes '''

In an animal study using mice by Suzuki Y, Ikeda K, Kawakami K.(2011) Firstly nominating "Six Genes" as a major component in gustatory development, stating that deficiencies in certain Six genes (specifically Six1 & Six4) leads to poor development. Their research also highlights evidence of cooperative relationships between Six genes for normal advance. This experiment involved breeding mice containing exclusively Six1 and Six4 genes and examining the expression of these genes in papillae under high powered microscope observation. Understanding the role of certain genes along with the intrinsic relationships they hold is crucial for the ability to identify possible causes and correction of any abnormalities <ref><pubmed>21978088</pubmed></ref>

'''Neural Crest responsibilities '''

Another Animal Study involving mice explores a new idea of Neural crest (NC) contribution in taste development, specifically the development of papillae and taste buds. Liu HX, Komatsu Y, Mishina Y, Mistretta CM. (2012) suggest that Neural crest cells travel to the location of the tongue in early embryonic stages, gain epithelium phenotypes, multiply and then differentiate to eventually form taste papillae. The experiment involved the comparison of 2 different types of Cre line mice, which both express Cre gene in neural crest protocol, the different distribution patterns where observed in specific regions that NC is responsible for.<ref><pubmed>22659543</pubmed></ref>

'''Augmentation of Endoderm'''

In an animal study conducted by Rothova M, Thompson H, Lickert H, Tucker AS.(2012) exploring the historically debated issue of endoderm contribution to tongue development showed promising evidence that position of taste buds are patterned by the border of ectoderm and endoderm derivative epithelium. This study was accomplished via microscopic examination of previously stained specimens. Concluding endoderm has direct influence on gustatory develoment <ref><pubmed>22581563</pubmed></ref>

'''Changes in Taste Cells over time'''

Research by
Ozdener H, Spielman AI, Rawson NE.(2012) developing a culture which allows taste cells to survive for up to 12 months, empowers researchers to study the processes of proliferation, differentiation and function. This experiment will provide a precidnet for future study of taste cells, as these cells are able to operate and grow normally. <ref><pubmed>22643728</pubmed></ref>

'''Shh key component of taste bud proginators'''

A tamoxifen treatment which supresses Sonic hedgehog (Shh) secretion in mice proving to reduce the number of cells visable within papillae, in contrast mice not treated with tamoxifen showed a mark increase of cells within papillae, these cells are assumed to become taste cells in later development.
Specific mice were bred to trace the destination of taste placode cells, the study concluded that Shh expressing placodes are taste bud proginators which in turn become taste cells within taste buds although do not have any prescuros relationship with pappilae. The results were obtain by examination of mice embryos using Bright-field or multichannel fluorescent images through the use of an "Axiocam CCD camera and Axioplan fluorescence microscope with Axiovision software" a study by Harlow, Yang, Williams, Barlow (2011)<ref><pubmed>PMC2674259</pubmed></ref>

'''WNT family exhibit various roles'''

The WNT gene family has a function of signally proteins for various reason such as development, In 2010 Liu, Staubach Grosse, Walton, Saims, Gumucio, Mistretta explored recent findings on the role of WNT's in tongue and papillae development, Concluding that WNT/β-catenin is essential for fungiform papillae differing to WNT5a which proved to be principle in tongue development. Intrinsic chemical mediators were considered by manipulating a tissue culture and then throughaly examined by scanning photomicrograph. <ref><pubmed>PMC2768563</pubmed></ref>

[http://www.surgicalneurologyint.com/article.asp?issn=2152-7806;year=2012;volume=3;issue=1;spage=23;epage=23;aulast=Manjila]
[[File:Abnormal of tongue.jpg|Left|thumb|200px|Image shows and example of tongue abnormalities, this is called "double tongue" each side has independent movement!]]

==Useful links==

==Glossary==

ectoderm- outer germ layer of embryo

endoderm - inner germ layer of embryo

epithelium - basic animal tissue that is composed of tightly packed cells, usually covering the outer portion of organs

exocystosis - movement of contents out of cell

ganglia - the accumulation of a nerve cell body

growth factor - a substance that stimulates the growth of cells

gustatory - anything that relates to the taste sense

hydrolysis - breakdown of a chemical when it reacts with water

mesoderm - middle germ layer of embryo

mesenchyme - multipotential cells

neural crest - a part of the ectoderm found on both sides of the neural tube

neuron - most simplistic unit of the nervous system

neurotransmitter - chemicals which allow the passing of signals from neuron to neuron via connecting part (synapse)

papillae - small rough surface projection

six genes - a family of genes

Sonic hedgehog (Shh) - signalling protein invloved in normal development

sulcus terminalis - describes a physical transition point separating the anterior 2/3 of the tongue from the posterior 1/3

tamoxifen - hormonal altering drug

==Image gallery==

== References ==
<references/>

==External Links==
{{External Links}}

--[[User:Z8600021|Mark Hill]] 12:22, 15 August 2012 (EST) Please leave the content listed below the line at the bottom of your project page.

----

{{2012Projects}}

2012 Group Project 3

2012-09-26T01:04:39Z

Z3289738:

=Taste Development=

== Introduction ==
**NEED TO ADD**

==History of Discoveries==

{| cellpadding=5 style="border:1px solid #BBB"
|- bgcolor="#faecc8"
|''' Date'''|| '''Significant Discovery'''
|- bgcolor="#faf6ed"
|'''350BC'''
|| Aristotle writes about the basic tastes, sweet and bitter, which can be modified, he says, by salty and acidic.
|- bgcolor="#faecc8"
|'''1901'''
|| D. Hanig publishes a paper containing data of taste sensitivity in different regions of the tongue. The data are later misinterpreted, giving rise to the myth of the ‘tongue map’

|- bgcolor="#faf6ed"
|style=white-space:nowrap|'''1908'''
|Fifth basic taste discovered: savouriness, described as umami, which is conferred by glutamate.

|- bgcolor="#faecc8"
|style=white-space:nowrap|'''1931'''
|Bitter taste sensitivity found to vary among humans (1)

|- bgcolor="#faf6ed"
|style=white-space:nowrap|'''1931-32'''
|Genetecists confirm findings about sensitivity to bitter tasting PTC and discover non-tasting is a recessive genetic trait (2,11)

|- bgcolor="#faecc8"
|style=white-space:nowrap|'''1939'''
|Geneticists show that chimpansees like humans, vary in their ability to perceive the bitterness of PTC

|- bgcolor="#faf6ed"
|style=white-space:nowrap|'''1992'''
|Discovery of gustucin, a teste cell-specific G-protein, in the taste buds. Gustucin is later shown to mark bitter, umami and sweet cells (13)

|- bgcolor="#faecc8"
|style=white-space:nowrap|'''1996'''
| Witt M and Reutter K of the Source Department of Anatomy, Technical University Dresden, Germany, carried out a transmission electron microscopy study to investigate the embryonic and fetal development of Human taste buds. Their results suggest an "at least dual function of embryonic/fetal taste buds", including non-gustatory, paracrine functions prior to the 14th week and gustatory after the 14th week. PMID 8955790

|- bgcolor="#faf6ed"
|style=white-space:nowrap|'''2000'''
|First taste sonsors, the T2R receptors, discovered (3)

|- bgcolor="#faecc8"
|style=white-space:nowrap|'''2001'''
|The sweet receptor is discovered (5): a combination of TaR2 and T1R3.

|- bgcolor="#faf6ed"
|style=white-space:nowrap|'''2002'''
|Amino acid detector, T1R1 and T1R3 identified (6) = Umami

|- bgcolor="#faecc8"
|style=white-space:nowrap|'''2005'''
|Sweet taste receptor found (15) in the GI tract

|- bgcolor="#faf6ed"
|style=white-space:nowrap|'''2006'''
|Cells for sour taste discovered, identified by PKD2L1 (4-7)

|- bgcolor="#faecc8"
|style=white-space:nowrap|'''2007'''
|Harlow DE, Barlow LA of the Department of Cell and Developmental Biology, Rocky Mountain Taste and Smell Center, University of Colorado Denver Health Sciences Center provide evidence of the '''embryonic origin of gustatory cranial sensory neurons''' PMID 17826760

|- bgcolor="#faf6ed"
|style=white-space:nowrap|'''2009'''
|The Car4 receptor, which senses the carbon dioxide in fizzy drinks is found on sour cells (8)

A study by Hevezi P et al, presents the first comprehensive characterization of gene expression in primate taste buds, as opposed to previous studies which focused on rodents. PMID 19636377

|- bgcolor="#faecc8"
|style=white-space:nowrap|'''2010'''
|ENaC identified as the sodium-salt taste receptor (9)
|}

*[http://www.nature.com/nature/journal/v486/n7403_supp/fig_tab/486S2a_F1.html Gustatory system: The finer points of taste] <ref><pubmed>22717400</pubmed></ref>

==Gustatory System==

[[Image:Taste qualities.gif|thumb|The five basic tastes]]

Taste or more appropriately gustation, is a fundamental survival tool in animals as it directs the consumption of essential nutrients. The five tastes that exist within the human gustatory system: salty, sweet, sour, bitter and umami, all signify basic physiological requirements. Salty tastes denote the presence of Na+, an important ion involved in the transportation and retention of water across cell membranes. Sweetness is the recognition of carbohydrates, essential for maintaining optimal brain function and providing the basis for energy production in muscle tissue via ATP hydrolysis. Similarly umami codes for the presence of L-amino acids, especially L-glutamate which is an integral component of protein synthesis.

These different modalities not only function to maintain the proper intake of nutrients within the body but also, by way of aversion, prohibit the consumption of undesired or poisonous materials. The bitter modality for example is generally regarded as displeasing to the human palate. It represents a high acid content which may be a result of foods which have become rotten or are inherently poisonous to the body.<ref name=PMID20696704><pubmed>20696704</pubmed></ref>

Research has historically limited itself to investigating the mechanisms of these five taste qualities though it must be noted many other modalities may exist. Of particular conjecture is the existence of fatty acid recognition. In the past the detection of fat in food has been attributed to somatosensory inputs <ref name=PMID20696704/> from the tongue, that is, the oily feel and texture of fat rather than its actual ‘taste’ allows the brain to encode for its presence. Further research is therefore required to elicit the precise mechanisms of fat detection.

