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	<title>Embryology - User contributions [en-gb]</title>
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	<updated>2026-05-12T22:31:18Z</updated>
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		<id>https://embryology.med.unsw.edu.au/embryology/index.php?title=User:Z3330795&amp;diff=107556</id>
		<title>User:Z3330795</title>
		<link rel="alternate" type="text/html" href="https://embryology.med.unsw.edu.au/embryology/index.php?title=User:Z3330795&amp;diff=107556"/>
		<updated>2012-10-17T03:45:04Z</updated>

		<summary type="html">&lt;p&gt;Z3330795: /* &amp;quot; lab 7 assessment &amp;quot; */&lt;/p&gt;
&lt;hr /&gt;
&lt;div&gt;==Lab Attendance ==&lt;br /&gt;
Lab 1&lt;br /&gt;
&lt;br /&gt;
Lab 2&lt;br /&gt;
&lt;br /&gt;
Lab 3&lt;br /&gt;
&lt;br /&gt;
Lab 4&lt;br /&gt;
&lt;br /&gt;
Lab 5&lt;br /&gt;
&lt;br /&gt;
Lab 6&lt;br /&gt;
&lt;br /&gt;
Lab 7--[[User:Z3330795|Z3330795]] 10:56, 12 September 2012 (EST)&lt;br /&gt;
--[[User:Z8600021|Mark Hill]] 17:26, 11 September 2012 (EST) You need to use the signature tool to log lab attendance.&lt;br /&gt;
&lt;br /&gt;
Lab 8--'''Z3330795'''  20 September 2012 (EST) this one i put in late, but i did attend just forgot to put it in that day.&lt;br /&gt;
&lt;br /&gt;
lab 9 --[[User:Z3330795|Z3330795]] 09:56, 26 September 2012 (EST)&lt;br /&gt;
&lt;br /&gt;
lab 10 --[[User:Z3330795|Z3330795]] 10:04, 3 October 2012 (EST)&lt;br /&gt;
&lt;br /&gt;
lab 11 --[[User:Z3330795|Z3330795]] 10:42, 10 October 2012 (EST)&lt;br /&gt;
&lt;br /&gt;
lab 12 --[[User:Z3330795|Z3330795]] 12:21, 17 October 2012 (EST)&lt;br /&gt;
&lt;br /&gt;
=='''Fertilization'''==&lt;br /&gt;
&lt;br /&gt;
The process in Simple Steps:&lt;br /&gt;
&lt;br /&gt;
Step 1 - Many sperm travel from the Male testes to the Female Egg located in the Fallopian tube.]&lt;br /&gt;
&lt;br /&gt;
Step 2 - Once the sperm reach the egg, many try and &amp;quot;enter&amp;quot; by releasing enzymes breaking down the outer layer of the egg.&lt;br /&gt;
&lt;br /&gt;
Step 3 - Only one sperm can penetrate and once this happens, a chemical reaction occurs &amp;quot;pushing&amp;quot; away any other sperm attempting to penetrate.&lt;br /&gt;
&lt;br /&gt;
'''This now fertilized egg is referred to as a zygote'''&lt;br /&gt;
&lt;br /&gt;
Step 4 - pronuclei of the egg merges with the pronuclei of the sperm resulting in cell division.&lt;br /&gt;
&lt;br /&gt;
Step 5 - days later this zygote is moved along the fallopian tube and is now called a blastocyst.&lt;br /&gt;
&lt;br /&gt;
Step 6 - the blastocyst is embedded in the uterine wall activating the start of pregnancy.&lt;br /&gt;
&lt;br /&gt;
'''References:'''&lt;br /&gt;
http://science.howstuffworks.com/&lt;br /&gt;
&lt;br /&gt;
==&amp;quot;Lab 1 Assessment&amp;quot;==&lt;br /&gt;
&lt;br /&gt;
1.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.&lt;br /&gt;
&lt;br /&gt;
The British scientist Robert Edwards has been researching and devloping IVF since the 1950's, the first successful IVF treatment was in 1978 when the worlds first baby was born from this fertilization technique. Following this success methods have been continually rejuvenated with state of the art techniques and research.&lt;br /&gt;
&lt;br /&gt;
Robert Edwards was the winner of the 2010 Nobel Prize in medicine for his efforts in the development of in-vitro fertilisation (IVF).&lt;br /&gt;
&lt;br /&gt;
[http://www.nobelprize.org/nobel_prizes/medicine/laureates/2010/press.html/]&lt;br /&gt;
&lt;br /&gt;
2.Identify and add a PubMed reference link to a recent paper on fertilisation and describe its key findings (1-2 paragraphs).&lt;br /&gt;
&lt;br /&gt;
This paper is explores the potential of screening sperm before fertilization, to predict fertilization rate depending on the &amp;quot;quality&amp;quot; of the sperm. This technology would be of extreme importance and make the IVF process more efficient.&lt;br /&gt;
&lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/pubmed/22762979]&lt;br /&gt;
&lt;br /&gt;
--[[User:Z8600021|Mark Hill]] 17:30, 11 September 2012 (EST) Question 1 has been answered correctly. Question 2 has been answered, but not in sufficient detail (2 lines) to describe the findings in full and the link is not correctly displayed. You should use just the number as here PMID 22762979 or remove the brackets around your link. You have lost marks for the lack of a full description, not the reference formatting.'''6/10'''&lt;br /&gt;
&lt;br /&gt;
==&amp;quot;Lab 2 Assessment&amp;quot;==&lt;br /&gt;
&lt;br /&gt;
Identify a protein associated with the implantation process, including a brief description of the protein's role.&lt;br /&gt;
&lt;br /&gt;
Chemokines are a protein directly associated with the implantation process. Current research has shown that Chemokines play an executive role within the endometrium, specifically throughout implantation. It has been proven that these proteins direct the invading trophoblasts within the maternal vasculature and decidua. This invading process is critical in early development and chemical signally from these proteins allows precise depth of insertion in preparation of the crucial weeks ahead.&lt;br /&gt;
&lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/pubmed/17495644]&lt;br /&gt;
&lt;br /&gt;
[[File:Sexual_development_of_MYT1_mutants.jpeg]]&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
--[[User:Z8600021|Mark Hill]] 17:38, 11 September 2012 (EST) Question 1 image has been uploaded correctly. In the summary box you have included the citation and copyright information, but not a template indicating that this is a student image. &amp;lt;nowiki&amp;gt;{{Template:Student Image}}&amp;lt;/nowiki&amp;gt;. There is also no legend describing what A, B and C are showing, this could have been derived from teh original figure template. Question 2 protein associated with the implantation, chemokines are a relevant &amp;quot;class of proteins&amp;quot;, not a specific protein and the  article you have selected is a review, not a big issue but you need to also clearly identify that it is a review and not a research article. '''7/10'''&lt;br /&gt;
&lt;br /&gt;
==&amp;quot;Lab 3 Assessment&amp;quot;==&lt;br /&gt;
&lt;br /&gt;
1.Identify the difference between &amp;quot;gestational age&amp;quot; and &amp;quot;post-fertilisation age&amp;quot; and explain why clinically &amp;quot;gestational age&amp;quot; is used in describing human development.&lt;br /&gt;
&lt;br /&gt;
a)&lt;br /&gt;
The overlap and confusion of these terms is very common due to physicians frequently using either one to describe the early stage of pregnancy. Technically there is a distinct difference between the two.&amp;quot;Post-fertilization age&amp;quot; is the time elapsed after egg fertilization, where as &amp;quot;Gestational age&amp;quot;(approximately 2 weeks later) is the time since the mothers last menstrual cycle prior to pregnancy.&lt;br /&gt;
&lt;br /&gt;
[http://www.livestrong.com/article/92683-embryo-fetus-development-stages/]&lt;br /&gt;
&lt;br /&gt;
b)&lt;br /&gt;
In a clinical setting is important to use consistant terminology, “Gestational age” is the preffered term used to describe this early stage of pregnacy for the obvious reason that the average women will know when their last menstral cycle began although she will typically have less certainty surrounding when ovulation occured. The delvery date is a simple caculation given acuracy of the Gestational age.&lt;br /&gt;
&lt;br /&gt;
[http://pediatrics.aappublications.org/content/114/5/1362.full]&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
2. Identify using histological descriptions at least 3 different types of tissues formed from somites&lt;br /&gt;
&lt;br /&gt;
Somites form Cartilage (ribs and vertabrae), skeltal muscle (ribs, limbs and back) and also the dermis of the dorsal skin. The cells of the Somites remain multipotential for a long time during development, therefor somite cells can become any somite structure until maturation where they become commited to form structures repective of their regions.&lt;br /&gt;
&lt;br /&gt;
The Somites have three different regions with different tissue outcomes. The somite cells located closest to neural tube turn into mesenchymal cell (through complex cellular processes) this is portion that become chrondocytes of the cartilage formed.&lt;br /&gt;
The cells in the two lateral portions of the somite structure divide to produce the myoblasts which are muscle precursers cells. This is now a 2 layered segment, the top layer is called dermamyotome, and the lower myotome. Depending on the location of the myoblasts determines their fate (epaxial or hypaxial muscles). the final area is located in the centre of the dermamyotome is called the dermatome, producing connective tissue of mesenchymal origin which will mature and eventually form the tissue of ventrally located skin. &lt;br /&gt;
&lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/books/NBK10085/]&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
--[[User:Z8600021|Mark Hill]] 17:43, 11 September 2012 (EST) Question 1 you have identified the difference between &amp;quot;gestational age&amp;quot; and &amp;quot;post-fertilisation age. Your terminology though is confusing &amp;quot;where as Gestational age (approximately 2 weeks later)&amp;quot;, you should have then said &amp;quot;than Post-fertilization age&amp;quot;. Question 2 you have identified 3 different tissues and the textbook link is appropriate. There are several typos throughout your answer that you should have corrected, I have not removed marks for this, but it suggests to the reader that you have not checked your work. '''9/10'''&lt;br /&gt;
&lt;br /&gt;
==&amp;quot;Lab 4 Assessment&amp;quot;==&lt;br /&gt;
&lt;br /&gt;
1. Identify the 2 invasive prenatal diagnostic techniques related to the placenta and 2 abnormalities that can be identified with these techniques.&lt;br /&gt;
&lt;br /&gt;
a)Fluorescence in-situ hybridization is an invasive technique which analyses fetal blood cells present in maternal blood samples. These cells gain access through placental villi. This test can screen for conditions such as the trisomies and monosomy X.&lt;br /&gt;
&lt;br /&gt;
b)Maternal serum alpha-fetoprotein is an invasive technique that measures the level of alpha-fetoprotein (AFP) in maternal blood, knowing that adults exclusively have albumin in their blood we exploit this technique. Typically the fetus will only release small amounts of AFP going across the placenta into the mother blood, although large amount of AFP in the maternal blood sample can indicate a neural tube defect or spina bifida.&lt;br /&gt;
&lt;br /&gt;
[http://library.med.utah.edu/WebPath/TUTORIAL/PRENATAL/PRENATAL.html]&lt;br /&gt;
&lt;br /&gt;
2. Identify a paper that uses cord stem cells therapeutically and write a brief (2-3 paragraph) description of the paper's findings.&lt;br /&gt;
&lt;br /&gt;
My selected Paper &amp;quot;Stem cell therapies for spinal cord injury.&amp;quot; describes the benefits of use along with its many implications. Spinal Cord injuries(SCI) either complete or incomplete pose a catastrophic stress on the individual both physical and emotional. The possibility of treatment for SCI is an area with enormous potential giving hope to those who are unfortunate enough to come across this terrible injury. &lt;br /&gt;
&lt;br /&gt;
There are currently many implications surrounding stem cell therapy such as tumor formation. The controversy surrounding research in this area is supported by data concluding that there is no way around biological implications caused by treatment.&lt;br /&gt;
&lt;br /&gt;
The basic principle behind stem cell therapy is using multipotential cells to create new and functional tissue, this therapy involves a combination of many complex treatments each addressing different components. Cutting edge research has involved using animal models although these types treatments are still in the development of making safe &amp;amp; ethical therapies that can be used in a clinical setting. As we look to the future of Stem cell therapies there are many more methods being explored for example using induced pluripotent stem cells (force expression of certain genes).&lt;br /&gt;
&lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/pubmed/20551948]&lt;br /&gt;
&lt;br /&gt;
--[[User:Z8600021|Mark Hill]] 17:50, 11 September 2012 (EST) Question 1 Fluorescence in-situ hybridization and Maternal serum alpha-fetoprotein are not an invasive technique, the analysis of fetal cells in maternal blood is exactly the opposite, it is replacing invasive techniques. I think you have misinterpreted what I meant by invasive technique, such as chorionic villi sampling or amniocentesis. Question 2 you have identified a stem cell paper, a review rather than research article. Though I did not specify this in the question I am usually asking for research articles. Your description is sufficient. '''5/10'''&lt;br /&gt;
&lt;br /&gt;
==&amp;quot;Lab 5 Assessment&amp;quot;==&lt;br /&gt;
&lt;br /&gt;
1.&lt;br /&gt;
&lt;br /&gt;
(A) Muscles satellite cells are sometimes reffered to as Myosatellite cells, these cells contain a single lobed nucleus and have tendency to differentiate into a specific cell type, similar to stem cells (mononuclear progenitor cell), they are located on the outer surface of muscle fibres and remain dormant until activation occurs&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
(B)  &lt;br /&gt;
&lt;br /&gt;
&amp;quot;Regeneration of adult skeletal muscle is an asynchronous process requiring the activation, proliferation and fusion of satellite cells, to form new muscle fibres.&amp;quot; Cooper, S. Tajbakhsh, V. Mouly, G. Cossu, M. Buckingham and G. S. Butler-Browne (1999). Satellite cells are responsible for the growth and regeneration of muscle, although there are chemical mediators that activate these cells proven by an experiment by Anderson J, Pilipowicz O.(2002),  concluding Nitric Oxide (in vivo) is required to activate satellite cells and also hepatocyte growth factor (HGF) and Nitric Oxide (NO) also participate in mobilizing satellite cells. Ryuichi Tatsumi, Xiaosong Liu, Antonio Pulido, Mark Morales, Tomowa Sakata, Sharon Dial, Akihito Hattori, Yoshihide Ikeuchi, and Ronald E. Allen (2005) Concluded that when a muscle is stretched beyond resting range Satellite cells are activated. This article also states that when muscle hypertrophy occurs satellites cells are recruited, although what is unsure is the chemical signalling involved. In conclusion 2 actions that activate Satellite cells are stretching and hypertrophy. The passive stretching of skeletal muscles triggers the release  and interaction of chemical mediators HGF and NO, which in turn are responsible for activation of satellite cells. If skeletal muscle receives any form of damage through exercise or injury, satellite cells are activated and are attracted to the site of disturbance. Hernandez and Kravitz (1999)&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
2.&lt;br /&gt;
Burnham, Martin, Stein, Bell, MacLean, Steadward (1997) concluded that after a Spinal Cord Injury (SCI) an individuals muscles fibres will undergo alteration from type 1 slow and type 2 fast, to become type 2 fast glycolytic fibres also known as &amp;quot;fast twitch B&amp;quot; which feature less myoglobin and mitochondria. Roberto Scelsi (2001) reported a change in the muscles fibers and micro vascular change after conducting various invasive tests on a paraplegic individual. These changes have a clear relationship with the time elapsed. Scelsi reported adaption of the muscle fibers after 1 month, although for the changes to be prominent 7-8 months has elapsed. To retard this unnatural transition, therapy must be used within week of the SCI such as, Functional Electrical Stimulation, (FES) is a recognised treatment allowing some kind of stimulation to these unused muscle fibres and could improve function. Christopher and Dana Reeves Foundation (2012)&lt;br /&gt;
&lt;br /&gt;
==&amp;quot; Lab 6 Assessment&amp;quot;==&lt;br /&gt;
&lt;br /&gt;
Vision development review:&lt;br /&gt;
&lt;br /&gt;
The key points are Cleary described and Topics have been divided in an efficient way allowing maximum information and an extensive insight into each of these segments, although at this stage there is not enough detail for each.&lt;br /&gt;
There is a substantial amount of visual stimulus although the quality of these stimuli is questionable. For example the images under the heading “research history” lack proper sized labelling, an individual must click on the each image in order to appreciate it. The initial image needs to decrease in size dramatically as is overwhelming and takes away from the product&lt;br /&gt;
Proper citation is evident however; there is a minority of untidy citations along with no copy write information for a certain image. Significant, deep research is not evident, I believe more research is required; there is a respectable attempt to relate content to learning aims of embryology. Information in the history section is insufficient and perhaps needs to be expanded upon.&lt;br /&gt;
To improve more information on each topic is required, review of visual displays (mainly balancing images between sections some have plenty where as other lack) and copy write information is essential&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
Somatosensory review:&lt;br /&gt;
&lt;br /&gt;
The key points are clearly presented at the top of the page efficiently formatted allowing viewer a perfect insight to the entire pages content. There is a severe lack of visual stimuli; this makes the page present as boring and text heavy. &lt;br /&gt;
Image citation is commendable although throughout the text there is unacceptable links to external sites that are not explained with a messy reference section. The information presented is quite detailed and promotes a significant amount of research and understanding, it is put forward in an excellent matter, sections that could easily be expanded are glossary, and perhaps a section specifically on development. Attempt to relate to the learning aims of embryology are apparent. There is a large amount of information presented in a fantastic way although the lack of visual stimuli takes away from the final product, perhaps a more summarised presentation matter would be appropriate to break up large amount of text; this along with the tidy up of referencing needs to be addressed.&lt;br /&gt;
&lt;br /&gt;
Olfaction review:&lt;br /&gt;
&lt;br /&gt;
Upon first glance of the page you immediately get the impression excellent presentation and a surplus of information. Most topics are well described although the history of discoveries layout is questionable and a table would present at a higher quality.&lt;br /&gt;
It is clear that the group has a high level of understanding through large amount of research; this is then transformed into chunks of knowledge in which are easily digestible for the reader. The page lacks visual encourage, I believe more detail into this would only benefit the page. The glossary could quite easily be expanded many terms throughout the text are absent from this list.&lt;br /&gt;
This page is almost parallel with embryological teaching aims. Citation &amp;amp; referencing is excellent. The way to improve this page would be reducing the weight of the text using innovative ideas to the present information in a more exciting way along side inclusion of more visual stimulus.&lt;br /&gt;
&lt;br /&gt;
Abnormal Vision review:&lt;br /&gt;
&lt;br /&gt;
An excellent straight forward introduction, presentation and layout of the page is questionable perhaps the use of different summary methods would improve this for example dot points along with image choice and size.  A common topic among all groups is to expand the glossary which is easily done and will only improve the finished merchandise. Language used throughout could be less primitive, very simplistic in certain sections. The referencing is satisfactory although external links section has been left out.&lt;br /&gt;
All the information is present although the organisation skills need to be assessed to allow optimum presentation of ideas. The text contains in-depth embryological teachings aims. The page looks promising and editing is the easiest part once corrected I expect a sound result.&lt;br /&gt;
&lt;br /&gt;
Hearing review:&lt;br /&gt;
&lt;br /&gt;
This group successfully energies the audience with a funny picture, along with a great introduction and an interactive writing style from the first paragraph. This page needs to address the reoccurring text to image ratio, allowing the reader more explanation complementing the hard work of explaining concepts. The highlight of this text was the abnormal hearing section which I found to be very interesting along with sound presentation of ideas. The demise of this page is the lack of information in current research and being starved of visual stimuli.&lt;br /&gt;
Overall a good attempt to line up embryological teaching concepts, when these easily addressable points are responded to a commendable finish will be apparent.&lt;br /&gt;
&lt;br /&gt;
==&amp;quot; lab 7 assessment &amp;quot;==&lt;br /&gt;
&lt;br /&gt;
1.&lt;br /&gt;
mutations in GATA6 have been linked to neonates with diabatetes, suggesting that mutations in GATA6 disrupts the development of this endocrine organ. Manipulation of genes using animal models helped provide this evidence.&lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/pubmed/23006330]&lt;br /&gt;
&lt;br /&gt;
2. &lt;br /&gt;
The embryonic tooth is derived from the mesodermal and ectodermal layers. The development of teeth originates when the dental lamina divides rapildly to form the future rows that teeth are located within. Their are enanmal organs present which produce circular outgrowths providing an apropriate site for tooth formation, This organ is also responsible for the complete morphology of the later devloped tooth.&lt;br /&gt;
&lt;br /&gt;
== Individual assessment ==&lt;br /&gt;
&lt;br /&gt;
Induced pluripotent cells are derived from adult somatic cells which are provoked to express sort after genes. In this study, human- induced pluripotent stem cells were segreagated in a culture, certain growth factors were added to frame the induced pluripotent stem cells to detect and then express changes. Techniques used included flow cytometry analysis, quantitative polymerase chain reaction along with western blotting. These cell frameworks were then inserted into animals (mice) and histologically examined. Results proved positive showing the desired phenotypic changes.&lt;br /&gt;
&lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/pubmed/23065721]&lt;/div&gt;</summary>
		<author><name>Z3330795</name></author>
	</entry>
	<entry>
		<id>https://embryology.med.unsw.edu.au/embryology/index.php?title=User:Z3330795&amp;diff=107522</id>
		<title>User:Z3330795</title>
		<link rel="alternate" type="text/html" href="https://embryology.med.unsw.edu.au/embryology/index.php?title=User:Z3330795&amp;diff=107522"/>
		<updated>2012-10-17T01:21:19Z</updated>

		<summary type="html">&lt;p&gt;Z3330795: /* Lab Attendance */&lt;/p&gt;
&lt;hr /&gt;
&lt;div&gt;==Lab Attendance ==&lt;br /&gt;
Lab 1&lt;br /&gt;
&lt;br /&gt;
Lab 2&lt;br /&gt;
&lt;br /&gt;
Lab 3&lt;br /&gt;
&lt;br /&gt;
Lab 4&lt;br /&gt;
&lt;br /&gt;
Lab 5&lt;br /&gt;
&lt;br /&gt;
Lab 6&lt;br /&gt;
&lt;br /&gt;
Lab 7--[[User:Z3330795|Z3330795]] 10:56, 12 September 2012 (EST)&lt;br /&gt;
--[[User:Z8600021|Mark Hill]] 17:26, 11 September 2012 (EST) You need to use the signature tool to log lab attendance.&lt;br /&gt;
&lt;br /&gt;
Lab 8--'''Z3330795'''  20 September 2012 (EST) this one i put in late, but i did attend just forgot to put it in that day.&lt;br /&gt;
&lt;br /&gt;
lab 9 --[[User:Z3330795|Z3330795]] 09:56, 26 September 2012 (EST)&lt;br /&gt;
&lt;br /&gt;
lab 10 --[[User:Z3330795|Z3330795]] 10:04, 3 October 2012 (EST)&lt;br /&gt;
&lt;br /&gt;
lab 11 --[[User:Z3330795|Z3330795]] 10:42, 10 October 2012 (EST)&lt;br /&gt;
&lt;br /&gt;
lab 12 --[[User:Z3330795|Z3330795]] 12:21, 17 October 2012 (EST)&lt;br /&gt;
&lt;br /&gt;
=='''Fertilization'''==&lt;br /&gt;
&lt;br /&gt;
The process in Simple Steps:&lt;br /&gt;
&lt;br /&gt;
Step 1 - Many sperm travel from the Male testes to the Female Egg located in the Fallopian tube.]&lt;br /&gt;
&lt;br /&gt;
Step 2 - Once the sperm reach the egg, many try and &amp;quot;enter&amp;quot; by releasing enzymes breaking down the outer layer of the egg.&lt;br /&gt;
&lt;br /&gt;
Step 3 - Only one sperm can penetrate and once this happens, a chemical reaction occurs &amp;quot;pushing&amp;quot; away any other sperm attempting to penetrate.&lt;br /&gt;
&lt;br /&gt;
'''This now fertilized egg is referred to as a zygote'''&lt;br /&gt;
&lt;br /&gt;
Step 4 - pronuclei of the egg merges with the pronuclei of the sperm resulting in cell division.&lt;br /&gt;
&lt;br /&gt;
Step 5 - days later this zygote is moved along the fallopian tube and is now called a blastocyst.&lt;br /&gt;
&lt;br /&gt;
Step 6 - the blastocyst is embedded in the uterine wall activating the start of pregnancy.&lt;br /&gt;
&lt;br /&gt;
'''References:'''&lt;br /&gt;
http://science.howstuffworks.com/&lt;br /&gt;
&lt;br /&gt;
==&amp;quot;Lab 1 Assessment&amp;quot;==&lt;br /&gt;
&lt;br /&gt;
1.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.&lt;br /&gt;
&lt;br /&gt;
The British scientist Robert Edwards has been researching and devloping IVF since the 1950's, the first successful IVF treatment was in 1978 when the worlds first baby was born from this fertilization technique. Following this success methods have been continually rejuvenated with state of the art techniques and research.&lt;br /&gt;
&lt;br /&gt;
Robert Edwards was the winner of the 2010 Nobel Prize in medicine for his efforts in the development of in-vitro fertilisation (IVF).&lt;br /&gt;
&lt;br /&gt;
[http://www.nobelprize.org/nobel_prizes/medicine/laureates/2010/press.html/]&lt;br /&gt;
&lt;br /&gt;
2.Identify and add a PubMed reference link to a recent paper on fertilisation and describe its key findings (1-2 paragraphs).&lt;br /&gt;
&lt;br /&gt;
This paper is explores the potential of screening sperm before fertilization, to predict fertilization rate depending on the &amp;quot;quality&amp;quot; of the sperm. This technology would be of extreme importance and make the IVF process more efficient.&lt;br /&gt;
&lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/pubmed/22762979]&lt;br /&gt;
&lt;br /&gt;
--[[User:Z8600021|Mark Hill]] 17:30, 11 September 2012 (EST) Question 1 has been answered correctly. Question 2 has been answered, but not in sufficient detail (2 lines) to describe the findings in full and the link is not correctly displayed. You should use just the number as here PMID 22762979 or remove the brackets around your link. You have lost marks for the lack of a full description, not the reference formatting.'''6/10'''&lt;br /&gt;
&lt;br /&gt;
==&amp;quot;Lab 2 Assessment&amp;quot;==&lt;br /&gt;
&lt;br /&gt;
Identify a protein associated with the implantation process, including a brief description of the protein's role.&lt;br /&gt;
&lt;br /&gt;
Chemokines are a protein directly associated with the implantation process. Current research has shown that Chemokines play an executive role within the endometrium, specifically throughout implantation. It has been proven that these proteins direct the invading trophoblasts within the maternal vasculature and decidua. This invading process is critical in early development and chemical signally from these proteins allows precise depth of insertion in preparation of the crucial weeks ahead.&lt;br /&gt;
&lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/pubmed/17495644]&lt;br /&gt;
&lt;br /&gt;
[[File:Sexual_development_of_MYT1_mutants.jpeg]]&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
--[[User:Z8600021|Mark Hill]] 17:38, 11 September 2012 (EST) Question 1 image has been uploaded correctly. In the summary box you have included the citation and copyright information, but not a template indicating that this is a student image. &amp;lt;nowiki&amp;gt;{{Template:Student Image}}&amp;lt;/nowiki&amp;gt;. There is also no legend describing what A, B and C are showing, this could have been derived from teh original figure template. Question 2 protein associated with the implantation, chemokines are a relevant &amp;quot;class of proteins&amp;quot;, not a specific protein and the  article you have selected is a review, not a big issue but you need to also clearly identify that it is a review and not a research article. '''7/10'''&lt;br /&gt;
&lt;br /&gt;
==&amp;quot;Lab 3 Assessment&amp;quot;==&lt;br /&gt;
&lt;br /&gt;
1.Identify the difference between &amp;quot;gestational age&amp;quot; and &amp;quot;post-fertilisation age&amp;quot; and explain why clinically &amp;quot;gestational age&amp;quot; is used in describing human development.&lt;br /&gt;
&lt;br /&gt;
a)&lt;br /&gt;
The overlap and confusion of these terms is very common due to physicians frequently using either one to describe the early stage of pregnancy. Technically there is a distinct difference between the two.&amp;quot;Post-fertilization age&amp;quot; is the time elapsed after egg fertilization, where as &amp;quot;Gestational age&amp;quot;(approximately 2 weeks later) is the time since the mothers last menstrual cycle prior to pregnancy.&lt;br /&gt;
&lt;br /&gt;
[http://www.livestrong.com/article/92683-embryo-fetus-development-stages/]&lt;br /&gt;
&lt;br /&gt;
b)&lt;br /&gt;
In a clinical setting is important to use consistant terminology, “Gestational age” is the preffered term used to describe this early stage of pregnacy for the obvious reason that the average women will know when their last menstral cycle began although she will typically have less certainty surrounding when ovulation occured. The delvery date is a simple caculation given acuracy of the Gestational age.&lt;br /&gt;
&lt;br /&gt;
[http://pediatrics.aappublications.org/content/114/5/1362.full]&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
2. Identify using histological descriptions at least 3 different types of tissues formed from somites&lt;br /&gt;
&lt;br /&gt;
Somites form Cartilage (ribs and vertabrae), skeltal muscle (ribs, limbs and back) and also the dermis of the dorsal skin. The cells of the Somites remain multipotential for a long time during development, therefor somite cells can become any somite structure until maturation where they become commited to form structures repective of their regions.&lt;br /&gt;
&lt;br /&gt;
The Somites have three different regions with different tissue outcomes. The somite cells located closest to neural tube turn into mesenchymal cell (through complex cellular processes) this is portion that become chrondocytes of the cartilage formed.&lt;br /&gt;
The cells in the two lateral portions of the somite structure divide to produce the myoblasts which are muscle precursers cells. This is now a 2 layered segment, the top layer is called dermamyotome, and the lower myotome. Depending on the location of the myoblasts determines their fate (epaxial or hypaxial muscles). the final area is located in the centre of the dermamyotome is called the dermatome, producing connective tissue of mesenchymal origin which will mature and eventually form the tissue of ventrally located skin. &lt;br /&gt;
&lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/books/NBK10085/]&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
--[[User:Z8600021|Mark Hill]] 17:43, 11 September 2012 (EST) Question 1 you have identified the difference between &amp;quot;gestational age&amp;quot; and &amp;quot;post-fertilisation age. Your terminology though is confusing &amp;quot;where as Gestational age (approximately 2 weeks later)&amp;quot;, you should have then said &amp;quot;than Post-fertilization age&amp;quot;. Question 2 you have identified 3 different tissues and the textbook link is appropriate. There are several typos throughout your answer that you should have corrected, I have not removed marks for this, but it suggests to the reader that you have not checked your work. '''9/10'''&lt;br /&gt;
&lt;br /&gt;
==&amp;quot;Lab 4 Assessment&amp;quot;==&lt;br /&gt;
&lt;br /&gt;
1. Identify the 2 invasive prenatal diagnostic techniques related to the placenta and 2 abnormalities that can be identified with these techniques.&lt;br /&gt;
&lt;br /&gt;
a)Fluorescence in-situ hybridization is an invasive technique which analyses fetal blood cells present in maternal blood samples. These cells gain access through placental villi. This test can screen for conditions such as the trisomies and monosomy X.&lt;br /&gt;
&lt;br /&gt;
b)Maternal serum alpha-fetoprotein is an invasive technique that measures the level of alpha-fetoprotein (AFP) in maternal blood, knowing that adults exclusively have albumin in their blood we exploit this technique. Typically the fetus will only release small amounts of AFP going across the placenta into the mother blood, although large amount of AFP in the maternal blood sample can indicate a neural tube defect or spina bifida.&lt;br /&gt;
&lt;br /&gt;
[http://library.med.utah.edu/WebPath/TUTORIAL/PRENATAL/PRENATAL.html]&lt;br /&gt;
&lt;br /&gt;
2. Identify a paper that uses cord stem cells therapeutically and write a brief (2-3 paragraph) description of the paper's findings.&lt;br /&gt;
&lt;br /&gt;
My selected Paper &amp;quot;Stem cell therapies for spinal cord injury.&amp;quot; describes the benefits of use along with its many implications. Spinal Cord injuries(SCI) either complete or incomplete pose a catastrophic stress on the individual both physical and emotional. The possibility of treatment for SCI is an area with enormous potential giving hope to those who are unfortunate enough to come across this terrible injury. &lt;br /&gt;
&lt;br /&gt;
There are currently many implications surrounding stem cell therapy such as tumor formation. The controversy surrounding research in this area is supported by data concluding that there is no way around biological implications caused by treatment.&lt;br /&gt;
&lt;br /&gt;
The basic principle behind stem cell therapy is using multipotential cells to create new and functional tissue, this therapy involves a combination of many complex treatments each addressing different components. Cutting edge research has involved using animal models although these types treatments are still in the development of making safe &amp;amp; ethical therapies that can be used in a clinical setting. As we look to the future of Stem cell therapies there are many more methods being explored for example using induced pluripotent stem cells (force expression of certain genes).&lt;br /&gt;
&lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/pubmed/20551948]&lt;br /&gt;
&lt;br /&gt;
--[[User:Z8600021|Mark Hill]] 17:50, 11 September 2012 (EST) Question 1 Fluorescence in-situ hybridization and Maternal serum alpha-fetoprotein are not an invasive technique, the analysis of fetal cells in maternal blood is exactly the opposite, it is replacing invasive techniques. I think you have misinterpreted what I meant by invasive technique, such as chorionic villi sampling or amniocentesis. Question 2 you have identified a stem cell paper, a review rather than research article. Though I did not specify this in the question I am usually asking for research articles. Your description is sufficient. '''5/10'''&lt;br /&gt;
&lt;br /&gt;
==&amp;quot;Lab 5 Assessment&amp;quot;==&lt;br /&gt;
&lt;br /&gt;
1.&lt;br /&gt;
&lt;br /&gt;
(A) Muscles satellite cells are sometimes reffered to as Myosatellite cells, these cells contain a single lobed nucleus and have tendency to differentiate into a specific cell type, similar to stem cells (mononuclear progenitor cell), they are located on the outer surface of muscle fibres and remain dormant until activation occurs&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
(B)  &lt;br /&gt;
&lt;br /&gt;
&amp;quot;Regeneration of adult skeletal muscle is an asynchronous process requiring the activation, proliferation and fusion of satellite cells, to form new muscle fibres.&amp;quot; Cooper, S. Tajbakhsh, V. Mouly, G. Cossu, M. Buckingham and G. S. Butler-Browne (1999). Satellite cells are responsible for the growth and regeneration of muscle, although there are chemical mediators that activate these cells proven by an experiment by Anderson J, Pilipowicz O.(2002),  concluding Nitric Oxide (in vivo) is required to activate satellite cells and also hepatocyte growth factor (HGF) and Nitric Oxide (NO) also participate in mobilizing satellite cells. Ryuichi Tatsumi, Xiaosong Liu, Antonio Pulido, Mark Morales, Tomowa Sakata, Sharon Dial, Akihito Hattori, Yoshihide Ikeuchi, and Ronald E. Allen (2005) Concluded that when a muscle is stretched beyond resting range Satellite cells are activated. This article also states that when muscle hypertrophy occurs satellites cells are recruited, although what is unsure is the chemical signalling involved. In conclusion 2 actions that activate Satellite cells are stretching and hypertrophy. The passive stretching of skeletal muscles triggers the release  and interaction of chemical mediators HGF and NO, which in turn are responsible for activation of satellite cells. If skeletal muscle receives any form of damage through exercise or injury, satellite cells are activated and are attracted to the site of disturbance. Hernandez and Kravitz (1999)&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
2.&lt;br /&gt;
Burnham, Martin, Stein, Bell, MacLean, Steadward (1997) concluded that after a Spinal Cord Injury (SCI) an individuals muscles fibres will undergo alteration from type 1 slow and type 2 fast, to become type 2 fast glycolytic fibres also known as &amp;quot;fast twitch B&amp;quot; which feature less myoglobin and mitochondria. Roberto Scelsi (2001) reported a change in the muscles fibers and micro vascular change after conducting various invasive tests on a paraplegic individual. These changes have a clear relationship with the time elapsed. Scelsi reported adaption of the muscle fibers after 1 month, although for the changes to be prominent 7-8 months has elapsed. To retard this unnatural transition, therapy must be used within week of the SCI such as, Functional Electrical Stimulation, (FES) is a recognised treatment allowing some kind of stimulation to these unused muscle fibres and could improve function. Christopher and Dana Reeves Foundation (2012)&lt;br /&gt;
&lt;br /&gt;
==&amp;quot; Lab 6 Assessment&amp;quot;==&lt;br /&gt;
&lt;br /&gt;
Vision development review:&lt;br /&gt;
&lt;br /&gt;
The key points are Cleary described and Topics have been divided in an efficient way allowing maximum information and an extensive insight into each of these segments, although at this stage there is not enough detail for each.&lt;br /&gt;
There is a substantial amount of visual stimulus although the quality of these stimuli is questionable. For example the images under the heading “research history” lack proper sized labelling, an individual must click on the each image in order to appreciate it. The initial image needs to decrease in size dramatically as is overwhelming and takes away from the product&lt;br /&gt;
Proper citation is evident however; there is a minority of untidy citations along with no copy write information for a certain image. Significant, deep research is not evident, I believe more research is required; there is a respectable attempt to relate content to learning aims of embryology. Information in the history section is insufficient and perhaps needs to be expanded upon.&lt;br /&gt;
To improve more information on each topic is required, review of visual displays (mainly balancing images between sections some have plenty where as other lack) and copy write information is essential&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
Somatosensory review:&lt;br /&gt;
&lt;br /&gt;
The key points are clearly presented at the top of the page efficiently formatted allowing viewer a perfect insight to the entire pages content. There is a severe lack of visual stimuli; this makes the page present as boring and text heavy. &lt;br /&gt;
Image citation is commendable although throughout the text there is unacceptable links to external sites that are not explained with a messy reference section. The information presented is quite detailed and promotes a significant amount of research and understanding, it is put forward in an excellent matter, sections that could easily be expanded are glossary, and perhaps a section specifically on development. Attempt to relate to the learning aims of embryology are apparent. There is a large amount of information presented in a fantastic way although the lack of visual stimuli takes away from the final product, perhaps a more summarised presentation matter would be appropriate to break up large amount of text; this along with the tidy up of referencing needs to be addressed.&lt;br /&gt;
&lt;br /&gt;
Olfaction review:&lt;br /&gt;
&lt;br /&gt;
Upon first glance of the page you immediately get the impression excellent presentation and a surplus of information. Most topics are well described although the history of discoveries layout is questionable and a table would present at a higher quality.&lt;br /&gt;
It is clear that the group has a high level of understanding through large amount of research; this is then transformed into chunks of knowledge in which are easily digestible for the reader. The page lacks visual encourage, I believe more detail into this would only benefit the page. The glossary could quite easily be expanded many terms throughout the text are absent from this list.&lt;br /&gt;
This page is almost parallel with embryological teaching aims. Citation &amp;amp; referencing is excellent. The way to improve this page would be reducing the weight of the text using innovative ideas to the present information in a more exciting way along side inclusion of more visual stimulus.&lt;br /&gt;
&lt;br /&gt;
Abnormal Vision review:&lt;br /&gt;
&lt;br /&gt;
An excellent straight forward introduction, presentation and layout of the page is questionable perhaps the use of different summary methods would improve this for example dot points along with image choice and size.  A common topic among all groups is to expand the glossary which is easily done and will only improve the finished merchandise. Language used throughout could be less primitive, very simplistic in certain sections. The referencing is satisfactory although external links section has been left out.&lt;br /&gt;
All the information is present although the organisation skills need to be assessed to allow optimum presentation of ideas. The text contains in-depth embryological teachings aims. The page looks promising and editing is the easiest part once corrected I expect a sound result.&lt;br /&gt;
&lt;br /&gt;
Hearing review:&lt;br /&gt;
&lt;br /&gt;
This group successfully energies the audience with a funny picture, along with a great introduction and an interactive writing style from the first paragraph. This page needs to address the reoccurring text to image ratio, allowing the reader more explanation complementing the hard work of explaining concepts. The highlight of this text was the abnormal hearing section which I found to be very interesting along with sound presentation of ideas. The demise of this page is the lack of information in current research and being starved of visual stimuli.&lt;br /&gt;
Overall a good attempt to line up embryological teaching concepts, when these easily addressable points are responded to a commendable finish will be apparent.&lt;br /&gt;
&lt;br /&gt;
==&amp;quot; lab 7 assessment &amp;quot;==&lt;br /&gt;
&lt;br /&gt;
1.&lt;br /&gt;
mutations in GATA6 have been linked to neonates with diabatetes, suggesting that mutations in GATA6 disrupts the development of this endocrine organ. Manipulation of genes using animal models helped provide this evidence.&lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/pubmed/23006330]&lt;br /&gt;
&lt;br /&gt;
2. &lt;br /&gt;
The embryonic tooth is derived from the mesodermal and ectodermal layers. The development of teeth originates when the dental lamina divides rapildly to form the future rows that teeth are located within. Their are enanmal organs present which produce circular outgrowths providing an apropriate site for tooth formation, This organ is also responsible for the complete morphology of the later devloped tooth.&lt;/div&gt;</summary>
		<author><name>Z3330795</name></author>
	</entry>
	<entry>
		<id>https://embryology.med.unsw.edu.au/embryology/index.php?title=User:Z3330795&amp;diff=106698</id>
		<title>User:Z3330795</title>
		<link rel="alternate" type="text/html" href="https://embryology.med.unsw.edu.au/embryology/index.php?title=User:Z3330795&amp;diff=106698"/>
		<updated>2012-10-09T23:42:39Z</updated>

		<summary type="html">&lt;p&gt;Z3330795: /* Lab Attendance */&lt;/p&gt;
&lt;hr /&gt;
&lt;div&gt;==Lab Attendance ==&lt;br /&gt;
Lab 1&lt;br /&gt;
&lt;br /&gt;
Lab 2&lt;br /&gt;
&lt;br /&gt;
Lab 3&lt;br /&gt;
&lt;br /&gt;
Lab 4&lt;br /&gt;
&lt;br /&gt;
Lab 5&lt;br /&gt;
&lt;br /&gt;
Lab 6&lt;br /&gt;
&lt;br /&gt;
Lab 7--[[User:Z3330795|Z3330795]] 10:56, 12 September 2012 (EST)&lt;br /&gt;
--[[User:Z8600021|Mark Hill]] 17:26, 11 September 2012 (EST) You need to use the signature tool to log lab attendance.&lt;br /&gt;
&lt;br /&gt;
Lab 8--'''Z3330795'''  20 September 2012 (EST) this one i put in late, but i did attend just forgot to put it in that day.&lt;br /&gt;
&lt;br /&gt;
lab 9 --[[User:Z3330795|Z3330795]] 09:56, 26 September 2012 (EST)&lt;br /&gt;
&lt;br /&gt;
lab 10 --[[User:Z3330795|Z3330795]] 10:04, 3 October 2012 (EST)&lt;br /&gt;
&lt;br /&gt;
lab 11 --[[User:Z3330795|Z3330795]] 10:42, 10 October 2012 (EST)&lt;br /&gt;
&lt;br /&gt;
=='''Fertilization'''==&lt;br /&gt;
&lt;br /&gt;
The process in Simple Steps:&lt;br /&gt;
&lt;br /&gt;
Step 1 - Many sperm travel from the Male testes to the Female Egg located in the Fallopian tube.]&lt;br /&gt;
&lt;br /&gt;
Step 2 - Once the sperm reach the egg, many try and &amp;quot;enter&amp;quot; by releasing enzymes breaking down the outer layer of the egg.&lt;br /&gt;
&lt;br /&gt;
Step 3 - Only one sperm can penetrate and once this happens, a chemical reaction occurs &amp;quot;pushing&amp;quot; away any other sperm attempting to penetrate.&lt;br /&gt;
&lt;br /&gt;