===Cell Biology===

The five taste qualities are not all detected by the same type of receptor cell located within the taste bud. Like rods and cones in the eye which detect different wavelengths of light, there are specific types of receptors for different tastes. For example, sweet, umami and bitter are recognised by Type II G-protein coupled receptors, whereas sour is related to Type III presynaptic cells. The cell type involved in salty taste transduction is unknown however it is known that sodium ions can enter the receptor cell membrane via ion channel permeation.

====Type II receptors====

When a bitter, sweet or umami ligand binds to a type II G-coupled receptor, a cascade of chemical reactions causes the release of Ca2+ which in turn mediates exocystosis of ATP. The function of this ATP is threefold:

# Stimulates gustatory nerve afferents which project to gustatory nuclei in the spinal cord
# Excites Type III presynaptic nerve fibres to release serotonin.
# Has a positive feedback effect on type II receptor cells, increasing the level of ATP production.

The role of serotonin is believed to be in the form of lateral inhibition i.e. when a bitter quality is recognised, adjacent receptors for sweetness are deactivated and thus the two tastes may be clearly differentiated. It also has a negative feedback effect on receptor cells, inhibiting umami, bitter and sweet taste transduction.

==Taste Map==
[[Image:Taste map.png|thumb|left|250px|Obsolete idea of the tongue map]]
The idea of a tongue map has disseminated through society for many years. This concept purports that different areas of the tongue are specialised to detect either sweet, salty, sour and bitter tastes. Recent research however has completely nullified such claims and suggests instead that different forms of taste are recognised all over the tongue as well as via the palate. Thus the term ''taste map'' has come to take on a new meaning and that is, the precise areas of taste modalities processing in areas of cortex and its subsequent neural inputs.

===Neural Pathways===

'''First order neurons''' - From the receptors located in the taste buds, gustatory nerve afferents project to the ipsilateral rostral 1/3 of the nucleus tractus solitarius (NTS), located in the medulla. This rostral 1/3 is commonly referred to as the ''gustatory nucleus''.

The ''gustatory nucleus'' receives input from cranial nerves VII (''Facial n.''), IX (''Hypglossal n.''), and X (''Vagus n.'') via special visceral afferent (SVA) nerve fibres. A summary of their functions is as follows:

* ''Facial nerve n''. - carries taste information from the anterior 2/3 of the tongue.
* ''Hypoglossal n.'' - carries taste information from the posterior 1/3 of the tongue.
* ''Vagus n''. - carries taste information from the palate

'''Second order neurons''' - From the NTS second order neurons carry taste information to the Ventral posteromedial (VPM) nucleus in the thalamus.<ref name=PMID21885776/>

Copious scientific conjecture surrounds how each taste modality is transmitted to the brain. The ‘labelled-line’ hypothesis suggests that there are taste specific neurons which exclusively carry that taste modality to cortical areas. In analogous terms it can be viewed like the pipelines leading toward a house. Each pipeline carries its own utility, there is one for gas, another for water and finally for electricity with each terminating in slightly different areas of the house. In the same way, on the tongues there are different receptors for each taste which concurrently have individual nerve tracts leading to the primary gustatory cortex.

Contrapuntally there is electrophysiological evidence that single nerve afferents carry multiple modalities. These studies show one nerve afferent may have both a strong and a weak activation in response to a multiple taste stimuli.

===Cortical Areas===

[[Image:Primary gustatory cortex.png|thumb|Primary gustatory cortex]]

The location of the taste perception centres has been observed via functional magnetic resonance imaging (fMRI) studies. The primary taste cortex has been identified as being located in the anterior insula/frontal operculum (I/fO)<ref name=PMID22245354><pubmed>22245354</pubmed></ref>, with the secondary taste cortex in the caudolateral orbitofrontal cortex.<ref name=PMID21305668><pubmed>21305668</pubmed></ref> Within the insula there are further subdivisions related to each taste modality. Two photon calcium imaging research has outlined certain ’hot-spots’ of activation which are clearly delineated in relation to each taste. For example, the bitter modality is represented on the insula cortex approximately 1mm posterior to the middle cerebral artery whereas the sweet modality is represented 2.5mm rostrodorsal to the bitter field with no apparent overlap.<ref name=PMID21885776><pubmed>21885776</pubmed></ref> These findings lend weight to the idea that there is only one receptor for each taste quality.

It is interesting to note the relationship between taste and the reward centres of the brain. There is evidence of neural input to the ventral tegmental area (the origin of the mesolimbic dopaminergic reward pathway) and nucleus accumbens (involved in the conversion of motivation into physical action).<ref name=PMID21885776/> Neural connections such as this provide the foundations in explaining concepts such as flavour learning and preference. It may also give some insight into chronic problems such as food addiction and craving. As of yet however the gustatory neural network is not well understood and more research is required to elucidate the relationship between pleasure and taste sensation

==Timeline of Developmental Processes of the Gustatory System==

{| cellpadding=5 style="border:1px solid #BBB"
|- bgcolor="#89CFF0"
|'''Postovulatory Week'''||'''Description'''||'''Image'''
|- bgcolor="#BCD4E6"
|'''Week 6''' ||
The surface of the developing tongue is covered by nearly flat epitheliuem (Figure 1) <ref name=PMID9455607/>. The first gustatory papillae of the tongue appears in the caudal midline near the foramen caecum and the first circumvallate papilla develop on the dorsal midline <ref name=PMID9455607/> .
||
image
|- bgcolor="#89CFF0"
| '''Weeks 6 to 7'''||
Nerve fibres approach the basal lamina of lingual epithelium <ref name=PMID8955790><pubmed>8955790</pubmed></ref>. At this stage the lingual epithelium consists of two to three cell layers and there is not yet any sign of cell specializations indicating early taste bud formation<ref name=PMID8955790/>.
||
Image
|- bgcolor="#BCD4E6"
| '''Week 7 '''||
A series of epithelial swellings in the anterior part and midline of the tongue indicate early forming fungiform papillae (figure 2) <ref name=PMID9455607/>.
||
Image
|- bgcolor="#89CFF0"
| ''' Week 8 ''' ||
The lingual epithelium shows first signs of taste bud development as nerve fibres penetrate epithelial basal lamina <ref name=PMID8955790/> and form synapses with taste bud progenitor cells. The synapses reach a maximum around the 12th to 13th week <ref name=PMID8955790/>. However, at this time these cells are still poorly differentiated, elongated epithelial cells <ref name=PMID8955790/> . The synapses demonstrate the neuronal connection between the taste bud primordium and the central nervous system <ref name=PMID8955790/>. Ciliated cells also appear around the 8th week, however the significance of these cells which are scattered randomly across the lingual surface remains unclear <ref name=PMID8955790/>.
||
Image
|- bgcolor="#BCD4E6"
|''' Weeks 8-9''' ||
“By this stage the top surface of circumvallate papillae usually contains a taste pit partly filled with microvilli of presumed underlying taste bud cells” (Figure 10) <ref name=PMID9455607/>
||
Image
|- bgcolor="#89CFF0"
|''' Weeks 10-11''' ||
At this stage, the lingual epithelium compromises of about four cell layers, and the first shallow grooves above the taste bud primordium are developed <ref name=PMID8955790/>.

Fungiform papillae appear on the lateral margins and the tip of the tongue <ref name=PMID9455607/>, containing taste bud primordial that display the first signs of a primitive pore formation <ref name=PMID8955790/>.

Untypically differentiated apical cellular processes extend onto the surface <ref name=PMID9455607/>

Some taste bud primordial contain cells that perforate the covering epithelial later with short, broad untypically differentiated apical cellular processes. (Figure 3,4) <ref name=PMID8955790/> <ref name=PMID9455607/>
||
Image
|- bgcolor="#BCD4E6"
|''' Week 12 ''' ||
Taste bud cells are more clearly differentiated into epithelial cell types II and III <ref name=PMID8955790/>.
||
Image
|- bgcolor="#89CFF0"
|''' Weeks 12-13 ''' ||
By this stage the taste bud primordial are all located on the top of dermal papillae (Fig 6a) <ref name=PMID8955790/>. There is also maximum synapses between cells and afferent nerve fibres, which intermingle with each other to form a plexus-like structure <ref name=PMID8955790/>.
||
Image
|- bgcolor="#BCD4E6"
|''' Weeks 14 -15 ''' ||
The shape of the taste buds primordial begins to resemble those of adult taste buds <ref name=PMID8955790/>. By the 14th week the taste pores develop as the taste pits are filled by microvilli <ref name=PMID8955790/>, indicating the possibility that the taste buds begin their gustatory function <ref name=PMID8955790/>, however they still lack an electron-dense mucous material (Fig.10) <ref name=PMID8955790/>. The tastebuds only achieve a fully developed function in week 15 of gestation with the development of type I cells to produce the mucous material in the taste pit <ref name=PMID8955790/>.
||
Image
|}

==Adult Tongue and Taste Buds – Structure and Function==

'''Structure'''

The tongue is located on the floor of the oral cavity, It is a muscular structure with sensory units crowning. The tongue is divided into an anterior two thirds and a posterior one third. These regions are divided by a V-shaped groove at the back of the tongue (sulcus terminalis). The anterior two thirds of the tongue is covered by stratified squamous epithelium, It contains a roughened surface and has projections called papillae that vary in shape and number.

''''The Image Below is a very simplistic Diagram of the surface of the Tongue showing the locations of the different papillae and other important features'''

{|
| [[Image:Drawing of Tongue.png|500px]]

'''Papillae'''
[[File:Papillae.jpg|Left|thumb|200px|Close up of Human Tongue Papillae]]

There are 4 types of papillae on the tongue.
The most numerous papillae are the filiform papillae, which function to provide a surface that aids in holding food on the tongue during chewing but do not contain taste buds. The larger, less numerous fungiform papillae which contain taste buds, as do foliate papillae. Circumvallate papillae form a wide V at the sulcus terminalis also containing taste bus. There are no papillae or taste buds located on the posterior third of the tongue, having mucosal folds and the lingual tonsils instead.

'''Function'''

The tongue is for tasting, swallowing, and speech.
The functional unit of the taste bud is a taste cell, there are between 50 and 100 taste cells in each taste bud these taste cells represent all 5 different tastes. Historically is was believed that different areas of the tongue were responsible for different taste sensations although this has since been disregarded.[http://users.rcn.com/jkimball.ma.ultranet/BiologyPages/W/Welcome.html] The papillae contain taste buds which are connected to the oral cavity via a taste pore, the function of the taste bud is to transmit a chemical signal from the oral cavity to a taste cell, this chemical signal is the converted into an electrical impulse and delivered to the brain via nerve fibres for interpretation.