'''This now fertilized egg is referred to as a zygote'''&lt;br /&gt;
&lt;br /&gt;
Step 4 - pronuclei of the egg merges with the pronuclei of the sperm resulting in cell division.&lt;br /&gt;
&lt;br /&gt;
Step 5 - days later this zygote is moved along the fallopian tube and is now called a blastocyst.&lt;br /&gt;
&lt;br /&gt;
Step 6 - the blastocyst is embedded in the uterine wall activating the start of pregnancy.&lt;br /&gt;
&lt;br /&gt;
'''References:'''&lt;br /&gt;
http://science.howstuffworks.com/&lt;br /&gt;
&lt;br /&gt;
==&amp;quot;Lab 1 Assessment&amp;quot;==&lt;br /&gt;
&lt;br /&gt;
1.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.&lt;br /&gt;
&lt;br /&gt;
The British scientist Robert Edwards has been researching and devloping IVF since the 1950's, the first successful IVF treatment was in 1978 when the worlds first baby was born from this fertilization technique. Following this success methods have been continually rejuvenated with state of the art techniques and research.&lt;br /&gt;
&lt;br /&gt;
Robert Edwards was the winner of the 2010 Nobel Prize in medicine for his efforts in the development of in-vitro fertilisation (IVF).&lt;br /&gt;
&lt;br /&gt;
[http://www.nobelprize.org/nobel_prizes/medicine/laureates/2010/press.html/]&lt;br /&gt;
&lt;br /&gt;
2.Identify and add a PubMed reference link to a recent paper on fertilisation and describe its key findings (1-2 paragraphs).&lt;br /&gt;
&lt;br /&gt;
This paper is explores the potential of screening sperm before fertilization, to predict fertilization rate depending on the &amp;quot;quality&amp;quot; of the sperm. This technology would be of extreme importance and make the IVF process more efficient.&lt;br /&gt;
&lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/pubmed/22762979]&lt;br /&gt;
&lt;br /&gt;
--[[User:Z8600021|Mark Hill]] 17:30, 11 September 2012 (EST) Question 1 has been answered correctly. Question 2 has been answered, but not in sufficient detail (2 lines) to describe the findings in full and the link is not correctly displayed. You should use just the number as here PMID 22762979 or remove the brackets around your link. You have lost marks for the lack of a full description, not the reference formatting.'''6/10'''&lt;br /&gt;
&lt;br /&gt;
==&amp;quot;Lab 2 Assessment&amp;quot;==&lt;br /&gt;
&lt;br /&gt;
Identify a protein associated with the implantation process, including a brief description of the protein's role.&lt;br /&gt;
&lt;br /&gt;
Chemokines are a protein directly associated with the implantation process. Current research has shown that Chemokines play an executive role within the endometrium, specifically throughout implantation. It has been proven that these proteins direct the invading trophoblasts within the maternal vasculature and decidua. This invading process is critical in early development and chemical signally from these proteins allows precise depth of insertion in preparation of the crucial weeks ahead.&lt;br /&gt;
&lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/pubmed/17495644]&lt;br /&gt;
&lt;br /&gt;
[[File:Sexual_development_of_MYT1_mutants.jpeg]]&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
--[[User:Z8600021|Mark Hill]] 17:38, 11 September 2012 (EST) Question 1 image has been uploaded correctly. In the summary box you have included the citation and copyright information, but not a template indicating that this is a student image. &amp;lt;nowiki&amp;gt;{{Template:Student Image}}&amp;lt;/nowiki&amp;gt;. There is also no legend describing what A, B and C are showing, this could have been derived from teh original figure template. Question 2 protein associated with the implantation, chemokines are a relevant &amp;quot;class of proteins&amp;quot;, not a specific protein and the  article you have selected is a review, not a big issue but you need to also clearly identify that it is a review and not a research article. '''7/10'''&lt;br /&gt;
&lt;br /&gt;
==&amp;quot;Lab 3 Assessment&amp;quot;==&lt;br /&gt;
&lt;br /&gt;
1.Identify the difference between &amp;quot;gestational age&amp;quot; and &amp;quot;post-fertilisation age&amp;quot; and explain why clinically &amp;quot;gestational age&amp;quot; is used in describing human development.&lt;br /&gt;
&lt;br /&gt;
a)&lt;br /&gt;
The overlap and confusion of these terms is very common due to physicians frequently using either one to describe the early stage of pregnancy. Technically there is a distinct difference between the two.&amp;quot;Post-fertilization age&amp;quot; is the time elapsed after egg fertilization, where as &amp;quot;Gestational age&amp;quot;(approximately 2 weeks later) is the time since the mothers last menstrual cycle prior to pregnancy.&lt;br /&gt;
&lt;br /&gt;
[http://www.livestrong.com/article/92683-embryo-fetus-development-stages/]&lt;br /&gt;
&lt;br /&gt;
b)&lt;br /&gt;
In a clinical setting is important to use consistant terminology, “Gestational age” is the preffered term used to describe this early stage of pregnacy for the obvious reason that the average women will know when their last menstral cycle began although she will typically have less certainty surrounding when ovulation occured. The delvery date is a simple caculation given acuracy of the Gestational age.&lt;br /&gt;
&lt;br /&gt;
[http://pediatrics.aappublications.org/content/114/5/1362.full]&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
2. Identify using histological descriptions at least 3 different types of tissues formed from somites&lt;br /&gt;
&lt;br /&gt;
Somites form Cartilage (ribs and vertabrae), skeltal muscle (ribs, limbs and back) and also the dermis of the dorsal skin. The cells of the Somites remain multipotential for a long time during development, therefor somite cells can become any somite structure until maturation where they become commited to form structures repective of their regions.&lt;br /&gt;
&lt;br /&gt;
The Somites have three different regions with different tissue outcomes. The somite cells located closest to neural tube turn into mesenchymal cell (through complex cellular processes) this is portion that become chrondocytes of the cartilage formed.&lt;br /&gt;
The cells in the two lateral portions of the somite structure divide to produce the myoblasts which are muscle precursers cells. This is now a 2 layered segment, the top layer is called dermamyotome, and the lower myotome. Depending on the location of the myoblasts determines their fate (epaxial or hypaxial muscles). the final area is located in the centre of the dermamyotome is called the dermatome, producing connective tissue of mesenchymal origin which will mature and eventually form the tissue of ventrally located skin. &lt;br /&gt;
&lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/books/NBK10085/]&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
--[[User:Z8600021|Mark Hill]] 17:43, 11 September 2012 (EST) Question 1 you have identified the difference between &amp;quot;gestational age&amp;quot; and &amp;quot;post-fertilisation age. Your terminology though is confusing &amp;quot;where as Gestational age (approximately 2 weeks later)&amp;quot;, you should have then said &amp;quot;than Post-fertilization age&amp;quot;. Question 2 you have identified 3 different tissues and the textbook link is appropriate. There are several typos throughout your answer that you should have corrected, I have not removed marks for this, but it suggests to the reader that you have not checked your work. '''9/10'''&lt;br /&gt;
&lt;br /&gt;
==&amp;quot;Lab 4 Assessment&amp;quot;==&lt;br /&gt;
&lt;br /&gt;
1. Identify the 2 invasive prenatal diagnostic techniques related to the placenta and 2 abnormalities that can be identified with these techniques.&lt;br /&gt;
&lt;br /&gt;
a)Fluorescence in-situ hybridization is an invasive technique which analyses fetal blood cells present in maternal blood samples. These cells gain access through placental villi. This test can screen for conditions such as the trisomies and monosomy X.&lt;br /&gt;
&lt;br /&gt;
b)Maternal serum alpha-fetoprotein is an invasive technique that measures the level of alpha-fetoprotein (AFP) in maternal blood, knowing that adults exclusively have albumin in their blood we exploit this technique. Typically the fetus will only release small amounts of AFP going across the placenta into the mother blood, although large amount of AFP in the maternal blood sample can indicate a neural tube defect or spina bifida.&lt;br /&gt;
&lt;br /&gt;
[http://library.med.utah.edu/WebPath/TUTORIAL/PRENATAL/PRENATAL.html]&lt;br /&gt;
&lt;br /&gt;
2. Identify a paper that uses cord stem cells therapeutically and write a brief (2-3 paragraph) description of the paper's findings.&lt;br /&gt;
&lt;br /&gt;
My selected Paper &amp;quot;Stem cell therapies for spinal cord injury.&amp;quot; describes the benefits of use along with its many implications. Spinal Cord injuries(SCI) either complete or incomplete pose a catastrophic stress on the individual both physical and emotional. The possibility of treatment for SCI is an area with enormous potential giving hope to those who are unfortunate enough to come across this terrible injury. &lt;br /&gt;
&lt;br /&gt;
There are currently many implications surrounding stem cell therapy such as tumor formation. The controversy surrounding research in this area is supported by data concluding that there is no way around biological implications caused by treatment.&lt;br /&gt;
&lt;br /&gt;
The basic principle behind stem cell therapy is using multipotential cells to create new and functional tissue, this therapy involves a combination of many complex treatments each addressing different components. Cutting edge research has involved using animal models although these types treatments are still in the development of making safe &amp;amp; ethical therapies that can be used in a clinical setting. As we look to the future of Stem cell therapies there are many more methods being explored for example using induced pluripotent stem cells (force expression of certain genes).&lt;br /&gt;
&lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/pubmed/20551948]&lt;br /&gt;
&lt;br /&gt;
--[[User:Z8600021|Mark Hill]] 17:50, 11 September 2012 (EST) Question 1 Fluorescence in-situ hybridization and Maternal serum alpha-fetoprotein are not an invasive technique, the analysis of fetal cells in maternal blood is exactly the opposite, it is replacing invasive techniques. I think you have misinterpreted what I meant by invasive technique, such as chorionic villi sampling or amniocentesis. Question 2 you have identified a stem cell paper, a review rather than research article. Though I did not specify this in the question I am usually asking for research articles. Your description is sufficient. '''5/10'''&lt;br /&gt;
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==&amp;quot;Lab 5 Assessment&amp;quot;==&lt;br /&gt;
&lt;br /&gt;
1.&lt;br /&gt;
&lt;br /&gt;
(A) Muscles satellite cells are sometimes reffered to as Myosatellite cells, these cells contain a single lobed nucleus and have tendency to differentiate into a specific cell type, similar to stem cells (mononuclear progenitor cell), they are located on the outer surface of muscle fibres and remain dormant until activation occurs&lt;br /&gt;
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&lt;br /&gt;
(B)  &lt;br /&gt;
&lt;br /&gt;
&amp;quot;Regeneration of adult skeletal muscle is an asynchronous process requiring the activation, proliferation and fusion of satellite cells, to form new muscle fibres.&amp;quot; Cooper, S. Tajbakhsh, V. Mouly, G. Cossu, M. Buckingham and G. S. Butler-Browne (1999). Satellite cells are responsible for the growth and regeneration of muscle, although there are chemical mediators that activate these cells proven by an experiment by Anderson J, Pilipowicz O.(2002),  concluding Nitric Oxide (in vivo) is required to activate satellite cells and also hepatocyte growth factor (HGF) and Nitric Oxide (NO) also participate in mobilizing satellite cells. Ryuichi Tatsumi, Xiaosong Liu, Antonio Pulido, Mark Morales, Tomowa Sakata, Sharon Dial, Akihito Hattori, Yoshihide Ikeuchi, and Ronald E. Allen (2005) Concluded that when a muscle is stretched beyond resting range Satellite cells are activated. This article also states that when muscle hypertrophy occurs satellites cells are recruited, although what is unsure is the chemical signalling involved. In conclusion 2 actions that activate Satellite cells are stretching and hypertrophy. The passive stretching of skeletal muscles triggers the release  and interaction of chemical mediators HGF and NO, which in turn are responsible for activation of satellite cells. If skeletal muscle receives any form of damage through exercise or injury, satellite cells are activated and are attracted to the site of disturbance. Hernandez and Kravitz (1999)&lt;br /&gt;
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2.&lt;br /&gt;
Burnham, Martin, Stein, Bell, MacLean, Steadward (1997) concluded that after a Spinal Cord Injury (SCI) an individuals muscles fibres will undergo alteration from type 1 slow and type 2 fast, to become type 2 fast glycolytic fibres also known as &amp;quot;fast twitch B&amp;quot; which feature less myoglobin and mitochondria. Roberto Scelsi (2001) reported a change in the muscles fibers and micro vascular change after conducting various invasive tests on a paraplegic individual. These changes have a clear relationship with the time elapsed. Scelsi reported adaption of the muscle fibers after 1 month, although for the changes to be prominent 7-8 months has elapsed. To retard this unnatural transition, therapy must be used within week of the SCI such as, Functional Electrical Stimulation, (FES) is a recognised treatment allowing some kind of stimulation to these unused muscle fibres and could improve function. Christopher and Dana Reeves Foundation (2012)&lt;br /&gt;
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==&amp;quot; Lab 6 Assessment&amp;quot;==&lt;br /&gt;
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Vision development review:&lt;br /&gt;
&lt;br /&gt;
The key points are Cleary described and Topics have been divided in an efficient way allowing maximum information and an extensive insight into each of these segments, although at this stage there is not enough detail for each.&lt;br /&gt;
There is a substantial amount of visual stimulus although the quality of these stimuli is questionable. For example the images under the heading “research history” lack proper sized labelling, an individual must click on the each image in order to appreciate it. The initial image needs to decrease in size dramatically as is overwhelming and takes away from the product&lt;br /&gt;
Proper citation is evident however; there is a minority of untidy citations along with no copy write information for a certain image. Significant, deep research is not evident, I believe more research is required; there is a respectable attempt to relate content to learning aims of embryology. Information in the history section is insufficient and perhaps needs to be expanded upon.&lt;br /&gt;
To improve more information on each topic is required, review of visual displays (mainly balancing images between sections some have plenty where as other lack) and copy write information is essential&lt;br /&gt;
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Somatosensory review:&lt;br /&gt;
&lt;br /&gt;
The key points are clearly presented at the top of the page efficiently formatted allowing viewer a perfect insight to the entire pages content. There is a severe lack of visual stimuli; this makes the page present as boring and text heavy. &lt;br /&gt;
Image citation is commendable although throughout the text there is unacceptable links to external sites that are not explained with a messy reference section. The information presented is quite detailed and promotes a significant amount of research and understanding, it is put forward in an excellent matter, sections that could easily be expanded are glossary, and perhaps a section specifically on development. Attempt to relate to the learning aims of embryology are apparent. There is a large amount of information presented in a fantastic way although the lack of visual stimuli takes away from the final product, perhaps a more summarised presentation matter would be appropriate to break up large amount of text; this along with the tidy up of referencing needs to be addressed.&lt;br /&gt;
&lt;br /&gt;
Olfaction review:&lt;br /&gt;
&lt;br /&gt;
Upon first glance of the page you immediately get the impression excellent presentation and a surplus of information. Most topics are well described although the history of discoveries layout is questionable and a table would present at a higher quality.&lt;br /&gt;
It is clear that the group has a high level of understanding through large amount of research; this is then transformed into chunks of knowledge in which are easily digestible for the reader. The page lacks visual encourage, I believe more detail into this would only benefit the page. The glossary could quite easily be expanded many terms throughout the text are absent from this list.&lt;br /&gt;
This page is almost parallel with embryological teaching aims. Citation &amp;amp; referencing is excellent. The way to improve this page would be reducing the weight of the text using innovative ideas to the present information in a more exciting way along side inclusion of more visual stimulus.&lt;br /&gt;
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Abnormal Vision review:&lt;br /&gt;
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An excellent straight forward introduction, presentation and layout of the page is questionable perhaps the use of different summary methods would improve this for example dot points along with image choice and size.  A common topic among all groups is to expand the glossary which is easily done and will only improve the finished merchandise. Language used throughout could be less primitive, very simplistic in certain sections. The referencing is satisfactory although external links section has been left out.&lt;br /&gt;
All the information is present although the organisation skills need to be assessed to allow optimum presentation of ideas. The text contains in-depth embryological teachings aims. The page looks promising and editing is the easiest part once corrected I expect a sound result.&lt;br /&gt;
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Hearing review:&lt;br /&gt;
&lt;br /&gt;
This group successfully energies the audience with a funny picture, along with a great introduction and an interactive writing style from the first paragraph. This page needs to address the reoccurring text to image ratio, allowing the reader more explanation complementing the hard work of explaining concepts. The highlight of this text was the abnormal hearing section which I found to be very interesting along with sound presentation of ideas. The demise of this page is the lack of information in current research and being starved of visual stimuli.&lt;br /&gt;
Overall a good attempt to line up embryological teaching concepts, when these easily addressable points are responded to a commendable finish will be apparent.&lt;br /&gt;
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==&amp;quot; lab 7 assessment &amp;quot;==&lt;br /&gt;
&lt;br /&gt;
1.&lt;br /&gt;
mutations in GATA6 have been linked to neonates with diabatetes, suggesting that mutations in GATA6 disrupts the development of this endocrine organ. Manipulation of genes using animal models helped provide this evidence.&lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/pubmed/23006330]&lt;br /&gt;
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2. &lt;br /&gt;
The embryonic tooth is derived from the mesodermal and ectodermal layers. The development of teeth originates when the dental lamina divides rapildly to form the future rows that teeth are located within. Their are enanmal organs present which produce circular outgrowths providing an apropriate site for tooth formation, This organ is also responsible for the complete morphology of the later devloped tooth.&lt;/div&gt;</summary>
		<author><name>Z3330795</name></author>
	</entry>
	<entry>
		<id>https://embryology.med.unsw.edu.au/embryology/index.php?title=2012_Group_Project_3&amp;diff=106020</id>
		<title>2012 Group Project 3</title>
		<link rel="alternate" type="text/html" href="https://embryology.med.unsw.edu.au/embryology/index.php?title=2012_Group_Project_3&amp;diff=106020"/>
		<updated>2012-10-05T00:42:27Z</updated>

		<summary type="html">&lt;p&gt;Z3330795: /* External Links */&lt;/p&gt;
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&lt;div&gt;=Taste Development=&lt;br /&gt;
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You are out to dinner and your meal arrives in front of you, the aromas and the presentation of your food strikes you immediately. Half way through, the waiter returns and asks “How does your meal taste?”  The answer is not as simple as one might think. Why does the meal taste pleasant? How do we experience different tastes? In the following page, we aim to discern how exactly one would answer these questions by looking at the embryological development of the taste system from week to week. &lt;br /&gt;
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Taste is a complex sensory system and its precise workings are to this day not fully understood. What makes it so complicated is the interaction between the structure of tongue and taste buds and how this contributes to the representation of taste qualities (salty, bitter, sweet, sour and umami) in the brain. We will also look at some current research on animal models being undertaken to evaluate the role of specific genes in the development of sensory structures. By looking at the taste system’s genetic basis, we now have a greater understanding of the abnormalities that may occur during development and a direction to pursue in future research to attempt to fill in the gaps of scientific knowledge.&lt;br /&gt;
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[[File:Baby tongue.jpg|centre|500px]]&lt;br /&gt;
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==History of Discoveries==&lt;br /&gt;
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{| cellpadding=5 style=&amp;quot;border:1px solid #BBB&amp;quot;&lt;br /&gt;
|- bgcolor=&amp;quot;#faecc8&amp;quot;&lt;br /&gt;
|''' Date'''|| '''Significant Discovery'''&lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#faf6ed&amp;quot;&lt;br /&gt;
|'''350BC'''&lt;br /&gt;
|| Aristotle writes about the basic tastes, sweet and bitter. He also notes that it can be modified by salty and acidic. &amp;lt;ref name=&amp;quot;PMID22717400&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;22717400&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#faecc8&amp;quot;&lt;br /&gt;
|'''1901'''&lt;br /&gt;
|| D. Hanig publishes a paper describing taste sensitivity in different regions of the tongue. &lt;br /&gt;
''Interesting fact:'' The modern concept of a 'tongue map' is a misinterpretation of this study. &amp;lt;ref name=&amp;quot;PMID22717400&amp;quot;/&amp;gt;&lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#faf6ed&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''1908'''&lt;br /&gt;
|Kikunae Ikeda, a professor of the Tokyo Imperial University, discovered and identified the fifth basic taste: umami (savouriness), made palatable by glutamate.  &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;12438213&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
[http://chemse.oxfordjournals.org/content/27/9/847.long New Seasonings]&lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#faecc8&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''1931-32'''&lt;br /&gt;
| A chemist named Arthur Fox and his college noted that they had different sensitivities to the bitter tasting Phenylthiocarbamide (PTC).&amp;lt;ref&amp;gt;Blakeslee AF, Fox AL. Our different taste worlds. J Hered. 1932;23:97–107.&amp;lt;/ref&amp;gt; Geneticists later confirm these findings, and discover that non-tasting is a recessive genetic trait. &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;17782493&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/pubmed/17782493 Inherited taste deficiency] &lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#faf6ed&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''1965'''&lt;br /&gt;
|Farbman's study of the developing taste but in rat fungiform papilla was significant in increasing our understanding of taste bud development. &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;14300090&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
[http://www.sciencedirect.com/science/article/pii/0012160665900400 Electron microscope study of the developing taste bud in rat fungiform papilla.]&lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#faecc8&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''1992'''&lt;br /&gt;
|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. &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;1608467 &amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
[http://www.nature.com/nature/journal/v357/n6379/abs/357563a0.html Gustducin is a taste-cell-specific G protein closely related to the transducins]&lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#faf6ed&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''1995'''&lt;br /&gt;
|Barlow et al. experimented with Axolotl salamanders and concluded that taste buds from this species arise exclusively from epithelial tissue, &amp;quot;oropharyngeal [[#Glossary |'''epithelium''']]&amp;quot;. &amp;lt;ref name=&amp;quot;PMID17826760&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;17826760&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/pubmed/17826760 Embryonic origin of gustatory cranial sensory neurons] &lt;br /&gt;
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|- bgcolor=&amp;quot;#faecc8&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''1996'''&lt;br /&gt;
| 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 &amp;quot;at least dual function of embryonic/fetal taste buds&amp;quot;, including non-gustatory, paracrine functions prior to the 14th week and gustatory after the 14th week. &amp;lt;ref name=&amp;quot;PMID8955790&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;8955790&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/pubmed/8955790 Embryonic and early fetal development of human taste buds: a transmission electron microscopical study]&lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#faf6ed&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''2000'''&lt;br /&gt;
|Chandrashekar, J. et al. discover the first taste sonsors, the T2R bitter taste receptors. &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;10761935&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
[http://www.sciencedirect.com/science/article/pii/S0092867400807060 T2Rs Function as Bitter Taste Receptors]&lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#faecc8&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''2001'''&lt;br /&gt;
|Nelson, G. et al. discover the sweet receptor: a combination of T1R2 and T1R3. &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;11509186&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/pubmed/11509186?dopt=Abstract&amp;amp;holding=npg Mammalian sweet taste receptors.]&lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#faf6ed&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''2002'''&lt;br /&gt;
|Nelson G. et al. discover the amino acid (umami) taste receptor: a combination of T1R1 and T1R3 identified.  &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;11894099&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/pubmed/11894099?dopt=Abstract&amp;amp;holding=npg An amino-acid taste receptor]&lt;br /&gt;
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|- bgcolor=&amp;quot;#faecc8&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''2005'''&lt;br /&gt;
|Dyer, J. et al. discover sweet taste receptors in the GI tract. &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;17855558&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1986582/ Sweet taste signaling in the gut]&lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#faf6ed&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''2006'''&lt;br /&gt;
|Huang, A. L et al. discover cells for sour taste, identified by PKD2L1 (a polycystic kidney disease-like ion channel). &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;16929298&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1571047/ The Cells and Logic for Mammalian Sour Taste detection]&lt;br /&gt;
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|- bgcolor=&amp;quot;#faecc8&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''2007'''&lt;br /&gt;
|Harlow DE, Barlow LA of the University of Colorado Denver Health Sciences Center provide evidence of the &amp;quot;embryonic origin of gustatory cranial sensory neurons&amp;quot;. &amp;lt;ref name=&amp;quot;PMID17826760&amp;quot;/&amp;gt;&lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/pubmed/17826760 Embryonic origin of gustatory cranial sensory neurons.]&lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#faf6ed&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''2009'''&lt;br /&gt;
|A study by Hevezi P et al, presents &amp;quot;the first comprehensive characterization of gene expression in primate taste buds&amp;quot;, as opposed to previous studies which focused on rodents. &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;19636377&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/pubmed/19636377 Genome-wide analysis of gene expression in primate taste buds reveals links to diverse processes]&lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#faecc8&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''2010'''&lt;br /&gt;
|Chandrashekar, J. et al. identify epithelial sodium channel (ENaC) as the sodium-salt taste receptor. &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;20107438&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/pubmed/20107438?dopt=Abstract&amp;amp;holding=npg The cells and peripheral representation of sodium taste in mice]&lt;br /&gt;
|}&lt;br /&gt;
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==Adult Tongue and Taste Buds – Structure and Function==&lt;br /&gt;
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'''Structure'''&lt;br /&gt;
&lt;br /&gt;
The tongue is located on the floor of the oral cavity, It is a muscular structure with sensory cells found on the surface. 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.  &lt;br /&gt;
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[http://www.webmd.com/oral-health/picture-of-the-tongue] &lt;br /&gt;
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''''The image below is a simplistic diagram of the surface of the tongue showing the locations of the different papillae and other important features'''&lt;br /&gt;
&lt;br /&gt;
{|&lt;br /&gt;
| [[Image:Drawing of Tongue.png|centre|500px]]&lt;br /&gt;
&lt;br /&gt;
[[File:Taste_pathway.jpg|right|thumb|200px|Simplistic Pathway of Taste]]&lt;br /&gt;
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'''Papillae'''&lt;br /&gt;
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There are 4 types of papillae on the tongue.&lt;br /&gt;
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.[http://www.tutorvista.com/content/biology/biology-iv/nervous-coordination/tongue-structure.php#parts-of-tongue]&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
[[File:Papillae.jpg|Left|thumb|200px|Close up of Human Tongue Papillae]]&lt;br /&gt;
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[[File:Fungiformpapillae.jpg|left|thumb|200px|Fungiform Papillae]]&lt;br /&gt;
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[[File:Circumvallatepapillae.jpg |left|thumb|200px|Circumvallate Papillae]]&lt;br /&gt;
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[[File:Filiformpapillae.jpg|left|200px|thumb|Foliate Papillae]]&lt;br /&gt;
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'''Function'''&lt;br /&gt;
&lt;br /&gt;
The Tongue has muscular and sensory functions, muscular functions include swallowing and speech where as sensory function involves taste. This section will focus on the sensory functions of the tongue.&lt;br /&gt;
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. [http://www.cf.ac.uk/biosi/staffinfo/jacob/teaching/sensory/taste.html]&lt;br /&gt;
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[[File:Taste_bud_1.jpg|right|thumb|200px|Cross section of a taste bud unit|centre|Cross section of a taste bud unit]]&lt;br /&gt;
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'''Link Between Taste and Smell'''&lt;br /&gt;
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The pathways of smell and taste are very similar (chemosensation). Pathways both involve the conversion of a dissolved chemical stimulus transformed into a electrical impulse for interpretation by the brain.	&lt;br /&gt;
Taste and smell overlap when humans experience flavour, flavour involves an interaction of taste, smell, texture and temperature, where taste is only a portion of this interaction. when the brain interprets a flavour, contribution from other senses has a significant role in identification. In conclusion Taste and Smell in combination with other senses help develop a sensory interpretation called flavour.[http://www.entnet.org/HealthInformation/smellTaste.cfm]&lt;br /&gt;
[[File:Human smelling.jpg|500px|centre]]&lt;br /&gt;
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== Human Weekly Development - Two Prominent Studies ==&lt;br /&gt;
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. &lt;br /&gt;
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The findings of these two studies are summarized in the table below. The figures provided relate to the images on their respective research papers.&lt;br /&gt;
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# [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] &lt;br /&gt;
# [http://chemse.oxfordjournals.org/content/22/6/601.long Scanning electron microscopical studies of developing gustatory papillae in humans, 1997]  &lt;br /&gt;
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===Timeline of Developmental Processes of Human Taste Buds===&lt;br /&gt;
{| cellpadding=5 style=&amp;quot;border:1px solid #BBB&amp;quot;&lt;br /&gt;
|- bgcolor=&amp;quot;#89CFF0&amp;quot;&lt;br /&gt;
|'''Postovulatory Week'''||'''Description'''&lt;br /&gt;
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|- bgcolor=&amp;quot;#BCD4E6&amp;quot;&lt;br /&gt;
|'''Week 6''' ||&lt;br /&gt;
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. &amp;lt;ref name=&amp;quot;PMID9455607&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;9455607&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
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|- bgcolor=&amp;quot;#89CFF0&amp;quot;&lt;br /&gt;
| '''Weeks 6 to 7'''|| &lt;br /&gt;
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. &amp;lt;ref name=PMID8955790/&amp;gt;&lt;br /&gt;
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|- bgcolor=&amp;quot;#BCD4E6&amp;quot;&lt;br /&gt;
| '''Week 7 '''||&lt;br /&gt;
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.  &amp;lt;ref name=PMID9455607/&amp;gt; &lt;br /&gt;
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|- bgcolor=&amp;quot;#89CFF0&amp;quot;&lt;br /&gt;
| ''' Week 8  ''' ||&lt;br /&gt;
* The taste bud primordium are still differentiated, elongated epithelial cells, resting on a slightly developed core of young dermal papilla.&lt;br /&gt;
* 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. &lt;br /&gt;
* Ciliated cells also appear around the 8th week, however the significance of these cells which are scattered randomly across the lingual surface remains unclear. &amp;lt;ref name=PMID8955790/&amp;gt; &lt;br /&gt;
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|- bgcolor=&amp;quot;#BCD4E6&amp;quot;&lt;br /&gt;
|'''  Week 9''' ||&lt;br /&gt;
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). &amp;lt;ref name=PMID9455607/&amp;gt;&lt;br /&gt;
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|- bgcolor=&amp;quot;#89CFF0&amp;quot;&lt;br /&gt;
|'''  Weeks 10-11''' ||&lt;br /&gt;
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). &amp;lt;ref name=PMID8955790/&amp;gt; &lt;br /&gt;
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|- bgcolor=&amp;quot;#BCD4E6&amp;quot;&lt;br /&gt;
|''' Week 12 ''' ||&lt;br /&gt;
Taste bud cells are more clearly differentiated into epithelial cell types II and III. &amp;lt;ref name=PMID8955790/&amp;gt; &lt;br /&gt;
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|- bgcolor=&amp;quot;#89CFF0&amp;quot;&lt;br /&gt;
|''' Weeks 12-13  ''' ||&lt;br /&gt;
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). &amp;lt;ref name=PMID8955790/&amp;gt; &lt;br /&gt;
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|- bgcolor=&amp;quot;#BCD4E6&amp;quot;&lt;br /&gt;
|''' Weeks 14 -15 ''' ||&lt;br /&gt;
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. &amp;lt;ref name=PMID8955790/&amp;gt; &lt;br /&gt;
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==Abnormalities==&lt;br /&gt;
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It should be mentioned that gustatory abnormalities have not been widely researched. Most research conducted in this field has been conducted through animal testing on mice and this is the basis of information provided below. &lt;br /&gt;
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===Knocking out P2X Receptors===&lt;br /&gt;
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[[File:Image of taste being evoked by visualising ATP release.jpeg|Left|thumb|200px|Evoking taste - ATP release in tongue]]&lt;br /&gt;
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The sensation of taste is made through neurotransmitters. But what happens when there is a disruption in this 'transmission', either through not releasing neurotransmitter or by a reduction in receptor number? Huang, 2008 &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;21940456&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; use the the premise that P2X receptors are essential in taste transduction and that their absence would lead to the inability to taste. &lt;br /&gt;
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This team used to the neurotransmitter ATP, as a quantitative measure of gustatory sensation and taste. ATP is only one neurotransmitter that is involved in taste transduction among others including ''&amp;quot;acetylcholine, glutamate, norepinephrine (NE), serotonin (5-HT), γ-aminobutyric acid (GABA) and a number of peptides.&amp;quot;''&lt;br /&gt;
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This was done by using a comparison of wild type (WT) and double knockout (DKO) mice. P2X receptors, namely 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. A tastant was administered to mucosal lingual epithelium the tongue of the nice and collected. The release of ATP was measured using luciferase and IHC (Immunohisto Chemistry).&lt;br /&gt;
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It should be noted that the taste buds in DKO are functional, but are not stimulated by the administration of tastants. &lt;br /&gt;
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The transmission of release of ATP is secreted through gap junction hemichannels (pannexin 1 gap junction).&lt;br /&gt;
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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.&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;21940456&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
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===FGF signalling and genes===&lt;br /&gt;
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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 (see image under 'Structure of the tongue').&lt;br /&gt;
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By knocking out ''Spry'' genes using mice which had both ''Spry1'' and ''Spry2'' knocked out showed that the number of CVP doubled. However, when Fibroblast [[#Glossary |'''Growth Factor''']] gene (&amp;quot;Fgf10&amp;quot;) 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 &amp;quot;Fgf10&amp;quot; to limit the size of the CVP progenitor placode. Exclusive expression of ''Fgf10'' in the [[#Glossary |'''mesenchyme''']] is necessary for the formation of CVP. &lt;br /&gt;
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{|&lt;br /&gt;
| [[File:Figure 1 Spry1-2.jpeg|160px|]]&lt;br /&gt;
| [[File:CVP of WT(top) and DKO(bottom) mice with H&amp;amp;E and SEM.png]]&lt;br /&gt;
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|-&lt;br /&gt;
| &amp;lt;center&amp;gt;[[Figure 1 Spry1-2.jpeg]]&amp;lt;/center&amp;gt;&lt;br /&gt;
| &amp;lt;center&amp;gt;[[CVP of WT(top) and DKO(bottom) mice with H&amp;amp;E and SEM.png]]&amp;lt;/center&amp;gt;&lt;br /&gt;
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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).&lt;br /&gt;
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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).&lt;br /&gt;
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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''&amp;amp; ''Spry 1&amp;amp;2''work antagonistically through receptor tyrosine kinase (RTK) signalling.&lt;br /&gt;
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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.&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;21655085&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
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==Gustatory System==&lt;br /&gt;
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[[Image:Taste qualities.gif|thumb|The five basic tastes]]&lt;br /&gt;
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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.&lt;br /&gt;
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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.&amp;lt;ref name=PMID20696704&amp;gt;&amp;lt;pubmed&amp;gt;20696704&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
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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 &amp;lt;ref name=PMID20696704/&amp;gt; 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.&lt;br /&gt;
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===Cell Biology===&lt;br /&gt;
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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.&lt;br /&gt;
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====Type II receptors====&lt;br /&gt;
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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:&lt;br /&gt;
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# Stimulates gustatory nerve afferents which project to gustatory nuclei  in the spinal cord&lt;br /&gt;
# Excites Type III presynaptic nerve fibers to release serotonin. &lt;br /&gt;
# Has a positive feedback effect on type II receptor cells, increasing the level of ATP production.&lt;br /&gt;
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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.&lt;br /&gt;
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==Taste Map==&lt;br /&gt;
[[Image:Taste map.png|thumb|left|250px|Obsolete idea of the tongue map]]&lt;br /&gt;
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.&lt;br /&gt;
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===Neural Pathways===&lt;br /&gt;
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'''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''. &lt;br /&gt;
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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:  &lt;br /&gt;
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* ''Facial nerve n''. -  carries taste information from the anterior 2/3 of the tongue.&lt;br /&gt;
* ''Hypoglossal n.'' - carries taste information from the posterior 1/3 of the tongue.&lt;br /&gt;
* ''Vagus n''. - carries taste information from the palate&lt;br /&gt;
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'''Second order neurons''' - From the NTS second order neurons carry taste information to the Ventral posteromedial (VPM) nucleus in the thalamus.&amp;lt;ref name=PMID21885776/&amp;gt;&lt;br /&gt;
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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.  &lt;br /&gt;
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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.&lt;br /&gt;
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===Cortical Areas===&lt;br /&gt;
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[[Image:Primary gustatory cortex.png|thumb|Primary gustatory cortex]]&lt;br /&gt;
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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)&amp;lt;ref name=PMID22245354&amp;gt;&amp;lt;pubmed&amp;gt;22245354&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;, with the secondary taste cortex in the caudolateral orbitofrontal cortex.&amp;lt;ref name=PMID21305668&amp;gt;&amp;lt;pubmed&amp;gt;21305668&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;  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.&amp;lt;ref name=PMID21885776&amp;gt;&amp;lt;pubmed&amp;gt;21885776&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; These findings lend weight to the idea that there is only one receptor for each taste quality.&lt;br /&gt;
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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).&amp;lt;ref name=PMID21885776/&amp;gt; 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&lt;br /&gt;
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===Neuronal Development===&lt;br /&gt;
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The gustatory system must not be solely thought of as being comprised of simply the tongue and palate. The types of neurons which carry taste information to the brain are also pivotal in constructing the expression of taste qualities.&lt;br /&gt;