'''The Image Below is a very simplistic Hand drawn Diagram of a taste bud, in an extreme close up, cross section view of the the taste bud unit, not to scale'''

[[File:Taste_bud_1.jpg]]

==Abnormalities==

===Knocking out P2X Receptors===

[[File:Image of taste being evoked by visualising ATP release.jpeg|Left|thumb|200px|Evoking taste - ATP release in tongue]]

Gustatory abnormalities has not been widely researched and what has been researched has been through animal testing, most commonly we have found on mice.

In Huang, 2008 this team used the release of the neurotransmitter, ATP (adenosine triphosphate) as a quantitative measurement of gustatory sensation and taste. This was done by using a comparison of wild type (WT) and double knockout (DKO) mice. P2X receptors, P2X2 and P2X3 were knocked out in the DKO mice. The premise of this article was that knocking out P2X receptors reduces transmitter secretion of ATP in taste buds, therefore they cannot taste.

It should be noted that the taste buds in DKO are functional, but are not stimulated by the administration of tastants.

The transmission of release of ATP is secretion through gap junction hemichannels (pannexin 1 gap junction).

When both P2X2 and P2X3 are knocked out, no taste is elicited. However they found that if either P2X2 OR P2X3 was knocked out there was a taste response. So the inference made from this is that if one of the two receptors from the P2X family was knocked out there still can have taste response. The WT mice showed significant stimulation by tastants whereas DKO had little to no stimulation of ATP release.<ref><pubmed>21940456</pubmed></ref>

===FGF signalling and genes===

Sprouty, or ''Srpy'', genes have been related to regulating the development of circumvillate papillae (CVP). The CVP are large dome shaped papillae, which form a 'V' just in front of the terminal sulcus.

By knocking out ''Spry'' genes using mice which had ''Spry1'' and ''Spry2'' knocked out showed that the number of CVP doubled. However, when Fibroblast Growth Factor gene ("Fgf10") was absent, the number of CVP was significantly reduced, if not completely absent. The correlation between ''Spry1/2'' and ''Fgf10'' is that ''Spry1/2'' antagonises "Fgf10" to limit the size of the CVP progenitor placode. Exclusive expression of ''Fgf10'' in the mesenchyme is necessary for the formation of CVP.

'''This image shows the CVP stained with H&E and scanned by Scanning Electron Microscope (SEM)'''
[[File:CVP of WT(top) and DKO(bottom) mice with H&E and SEM.png]]

'''This image shows the location of the CVP and the increased number in DKO mice by SEM'''
[[File:Mouse circumvallate papilla 01.jpg|300px]]

Taste buds develop from the mesenchyme but require local signalling to properly differentiate. Some signalling factors for proper development of taste buds besides FGF are: Sonic Hedgehog (SHH), Bone Morphogenetic Proteins (BMPs), Epidermal Growth Factor (EGF).

Additionally, this proves that the anterior and posterior developments of the tongue are derived from embryonic tissues, where the anterior tongue is derived from the ectoderm and the posterior tongue is derived from the endoderm. Taste buds develop from the mesenchyme but require local signalling to properly differentiate. Some signalling factors for proper development of taste buds besides FGF are: Sonic Hedgehog (SHH), Bone Morphogenetic Proteins (BMPs), Epidermal Growth Factor (EGF).

As mentioned above, this article shows that the anterior and posterior developments of the tongue are derived from embryonic tissues, where the anterior tongue is derived front the ectoderm and the posterior tongue is derived from the endoderm. Secondly, FGF is required to regulate the growth of taste buds, while ''Spry'' genes limit the number of CVP. ''Fgf10''& ''Spry 1&2''work antagonistically through receptor tyrosine kinase (RTK)signalling.

However, the deletion of ''Spry2''led to the increase of CVPs it should be noted that they found that a significant decrease in number of fungiform papillae. Contrastingly, the absence of ''Fgf10'', while leading to the absence of CVPs lead to an increase in number and size of fungiform papillae. Therefore these genes have different effects on the anterior and posterior developing tongue and taste buds.<ref><pubmed>21655085</pubmed></ref>

==Current Research==
We have an evolving understanding of Embryonic Taste development, through the use of state-of-the-art technology and research techniques we are able to make brilliant discoveries that continue to connect the dots of this amazing natural process of human development.
The majority of research in taste development is involving mice, these mammals show similar embryonic pathways to humans and research is performed in ethical and humane methods.

[[File:Histology.jpg|Left|thumb|200px|Image shows histological stains of a mice tongue showing dysplasia]]

'''Synergistic relationships of Six Genes '''

In an animal study using mice by Suzuki Y, Ikeda K, Kawakami K.(2011) Firstly nominating "Six Genes" as a major component in gustatory development, stating that deficiencies in certain Six genes (specifically Six1 & Six4) leads to poor development. Their research also highlights evidence of cooperative relationships between Six genes for normal advance. This experiment involved breeding mice containing exclusively Six1 and Six4 genes and examining the expression of these genes in papillae under high powered microscope observation. Understanding the role of certain genes along with the intrinsic relationships they hold is crucial for the ability to identify possible causes and correction of any abnormalities <ref><pubmed>21978088</pubmed></ref>

'''Neural Crest responsibilities '''

Another Animal Study involving mice explores a new idea of Neural crest (NC) contribution in taste development, specifically the development of papillae and taste buds. Liu HX, Komatsu Y, Mishina Y, Mistretta CM. (2012) suggest that Neural crest cells travel to the location of the tongue in early embryonic stages, gain epithelium phenotypes, multiply and then differentiate to eventually form taste papillae. The experiment involved the comparison of 2 different types of Cre line mice, which both express Cre gene in neural crest protocol, the different distribution patterns where observed in specific regions that NC is responsible for.<ref><pubmed>22659543</pubmed></ref>

'''Augmentation of Endoderm'''

In an animal study conducted by Rothova M, Thompson H, Lickert H, Tucker AS.(2012) exploring the historically debated issue of endoderm contribution to tongue development showed promising evidence that position of taste buds are patterned by the border of ectoderm and endoderm derivative epithelium. This study was accomplished via microscopic examination of previously stained specimens. Concluding endoderm has direct influence on gustatory develoment <ref><pubmed>22581563</pubmed></ref>

'''Changes in Taste Cells over time'''

Research by
Ozdener H, Spielman AI, Rawson NE.(2012) developing a culture which allows taste cells to survive for up to 12 months, empowers researchers to study the processes of proliferation, differentiation and function. This experiment will provide a precidnet for future study of taste cells, as these cells are able to operate and grow normally. <ref><pubmed>22643728</pubmed></ref>

'''Shh key component of taste bud proginators'''

A tamoxifen treatment which supresses Sonic hedgehog (Shh) secretion in mice proving to reduce the number of cells visable within papillae, in contrast mice not treated with tamoxifen showed a mark increase of cells within papillae, these cells are assumed to become taste cells in later development.
Specific mice were bred to trace the destination of taste placode cells, the study concluded that Shh expressing placodes are taste bud proginators which in turn become taste cells within taste buds although do not have any prescuros relationship with pappilae. The results were obtain by examination of mice embryos using Bright-field or multichannel fluorescent images through the use of an "Axiocam CCD camera and Axioplan fluorescence microscope with Axiovision software" a study by Harlow, Yang, Williams, Barlow (2011)<ref><pubmed>PMC2674259</pubmed></ref>

'''WNT family exhibit various roles'''

The WNT gene family has a function of signally proteins for various reason such as development, In 2010 Liu, Staubach Grosse, Walton, Saims, Gumucio, Mistretta explored recent findings on the role of WNT's in tongue and papillae development, Concluding that WNT/β-catenin is essential for fungiform papillae differing to WNT5a which proved to be principle in tongue development. Intrinsic chemical mediators were considered by manipulating a tissue culture and then throughaly examined by scanning photomicrograph. <ref><pubmed>PMC2768563</pubmed></ref>

[http://www.surgicalneurologyint.com/article.asp?issn=2152-7806;year=2012;volume=3;issue=1;spage=23;epage=23;aulast=Manjila]
[[File:Abnormal of tongue.jpg|Left|thumb|200px|Image shows and example of tongue abnormalities, this is called "double tongue" each side has independent movement!]]

==Useful links==

==Glossary==

ectoderm- outer germ layer of embryo

endoderm - inner germ layer of embryo

epithelium - basic animal tissue that is composed of tightly packed cells, usually covering the outer portion of organs

exocystosis - movement of contents out of cell

ganglia - the accumulation of a nerve cell body

growth factor - a substance that stimulates the growth of cells

gustatory - anything that relates to the taste sense

hydrolysis - breakdown of a chemical when it reacts with water

mesoderm - middle germ layer of embryo

mesenchyme - multipotential cells

neural crest - a part of the ectoderm found on both sides of the neural tube

neuron - most simplistic unit of the nervous system

neurotransmitter - chemicals which allow the passing of signals from neuron to neuron via connecting part (synapse)

papillae - small rough surface projection

six genes - a family of genes

Sonic hedgehog (Shh) - signalling protein invloved in normal development

sulcus terminalis - describes a physical transition point separating the anterior 2/3 of the tongue from the posterior 1/3

tamoxifen - hormonal altering drug

==Image gallery==

== References ==
<references/>

==External Links==
{{External Links}}

--[[User:Z8600021|Mark Hill]] 12:22, 15 August 2012 (EST) Please leave the content listed below the line at the bottom of your project page.

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User:Z3289738

2012-09-26T00:08:32Z

Z3289738:

==Lab Attendance==
Lab 1: --[[User:Z3289738|Z3289738]] 11:49, 25 July 2012 (EST)

Lab 2: --[[User:Z3289738|Z3289738]] 10:12, 1 August 2012 (EST)

Lab 3: --[[User:Z3289738|Z3289738]] 10:08, 8 August 2012 (EST)

Lab 4: --[[User:Z3289738|Z3289738]] 10:20, 15 August 2012 (EST)

Lab 5: --[[User:Z3289738|Z3289738]] 10:13, 22 August 2012 (EST)

Lab 6: --[[User:Z3289738|Z3289738]] 10:16, 29 August 2012 (EST)

Lab 7: --[[User:Z3289738|Z3289738]] 10:27, 12 September 2012 (EST)

Lab 8: --[[User:Z3289738|Z3289738]] 10:30, 19 September 2012 (EST)

Lab 9: --[[User:Z3289738|Z3289738]] 10:08, 26 September 2012 (EST)

==Individual Assessments==
===Lab 1 Assessment===

''Q1. Identify the origin of In Vitro Fertilization and the 2010 nobel prize winner associated with this technique and add a correctly formatted link to the Nobel page.''