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The two main gustatory neurons which develop are the geniculate ganglion and the petrosal ganglion. These are the visceral sensory ganglion of cranial nerves VII (Facial) and  IX (Hypoglossal) respectively which carry taste information from the tongue to the nucleus tractus solitarius. They arise at the posterior placodal region from the epibranchial placodes, a thickening of ectoderm. The first epibranchial placode gives rise to the geniculate ganglion and the second to the petrosal ganglion.&lt;br /&gt;
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The molecular basis for gustatory neuron formation is not completely understood though there are a number of transcription factors which are thought to play an important role in firstly, placode formation and secondly, neuron differentiation.&lt;br /&gt;
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*Six1/2, Six1/5 and Eya – transcription factors which cause differentiation of epibranchial placodes into the petrosal and geniculate ganglion.&lt;br /&gt;
*Bone morphogenic Protein 7 (BMP7) – a signal arising from the pharyngeal pouch which is believed to induce epibranchial placode formation. May not be solely responsible for this process, current research has been inconclusive as to how it may work with other proteins of the same family.&lt;br /&gt;
*NGN2 - Following the initial differentiation of the placodes, further differentiation occurs to form neuroblasts. NGN2 causes the delamination and migration of these neuroblasts, which subsequently migrate and fuse to form neurons.&lt;br /&gt;
*Phox2b – maintains the structural integrity of neurons. Knockout of these genes in mice causes marked atrophy of the petrosal and geniculate ganglia.&lt;br /&gt;
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The neurons involved in the gustatory system are overproduced and thus in the embryonic stage, undergo programmed cell death (apoptosis). The total amount of neurons in the geniculate ganglion, appears to be quite stable over the embryonic stages. This suggests, unlike the petrosal ganglion, the levels of neuroblast proliferation and apoptosis are fairly similar. The factors which regulate these processes remains unclear. It is posited that neurotrophins BDNF, NT4/5 and NT3 may regulate neuronal survival whilst also playing a part in axon growth from the sensory ganglion. More research is required to discern the exact individual functions of each of the neurotrophins.&lt;br /&gt;
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==Current Research==&lt;br /&gt;
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[[File:Mousetounge histologicalstain.jpg|right|thumb|200px|Image shows histological stains of a mice tongue showing dysplasia]]&lt;br /&gt;
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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. &lt;br /&gt;
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.&lt;br /&gt;
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'''Synergistic relationships of Six Genes '''&lt;br /&gt;
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In an animal study using mice by Suzuki Y, Ikeda K, Kawakami K.(2011)  Firstly nominating &amp;quot;[[#Glossary |'''Six Genes''']]&amp;quot; as a major component in [[#Glossary |'''gustatory ''']] development, stating that deficiencies in certain Six genes (specifically Six1 &amp;amp; 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 &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;21978088&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
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[[File:Abnormal of tongue.jpg|thumb|200px|Image shows an example of tongue abnormalities, this is called &amp;quot;double tongue&amp;quot; each side has independent movement!]]&lt;br /&gt;
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'''Neural Crest responsibilities '''&lt;br /&gt;
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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 &amp;quot;[[#Glossary |'''epithelium''']]&amp;quot; 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.&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;22659543&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
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'''Augmentation of Endoderm'''&lt;br /&gt;
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In an animal study conducted by Rothova M, Thompson H, Lickert H, Tucker AS.(2012) exploring the historically debated issue of &amp;quot;[[#Glossary |'''endoderm''']]&amp;quot; contribution to tongue development showed promising evidence that position of taste buds are patterned by the border of &amp;quot;[[#Glossary |'''ectoderm''']]&amp;quot; and endoderm derivative epithelium. This study was accomplished via microscopic examination of previously stained specimens. Concluding endoderm has direct influence on gustatory development &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;22581563&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
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'''Changes in Taste Cells over time'''&lt;br /&gt;
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Research by &lt;br /&gt;
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.  &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;22643728&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
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'''Shh key component of taste bud proginators'''&lt;br /&gt;
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A [[#Glossary |'''tamoxifen''']] treatment which suppresses &amp;quot;[[#Glossary |'''Sonic hedgehog''']]&amp;quot; (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.&lt;br /&gt;
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 &amp;quot;Axiocam CCD camera and Axioplan fluorescence microscope with Axiovision software&amp;quot; a study by Harlow, Yang, Williams, Barlow (2011)&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;PMC2674259&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
'''WNT family exhibit various roles'''&lt;br /&gt;
&lt;br /&gt;
 &lt;br /&gt;
The WNT gene family has a function of directing work antagonistically through receptor tyrosine kinase (RTK) signaling. However, the deletion of Sprouty Homolog 2 (Spry2) led to the increase of chimaeric virus particles (CVPs) and a significant decrease in number of fungiform papillae. In contrast, the absence of Fibroblast growth factor 10 (Fgf10) in conjunction with 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. 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. &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;PMC2768563&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
[[File:Developing_tongue_histology_001.jpg|right|thumb|200px|HIstological stain of a developing rat tongue]]&lt;br /&gt;
&lt;br /&gt;
==Glossary==&lt;br /&gt;
&lt;br /&gt;
* '''Circumvallate papillae''' - papillae that contain taste buds, that help form the Sulcus terminalis&lt;br /&gt;
&lt;br /&gt;
* '''Ectoderm'''- outer germ layer of embryo&lt;br /&gt;
&lt;br /&gt;
* '''Endoderm''' - inner germ layer of embryo&lt;br /&gt;
&lt;br /&gt;
* '''Epithelium''' - basic animal tissue that is composed of tightly packed cells, usually covering the outer portion of organs&lt;br /&gt;
&lt;br /&gt;
* '''Exocystosis''' - movement of contents out of cell&lt;br /&gt;
&lt;br /&gt;
* '''Filiform papillae''' - numerous papillae that do not contain taste buds&lt;br /&gt;
&lt;br /&gt;
* '''Foliate papillae''' - papillae that contain taste buds&lt;br /&gt;
&lt;br /&gt;
* '''Fungiform papillae''' - papillae that contain taste buds&lt;br /&gt;
&lt;br /&gt;
* '''Ganglia''' - the accumulation of a nerve cell body&lt;br /&gt;
&lt;br /&gt;
* '''Growth factor''' - a substance that stimulates the growth of cells&lt;br /&gt;
&lt;br /&gt;
* '''Gustatory''' - anything that relates to the taste sense&lt;br /&gt;
&lt;br /&gt;
* '''Hydrolysis''' - breakdown of a chemical when it reacts with water&lt;br /&gt;
&lt;br /&gt;
* '''Mesoderm''' - middle germ layer of embryo&lt;br /&gt;
&lt;br /&gt;
* '''Mesenchyme''' - multipotential cells&lt;br /&gt;
&lt;br /&gt;
* '''Neural crest''' - a part of the ectoderm found on both sides of the neural tube&lt;br /&gt;
&lt;br /&gt;
* '''Neuron''' - most simplistic unit of the nervous system&lt;br /&gt;
&lt;br /&gt;
* '''Neurotransmitter''' - chemicals which allow the passing of signals from neuron to neuron via connecting part (synapse) &lt;br /&gt;
&lt;br /&gt;
* '''Papillae''' - small rough surface projection&lt;br /&gt;
&lt;br /&gt;
*'''Placode''' - an area of thickened epithelium which eventually produces other structures.&lt;br /&gt;
&lt;br /&gt;
* '''Six genes''' - a family of genes&lt;br /&gt;
&lt;br /&gt;
* '''Sonic hedgehog (Shh)''' - signalling protein involved in normal development&lt;br /&gt;
&lt;br /&gt;
* '''Sulcus terminalis''' - describes a physical transition point separating the anterior 2/3 of the tongue from the posterior 1/3&lt;br /&gt;
&lt;br /&gt;
* '''Tamoxifen''' - hormonal altering drug&lt;br /&gt;
&lt;br /&gt;
* '''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).&lt;br /&gt;
&lt;br /&gt;
* '''Type II taste cells''' - Receptor cells acting as primary detectors of sweet, bitter or umami taste.&lt;br /&gt;
&lt;br /&gt;
* '''Type III taste cells''' - Presynaptic cells that respond to sweet, salty, sour, bitter and umami compounds.&lt;br /&gt;
&lt;br /&gt;
== References ==&lt;br /&gt;
&amp;lt;references/&amp;gt;&lt;br /&gt;
&lt;br /&gt;
==External Links==&lt;br /&gt;
{{External Links}}&lt;br /&gt;
&lt;br /&gt;
1.http://www.surgicalneurologyint.com/article.asp?issn=2152-7806;year=2012;volume=3;issue=1;spage=23;epage=23;aulast=Manjila&lt;br /&gt;
&lt;br /&gt;
2.http://embryology.med.unsw.edu.au/embryology/index.php?title=2012_Group_Project_4&lt;br /&gt;
&lt;br /&gt;
3.http://www.webmd.com/oral-health/picture-of-the-tongue&lt;br /&gt;
&lt;br /&gt;
4.http://www.tutorvista.com/content/biology/biology-iv/nervous-coordination/tongue-structure.php#parts-of-tongue&lt;br /&gt;
&lt;br /&gt;
5.http://www.cf.ac.uk/biosi/staffinfo/jacob/teaching/sensory/taste.html&lt;br /&gt;
&lt;br /&gt;
--[[User:Z8600021|Mark Hill]] 00:19, 5 October 2012 (EST) There should be text with these links.&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
--[[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.&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
----&lt;br /&gt;
&lt;br /&gt;
{{2012Projects}}&lt;/div&gt;</summary>
		<author><name>Z3330795</name></author>
	</entry>
	<entry>
		<id>https://embryology.med.unsw.edu.au/embryology/index.php?title=2012_Group_Project_3&amp;diff=106019</id>
		<title>2012 Group Project 3</title>
		<link rel="alternate" type="text/html" href="https://embryology.med.unsw.edu.au/embryology/index.php?title=2012_Group_Project_3&amp;diff=106019"/>
		<updated>2012-10-05T00:38:56Z</updated>

		<summary type="html">&lt;p&gt;Z3330795: /* Adult Tongue and Taste Buds – Structure and Function */&lt;/p&gt;
&lt;hr /&gt;
&lt;div&gt;=Taste Development=&lt;br /&gt;
&lt;br /&gt;
You are out to dinner and your meal arrives in front of you, the aromas and the presentation of your food strikes you immediately. Half way through, the waiter returns and asks “How does your meal taste?”  The answer is not as simple as one might think. Why does the meal taste pleasant? How do we experience different tastes? In the following page, we aim to discern how exactly one would answer these questions by looking at the embryological development of the taste system from week to week. &lt;br /&gt;
&lt;br /&gt;
Taste is a complex sensory system and its precise workings are to this day not fully understood. What makes it so complicated is the interaction between the structure of tongue and taste buds and how this contributes to the representation of taste qualities (salty, bitter, sweet, sour and umami) in the brain. We will also look at some current research on animal models being undertaken to evaluate the role of specific genes in the development of sensory structures. By looking at the taste system’s genetic basis, we now have a greater understanding of the abnormalities that may occur during development and a direction to pursue in future research to attempt to fill in the gaps of scientific knowledge.&lt;br /&gt;
&lt;br /&gt;
[[File:Baby tongue.jpg|centre|500px]]&lt;br /&gt;
&lt;br /&gt;
==History of Discoveries==&lt;br /&gt;
&lt;br /&gt;
{| cellpadding=5 style=&amp;quot;border:1px solid #BBB&amp;quot;&lt;br /&gt;
|- bgcolor=&amp;quot;#faecc8&amp;quot;&lt;br /&gt;
|''' Date'''|| '''Significant Discovery'''&lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#faf6ed&amp;quot;&lt;br /&gt;
|'''350BC'''&lt;br /&gt;
|| Aristotle writes about the basic tastes, sweet and bitter. He also notes that it can be modified by salty and acidic. &amp;lt;ref name=&amp;quot;PMID22717400&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;22717400&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#faecc8&amp;quot;&lt;br /&gt;
|'''1901'''&lt;br /&gt;
|| D. Hanig publishes a paper describing taste sensitivity in different regions of the tongue. &lt;br /&gt;
''Interesting fact:'' The modern concept of a 'tongue map' is a misinterpretation of this study. &amp;lt;ref name=&amp;quot;PMID22717400&amp;quot;/&amp;gt;&lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#faf6ed&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''1908'''&lt;br /&gt;
|Kikunae Ikeda, a professor of the Tokyo Imperial University, discovered and identified the fifth basic taste: umami (savouriness), made palatable by glutamate.  &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;12438213&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
[http://chemse.oxfordjournals.org/content/27/9/847.long New Seasonings]&lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#faecc8&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''1931-32'''&lt;br /&gt;
| A chemist named Arthur Fox and his college noted that they had different sensitivities to the bitter tasting Phenylthiocarbamide (PTC).&amp;lt;ref&amp;gt;Blakeslee AF, Fox AL. Our different taste worlds. J Hered. 1932;23:97–107.&amp;lt;/ref&amp;gt; Geneticists later confirm these findings, and discover that non-tasting is a recessive genetic trait. &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;17782493&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/pubmed/17782493 Inherited taste deficiency] &lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#faf6ed&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''1965'''&lt;br /&gt;
|Farbman's study of the developing taste but in rat fungiform papilla was significant in increasing our understanding of taste bud development. &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;14300090&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
[http://www.sciencedirect.com/science/article/pii/0012160665900400 Electron microscope study of the developing taste bud in rat fungiform papilla.]&lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#faecc8&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''1992'''&lt;br /&gt;
|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. &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;1608467 &amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
[http://www.nature.com/nature/journal/v357/n6379/abs/357563a0.html Gustducin is a taste-cell-specific G protein closely related to the transducins]&lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#faf6ed&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''1995'''&lt;br /&gt;
|Barlow et al. experimented with Axolotl salamanders and concluded that taste buds from this species arise exclusively from epithelial tissue, &amp;quot;oropharyngeal [[#Glossary |'''epithelium''']]&amp;quot;. &amp;lt;ref name=&amp;quot;PMID17826760&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;17826760&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/pubmed/17826760 Embryonic origin of gustatory cranial sensory neurons] &lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#faecc8&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''1996'''&lt;br /&gt;
| 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 &amp;quot;at least dual function of embryonic/fetal taste buds&amp;quot;, including non-gustatory, paracrine functions prior to the 14th week and gustatory after the 14th week. &amp;lt;ref name=&amp;quot;PMID8955790&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;8955790&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/pubmed/8955790 Embryonic and early fetal development of human taste buds: a transmission electron microscopical study]&lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#faf6ed&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''2000'''&lt;br /&gt;
|Chandrashekar, J. et al. discover the first taste sonsors, the T2R bitter taste receptors. &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;10761935&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
[http://www.sciencedirect.com/science/article/pii/S0092867400807060 T2Rs Function as Bitter Taste Receptors]&lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#faecc8&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''2001'''&lt;br /&gt;
|Nelson, G. et al. discover the sweet receptor: a combination of T1R2 and T1R3. &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;11509186&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/pubmed/11509186?dopt=Abstract&amp;amp;holding=npg Mammalian sweet taste receptors.]&lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#faf6ed&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''2002'''&lt;br /&gt;
|Nelson G. et al. discover the amino acid (umami) taste receptor: a combination of T1R1 and T1R3 identified.  &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;11894099&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/pubmed/11894099?dopt=Abstract&amp;amp;holding=npg An amino-acid taste receptor]&lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#faecc8&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''2005'''&lt;br /&gt;
|Dyer, J. et al. discover sweet taste receptors in the GI tract. &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;17855558&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1986582/ Sweet taste signaling in the gut]&lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#faf6ed&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''2006'''&lt;br /&gt;
|Huang, A. L et al. discover cells for sour taste, identified by PKD2L1 (a polycystic kidney disease-like ion channel). &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;16929298&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1571047/ The Cells and Logic for Mammalian Sour Taste detection]&lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#faecc8&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''2007'''&lt;br /&gt;
|Harlow DE, Barlow LA of the University of Colorado Denver Health Sciences Center provide evidence of the &amp;quot;embryonic origin of gustatory cranial sensory neurons&amp;quot;. &amp;lt;ref name=&amp;quot;PMID17826760&amp;quot;/&amp;gt;&lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/pubmed/17826760 Embryonic origin of gustatory cranial sensory neurons.]&lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#faf6ed&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''2009'''&lt;br /&gt;
|A study by Hevezi P et al, presents &amp;quot;the first comprehensive characterization of gene expression in primate taste buds&amp;quot;, as opposed to previous studies which focused on rodents. &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;19636377&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/pubmed/19636377 Genome-wide analysis of gene expression in primate taste buds reveals links to diverse processes]&lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#faecc8&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''2010'''&lt;br /&gt;
|Chandrashekar, J. et al. identify epithelial sodium channel (ENaC) as the sodium-salt taste receptor. &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;20107438&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/pubmed/20107438?dopt=Abstract&amp;amp;holding=npg The cells and peripheral representation of sodium taste in mice]&lt;br /&gt;
|}&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
==Adult Tongue and Taste Buds – Structure and Function==&lt;br /&gt;
&lt;br /&gt;
'''Structure'''&lt;br /&gt;
&lt;br /&gt;
The tongue is located on the floor of the oral cavity, It is a muscular structure with sensory cells found on the surface. 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.  &lt;br /&gt;
&lt;br /&gt;
[http://www.webmd.com/oral-health/picture-of-the-tongue] &lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
''''The image below is a simplistic diagram of the surface of the tongue showing the locations of the different papillae and other important features'''&lt;br /&gt;
&lt;br /&gt;
{|&lt;br /&gt;
| [[Image:Drawing of Tongue.png|centre|500px]]&lt;br /&gt;
&lt;br /&gt;
[[File:Taste_pathway.jpg|right|thumb|200px|Simplistic Pathway of Taste]]&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
'''Papillae'''&lt;br /&gt;
&lt;br /&gt;
There are 4 types of papillae on the tongue.&lt;br /&gt;
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.[http://www.tutorvista.com/content/biology/biology-iv/nervous-coordination/tongue-structure.php#parts-of-tongue]&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
[[File:Papillae.jpg|Left|thumb|200px|Close up of Human Tongue Papillae]]&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
[[File:Fungiformpapillae.jpg|left|thumb|200px|Fungiform Papillae]]&lt;br /&gt;
&lt;br /&gt;
[[File:Circumvallatepapillae.jpg |left|thumb|200px|Circumvallate Papillae]]&lt;br /&gt;
&lt;br /&gt;
[[File:Filiformpapillae.jpg|left|200px|thumb|Foliate Papillae]]&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
'''Function'''&lt;br /&gt;
&lt;br /&gt;
The Tongue has muscular and sensory functions, muscular functions include swallowing and speech where as sensory function involves taste. This section will focus on the sensory functions of the tongue.&lt;br /&gt;
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. [http://www.cf.ac.uk/biosi/staffinfo/jacob/teaching/sensory/taste.html]&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
[[File:Taste_bud_1.jpg|right|thumb|200px|Cross section of a taste bud unit|centre|Cross section of a taste bud unit]]&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
'''Link Between Taste and Smell'''&lt;br /&gt;
&lt;br /&gt;
The pathways of smell and taste are very similar (chemosensation). Pathways both involve the conversion of a dissolved chemical stimulus transformed into a electrical impulse for interpretation by the brain.	&lt;br /&gt;
Taste and smell overlap when humans experience flavour, flavour involves an interaction of taste, smell, texture and temperature, where taste is only a portion of this interaction. when the brain interprets a flavour, contribution from other senses has a significant role in identification. In conclusion Taste and Smell in combination with other senses help develop a sensory interpretation called flavour.[http://www.entnet.org/HealthInformation/smellTaste.cfm]&lt;br /&gt;
[[File:Human smelling.jpg|500px|centre]]&lt;br /&gt;
&lt;br /&gt;
== Human Weekly Development - Two Prominent Studies ==&lt;br /&gt;
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. &lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
The findings of these two studies are summarized in the table below. The figures provided relate to the images on their respective research papers.&lt;br /&gt;
&lt;br /&gt;
# [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] &lt;br /&gt;
# [http://chemse.oxfordjournals.org/content/22/6/601.long Scanning electron microscopical studies of developing gustatory papillae in humans, 1997]  &lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
===Timeline of Developmental Processes of Human Taste Buds===&lt;br /&gt;
{| cellpadding=5 style=&amp;quot;border:1px solid #BBB&amp;quot;&lt;br /&gt;
|- bgcolor=&amp;quot;#89CFF0&amp;quot;&lt;br /&gt;
|'''Postovulatory Week'''||'''Description'''&lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#BCD4E6&amp;quot;&lt;br /&gt;
|'''Week 6''' ||&lt;br /&gt;
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. &amp;lt;ref name=&amp;quot;PMID9455607&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;9455607&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
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| '''Weeks 6 to 7'''|| &lt;br /&gt;
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. &amp;lt;ref name=PMID8955790/&amp;gt;&lt;br /&gt;
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| '''Week 7 '''||&lt;br /&gt;
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.  &amp;lt;ref name=PMID9455607/&amp;gt; &lt;br /&gt;
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| ''' Week 8  ''' ||&lt;br /&gt;
* The taste bud primordium are still differentiated, elongated epithelial cells, resting on a slightly developed core of young dermal papilla.&lt;br /&gt;
* 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. &lt;br /&gt;
* Ciliated cells also appear around the 8th week, however the significance of these cells which are scattered randomly across the lingual surface remains unclear. &amp;lt;ref name=PMID8955790/&amp;gt; &lt;br /&gt;
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|'''  Week 9''' ||&lt;br /&gt;
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). &amp;lt;ref name=PMID9455607/&amp;gt;&lt;br /&gt;
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|'''  Weeks 10-11''' ||&lt;br /&gt;
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). &amp;lt;ref name=PMID8955790/&amp;gt; &lt;br /&gt;
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|''' Week 12 ''' ||&lt;br /&gt;
Taste bud cells are more clearly differentiated into epithelial cell types II and III. &amp;lt;ref name=PMID8955790/&amp;gt; &lt;br /&gt;
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|''' Weeks 12-13  ''' ||&lt;br /&gt;
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). &amp;lt;ref name=PMID8955790/&amp;gt; &lt;br /&gt;
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|''' Weeks 14 -15 ''' ||&lt;br /&gt;
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. &amp;lt;ref name=PMID8955790/&amp;gt; &lt;br /&gt;
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==Abnormalities==&lt;br /&gt;
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It should be mentioned that gustatory abnormalities have not been widely researched. Most research conducted in this field has been conducted through animal testing on mice and this is the basis of information provided below. &lt;br /&gt;
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===Knocking out P2X Receptors===&lt;br /&gt;
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[[File:Image of taste being evoked by visualising ATP release.jpeg|Left|thumb|200px|Evoking taste - ATP release in tongue]]&lt;br /&gt;
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The sensation of taste is made through neurotransmitters. But what happens when there is a disruption in this 'transmission', either through not releasing neurotransmitter or by a reduction in receptor number? Huang, 2008 &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;21940456&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; use the the premise that P2X receptors are essential in taste transduction and that their absence would lead to the inability to taste. &lt;br /&gt;
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This team used to the neurotransmitter ATP, as a quantitative measure of gustatory sensation and taste. ATP is only one neurotransmitter that is involved in taste transduction among others including ''&amp;quot;acetylcholine, glutamate, norepinephrine (NE), serotonin (5-HT), γ-aminobutyric acid (GABA) and a number of peptides.&amp;quot;''&lt;br /&gt;
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This was done by using a comparison of wild type (WT) and double knockout (DKO) mice. P2X receptors, namely 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. A tastant was administered to mucosal lingual epithelium the tongue of the nice and collected. The release of ATP was measured using luciferase and IHC (Immunohisto Chemistry).&lt;br /&gt;
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It should be noted that the taste buds in DKO are functional, but are not stimulated by the administration of tastants. &lt;br /&gt;
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The transmission of release of ATP is secreted through gap junction hemichannels (pannexin 1 gap junction).&lt;br /&gt;
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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.&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;21940456&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
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===FGF signalling and genes===&lt;br /&gt;
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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 (see image under 'Structure of the tongue').&lt;br /&gt;
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By knocking out ''Spry'' genes using mice which had both ''Spry1'' and ''Spry2'' knocked out showed that the number of CVP doubled. However, when Fibroblast [[#Glossary |'''Growth Factor''']] gene (&amp;quot;Fgf10&amp;quot;) 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 &amp;quot;Fgf10&amp;quot; to limit the size of the CVP progenitor placode. Exclusive expression of ''Fgf10'' in the [[#Glossary |'''mesenchyme''']] is necessary for the formation of CVP. &lt;br /&gt;
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{|&lt;br /&gt;
| [[File:Figure 1 Spry1-2.jpeg|160px|]]&lt;br /&gt;
| [[File:CVP of WT(top) and DKO(bottom) mice with H&amp;amp;E and SEM.png]]&lt;br /&gt;
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| &amp;lt;center&amp;gt;[[Figure 1 Spry1-2.jpeg]]&amp;lt;/center&amp;gt;&lt;br /&gt;
| &amp;lt;center&amp;gt;[[CVP of WT(top) and DKO(bottom) mice with H&amp;amp;E and SEM.png]]&amp;lt;/center&amp;gt;&lt;br /&gt;
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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).&lt;br /&gt;
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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).&lt;br /&gt;
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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''&amp;amp; ''Spry 1&amp;amp;2''work antagonistically through receptor tyrosine kinase (RTK) signalling.&lt;br /&gt;
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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.&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;21655085&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
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==Gustatory System==&lt;br /&gt;
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[[Image:Taste qualities.gif|thumb|The five basic tastes]]&lt;br /&gt;
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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.&lt;br /&gt;
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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.&amp;lt;ref name=PMID20696704&amp;gt;&amp;lt;pubmed&amp;gt;20696704&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
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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 &amp;lt;ref name=PMID20696704/&amp;gt; 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.&lt;br /&gt;
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===Cell Biology===&lt;br /&gt;
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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.&lt;br /&gt;
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====Type II receptors====&lt;br /&gt;
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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:&lt;br /&gt;
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# Stimulates gustatory nerve afferents which project to gustatory nuclei  in the spinal cord&lt;br /&gt;
# Excites Type III presynaptic nerve fibers to release serotonin. &lt;br /&gt;
# Has a positive feedback effect on type II receptor cells, increasing the level of ATP production.&lt;br /&gt;
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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.&lt;br /&gt;
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==Taste Map==&lt;br /&gt;
[[Image:Taste map.png|thumb|left|250px|Obsolete idea of the tongue map]]&lt;br /&gt;
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.&lt;br /&gt;
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===Neural Pathways===&lt;br /&gt;
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'''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''. &lt;br /&gt;
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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:  &lt;br /&gt;
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* ''Facial nerve n''. -  carries taste information from the anterior 2/3 of the tongue.&lt;br /&gt;
* ''Hypoglossal n.'' - carries taste information from the posterior 1/3 of the tongue.&lt;br /&gt;
* ''Vagus n''. - carries taste information from the palate&lt;br /&gt;
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'''Second order neurons''' - From the NTS second order neurons carry taste information to the Ventral posteromedial (VPM) nucleus in the thalamus.&amp;lt;ref name=PMID21885776/&amp;gt;&lt;br /&gt;
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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.  &lt;br /&gt;
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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.&lt;br /&gt;
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===Cortical Areas===&lt;br /&gt;
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[[Image:Primary gustatory cortex.png|thumb|Primary gustatory cortex]]&lt;br /&gt;
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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)&amp;lt;ref name=PMID22245354&amp;gt;&amp;lt;pubmed&amp;gt;22245354&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;, with the secondary taste cortex in the caudolateral orbitofrontal cortex.&amp;lt;ref name=PMID21305668&amp;gt;&amp;lt;pubmed&amp;gt;21305668&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;  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.&amp;lt;ref name=PMID21885776&amp;gt;&amp;lt;pubmed&amp;gt;21885776&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; These findings lend weight to the idea that there is only one receptor for each taste quality.&lt;br /&gt;
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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).&amp;lt;ref name=PMID21885776/&amp;gt; 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&lt;br /&gt;
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===Neuronal Development===&lt;br /&gt;
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The gustatory system must not be solely thought of as being comprised of simply the tongue and palate. The types of neurons which carry taste information to the brain are also pivotal in constructing the expression of taste qualities.&lt;br /&gt;
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The two main gustatory neurons which develop are the geniculate ganglion and the petrosal ganglion. These are the visceral sensory ganglion of cranial nerves VII (Facial) and  IX (Hypoglossal) respectively which carry taste information from the tongue to the nucleus tractus solitarius. They arise at the posterior placodal region from the epibranchial placodes, a thickening of ectoderm. The first epibranchial placode gives rise to the geniculate ganglion and the second to the petrosal ganglion.&lt;br /&gt;
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The molecular basis for gustatory neuron formation is not completely understood though there are a number of transcription factors which are thought to play an important role in firstly, placode formation and secondly, neuron differentiation.&lt;br /&gt;
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*Six1/2, Six1/5 and Eya – transcription factors which cause differentiation of epibranchial placodes into the petrosal and geniculate ganglion.&lt;br /&gt;
*Bone morphogenic Protein 7 (BMP7) – a signal arising from the pharyngeal pouch which is believed to induce epibranchial placode formation. May not be solely responsible for this process, current research has been inconclusive as to how it may work with other proteins of the same family.&lt;br /&gt;
*NGN2 - Following the initial differentiation of the placodes, further differentiation occurs to form neuroblasts. NGN2 causes the delamination and migration of these neuroblasts, which subsequently migrate and fuse to form neurons.&lt;br /&gt;
*Phox2b – maintains the structural integrity of neurons. Knockout of these genes in mice causes marked atrophy of the petrosal and geniculate ganglia.&lt;br /&gt;
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The neurons involved in the gustatory system are overproduced and thus in the embryonic stage, undergo programmed cell death (apoptosis). The total amount of neurons in the geniculate ganglion, appears to be quite stable over the embryonic stages. This suggests, unlike the petrosal ganglion, the levels of neuroblast proliferation and apoptosis are fairly similar. The factors which regulate these processes remains unclear. It is posited that neurotrophins BDNF, NT4/5 and NT3 may regulate neuronal survival whilst also playing a part in axon growth from the sensory ganglion. More research is required to discern the exact individual functions of each of the neurotrophins.&lt;br /&gt;
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==Current Research==&lt;br /&gt;
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[[File:Mousetounge histologicalstain.jpg|right|thumb|200px|Image shows histological stains of a mice tongue showing dysplasia]]&lt;br /&gt;
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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. &lt;br /&gt;
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.&lt;br /&gt;
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'''Synergistic relationships of Six Genes '''&lt;br /&gt;
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In an animal study using mice by Suzuki Y, Ikeda K, Kawakami K.(2011)  Firstly nominating &amp;quot;[[#Glossary |'''Six Genes''']]&amp;quot; as a major component in [[#Glossary |'''gustatory ''']] development, stating that deficiencies in certain Six genes (specifically Six1 &amp;amp; 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 &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;21978088&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
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[[File:Abnormal of tongue.jpg|thumb|200px|Image shows an example of tongue abnormalities, this is called &amp;quot;double tongue&amp;quot; each side has independent movement!]]&lt;br /&gt;
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'''Neural Crest responsibilities '''&lt;br /&gt;
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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 &amp;quot;[[#Glossary |'''epithelium''']]&amp;quot; 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.&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;22659543&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
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'''Augmentation of Endoderm'''&lt;br /&gt;
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In an animal study conducted by Rothova M, Thompson H, Lickert H, Tucker AS.(2012) exploring the historically debated issue of &amp;quot;[[#Glossary |'''endoderm''']]&amp;quot; contribution to tongue development showed promising evidence that position of taste buds are patterned by the border of &amp;quot;[[#Glossary |'''ectoderm''']]&amp;quot; and endoderm derivative epithelium. This study was accomplished via microscopic examination of previously stained specimens. Concluding endoderm has direct influence on gustatory development &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;22581563&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
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'''Changes in Taste Cells over time'''&lt;br /&gt;
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Research by &lt;br /&gt;
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.  &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;22643728&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
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'''Shh key component of taste bud proginators'''&lt;br /&gt;
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A [[#Glossary |'''tamoxifen''']] treatment which suppresses &amp;quot;[[#Glossary |'''Sonic hedgehog''']]&amp;quot; (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.&lt;br /&gt;
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 &amp;quot;Axiocam CCD camera and Axioplan fluorescence microscope with Axiovision software&amp;quot; a study by Harlow, Yang, Williams, Barlow (2011)&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;PMC2674259&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
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'''WNT family exhibit various roles'''&lt;br /&gt;
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The WNT gene family has a function of directing work antagonistically through receptor tyrosine kinase (RTK) signaling. However, the deletion of Sprouty Homolog 2 (Spry2) led to the increase of chimaeric virus particles (CVPs) and a significant decrease in number of fungiform papillae. In contrast, the absence of Fibroblast growth factor 10 (Fgf10) in conjunction with 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. 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. &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;PMC2768563&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
[[File:Developing_tongue_histology_001.jpg|right|thumb|200px|HIstological stain of a developing rat tongue]]&lt;br /&gt;
&lt;br /&gt;
==Glossary==&lt;br /&gt;
&lt;br /&gt;
* '''Circumvallate papillae''' - papillae that contain taste buds, that help form the Sulcus terminalis&lt;br /&gt;
&lt;br /&gt;
* '''Ectoderm'''- outer germ layer of embryo&lt;br /&gt;
&lt;br /&gt;
* '''Endoderm''' - inner germ layer of embryo&lt;br /&gt;
&lt;br /&gt;
* '''Epithelium''' - basic animal tissue that is composed of tightly packed cells, usually covering the outer portion of organs&lt;br /&gt;
&lt;br /&gt;
* '''Exocystosis''' - movement of contents out of cell&lt;br /&gt;
&lt;br /&gt;
* '''Filiform papillae''' - numerous papillae that do not contain taste buds&lt;br /&gt;
&lt;br /&gt;
* '''Foliate papillae''' - papillae that contain taste buds&lt;br /&gt;
&lt;br /&gt;
* '''Fungiform papillae''' - papillae that contain taste buds&lt;br /&gt;
&lt;br /&gt;
* '''Ganglia''' - the accumulation of a nerve cell body&lt;br /&gt;
&lt;br /&gt;
* '''Growth factor''' - a substance that stimulates the growth of cells&lt;br /&gt;
&lt;br /&gt;
* '''Gustatory''' - anything that relates to the taste sense&lt;br /&gt;
&lt;br /&gt;
* '''Hydrolysis''' - breakdown of a chemical when it reacts with water&lt;br /&gt;
&lt;br /&gt;
* '''Mesoderm''' - middle germ layer of embryo&lt;br /&gt;
&lt;br /&gt;
* '''Mesenchyme''' - multipotential cells&lt;br /&gt;
&lt;br /&gt;
* '''Neural crest''' - a part of the ectoderm found on both sides of the neural tube&lt;br /&gt;
&lt;br /&gt;
* '''Neuron''' - most simplistic unit of the nervous system&lt;br /&gt;
&lt;br /&gt;
* '''Neurotransmitter''' - chemicals which allow the passing of signals from neuron to neuron via connecting part (synapse) &lt;br /&gt;
&lt;br /&gt;
* '''Papillae''' - small rough surface projection&lt;br /&gt;
&lt;br /&gt;
*'''Placode''' - an area of thickened epithelium which eventually produces other structures.&lt;br /&gt;
&lt;br /&gt;
* '''Six genes''' - a family of genes&lt;br /&gt;
&lt;br /&gt;
* '''Sonic hedgehog (Shh)''' - signalling protein involved in normal development&lt;br /&gt;
&lt;br /&gt;
* '''Sulcus terminalis''' - describes a physical transition point separating the anterior 2/3 of the tongue from the posterior 1/3&lt;br /&gt;
&lt;br /&gt;
* '''Tamoxifen''' - hormonal altering drug&lt;br /&gt;
&lt;br /&gt;
* '''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).&lt;br /&gt;
&lt;br /&gt;
* '''Type II taste cells''' - Receptor cells acting as primary detectors of sweet, bitter or umami taste.&lt;br /&gt;
&lt;br /&gt;
* '''Type III taste cells''' - Presynaptic cells that respond to sweet, salty, sour, bitter and umami compounds.&lt;br /&gt;
&lt;br /&gt;
== References ==&lt;br /&gt;
&amp;lt;references/&amp;gt;&lt;br /&gt;
&lt;br /&gt;
==External Links==&lt;br /&gt;
{{External Links}}&lt;br /&gt;
&lt;br /&gt;
1.[http://www.surgicalneurologyint.com/article.asp?issn=2152-7806;year=2012;volume=3;issue=1;spage=23;epage=23;aulast=Manjila]&lt;br /&gt;
&lt;br /&gt;
2.[http://embryology.med.unsw.edu.au/embryology/index.php?title=2012_Group_Project_4]&lt;br /&gt;
&lt;br /&gt;
3.[http://www.webmd.com/oral-health/picture-of-the-tongue]&lt;br /&gt;
&lt;br /&gt;
4.[http://www.tutorvista.com/content/biology/biology-iv/nervous-coordination/tongue-structure.php#parts-of-tongue]&lt;br /&gt;
&lt;br /&gt;
5.[http://www.cf.ac.uk/biosi/staffinfo/jacob/teaching/sensory/taste.html]&lt;br /&gt;
&lt;br /&gt;
--[[User:Z8600021|Mark Hill]] 00:19, 5 October 2012 (EST) There should be text with these links.&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
--[[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.&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
----&lt;br /&gt;
&lt;br /&gt;
{{2012Projects}}&lt;/div&gt;</summary>
		<author><name>Z3330795</name></author>
	</entry>
	<entry>
		<id>https://embryology.med.unsw.edu.au/embryology/index.php?title=2012_Group_Project_3&amp;diff=106017</id>
		<title>2012 Group Project 3</title>
		<link rel="alternate" type="text/html" href="https://embryology.med.unsw.edu.au/embryology/index.php?title=2012_Group_Project_3&amp;diff=106017"/>
		<updated>2012-10-05T00:35:22Z</updated>