The idea of In Vitro Fertilization began to formulate in the 1890s, when Walter Heape reported the first known case of embryo transplantation in rabbits. In 1953 John Rock extracted the first intact human fertilized egg. The first successful attempt at IVF was in 1978 by Steptoe and Edward.

Robert G. Edwards, the physiologist who developed the In Vitro Fertilization treatment, was awarded the Nobel Prize in Physiology or Medicine in 2010. [http://www.nobelprize.org/nobel_prizes/medicine/laureates/2010/press.html/# Nobel Prize Page]

''Q2. Identify and add a PubMed reference link to a recent paper on fertilization and describe its key findings (1-2 paragraphs).''

This article looks into the process of embryo implantation. It demonstrates how the activation of the epithelial Na(+) channel triggers prostoglandin E(2) release,phosphorylation of teh transcription factor CREB and upregulation of cyclooxygenase 2, the enzyme required for prostaglandin production and implantation. They detected maximum Epithelial Na(+) channel activation at the time of implantation in mice, and that blocking or knocking down this channel in mice resulted in failure to implant. These results indicate the importance of the Epithelial Na(+) Channel in the process of implantation, and the consequences of defects such as miscarriage and low success rates in IVF.

<pubmed> 22729284</pubmed>

===Lab 2 Assessment===
''Q1. Upload an image from a journal source relating to fertilization or the first 2 weeks of development as demonstrated in the practical class. Including in the image “Summary” window: An image name as a section heading, Any further description of what the image shows, A subsection labeled “Reference” and under this the original image source, appropriate reference and all copyright information and finally a template indicating that this is a student image.

[[File:Z3289738 ANAT Lab 2.jpg|200px|thumb|right|Zygotes showing different distribution of NPB in the 2PN and different PB aligment]]

''Q2. Identify a protein associated with the implantation process, including a brief description of the protein's role (1-2 paragraphs)''

'''Trophinin'''

Trophinin is an membrane adhesive protein expressed on human trophoblastic cells and on uterine endometrium epithelial cells. The protein mediates apical cell adhesion and activate trophectoderm cells for implantation via proliferation and invasion. <ref><pubmed>17487845</pubmed></ref>

===Lab 3 Assessment===

''Q1. Identify the difference between "gestational age" and "post-fertilisation age" and explain why clinically "gestational age" is used in describing human development.''

"Gestational age" is measured from the first day of the woman's last menstrual cycle, whereas "post-fertilisation age" measures the time passed since fertilization of the oocyte. Gestational age is more clinically relevant as it is easier to determine the date of the woman's last menstrual cycle than it is to determine the date of fertilization. Furthermore, gestational age can also be determined before and after birth by measuring the size of the head, thigh bone and abdomen (before birth), and the size of the head and weight after birth. Gestational age is therefore used to determine the infant's medical history and medical plan.

''Q2. Identify using histological descriptions at least 3 different types of tissues formed from somites.''

Somites differentiate to form: (1) '''the axial skeleton (vertebral body & inter-vertebral disk)''', (2) '''dermis''' and (3) '''skeletal muscle'''.

# Cells in the ventromedial half of each somite differentiate into the sclerotome via Sonic hedgehog signalling mechanisms. The Pax 1 transcription factor then converts the sclerotome into chondrocytes (cartilage), which is essential for the functioning of the vertebral column.
# Cells in the dorsolateral portion of the somites differentiate to form the dermomyotone. This is then divided into:
## Dorsal dermatome which later contributes to the formation of the dermis in response to neutropin 3 factors.
## Wnt1 and Wnt3 factors contribute to the formation of the ventral myotome, which is further split into the epaxial myotome (gives rise to erector spinae muscles) and the hypaxial myotome (gives rise to the muscles of the trunk and limbs).

===Lab 4 Assessment===

''Q1. Identify the 2 invasive prenatal diagnostic techniques related to the placenta and 2 abnormalities that can be identified with these techniques.''
# '''Chorionic villus sampling''' (CVS)is an invasive prenatal diagnostic technique that is used to detect genetic abnormalities such as Down syndrome or cystic fibrosis. During the procedure a sample of the placenta is removed via a needle through the abdomen and then examined in a laboratory. It is commonly performed between 10 and 12 weeks of pregnancy/
# '''Amniocentesis''' procedures involve collecting samples of amniotic fluid via a needle through the abdomen to check for genetic abnormalities such as Down syndrome, cystic fibrosis or spina bifida.

''Q2. Identify a paper that uses cord stem cells therapeutically and write a brief (2-3 paragraph) description of the paper's findings.''

F. Ramirez, D. Steenblock, A. Payne and L. Darnall (2006) '''Umbilical Cord Stem Cell Therapy for Cerebral Palsy'''. MED HYPOTHESES RES 3: 679-686 [http://www.journal-mhr.com/PDF_Files/vol_3_2/3_2_PDFs/3_2_2.pdf | Umbilical Cord Stem Cell Therapy for Cerebral Palsy]

This article describes a six month study to evaluate the effectiveness of umbilical cord stem cells in treatment for various brain injuries and disorders, in particular Cerebral Palsy. The study began in 2004, whereby 8 children between the ages of 3-12 who had been diagnosed with Cerebral Palsy underwent transplants with 1.5 million umbilical cord stem cells. The study reported eight of of eight children showed some improvement in mobility and/or cognitive function. Furthermore, one aphasic child started talking again and another who had been blind since birth was able to see after post-treatment.

The results from this preliminary observational pilot study suggests that umbilical cord stem cells may be a safe and promising treatment for children with cerebral palsy.

===Lab 7===
====a) Class exercises====
1. Maturation Hypertrophy - In your groups, design a method to estimate the degree of hypertrophy that occurs during the transition from birth to adulthood. Use the rulers to make rough measurements on the screen and then estimate the degree of hypertrophy as a mean increase in fibre size. Discuss the result as a class. (ie Try estimate the degree of hypertrophy from child to adult cells)

Method: Measured area of the child and adult cells, found an average for each and then worked out the percentage increase.

Answer: 7x increase in area size.

2. The role of satellite cells in muscle hypertrophy - class discussion of data presented in a recent paper - McCarthy et al. 2011. (ie How to we achieve hypertrophy? How do we get proteins into the cells? Degeneration of the myonucleus - Can activate the satellite cells as if the cell is undergoing repair; the nuclei within the cells becomes more active, produces more RNA and the cells get bigger.)

3. Fibre type shift - Discuss an experiment on fiber type shift that has been induced by chronic low frequency stimulation - Martins et al. 2006

====b) Assessment====
''Q1. (a) Provide a one sentence definition of a muscle satellite cell.''

Satellite cells are quiescent stem cells present in adult muscle tissue between the basal lamina of a muscle fiber and are responsible for postnatal hypertrophy and regeneration. <ref><pubmed>16243526</pubmed></ref>

''Q1. (b) In one paragraph, briefly discuss two examples of when satellite cells are activated?''

These cells are normally quiescent in adult muscle, by are activated in response to injury and muscle disease. When activated, the cells begin to proliferate and after aligning they fuse to allow for repair and/or regenration of muscle fibres. Satellite cells assist in the regeneration of muscle tissues in response to muscle injury by either forming multinucleated myotubes or additional quiescent satellite cells. <ref><pubmed>21849021</pubmed></ref>. Furthermore, studies have provided evidence of an increased level of satellite cells in muscular diseases such as Duchenne muscular dystrophy (DMD). <ref><pubmed>16818602</pubmed></ref>

''Q2. In one brief paragraph, describe what happens to skeletal muscle fibre type and size when the innervating motor nerve sustains long term damage such as in spinal cord injury?''

Spinal cord injuries which lead to long term damage to the innervating motor nerve would result in muscle partial or complete paralysis of muscles, leading to muscle atrophy. <ref><pubmed>16940987</pubmed></ref> This results in a significant decrease in cross-sectional area of the immobilized muscle do to lack of use. <ref><pubmed>10483809</pubmed></ref> Another consequence of the decreased muscle mass is an increased level of connective tissues and fat in order to assist the transfer of forces to the tendons.<ref><pubmed>15303112</pubmed></ref> Furthermore, the composition of muscle fibre types are transformed from a mix of type I and type II fibres to predominantly type II (fast twitch) muscle fibres. <ref name="PMID9755066"><pubmed>9755066</pubmed></ref> This is a result of the muscle no longer being used for endurance-type excersises.

=== Lab 8 - Peer Reviews ===

==== Group 1====
Group Assessment Criteria:
# ''The key points relating to the topic that your group was allocated are clearly described'' The introduction explains why the eye is important and lists the anatomical structures, however there is no indication that this project page is about the development of the eye!
# ''The choice of content, headings and sub-headings, diagrams, tables, graphs show a good understanding of the topic area''. The project predominantly focuses on the development of the eye, and goes into detail the development of each individual structure. There are also a lot of student-drawn images and diagrams of developmental stages which shows a good understanding of the topic area.
# ''Content is correctly cited and referenced''. There is no copyright notices for any of the images and they all lack explanations.
# ''The wiki has an element of teaching at a peer level using the student’s own innovative diagrams, tables or figures and/or using interesting examples or explanations''. The text is easy to understand and there are many student-drawn diagrams, which makes the content more interesting to read.
# ''Evidence of significant research relating to basic and applied sciences that goes beyond the formal teaching activities''. I would say the information provided satisfies the aims of the project, however the research does not go ‘beyond the formal teaching activities’ as it lacks additional information such as abnormalities, normal functioning etc.
# ''Relates the topics and content of the Wiki entry to learning aims of embryology.'' The contents and topics are strongly related to the learning aims of embryology.
# ''The content of the wiki should demonstrate to the reader that your group has researched adequately on this topic and covered the key areas necessary to inform your peers in their learning.'' All the content provided is well researched and relevant to the aims of the project. They key areas are well described.

Additional points:
* I feel that this page would benefit from a timeline or ‘weekly development’ table that briefly describes what structures are developed in each week. This would provide a good summary of the content as well as allow reader to be able to understand how the development of each structure relates to each other.
* Good referencing of images throughout project page – relating images to content
* Less paragraphs, more tables, bullet points, emphasize certain important points
* History & research sections look incomplete.

====Group 2====
Group Assessment Criteria:
# ''The key points relating to the topic that your group was allocated are clearly described.'' The introduction outlines the importance of the somatosensory system and provides a good summary of the developmental stages. More emphasis could be made on the key points of the project page.
# ''The choice of content, headings and sub-headings, diagrams, tables, graphs show a good understanding of the topic area.'' The content shows an understanding of the topic area, however the layout makes the text difficult to follow. There is not a clear connection between the ‘Central Somatosensory Differentiation’ and the somatosensory system. There is a lack of diagrams, tables and graphs to explain the written content.
# ''Content is correctly cited and referenced.'' Some sections are correctly referenced whilst others are completely lacking. This area needs working on.
# ''The wiki has an element of teaching at a peer level using the student’s own innovative diagrams, tables or figures and/or using interesting examples or explanations.'' The information is broken down well by headings and subheadings, however there is a lack of relating images to compliment the information. The one student drawn image is very useful.
# ''Evidence of significant research relating to basic and applied sciences that goes beyond the formal teaching activities.'' The information provided is well researched and satisfies the aims of the project in terms of developmental stages, however in order to go ‘beyond the formal teaching activities’ it needs to include sections such as abnormal development and more on the history, current and future research.
# ''Relates the topics and content of the Wiki entry to learning aims of embryology.'' The topics and content relate to the learning aims of embryology by describing the developmental stages if the somatosensory cortex.
# ''The content of the wiki should demonstrate to the reader that your group has researched adequately on this topic and covered the key areas necessary to inform your peers in their learning.'' There has been a fair amount of research into the topic, however a bulk of the information is focused on descriptions of each of the senses. More emphasis should be placed on the development of each of these sense as that is the key topic area.

Additional points:
* The Introduction and Central Somatosensory Differentiation sections were well written and the accompanying diagram was very useful.
* The layout of the page could be improved with the use of tables and diagrams to reduce/replace the amount of text
* The project seems largely incomplete; more research needs to go into the History and research sections and there is a lack of images

==== Group 4 ====
* '''Introduction''': The information is very interesting and provides a good overview of the olfactory system. The only improvement that could be made is clearly stating what content is going to be covered on this project page. Also, “The olfactory system are often '''divide''' into a peripheral mechanism”
* '''History of Discovery''': This sections presents a good summary of each research paper, detailing a background of the researchers and the importance of each discovery. Well done!
* '''Time line of developmental process''': This section shows a good depth of research and provides detailed descriptions of each stage of development. However, the information provided is quite complicated and would not be easily understood by peers. This could be overcome by the use of labeled diagrams or hand drawn images, which I can see is yet to come. Overall this is a well done section, the colors draw the readers attention and I like the use of bolded text to highlight important information.
* '''Anatomy of the Olfactory System & Normal Function''': This provides a good amount of information seeing as the focus of the page is about olfactory development, not the function & final structure. The only improvement could be providing an explanation in the figure provided.
* '''Congenital Abnormalities''': This section is well organized and includes all relevant content. Very interesting to read.
* '''Current Research''': A well researched section and coverage of content. Each paper is summarized and the importance of each discovery is made clear. It would be nice to include a direct link to each article.

====Group 5 ====
*'''Introduction:''' The introduction is quite well written and very detailed. Rather than going straight into details of development, perhaps first make it clear from the exactly what this project page is about and what content you will be covering. There are also some grammatical errors, such as “treatments or cures ‘’’maybe’’’ developed in the future and these conditions can be better managed.” Maybe = may be
* '''Normal eye development:''' This section shows a good depth of research, is strongly related to the aims of the embryology course and shows a good depth of research. Improvements could be made by the use of bullet points, tables or bold text to highlight key points. Also, labeled images or hand-drawn diagrams would go well to compliment the text.
* '''Abnormal Development:''' There is a good depth of research and it is well written. The use of headings, figures and italics makes it easy to follow the flow of information. Improvements could be made by providing more information about the diseases, for example, what is Peters' anomaly (Corneal Opacity) and aniridia (lack of Iris)? Is it curable? What are methods of detection? How will it effect the future baby?
*'''Ocular Manifestations:''' This section seems incomplete; or maybe its just poorly organized? What are the two separate sections? Is this related to the sections that follow?
* '''Research Time line:''' This is a good time line, however only one source has been used. This provides a good summary of significant discoveries, but it has not been explained why these discoveries were important or how it is relevant to the development of the eye.
* '''New Research Development:''' This section is well researched, however the poor structuring and layout of the information makes it difficult to read and follow. For example there are many headings and subheadings however it is unclear what sections of information are grouped together. The images draw the readers attention and there seems to be a good depth of research into the topic.
*'''Group Assessment Criteria:''' The key points relating to the topic that your group was allocated are clearly described in the introduction. The choice of content and depth of research shows a good understanding of the topic area, however the information could be better organized by the use of tables, bullet points and bolded text to highlight key points. The content is correctly cited and referenced. Most sections are well paraphrased for teaching at a peer level, however the use of hand-drawn diagrams and/or labeled images could enhance the information in the text. The information covered is strongly related the the learning aims of embryology.

====Group 6====
Group Assessment Criteria:
# ''The key points relating to the topic that your group was allocated are clearly described.'' The introduction clearly outlines the key points of the project and the content is well described in the text.
# ''The choice of content, headings and sub-headings, diagrams, tables, graphs show a good understanding of the topic area.'' The choice of content and headings shows a good depth of research and understanding of the topic area. The ‘Summary of the inner ear’ table was a good idea and ties in all the information nicely.
# ''Content is correctly cited and referenced.'' There are large paragraphs of texts that have no references. The images provided display the copyright notices and explanations.
# ''The wiki has an element of teaching at a peer level using the student’s own innovative diagrams, tables or figures and/or using interesting examples or explanations.'' The introduction is well written and catches the readers interest and attention. Most of the normal development section is easy to understand, however the abnormalities section is difficult to understand due to the scientific jargon. Some hand-drawn images and tables would be beneficial in order to reduce the large paragraphs of text.
# ''Evidence of significant research relating to basic and applied sciences that goes beyond the formal teaching activities.'' The amount of information provided is evidence of the significant research that went into this project, and the sections such as ‘Technologies to overcome the problems’ shows research that goes ‘beyond the formal teaching activities’.
# ''Relates the topics and content of the Wiki entry to learning aims of embryology.'' The topics and content are well related to the learning aims of embryology
# ''The content of the wiki should demonstrate to the reader that your group has researched adequately on this topic and covered the key areas necessary to inform your peers in their learning.'' All the content is relevant to the key areas of the development of the eye and demonstrates an extensive amount of research into the topic.

Additional points:
* The amount of text is overwhelming. You should make better use of tables, figures and diagrams to breakup/replace the text.
* Adult anatomy and histology: no reference to histology. Would be beneficial to have a brief explanation of the functions of each structure.
* Overall impression: Very well researched topic and I'm sure the use of tables, pictures and diagrams will make it more appealing to read!

==References==

<references/>

User:Z3289738

2012-09-25T03:59:56Z

Z3289738: /* b) Assessment */

==Lab Attendance==
Lab 1: --[[User:Z3289738|Z3289738]] 11:49, 25 July 2012 (EST)

Lab 2: --[[User:Z3289738|Z3289738]] 10:12, 1 August 2012 (EST)

Lab 3: --[[User:Z3289738|Z3289738]] 10:08, 8 August 2012 (EST)

Lab 4: --[[User:Z3289738|Z3289738]] 10:20, 15 August 2012 (EST)

Lab 5: --[[User:Z3289738|Z3289738]] 10:13, 22 August 2012 (EST)

Lab 6: --[[User:Z3289738|Z3289738]] 10:16, 29 August 2012 (EST)

Lab 7: --[[User:Z3289738|Z3289738]] 10:27, 12 September 2012 (EST)

Lab 8: --[[User:Z3289738|Z3289738]] 10:30, 19 September 2012 (EST)

==Individual Assessments==
===Lab 1 Assessment===

''Q1. Identify the origin of In Vitro Fertilization and the 2010 nobel prize winner associated with this technique and add a correctly formatted link to the Nobel page.''

The idea of In Vitro Fertilization began to formulate in the 1890s, when Walter Heape reported the first known case of embryo transplantation in rabbits. In 1953 John Rock extracted the first intact human fertilized egg. The first successful attempt at IVF was in 1978 by Steptoe and Edward.

Robert G. Edwards, the physiologist who developed the In Vitro Fertilization treatment, was awarded the Nobel Prize in Physiology or Medicine in 2010. [http://www.nobelprize.org/nobel_prizes/medicine/laureates/2010/press.html/# Nobel Prize Page]

''Q2. Identify and add a PubMed reference link to a recent paper on fertilization and describe its key findings (1-2 paragraphs).''

This article looks into the process of embryo implantation. It demonstrates how the activation of the epithelial Na(+) channel triggers prostoglandin E(2) release,phosphorylation of teh transcription factor CREB and upregulation of cyclooxygenase 2, the enzyme required for prostaglandin production and implantation. They detected maximum Epithelial Na(+) channel activation at the time of implantation in mice, and that blocking or knocking down this channel in mice resulted in failure to implant. These results indicate the importance of the Epithelial Na(+) Channel in the process of implantation, and the consequences of defects such as miscarriage and low success rates in IVF.

<pubmed> 22729284</pubmed>

===Lab 2 Assessment===
''Q1. Upload an image from a journal source relating to fertilization or the first 2 weeks of development as demonstrated in the practical class. Including in the image “Summary” window: An image name as a section heading, Any further description of what the image shows, A subsection labeled “Reference” and under this the original image source, appropriate reference and all copyright information and finally a template indicating that this is a student image.