		<summary type="html">&lt;p&gt;Z3330795: /* Glossary */&lt;/p&gt;
&lt;hr /&gt;
&lt;div&gt;=Taste Development=&lt;br /&gt;
&lt;br /&gt;
You are out to dinner and your meal arrives in front of you, the aromas and the presentation of your food strikes you immediately. Half way through, the waiter returns and asks “How does your meal taste?”  The answer is not as simple as one might think. Why does the meal taste pleasant? How do we experience different tastes? In the following page, we aim to discern how exactly one would answer these questions by looking at the embryological development of the taste system from week to week. &lt;br /&gt;
&lt;br /&gt;
Taste is a complex sensory system and its precise workings are to this day not fully understood. What makes it so complicated is the interaction between the structure of tongue and taste buds and how this contributes to the representation of taste qualities (salty, bitter, sweet, sour and umami) in the brain. We will also look at some current research on animal models being undertaken to evaluate the role of specific genes in the development of sensory structures. By looking at the taste system’s genetic basis, we now have a greater understanding of the abnormalities that may occur during development and a direction to pursue in future research to attempt to fill in the gaps of scientific knowledge.&lt;br /&gt;
&lt;br /&gt;
[[File:Baby tongue.jpg|centre|500px]]&lt;br /&gt;
&lt;br /&gt;
==History of Discoveries==&lt;br /&gt;
&lt;br /&gt;
{| cellpadding=5 style=&amp;quot;border:1px solid #BBB&amp;quot;&lt;br /&gt;
|- bgcolor=&amp;quot;#faecc8&amp;quot;&lt;br /&gt;
|''' Date'''|| '''Significant Discovery'''&lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#faf6ed&amp;quot;&lt;br /&gt;
|'''350BC'''&lt;br /&gt;
|| Aristotle writes about the basic tastes, sweet and bitter. He also notes that it can be modified by salty and acidic. &amp;lt;ref name=&amp;quot;PMID22717400&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;22717400&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#faecc8&amp;quot;&lt;br /&gt;
|'''1901'''&lt;br /&gt;
|| D. Hanig publishes a paper describing taste sensitivity in different regions of the tongue. &lt;br /&gt;
''Interesting fact:'' The modern concept of a 'tongue map' is a misinterpretation of this study. &amp;lt;ref name=&amp;quot;PMID22717400&amp;quot;/&amp;gt;&lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#faf6ed&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''1908'''&lt;br /&gt;
|Kikunae Ikeda, a professor of the Tokyo Imperial University, discovered and identified the fifth basic taste: umami (savouriness), made palatable by glutamate.  &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;12438213&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
[http://chemse.oxfordjournals.org/content/27/9/847.long New Seasonings]&lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#faecc8&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''1931-32'''&lt;br /&gt;
| A chemist named Arthur Fox and his college noted that they had different sensitivities to the bitter tasting Phenylthiocarbamide (PTC).&amp;lt;ref&amp;gt;Blakeslee AF, Fox AL. Our different taste worlds. J Hered. 1932;23:97–107.&amp;lt;/ref&amp;gt; Geneticists later confirm these findings, and discover that non-tasting is a recessive genetic trait. &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;17782493&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/pubmed/17782493 Inherited taste deficiency] &lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#faf6ed&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''1965'''&lt;br /&gt;
|Farbman's study of the developing taste but in rat fungiform papilla was significant in increasing our understanding of taste bud development. &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;14300090&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
[http://www.sciencedirect.com/science/article/pii/0012160665900400 Electron microscope study of the developing taste bud in rat fungiform papilla.]&lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#faecc8&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''1992'''&lt;br /&gt;
|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. &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;1608467 &amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
[http://www.nature.com/nature/journal/v357/n6379/abs/357563a0.html Gustducin is a taste-cell-specific G protein closely related to the transducins]&lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#faf6ed&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''1995'''&lt;br /&gt;
|Barlow et al. experimented with Axolotl salamanders and concluded that taste buds from this species arise exclusively from epithelial tissue, &amp;quot;oropharyngeal [[#Glossary |'''epithelium''']]&amp;quot;. &amp;lt;ref name=&amp;quot;PMID17826760&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;17826760&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/pubmed/17826760 Embryonic origin of gustatory cranial sensory neurons] &lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#faecc8&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''1996'''&lt;br /&gt;
| 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 &amp;quot;at least dual function of embryonic/fetal taste buds&amp;quot;, including non-gustatory, paracrine functions prior to the 14th week and gustatory after the 14th week. &amp;lt;ref name=&amp;quot;PMID8955790&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;8955790&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/pubmed/8955790 Embryonic and early fetal development of human taste buds: a transmission electron microscopical study]&lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#faf6ed&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''2000'''&lt;br /&gt;
|Chandrashekar, J. et al. discover the first taste sonsors, the T2R bitter taste receptors. &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;10761935&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
[http://www.sciencedirect.com/science/article/pii/S0092867400807060 T2Rs Function as Bitter Taste Receptors]&lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#faecc8&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''2001'''&lt;br /&gt;
|Nelson, G. et al. discover the sweet receptor: a combination of T1R2 and T1R3. &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;11509186&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/pubmed/11509186?dopt=Abstract&amp;amp;holding=npg Mammalian sweet taste receptors.]&lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#faf6ed&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''2002'''&lt;br /&gt;
|Nelson G. et al. discover the amino acid (umami) taste receptor: a combination of T1R1 and T1R3 identified.  &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;11894099&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/pubmed/11894099?dopt=Abstract&amp;amp;holding=npg An amino-acid taste receptor]&lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#faecc8&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''2005'''&lt;br /&gt;
|Dyer, J. et al. discover sweet taste receptors in the GI tract. &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;17855558&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1986582/ Sweet taste signaling in the gut]&lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#faf6ed&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''2006'''&lt;br /&gt;
|Huang, A. L et al. discover cells for sour taste, identified by PKD2L1 (a polycystic kidney disease-like ion channel). &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;16929298&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1571047/ The Cells and Logic for Mammalian Sour Taste detection]&lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#faecc8&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''2007'''&lt;br /&gt;
|Harlow DE, Barlow LA of the University of Colorado Denver Health Sciences Center provide evidence of the &amp;quot;embryonic origin of gustatory cranial sensory neurons&amp;quot;. &amp;lt;ref name=&amp;quot;PMID17826760&amp;quot;/&amp;gt;&lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/pubmed/17826760 Embryonic origin of gustatory cranial sensory neurons.]&lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#faf6ed&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''2009'''&lt;br /&gt;
|A study by Hevezi P et al, presents &amp;quot;the first comprehensive characterization of gene expression in primate taste buds&amp;quot;, as opposed to previous studies which focused on rodents. &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;19636377&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/pubmed/19636377 Genome-wide analysis of gene expression in primate taste buds reveals links to diverse processes]&lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#faecc8&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''2010'''&lt;br /&gt;
|Chandrashekar, J. et al. identify epithelial sodium channel (ENaC) as the sodium-salt taste receptor. &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;20107438&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/pubmed/20107438?dopt=Abstract&amp;amp;holding=npg The cells and peripheral representation of sodium taste in mice]&lt;br /&gt;
|}&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
==Adult Tongue and Taste Buds – Structure and Function==&lt;br /&gt;
&lt;br /&gt;
'''Structure'''&lt;br /&gt;
&lt;br /&gt;
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.  &lt;br /&gt;
&lt;br /&gt;
[http://www.webmd.com/oral-health/picture-of-the-tongue] &lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
''''The image below is a simplistic diagram of the surface of the tongue showing the locations of the different papillae and other important features'''&lt;br /&gt;
&lt;br /&gt;
{|&lt;br /&gt;
| [[Image:Drawing of Tongue.png|centre|500px]]&lt;br /&gt;
&lt;br /&gt;
[[File:Taste_pathway.jpg|right|thumb|200px|Simplistic Pathway of Taste]]&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
'''Papillae'''&lt;br /&gt;
&lt;br /&gt;
There are 4 types of papillae on the tongue.&lt;br /&gt;
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.[http://www.tutorvista.com/content/biology/biology-iv/nervous-coordination/tongue-structure.php#parts-of-tongue]&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
[[File:Papillae.jpg|Left|thumb|200px|Close up of Human Tongue Papillae]]&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
[[File:Fungiformpapillae.jpg|left|thumb|200px|Fungiform Papillae]]&lt;br /&gt;
&lt;br /&gt;
[[File:Circumvallatepapillae.jpg |left|thumb|200px|Circumvallate Papillae]]&lt;br /&gt;
&lt;br /&gt;
[[File:Filiformpapillae.jpg|left|200px|thumb|Foliate Papillae]]&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
'''Function'''&lt;br /&gt;
&lt;br /&gt;
The Tongue has muscular and sensory functions, muscular functions include swallowing and speech where as sensory function involves taste. This section will focus on the sensory functions of the tongue.&lt;br /&gt;
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. [http://www.cf.ac.uk/biosi/staffinfo/jacob/teaching/sensory/taste.html]&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
[[File:Taste_bud_1.jpg|right|thumb|200px|Cross section of a taste bud unit|centre|Cross section of a taste bud unit]]&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
'''Link Between Taste and Smell'''&lt;br /&gt;
&lt;br /&gt;
The pathways of smell and taste are very similar (chemosensation). Pathways both involve the conversion of a dissolved chemical stimulus transformed into a electrical impulse for interpretation by the brain.	&lt;br /&gt;
Taste and smell overlap when humans experience flavour, flavour involves an interaction of taste, smell, texture and temperature, where taste is only a portion of this interaction. when the brain interprets a flavour, contribution from other senses has a significant role in identification. In conclusion Taste and Smell in combination with other senses help develop a sensory interpretation called flavour.[http://www.entnet.org/HealthInformation/smellTaste.cfm]&lt;br /&gt;
[[File:Human smelling.jpg|500px|centre]]&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
== Human Weekly Development - Two Prominent Studies ==&lt;br /&gt;
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. &lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
The findings of these two studies are summarized in the table below. The figures provided relate to the images on their respective research papers.&lt;br /&gt;
&lt;br /&gt;
# [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] &lt;br /&gt;
# [http://chemse.oxfordjournals.org/content/22/6/601.long Scanning electron microscopical studies of developing gustatory papillae in humans, 1997]  &lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
===Timeline of Developmental Processes of Human Taste Buds===&lt;br /&gt;
{| cellpadding=5 style=&amp;quot;border:1px solid #BBB&amp;quot;&lt;br /&gt;
|- bgcolor=&amp;quot;#89CFF0&amp;quot;&lt;br /&gt;
|'''Postovulatory Week'''||'''Description'''&lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#BCD4E6&amp;quot;&lt;br /&gt;
|'''Week 6''' ||&lt;br /&gt;
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. &amp;lt;ref name=&amp;quot;PMID9455607&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;9455607&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#89CFF0&amp;quot;&lt;br /&gt;
| '''Weeks 6 to 7'''|| &lt;br /&gt;
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. &amp;lt;ref name=PMID8955790/&amp;gt;&lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#BCD4E6&amp;quot;&lt;br /&gt;
| '''Week 7 '''||&lt;br /&gt;
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.  &amp;lt;ref name=PMID9455607/&amp;gt; &lt;br /&gt;
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| ''' Week 8  ''' ||&lt;br /&gt;
* The taste bud primordium are still differentiated, elongated epithelial cells, resting on a slightly developed core of young dermal papilla.&lt;br /&gt;
* 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. &lt;br /&gt;
* Ciliated cells also appear around the 8th week, however the significance of these cells which are scattered randomly across the lingual surface remains unclear. &amp;lt;ref name=PMID8955790/&amp;gt; &lt;br /&gt;
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|'''  Week 9''' ||&lt;br /&gt;
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). &amp;lt;ref name=PMID9455607/&amp;gt;&lt;br /&gt;
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|- bgcolor=&amp;quot;#89CFF0&amp;quot;&lt;br /&gt;
|'''  Weeks 10-11''' ||&lt;br /&gt;
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). &amp;lt;ref name=PMID8955790/&amp;gt; &lt;br /&gt;
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|''' Week 12 ''' ||&lt;br /&gt;
Taste bud cells are more clearly differentiated into epithelial cell types II and III. &amp;lt;ref name=PMID8955790/&amp;gt; &lt;br /&gt;
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|''' Weeks 12-13  ''' ||&lt;br /&gt;
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). &amp;lt;ref name=PMID8955790/&amp;gt; &lt;br /&gt;
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|''' Weeks 14 -15 ''' ||&lt;br /&gt;
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. &amp;lt;ref name=PMID8955790/&amp;gt; &lt;br /&gt;
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==Abnormalities==&lt;br /&gt;
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It should be mentioned that gustatory abnormalities have not been widely researched. Most research conducted in this field has been conducted through animal testing on mice and this is the basis of information provided below. &lt;br /&gt;
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===Knocking out P2X Receptors===&lt;br /&gt;
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[[File:Image of taste being evoked by visualising ATP release.jpeg|Left|thumb|200px|Evoking taste - ATP release in tongue]]&lt;br /&gt;
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The sensation of taste is made through neurotransmitters. But what happens when there is a disruption in this 'transmission', either through not releasing neurotransmitter or by a reduction in receptor number? Huang, 2008 &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;21940456&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; use the the premise that P2X receptors are essential in taste transduction and that their absence would lead to the inability to taste. &lt;br /&gt;
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This team used to the neurotransmitter ATP, as a quantitative measure of gustatory sensation and taste. ATP is only one neurotransmitter that is involved in taste transduction among others including ''&amp;quot;acetylcholine, glutamate, norepinephrine (NE), serotonin (5-HT), γ-aminobutyric acid (GABA) and a number of peptides.&amp;quot;''&lt;br /&gt;
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This was done by using a comparison of wild type (WT) and double knockout (DKO) mice. P2X receptors, namely 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. A tastant was administered to mucosal lingual epithelium the tongue of the nice and collected. The release of ATP was measured using luciferase and IHC (Immunohisto Chemistry).&lt;br /&gt;
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It should be noted that the taste buds in DKO are functional, but are not stimulated by the administration of tastants. &lt;br /&gt;
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The transmission of release of ATP is secreted through gap junction hemichannels (pannexin 1 gap junction).&lt;br /&gt;
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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.&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;21940456&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
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===FGF signalling and genes===&lt;br /&gt;
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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 (see image under 'Structure of the tongue').&lt;br /&gt;
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By knocking out ''Spry'' genes using mice which had both ''Spry1'' and ''Spry2'' knocked out showed that the number of CVP doubled. However, when Fibroblast [[#Glossary |'''Growth Factor''']] gene (&amp;quot;Fgf10&amp;quot;) 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 &amp;quot;Fgf10&amp;quot; to limit the size of the CVP progenitor placode. Exclusive expression of ''Fgf10'' in the [[#Glossary |'''mesenchyme''']] is necessary for the formation of CVP. &lt;br /&gt;
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{|&lt;br /&gt;
| [[File:Figure 1 Spry1-2.jpeg|160px|]]&lt;br /&gt;
| [[File:CVP of WT(top) and DKO(bottom) mice with H&amp;amp;E and SEM.png]]&lt;br /&gt;
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|-&lt;br /&gt;
| &amp;lt;center&amp;gt;[[Figure 1 Spry1-2.jpeg]]&amp;lt;/center&amp;gt;&lt;br /&gt;
| &amp;lt;center&amp;gt;[[CVP of WT(top) and DKO(bottom) mice with H&amp;amp;E and SEM.png]]&amp;lt;/center&amp;gt;&lt;br /&gt;
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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).&lt;br /&gt;
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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).&lt;br /&gt;
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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''&amp;amp; ''Spry 1&amp;amp;2''work antagonistically through receptor tyrosine kinase (RTK) signalling.&lt;br /&gt;
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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.&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;21655085&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
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==Gustatory System==&lt;br /&gt;
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[[Image:Taste qualities.gif|thumb|The five basic tastes]]&lt;br /&gt;
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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.&lt;br /&gt;
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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.&amp;lt;ref name=PMID20696704&amp;gt;&amp;lt;pubmed&amp;gt;20696704&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
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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 &amp;lt;ref name=PMID20696704/&amp;gt; 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.&lt;br /&gt;
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===Cell Biology===&lt;br /&gt;
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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.&lt;br /&gt;
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====Type II receptors====&lt;br /&gt;
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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:&lt;br /&gt;
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# Stimulates gustatory nerve afferents which project to gustatory nuclei  in the spinal cord&lt;br /&gt;
# Excites Type III presynaptic nerve fibers to release serotonin. &lt;br /&gt;
# Has a positive feedback effect on type II receptor cells, increasing the level of ATP production.&lt;br /&gt;
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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.&lt;br /&gt;
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==Taste Map==&lt;br /&gt;
[[Image:Taste map.png|thumb|left|250px|Obsolete idea of the tongue map]]&lt;br /&gt;
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.&lt;br /&gt;
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===Neural Pathways===&lt;br /&gt;
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'''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''. &lt;br /&gt;
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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:  &lt;br /&gt;
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* ''Facial nerve n''. -  carries taste information from the anterior 2/3 of the tongue.&lt;br /&gt;
* ''Hypoglossal n.'' - carries taste information from the posterior 1/3 of the tongue.&lt;br /&gt;
* ''Vagus n''. - carries taste information from the palate&lt;br /&gt;
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'''Second order neurons''' - From the NTS second order neurons carry taste information to the Ventral posteromedial (VPM) nucleus in the thalamus.&amp;lt;ref name=PMID21885776/&amp;gt;&lt;br /&gt;
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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.  &lt;br /&gt;
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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.&lt;br /&gt;
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===Cortical Areas===&lt;br /&gt;
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[[Image:Primary gustatory cortex.png|thumb|Primary gustatory cortex]]&lt;br /&gt;