[[File:Z3289738 ANAT Lab 2.jpg|200px|thumb|right|Zygotes showing different distribution of NPB in the 2PN and different PB aligment]]

''Q2. Identify a protein associated with the implantation process, including a brief description of the protein's role (1-2 paragraphs)''

'''Trophinin'''

Trophinin is an membrane adhesive protein expressed on human trophoblastic cells and on uterine endometrium epithelial cells. The protein mediates apical cell adhesion and activate trophectoderm cells for implantation via proliferation and invasion. <ref><pubmed>17487845</pubmed></ref>

===Lab 3 Assessment===

''Q1. Identify the difference between "gestational age" and "post-fertilisation age" and explain why clinically "gestational age" is used in describing human development.''

"Gestational age" is measured from the first day of the woman's last menstrual cycle, whereas "post-fertilisation age" measures the time passed since fertilization of the oocyte. Gestational age is more clinically relevant as it is easier to determine the date of the woman's last menstrual cycle than it is to determine the date of fertilization. Furthermore, gestational age can also be determined before and after birth by measuring the size of the head, thigh bone and abdomen (before birth), and the size of the head and weight after birth. Gestational age is therefore used to determine the infant's medical history and medical plan.

''Q2. Identify using histological descriptions at least 3 different types of tissues formed from somites.''

Somites differentiate to form: (1) '''the axial skeleton (vertebral body & inter-vertebral disk)''', (2) '''dermis''' and (3) '''skeletal muscle'''.

# Cells in the ventromedial half of each somite differentiate into the sclerotome via Sonic hedgehog signalling mechanisms. The Pax 1 transcription factor then converts the sclerotome into chondrocytes (cartilage), which is essential for the functioning of the vertebral column.
# Cells in the dorsolateral portion of the somites differentiate to form the dermomyotone. This is then divided into:
## Dorsal dermatome which later contributes to the formation of the dermis in response to neutropin 3 factors.
## Wnt1 and Wnt3 factors contribute to the formation of the ventral myotome, which is further split into the epaxial myotome (gives rise to erector spinae muscles) and the hypaxial myotome (gives rise to the muscles of the trunk and limbs).

===Lab 4 Assessment===

''Q1. Identify the 2 invasive prenatal diagnostic techniques related to the placenta and 2 abnormalities that can be identified with these techniques.''
# '''Chorionic villus sampling''' (CVS)is an invasive prenatal diagnostic technique that is used to detect genetic abnormalities such as Down syndrome or cystic fibrosis. During the procedure a sample of the placenta is removed via a needle through the abdomen and then examined in a laboratory. It is commonly performed between 10 and 12 weeks of pregnancy/
# '''Amniocentesis''' procedures involve collecting samples of amniotic fluid via a needle through the abdomen to check for genetic abnormalities such as Down syndrome, cystic fibrosis or spina bifida.

''Q2. Identify a paper that uses cord stem cells therapeutically and write a brief (2-3 paragraph) description of the paper's findings.''

F. Ramirez, D. Steenblock, A. Payne and L. Darnall (2006) '''Umbilical Cord Stem Cell Therapy for Cerebral Palsy'''. MED HYPOTHESES RES 3: 679-686 [http://www.journal-mhr.com/PDF_Files/vol_3_2/3_2_PDFs/3_2_2.pdf | Umbilical Cord Stem Cell Therapy for Cerebral Palsy]

This article describes a six month study to evaluate the effectiveness of umbilical cord stem cells in treatment for various brain injuries and disorders, in particular Cerebral Palsy. The study began in 2004, whereby 8 children between the ages of 3-12 who had been diagnosed with Cerebral Palsy underwent transplants with 1.5 million umbilical cord stem cells. The study reported eight of of eight children showed some improvement in mobility and/or cognitive function. Furthermore, one aphasic child started talking again and another who had been blind since birth was able to see after post-treatment.

The results from this preliminary observational pilot study suggests that umbilical cord stem cells may be a safe and promising treatment for children with cerebral palsy.

===Lab 7===
====a) Class exercises====
1. Maturation Hypertrophy - In your groups, design a method to estimate the degree of hypertrophy that occurs during the transition from birth to adulthood. Use the rulers to make rough measurements on the screen and then estimate the degree of hypertrophy as a mean increase in fibre size. Discuss the result as a class. (ie Try estimate the degree of hypertrophy from child to adult cells)

Method: Measured area of the child and adult cells, found an average for each and then worked out the percentage increase.

Answer: 7x increase in area size.

2. The role of satellite cells in muscle hypertrophy - class discussion of data presented in a recent paper - McCarthy et al. 2011. (ie How to we achieve hypertrophy? How do we get proteins into the cells? Degeneration of the myonucleus - Can activate the satellite cells as if the cell is undergoing repair; the nuclei within the cells becomes more active, produces more RNA and the cells get bigger.)

3. Fibre type shift - Discuss an experiment on fiber type shift that has been induced by chronic low frequency stimulation - Martins et al. 2006

====b) Assessment====
''Q1. (a) Provide a one sentence definition of a muscle satellite cell.''

Satellite cells are quiescent stem cells present in adult muscle tissue between the basal lamina of a muscle fiber and are responsible for postnatal hypertrophy and regeneration. <ref><pubmed>16243526</pubmed></ref>

''Q1. (b) In one paragraph, briefly discuss two examples of when satellite cells are activated?''

These cells are normally quiescent in adult muscle, by are activated in response to injury and muscle disease. When activated, the cells begin to proliferate and after aligning they fuse to allow for repair and/or regenration of muscle fibres. Satellite cells assist in the regeneration of muscle tissues in response to muscle injury by either forming multinucleated myotubes or additional quiescent satellite cells. <ref><pubmed>21849021</pubmed></ref>. Furthermore, studies have provided evidence of an increased level of satellite cells in muscular diseases such as Duchenne muscular dystrophy (DMD). <ref><pubmed>16818602</pubmed></ref>

''Q2. In one brief paragraph, describe what happens to skeletal muscle fibre type and size when the innervating motor nerve sustains long term damage such as in spinal cord injury?''

Spinal cord injuries which lead to long term damage to the innervating motor nerve would result in muscle partial or complete paralysis of muscles, leading to muscle atrophy. <ref><pubmed>16940987</pubmed></ref> This results in a significant decrease in cross-sectional area of the immobilized muscle do to lack of use. <ref><pubmed>10483809</pubmed></ref> Another consequence of the decreased muscle mass is an increased level of connective tissues and fat in order to assist the transfer of forces to the tendons.<ref><pubmed>15303112</pubmed></ref> Furthermore, the composition of muscle fibre types are transformed from a mix of type I and type II fibres to predominantly type II (fast twitch) muscle fibres. <ref name="PMID9755066"><pubmed>9755066</pubmed></ref> This is a result of the muscle no longer being used for endurance-type excersises.

=== Lab 8 - Peer Reviews ===

==== Group 1====
Group Assessment Criteria:
# ''The key points relating to the topic that your group was allocated are clearly described'' The introduction explains why the eye is important and lists the anatomical structures, however there is no indication that this project page is about the development of the eye!
# ''The choice of content, headings and sub-headings, diagrams, tables, graphs show a good understanding of the topic area''. The project predominantly focuses on the development of the eye, and goes into detail the development of each individual structure. There are also a lot of student-drawn images and diagrams of developmental stages which shows a good understanding of the topic area.
# ''Content is correctly cited and referenced''. There is no copyright notices for any of the images and they all lack explanations.
# ''The wiki has an element of teaching at a peer level using the student’s own innovative diagrams, tables or figures and/or using interesting examples or explanations''. The text is easy to understand and there are many student-drawn diagrams, which makes the content more interesting to read.
# ''Evidence of significant research relating to basic and applied sciences that goes beyond the formal teaching activities''. I would say the information provided satisfies the aims of the project, however the research does not go ‘beyond the formal teaching activities’ as it lacks additional information such as abnormalities, normal functioning etc.
# ''Relates the topics and content of the Wiki entry to learning aims of embryology.'' The contents and topics are strongly related to the learning aims of embryology.
# ''The content of the wiki should demonstrate to the reader that your group has researched adequately on this topic and covered the key areas necessary to inform your peers in their learning.'' All the content provided is well researched and relevant to the aims of the project. They key areas are well described.

Additional points:
* I feel that this page would benefit from a timeline or ‘weekly development’ table that briefly describes what structures are developed in each week. This would provide a good summary of the content as well as allow reader to be able to understand how the development of each structure relates to each other.
* Good referencing of images throughout project page – relating images to content
* Less paragraphs, more tables, bullet points, emphasize certain important points
* History & research sections look incomplete.

====Group 2====
Group Assessment Criteria:
# ''The key points relating to the topic that your group was allocated are clearly described.'' The introduction outlines the importance of the somatosensory system and provides a good summary of the developmental stages. More emphasis could be made on the key points of the project page.
# ''The choice of content, headings and sub-headings, diagrams, tables, graphs show a good understanding of the topic area.'' The content shows an understanding of the topic area, however the layout makes the text difficult to follow. There is not a clear connection between the ‘Central Somatosensory Differentiation’ and the somatosensory system. There is a lack of diagrams, tables and graphs to explain the written content.
# ''Content is correctly cited and referenced.'' Some sections are correctly referenced whilst others are completely lacking. This area needs working on.
# ''The wiki has an element of teaching at a peer level using the student’s own innovative diagrams, tables or figures and/or using interesting examples or explanations.'' The information is broken down well by headings and subheadings, however there is a lack of relating images to compliment the information. The one student drawn image is very useful.
# ''Evidence of significant research relating to basic and applied sciences that goes beyond the formal teaching activities.'' The information provided is well researched and satisfies the aims of the project in terms of developmental stages, however in order to go ‘beyond the formal teaching activities’ it needs to include sections such as abnormal development and more on the history, current and future research.
# ''Relates the topics and content of the Wiki entry to learning aims of embryology.'' The topics and content relate to the learning aims of embryology by describing the developmental stages if the somatosensory cortex.
# ''The content of the wiki should demonstrate to the reader that your group has researched adequately on this topic and covered the key areas necessary to inform your peers in their learning.'' There has been a fair amount of research into the topic, however a bulk of the information is focused on descriptions of each of the senses. More emphasis should be placed on the development of each of these sense as that is the key topic area.

Additional points:
* The Introduction and Central Somatosensory Differentiation sections were well written and the accompanying diagram was very useful.
* The layout of the page could be improved with the use of tables and diagrams to reduce/replace the amount of text
* The project seems largely incomplete; more research needs to go into the History and research sections and there is a lack of images

==== Group 4 ====
* '''Introduction''': The information is very interesting and provides a good overview of the olfactory system. The only improvement that could be made is clearly stating what content is going to be covered on this project page. Also, “The olfactory system are often '''divide''' into a peripheral mechanism”
* '''History of Discovery''': This sections presents a good summary of each research paper, detailing a background of the researchers and the importance of each discovery. Well done!
* '''Time line of developmental process''': This section shows a good depth of research and provides detailed descriptions of each stage of development. However, the information provided is quite complicated and would not be easily understood by peers. This could be overcome by the use of labeled diagrams or hand drawn images, which I can see is yet to come. Overall this is a well done section, the colors draw the readers attention and I like the use of bolded text to highlight important information.
* '''Anatomy of the Olfactory System & Normal Function''': This provides a good amount of information seeing as the focus of the page is about olfactory development, not the function & final structure. The only improvement could be providing an explanation in the figure provided.
* '''Congenital Abnormalities''': This section is well organized and includes all relevant content. Very interesting to read.
* '''Current Research''': A well researched section and coverage of content. Each paper is summarized and the importance of each discovery is made clear. It would be nice to include a direct link to each article.

====Group 5 ====
*'''Introduction:''' The introduction is quite well written and very detailed. Rather than going straight into details of development, perhaps first make it clear from the exactly what this project page is about and what content you will be covering. There are also some grammatical errors, such as “treatments or cures ‘’’maybe’’’ developed in the future and these conditions can be better managed.” Maybe = may be
* '''Normal eye development:''' This section shows a good depth of research, is strongly related to the aims of the embryology course and shows a good depth of research. Improvements could be made by the use of bullet points, tables or bold text to highlight key points. Also, labeled images or hand-drawn diagrams would go well to compliment the text.
* '''Abnormal Development:''' There is a good depth of research and it is well written. The use of headings, figures and italics makes it easy to follow the flow of information. Improvements could be made by providing more information about the diseases, for example, what is Peters' anomaly (Corneal Opacity) and aniridia (lack of Iris)? Is it curable? What are methods of detection? How will it effect the future baby?
*'''Ocular Manifestations:''' This section seems incomplete; or maybe its just poorly organized? What are the two separate sections? Is this related to the sections that follow?
* '''Research Time line:''' This is a good time line, however only one source has been used. This provides a good summary of significant discoveries, but it has not been explained why these discoveries were important or how it is relevant to the development of the eye.
* '''New Research Development:''' This section is well researched, however the poor structuring and layout of the information makes it difficult to read and follow. For example there are many headings and subheadings however it is unclear what sections of information are grouped together. The images draw the readers attention and there seems to be a good depth of research into the topic.
*'''Group Assessment Criteria:''' The key points relating to the topic that your group was allocated are clearly described in the introduction. The choice of content and depth of research shows a good understanding of the topic area, however the information could be better organized by the use of tables, bullet points and bolded text to highlight key points. The content is correctly cited and referenced. Most sections are well paraphrased for teaching at a peer level, however the use of hand-drawn diagrams and/or labeled images could enhance the information in the text. The information covered is strongly related the the learning aims of embryology.

====Group 6====
Group Assessment Criteria:
# ''The key points relating to the topic that your group was allocated are clearly described.'' The introduction clearly outlines the key points of the project and the content is well described in the text.
# ''The choice of content, headings and sub-headings, diagrams, tables, graphs show a good understanding of the topic area.'' The choice of content and headings shows a good depth of research and understanding of the topic area. The ‘Summary of the inner ear’ table was a good idea and ties in all the information nicely.
# ''Content is correctly cited and referenced.'' There are large paragraphs of texts that have no references. The images provided display the copyright notices and explanations.
# ''The wiki has an element of teaching at a peer level using the student’s own innovative diagrams, tables or figures and/or using interesting examples or explanations.'' The introduction is well written and catches the readers interest and attention. Most of the normal development section is easy to understand, however the abnormalities section is difficult to understand due to the scientific jargon. Some hand-drawn images and tables would be beneficial in order to reduce the large paragraphs of text.
# ''Evidence of significant research relating to basic and applied sciences that goes beyond the formal teaching activities.'' The amount of information provided is evidence of the significant research that went into this project, and the sections such as ‘Technologies to overcome the problems’ shows research that goes ‘beyond the formal teaching activities’.
# ''Relates the topics and content of the Wiki entry to learning aims of embryology.'' The topics and content are well related to the learning aims of embryology
# ''The content of the wiki should demonstrate to the reader that your group has researched adequately on this topic and covered the key areas necessary to inform your peers in their learning.'' All the content is relevant to the key areas of the development of the eye and demonstrates an extensive amount of research into the topic.

Additional points:
* The amount of text is overwhelming. You should make better use of tables, figures and diagrams to breakup/replace the text.
* Adult anatomy and histology: no reference to histology. Would be beneficial to have a brief explanation of the functions of each structure.
* Overall impression: Very well researched topic and I'm sure the use of tables, pictures and diagrams will make it more appealing to read!

==References==

<references/>

Talk:2012 Group Project 4

2012-09-25T03:54:37Z

Z3289738:

{{2012GroupDiscussion}}

--[[User:Z8600021|Mark Hill]] 09:59, 18 September 2012 (EST) This is a recent review on smell. http://jcb.rupress.org/content/191/3/443.full JCB content allows reuse.

Not for reuse but good reading - [http://www.ncbi.nlm.nih.gov/books/NBK55980 The Neurobiology of Olfaction]

==Group evaluation==

The introduction was very interesting to read - 1000 genes related to olfactory system is amazing. The introduction isn't too long which is great. However, it would be good to include in text citations. Where did you get your information from?

The history section will look better if it was put into a table.

The 'Timeline of Development process' is excellent because it clearly presents so much information with respect to the time the differentiations took place. I can't wait to see the images though because some of the concepts were hard to understand without visual aids. For example, 'specialized areas in rostrolateral regions of head of olfactory placodes' - where is that on the embryo?

The normal function section was short. This is nice to see because this project is about development, not about the function. It would be good to include a diagram of the signaling pathway in this section, just to make it interesting.

The structure section needs a bit more information. Maybe put the olfactory bulb image in this section as it relates more to structure. You can also put some images of the cribiform plate in here too.

Abnormality section on Kallmann's syndrome was very well written. It had lots of detail, presented clearly in point form. Can you describe some of the other diseases in just as much detail as well? It just seems like Kallmann's syndrome is the main disease and there's not a lot of focus in other abnormalities.

In current research, 'the 'role of Odorant receptors' need to have some text and content in that section, not just the reference.

--[[User:Z3332863|Z3332863]] 16:58, 23 September 2012 (EST)

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Your introduction is good and gives a brief overview of what the olfactory system entails. There were a few spelling mistakes, which can easily be corrected. Make sure you do tell the reader what you will be discussing on your page – development of the olfactory system and the particular subheadings you will focus on. The image could do with a few more labels for orientation, but besides that it complements the text and contains the correct citation, student template, etc.

The history section is good and quite extensively researched. Most groups will provide the history in a table, with dates in chronological order (to clearly show history and developing knowledge over time). This might be something to think about. I would suggest a ‘date – description – significant person’ type of format for a table. Good image, but it is displayed next to Pearson instead of Kollman. It is also difficult to see what it is and read the labels without opening the larger version, so you might want to increase its size slightly. Because this is a student image I would like to see the original – if possible provide a link to the Atlas of the Development of Man 2.
You should also explain what Kallmann’s Syndrome actually is, because this seems a little vague.

Your timeline of developmental process looks amazing and is enjoyable to read. Some of your words are printed in bold and link to the glossary. In one of your next sections the words link directly to the glossary, so you should probably do he same thing here. I really hope you can add pictures to this table to complement your text! Not quite sure what the line at the bottom (SINUSES:A:…) is doing there… either delete or expand upon this.

Structure: you only have a link here. Please provide text and image to explain the structure briefly. The YouTube link should be there to help the reader understand this section, instead of being the only thing this section is made up of. The video is not your own work, so please add your own work to this!

The normal function section was alright. It has some useful information in there, however, only a single reference listed at the end. It seemed like more references should be included within the paragraph. I would also include the fact that depolarization is an all-or-nothing response. The threshold needs to be reached for depolarization to occur, but there is no build-up over time to reach this threshold. It has to happen at that one instance. The links should be listed under the heading ‘external links’ or, if used as references, incorporated as proper references within the text. The olfactory bulb image is a little small and the description is quite brief. Though, good citation of the source and a student template is present.
I think the olfactory bulb image and the epithelium image should be included in the ‘structure’ section.

The abnormality section includes Kallmann’s syndrome and a quick definition has finally been provided! Please include this in the history section too. This section was a joy to read! Very interesting! A lot of effort has been put into the research and references have been done very well. I assume OB stands for olfactory bulb – please indicate this in the text. The dotpoints listed in the ‘clinical features’ section could do with a brief explanations instead of me having to scroll up and down between the text and the glossary. The image is excellent and shows a good simplified concept of what happens. Good descriptions, source citations, etc are added too. It was good to see diagnosis and treatment included.

Current research starts with a link, which seems quite random – include this in the external links section. You found some interesting and current research. References are only listed at the end of each paragraph, but should probably be included within as well. The image relates to one of the projects and descriptions are appropriate. Nothing has been added to the ‘role of odorant receptors’ though (apart from a reference). Please add a brief paragraph to this section.

Terms should be added to the glossary. The reference list also needs checking, because some are the same (eg. 11 & 12) and others do not have a reference (eg. 7 & 17).

Hope this helps!
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The introduction is quite small but very precise, indicating the function and the components of the olfactory system but maybe include one or two sentences in the introduction telling readers that it is actually about the development of the olfactory system, not just the function and components of it. After all, introduction is meant to show others what your project is about. The hand-drawn image there is very nice but maybe more information need to be provided other than just labelling parts of it. Along with the image, there are the important informations such as the copyright notice which is good to see.

The history of discoveries section is very well-researched but it will be easier to read if it was in a table. The timeline, i thought was very good because there are a lot of useful information about the development of olfaction which relates to the research topic. The developmental process is explained in quite simple terms but i notice some of the scientific terms in the timeline are not explained in the glossary, this makes it a little bit hard to understand the whole process. It is very interesting that a youtube link has been included in the structure section, this is really a good peer teaching but make sure you referenced the video correctly to avoid plagiarism. The section on Kallman's syndrome is quite interesting but the structure of that section is a bit messy, maybe try clarifying and tidy it up a lit. But i can see that a lot of research effort has been put into it which is good and the variety of resources used in the section is very broad. More images should be put here because right now, there is just a huge block of text in the section. Images will balance out the heavy text load and attract readers more.

The current research section contains a lot of useful information and it relates to the research topic well. Again, images should be put here because right now, there are just small blocks of text in the section without any images, this maybe a little bit boring for readers.

Overall, the project looks well-researched and relates pretty well to the research topic. The balance of the images and text still needs to be fixed but in terms of the text and information on the page, i think it is pretty sufficient and in-depth especially the timeline of development and current research section. There are some terms in the glossary which is good but maybe more terms should be added. The structure of the page is good, very easy to follow. There are a few external links which is always good to put there for anyone that are interested by the topic and want some further information about it. Referencing is good, there is only one minor citing error (no.7), but it should be easy to fix. Hope this helps :)

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The introduction provides a good overview to the topic and the associated images have all the appropriate referencing information.

The history section is interesting and well researched with good use of subheadings.

The timeline of development is very useful and informative however is quite text-heavy, some diagrams may be able to help here.

The anatomy and normal function sections don't add very much to the page, especially in terms of embryological development. Adding more to these sections may help.

The abnormalities section is good, with a lot of information on Kallmann's syndrome, however other abnormalities (if there are any?) could be included to expand this section.

The current research section contains a lot of information in a small amount of space. It is quite jargon-heavy although this might not be able to be avoided. The subheadings are good as they act to split this section into discrete units.

The glossary and external links are very good, and the references are extensive which is good.

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* '''Introduction''': The information is very interesting and provides a good overview of the olfactory system. The only improvement that could be made is clearly stating what content is going to be covered on this project page. Also, “The olfactory system are often ‘’’divide’’’ into a peripheral mechanism”
* '''History of Discovery''': This sections presents a good summary of each research paper, detailing a background of the researchers and the importance of each discovery. Well done!
* '''Time line of developmental process''': This section shows a good depth of research and provides detailed descriptions of each stage of development. However, the information provided is quite complicated and would not be easily understood by peers. This could be overcome by the use of labeled diagrams or hand drawn images, which I can see is yet to come. Overall this is a well done section, the colors draw the readers attention and I like the use of bolded text to highlight important information.
* '''Anatomy of the Olfactory System & Normal Function''': This provides a good amount of information seeing as the focus of the page is about olfactory development, not the function & final structure. The only improvement could be providing an explanation in the figure provided.
* '''Congenital Abnormalities''': This section is well organized and includes all relevant content. Very interesting to read.
* '''Current Research''': A well researched section and coverage of content. Each paper is summarized and the importance of each discovery is made clear. It would be nice to include a direct link to each article.

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== External Links ==

Hey team... make sure you check the links i added to the external link section. They are great resources to use in your sections.

[[User:Z3333427|Z3333427]] 10:19, 21 August 2012 (EST)

== Group Topic Selection ==

So we have a choice between:

stem cells

Neuronal development

Sensory development

I personally don't have a particular preference but I think neural or sensory would be something different to touch on since there's still so much progressing research in the field.

'''Hey all :-). Thanks for getting the ball rolling. I like the latter two options, in particular neuronal development - from there we can pick a certain aspect and explore not only normal development but perhaps research complications and genes/factors implicated when things go wrong.
p.s. It would be great if we could figure out a regular time to meet during the week outside the lab so we can properly discuss and share our research'''

Just a heads up- Mark preferred that we don't put our names up anywhere on the wikipage for privacy purposes!

'''sensory system'''
hello everyone, it seems like the options we had chosen for sensory were picked before we had a chance and therefore I have asked Dr Hill for us to do the "hearing" system. I don't mind changing if the group chooses to do so, however, I thought it would be a good idea to have a topic locked in. Please let me know if you want to do a different topic

--[[User:Z3333427|Z3333427]] 11:32, 14 August 2012 (EST)

=Designation of parts=

There must be an addition of current research and technologies in each area

Make sure this is not presented as an essay (balance text and writing with images, tables etc)

Possibly a history of the development of understanding

[[User:Z3331264|Z3331264]] 11:54, 15 August 2012 (EST) Timeline and processes of development

--[[User:Z3374215|Z3374215]] 11:59, 15 August 2012 (EST)I would like to do a history section and the introduction

Please identify which part you want to be responsible for, keep in mind that you can work at any topic you would like.

Introduction: Andrew

History: Libby

Abnormalities: Stephanie

Future research: Libby (future research on normal function) Stephanie (future research on abnormalities/treatments)

Timeline: [[User:Z3331264|Z3331264]] 20:18, 22 August 2012 (EST)

==Progress of individual tasks and project queries==

[[User:Z3331264|Z3331264]] 20:18, 22 August 2012 (EST): I will be creating a table to indicate the timeline of development of olfaction during embryonic development. I will make changes to the initial table as I go along so as to avoid not contributing any online material until the end.

--[[User:Z3333427|Z3333427]] 00:58, 25 August 2012 (EST)The table is a really good idea, we should probably have at least another one as information becomes much more organised. Just to let you know that I changed it to Carnegie stages as most sources organise their information based on those stages, and keep in mind that the placodes dont form until week 11 or 12, so there is no need to have stages 1-10.

--[[User:Z3374215|Z3374215]] 17:52, 27 August 2012 (EST) I've got some information on historical developments but information is really difficult to find. I've made some progress but not sure how much more there is that I can do. In light of that I might also take a look at the subheading "Structure". It's referring to the physical structure of the developing olfactory system?

--[[User:Z3331264|Z3331264]] 19:33, 27 August 2012 (EST) Carnegie stages are a good idea! I also think its important to include a brief description of the development of the anatomy of the nose (turbinates etc) as well as a bit about the brain development in the locations of the olfactory nerve. Don't freak out when you read my additions, I do my research gradually, which means I will first add what I found in the textbook and then later on fill in the gaps plus add a research dimension with current lit.

--[[User:Z3333038|Z3333038]] 10:09, 29 August 2012 (EST) Hi all, you heard it from Mark today but just restating, even when doing draft work you must reference properly as you go along or you will be penalised.

--[[User:Z3331264|Z3331264]] 11:22, 29 August 2012 (EST) Decided to just stick to weeks rather than carnegie stages because sometimes between carnegies stages, little events occur which will make the table larger and more confusing!

--[[User:Z3333038|Z3333038]] 18:01, 29 August 2012 (EST) Hey Libby, I found a review article which contains a brief history on olfaction abnormalities in development in the introduction: http://www.springerlink.com.wwwproxy0.library.unsw.edu.au/content/288u546105v08575/fulltext.pdf

--[[User:Z3333038|Z3333038]] 19:26, 29 August 2012 (EST) Hi all, just letting you know im working through pathophysiology for Kallmann's syndrome on a word document at the moment and will post some as I go online to document progress. Currently working on a diagram demonstrating the abnormalities in the olfactory bulb neuronal connections.

--[[User:Z3333038|Z3333038]] 21:18, 30 August 2012 (EST) Completed my diagram and have uploaded it with referencing. I based my diagram on an image from a review article which I have referenced - have emailed Dr. Hill to check that all is alright in terms of copyright.

--[[User:Z3331264|Z3331264]] 22:25, 4 September 2012 (EST) : Hey everyone, this is the html code to add to your parts whenever you wish to place a link of a word to the glossary:

[[#Glossary |'''put the word you want linked to glossary here''']]

--[[User:Z3374215|Z3374215]] 17:18, 5 September 2012 (EST) Hi Stephanie, I found an interesting article about abnormal development of the olfaction bulb of mice when exposed to alcohol. Don't know if you'd seen it. http://www.ncbi.nlm.nih.gov/pubmed/21736737

I also read that article! Pretty interesting stuff

[[User:Z3333427|Z3333427]] 17:48, 7 September 2012 (EST) That is a good idea, please email Dr. Hill if you are unsure about anything as huge penalties apply for ignoring copyright. By the way our group project is looking good, more diagrams and tables similar to the one we have now would be great.

--[[User:Z3333038|Z3333038]] 08:21, 11 September 2012 (EST) Thanks for the article :-). I will add it to a section on congenital anosmia. I emailed him and he said it was absolutely fine, as long as I referenced my source information.

--[[User:Z3374215|Z3374215]] 12:00, 12 September 2012 (EST) Just a note to myself more than anything. I need to reference Julius Kollmann's textbook in the history section and add a diagram.

--[[User:Z3333038|Z3333038]] 20:12, 14 September 2012 (EST) Loving the page team! The drawings are great! Nearly finished my bit, just have to add a brief paragraph for the other congenital abnormalities and one more research article.

--[[User:Z3333038|Z3333038]] 22:35, 14 September 2012 (EST)Hey Libby I found this website for timeline/history: http://www.medlink.com/medlinkcontent.asp...it talks about discoveries of congenital olfactory defects.
--[[User:Z3333038|Z3333038]] 09:15, 15 September 2012 (EST)Completed abnormalities and submitted 3 current research articles. Happy to take on extra parts.

--[[User:Z3374215|Z3374215]] 12:06, 15 September 2012 (EST) Thanks Stephanie that site looks great! I'll check it out soon.

--[[User:Z3333038|Z3333038]] 11:06, 19 September 2012 (EST) Important! Hey guys, we really need to work on the development of each structure and the genes involved. Who can help me out?

--[[User:Z3333038|Z3333038]] 11:47, 19 September 2012 (EST)Note to self: Make section on external links.

--[[User:Z3331264|Z3331264]] 17:49, 20 September 2012 (EST) The table that I included walks through the timeline of development. I have slowly been adding more and more research including genes involved in patterning. But at the same time, I don't want to dive into too much information in order to maintain the balance between text and images. I have figured out a way to do this without making it all seem too simple, so just bear with me for the next week and you'll see it tie in well. Cheers

--[[User:Z3333038|Z3333038]] 09:52, 25 September 2012 (EST) I have stumbled across an extra abnormality - although it is more a structural defect rather than a sensory defect, it still relates to olfaction so I have added it in. Will keep it brief though as whilst it is a common nasal abnormality, it is not so much a sensory one. Also, Z3374215 and I are concerned - are you two alright with your parts? We know, like the rest of us you have other assessments but it's been a long while since we've seen any major contribution - if you're stuck we are happy to give you a hand.