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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)&amp;lt;ref name=PMID22245354&amp;gt;&amp;lt;pubmed&amp;gt;22245354&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;, with the secondary taste cortex in the caudolateral orbitofrontal cortex.&amp;lt;ref name=PMID21305668&amp;gt;&amp;lt;pubmed&amp;gt;21305668&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;  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.&amp;lt;ref name=PMID21885776&amp;gt;&amp;lt;pubmed&amp;gt;21885776&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; These findings lend weight to the idea that there is only one receptor for each taste quality.&lt;br /&gt;
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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).&amp;lt;ref name=PMID21885776/&amp;gt; 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&lt;br /&gt;
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===Neuronal Development===&lt;br /&gt;
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The gustatory system must not be solely thought of as being comprised of simply the tongue and palate. The types of neurons which carry taste information to the brain are also pivotal in constructing the expression of taste qualities.&lt;br /&gt;
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The two main gustatory neurons which develop are the geniculate ganglion and the petrosal ganglion. These are the visceral sensory ganglion of cranial nerves VII (Facial) and  IX (Hypoglossal) respectively which carry taste information from the tongue to the nucleus tractus solitarius. They arise at the posterior placodal region from the epibranchial placodes, a thickening of ectoderm. The first epibranchial placode gives rise to the geniculate ganglion and the second to the petrosal ganglion.&lt;br /&gt;
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The molecular basis for gustatory neuron formation is not completely understood though there are a number of transcription factors which are thought to play an important role in firstly, placode formation and secondly, neuron differentiation.&lt;br /&gt;
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*Six1/2, Six1/5 and Eya – transcription factors which cause differentiation of epibranchial placodes into the petrosal and geniculate ganglion.&lt;br /&gt;
*Bone morphogenic Protein 7 (BMP7) – a signal arising from the pharyngeal pouch which is believed to induce epibranchial placode formation. May not be solely responsible for this process, current research has been inconclusive as to how it may work with other proteins of the same family.&lt;br /&gt;
*NGN2 - Following the initial differentiation of the placodes, further differentiation occurs to form neuroblasts. NGN2 causes the delamination and migration of these neuroblasts, which subsequently migrate and fuse to form neurons.&lt;br /&gt;
*Phox2b – maintains the structural integrity of neurons. Knockout of these genes in mice causes marked atrophy of the petrosal and geniculate ganglia.&lt;br /&gt;
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The neurons involved in the gustatory system are overproduced and thus in the embryonic stage, undergo programmed cell death (apoptosis). The total amount of neurons in the geniculate ganglion, appears to be quite stable over the embryonic stages. This suggests, unlike the petrosal ganglion, the levels of neuroblast proliferation and apoptosis are fairly similar. The factors which regulate these processes remains unclear. It is posited that neurotrophins BDNF, NT4/5 and NT3 may regulate neuronal survival whilst also playing a part in axon growth from the sensory ganglion. More research is required to discern the exact individual functions of each of the neurotrophins.&lt;br /&gt;
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==Current Research==&lt;br /&gt;
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[[File:Mousetounge histologicalstain.jpg|right|thumb|200px|Image shows histological stains of a mice tongue showing dysplasia]]&lt;br /&gt;
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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. &lt;br /&gt;
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.&lt;br /&gt;
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'''Synergistic relationships of Six Genes '''&lt;br /&gt;
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In an animal study using mice by Suzuki Y, Ikeda K, Kawakami K.(2011)  Firstly nominating &amp;quot;[[#Glossary |'''Six Genes''']]&amp;quot; as a major component in [[#Glossary |'''gustatory ''']] development, stating that deficiencies in certain Six genes (specifically Six1 &amp;amp; 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 &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;21978088&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
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[[File:Abnormal of tongue.jpg|thumb|200px|Image shows an example of tongue abnormalities, this is called &amp;quot;double tongue&amp;quot; each side has independent movement!]]&lt;br /&gt;
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'''Neural Crest responsibilities '''&lt;br /&gt;
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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 &amp;quot;[[#Glossary |'''epithelium''']]&amp;quot; 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.&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;22659543&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
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'''Augmentation of Endoderm'''&lt;br /&gt;
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In an animal study conducted by Rothova M, Thompson H, Lickert H, Tucker AS.(2012) exploring the historically debated issue of &amp;quot;[[#Glossary |'''endoderm''']]&amp;quot; contribution to tongue development showed promising evidence that position of taste buds are patterned by the border of &amp;quot;[[#Glossary |'''ectoderm''']]&amp;quot; and endoderm derivative epithelium. This study was accomplished via microscopic examination of previously stained specimens. Concluding endoderm has direct influence on gustatory development &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;22581563&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
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'''Changes in Taste Cells over time'''&lt;br /&gt;
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Research by &lt;br /&gt;
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.  &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;22643728&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
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'''Shh key component of taste bud proginators'''&lt;br /&gt;
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A [[#Glossary |'''tamoxifen''']] treatment which suppresses &amp;quot;[[#Glossary |'''Sonic hedgehog''']]&amp;quot; (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.&lt;br /&gt;
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 &amp;quot;Axiocam CCD camera and Axioplan fluorescence microscope with Axiovision software&amp;quot; a study by Harlow, Yang, Williams, Barlow (2011)&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;PMC2674259&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
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'''WNT family exhibit various roles'''&lt;br /&gt;
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The WNT gene family has a function of directing work antagonistically through receptor tyrosine kinase (RTK) signaling. However, the deletion of Sprouty Homolog 2 (Spry2) led to the increase of chimaeric virus particles (CVPs) and a significant decrease in number of fungiform papillae. In contrast, the absence of Fibroblast growth factor 10 (Fgf10) in conjunction with 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. 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. &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;PMC2768563&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
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[[File:Developing_tongue_histology_001.jpg|right|thumb|200px|HIstological stain of a developing rat tongue]]&lt;br /&gt;
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==Glossary==&lt;br /&gt;
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* '''Circumvallate papillae''' - papillae that contain taste buds, that help form the Sulcus terminalis&lt;br /&gt;
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* '''Ectoderm'''- outer germ layer of embryo&lt;br /&gt;
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* '''Endoderm''' - inner germ layer of embryo&lt;br /&gt;
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* '''Epithelium''' - basic animal tissue that is composed of tightly packed cells, usually covering the outer portion of organs&lt;br /&gt;
&lt;br /&gt;
* '''Exocystosis''' - movement of contents out of cell&lt;br /&gt;
&lt;br /&gt;
* '''Filiform papillae''' - numerous papillae that do not contain taste buds&lt;br /&gt;
&lt;br /&gt;
* '''Foliate papillae''' - papillae that contain taste buds&lt;br /&gt;
&lt;br /&gt;
* '''Fungiform papillae''' - papillae that contain taste buds&lt;br /&gt;
&lt;br /&gt;
* '''Ganglia''' - the accumulation of a nerve cell body&lt;br /&gt;
&lt;br /&gt;
* '''Growth factor''' - a substance that stimulates the growth of cells&lt;br /&gt;
&lt;br /&gt;
* '''Gustatory''' - anything that relates to the taste sense&lt;br /&gt;
&lt;br /&gt;
* '''Hydrolysis''' - breakdown of a chemical when it reacts with water&lt;br /&gt;
&lt;br /&gt;
* '''Mesoderm''' - middle germ layer of embryo&lt;br /&gt;
&lt;br /&gt;
* '''Mesenchyme''' - multipotential cells&lt;br /&gt;
&lt;br /&gt;
* '''Neural crest''' - a part of the ectoderm found on both sides of the neural tube&lt;br /&gt;
&lt;br /&gt;
* '''Neuron''' - most simplistic unit of the nervous system&lt;br /&gt;
&lt;br /&gt;
* '''Neurotransmitter''' - chemicals which allow the passing of signals from neuron to neuron via connecting part (synapse) &lt;br /&gt;
&lt;br /&gt;
* '''Papillae''' - small rough surface projection&lt;br /&gt;
&lt;br /&gt;
*'''Placode''' - an area of thickened epithelium which eventually produces other structures.&lt;br /&gt;
&lt;br /&gt;
* '''Six genes''' - a family of genes&lt;br /&gt;
&lt;br /&gt;
* '''Sonic hedgehog (Shh)''' - signalling protein involved in normal development&lt;br /&gt;
&lt;br /&gt;
* '''Sulcus terminalis''' - describes a physical transition point separating the anterior 2/3 of the tongue from the posterior 1/3&lt;br /&gt;
&lt;br /&gt;
* '''Tamoxifen''' - hormonal altering drug&lt;br /&gt;
&lt;br /&gt;
* '''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).&lt;br /&gt;
&lt;br /&gt;
* '''Type II taste cells''' - Receptor cells acting as primary detectors of sweet, bitter or umami taste.&lt;br /&gt;
&lt;br /&gt;
* '''Type III taste cells''' - Presynaptic cells that respond to sweet, salty, sour, bitter and umami compounds.&lt;br /&gt;
&lt;br /&gt;
== References ==&lt;br /&gt;
&amp;lt;references/&amp;gt;&lt;br /&gt;
&lt;br /&gt;
==External Links==&lt;br /&gt;
{{External Links}}&lt;br /&gt;
&lt;br /&gt;
1.[http://www.surgicalneurologyint.com/article.asp?issn=2152-7806;year=2012;volume=3;issue=1;spage=23;epage=23;aulast=Manjila]&lt;br /&gt;
&lt;br /&gt;
2.[http://embryology.med.unsw.edu.au/embryology/index.php?title=2012_Group_Project_4]&lt;br /&gt;
&lt;br /&gt;
3.[http://www.webmd.com/oral-health/picture-of-the-tongue]&lt;br /&gt;
&lt;br /&gt;
4.[http://www.tutorvista.com/content/biology/biology-iv/nervous-coordination/tongue-structure.php#parts-of-tongue]&lt;br /&gt;
&lt;br /&gt;
5.[http://www.cf.ac.uk/biosi/staffinfo/jacob/teaching/sensory/taste.html]&lt;br /&gt;
&lt;br /&gt;
--[[User:Z8600021|Mark Hill]] 00:19, 5 October 2012 (EST) There should be text with these links.&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
--[[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.&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
----&lt;br /&gt;
&lt;br /&gt;
{{2012Projects}}&lt;/div&gt;</summary>
		<author><name>Z3330795</name></author>
	</entry>
	<entry>
		<id>https://embryology.med.unsw.edu.au/embryology/index.php?title=2012_Group_Project_3&amp;diff=106010</id>
		<title>2012 Group Project 3</title>
		<link rel="alternate" type="text/html" href="https://embryology.med.unsw.edu.au/embryology/index.php?title=2012_Group_Project_3&amp;diff=106010"/>
		<updated>2012-10-05T00:29:16Z</updated>

		<summary type="html">&lt;p&gt;Z3330795: /* Current Research */&lt;/p&gt;
&lt;hr /&gt;
&lt;div&gt;=Taste Development=&lt;br /&gt;
&lt;br /&gt;
You are out to dinner and your meal arrives in front of you, the aromas and the presentation of your food strikes you immediately. Half way through, the waiter returns and asks “How does your meal taste?”  The answer is not as simple as one might think. Why does the meal taste pleasant? How do we experience different tastes? In the following page, we aim to discern how exactly one would answer these questions by looking at the embryological development of the taste system from week to week. &lt;br /&gt;
&lt;br /&gt;
Taste is a complex sensory system and its precise workings are to this day not fully understood. What makes it so complicated is the interaction between the structure of tongue and taste buds and how this contributes to the representation of taste qualities (salty, bitter, sweet, sour and umami) in the brain. We will also look at some current research on animal models being undertaken to evaluate the role of specific genes in the development of sensory structures. By looking at the taste system’s genetic basis, we now have a greater understanding of the abnormalities that may occur during development and a direction to pursue in future research to attempt to fill in the gaps of scientific knowledge.&lt;br /&gt;
&lt;br /&gt;
[[File:Baby tongue.jpg|centre|500px]]&lt;br /&gt;
&lt;br /&gt;
==History of Discoveries==&lt;br /&gt;
&lt;br /&gt;
{| cellpadding=5 style=&amp;quot;border:1px solid #BBB&amp;quot;&lt;br /&gt;
|- bgcolor=&amp;quot;#faecc8&amp;quot;&lt;br /&gt;
|''' Date'''|| '''Significant Discovery'''&lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#faf6ed&amp;quot;&lt;br /&gt;
|'''350BC'''&lt;br /&gt;
|| Aristotle writes about the basic tastes, sweet and bitter. He also notes that it can be modified by salty and acidic. &amp;lt;ref name=&amp;quot;PMID22717400&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;22717400&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#faecc8&amp;quot;&lt;br /&gt;
|'''1901'''&lt;br /&gt;
|| D. Hanig publishes a paper describing taste sensitivity in different regions of the tongue. &lt;br /&gt;
''Interesting fact:'' The modern concept of a 'tongue map' is a misinterpretation of this study. &amp;lt;ref name=&amp;quot;PMID22717400&amp;quot;/&amp;gt;&lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#faf6ed&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''1908'''&lt;br /&gt;
|Kikunae Ikeda, a professor of the Tokyo Imperial University, discovered and identified the fifth basic taste: umami (savouriness), made palatable by glutamate.  &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;12438213&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
[http://chemse.oxfordjournals.org/content/27/9/847.long New Seasonings]&lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#faecc8&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''1931-32'''&lt;br /&gt;
| A chemist named Arthur Fox and his college noted that they had different sensitivities to the bitter tasting Phenylthiocarbamide (PTC).&amp;lt;ref&amp;gt;Blakeslee AF, Fox AL. Our different taste worlds. J Hered. 1932;23:97–107.&amp;lt;/ref&amp;gt; Geneticists later confirm these findings, and discover that non-tasting is a recessive genetic trait. &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;17782493&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/pubmed/17782493 Inherited taste deficiency] &lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#faf6ed&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''1965'''&lt;br /&gt;
|Farbman's study of the developing taste but in rat fungiform papilla was significant in increasing our understanding of taste bud development. &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;14300090&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
[http://www.sciencedirect.com/science/article/pii/0012160665900400 Electron microscope study of the developing taste bud in rat fungiform papilla.]&lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#faecc8&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''1992'''&lt;br /&gt;
|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. &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;1608467 &amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
[http://www.nature.com/nature/journal/v357/n6379/abs/357563a0.html Gustducin is a taste-cell-specific G protein closely related to the transducins]&lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#faf6ed&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''1995'''&lt;br /&gt;
|Barlow et al. experimented with Axolotl salamanders and concluded that taste buds from this species arise exclusively from epithelial tissue, &amp;quot;oropharyngeal [[#Glossary |'''epithelium''']]&amp;quot;. &amp;lt;ref name=&amp;quot;PMID17826760&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;17826760&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/pubmed/17826760 Embryonic origin of gustatory cranial sensory neurons] &lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#faecc8&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''1996'''&lt;br /&gt;
| 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 &amp;quot;at least dual function of embryonic/fetal taste buds&amp;quot;, including non-gustatory, paracrine functions prior to the 14th week and gustatory after the 14th week. &amp;lt;ref name=&amp;quot;PMID8955790&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;8955790&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/pubmed/8955790 Embryonic and early fetal development of human taste buds: a transmission electron microscopical study]&lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#faf6ed&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''2000'''&lt;br /&gt;
|Chandrashekar, J. et al. discover the first taste sonsors, the T2R bitter taste receptors. &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;10761935&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
[http://www.sciencedirect.com/science/article/pii/S0092867400807060 T2Rs Function as Bitter Taste Receptors]&lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#faecc8&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''2001'''&lt;br /&gt;
|Nelson, G. et al. discover the sweet receptor: a combination of T1R2 and T1R3. &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;11509186&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/pubmed/11509186?dopt=Abstract&amp;amp;holding=npg Mammalian sweet taste receptors.]&lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#faf6ed&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''2002'''&lt;br /&gt;
|Nelson G. et al. discover the amino acid (umami) taste receptor: a combination of T1R1 and T1R3 identified.  &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;11894099&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/pubmed/11894099?dopt=Abstract&amp;amp;holding=npg An amino-acid taste receptor]&lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#faecc8&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''2005'''&lt;br /&gt;
|Dyer, J. et al. discover sweet taste receptors in the GI tract. &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;17855558&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1986582/ Sweet taste signaling in the gut]&lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#faf6ed&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''2006'''&lt;br /&gt;
|Huang, A. L et al. discover cells for sour taste, identified by PKD2L1 (a polycystic kidney disease-like ion channel). &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;16929298&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1571047/ The Cells and Logic for Mammalian Sour Taste detection]&lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#faecc8&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''2007'''&lt;br /&gt;
|Harlow DE, Barlow LA of the University of Colorado Denver Health Sciences Center provide evidence of the &amp;quot;embryonic origin of gustatory cranial sensory neurons&amp;quot;. &amp;lt;ref name=&amp;quot;PMID17826760&amp;quot;/&amp;gt;&lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/pubmed/17826760 Embryonic origin of gustatory cranial sensory neurons.]&lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#faf6ed&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''2009'''&lt;br /&gt;
|A study by Hevezi P et al, presents &amp;quot;the first comprehensive characterization of gene expression in primate taste buds&amp;quot;, as opposed to previous studies which focused on rodents. &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;19636377&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/pubmed/19636377 Genome-wide analysis of gene expression in primate taste buds reveals links to diverse processes]&lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#faecc8&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''2010'''&lt;br /&gt;
|Chandrashekar, J. et al. identify epithelial sodium channel (ENaC) as the sodium-salt taste receptor. &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;20107438&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/pubmed/20107438?dopt=Abstract&amp;amp;holding=npg The cells and peripheral representation of sodium taste in mice]&lt;br /&gt;
|}&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
==Adult Tongue and Taste Buds – Structure and Function==&lt;br /&gt;
&lt;br /&gt;
'''Structure'''&lt;br /&gt;
&lt;br /&gt;
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.  &lt;br /&gt;
&lt;br /&gt;
[http://www.webmd.com/oral-health/picture-of-the-tongue] &lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
''''The image below is a simplistic diagram of the surface of the tongue showing the locations of the different papillae and other important features'''&lt;br /&gt;
&lt;br /&gt;
{|&lt;br /&gt;
| [[Image:Drawing of Tongue.png|centre|500px]]&lt;br /&gt;
&lt;br /&gt;
[[File:Taste_pathway.jpg|right|thumb|200px|Simplistic Pathway of Taste]]&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
'''Papillae'''&lt;br /&gt;
&lt;br /&gt;
There are 4 types of papillae on the tongue.&lt;br /&gt;
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.[http://www.tutorvista.com/content/biology/biology-iv/nervous-coordination/tongue-structure.php#parts-of-tongue]&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
[[File:Papillae.jpg|Left|thumb|200px|Close up of Human Tongue Papillae]]&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
[[File:Fungiformpapillae.jpg|left|thumb|200px|Fungiform Papillae]]&lt;br /&gt;
&lt;br /&gt;
[[File:Circumvallatepapillae.jpg |left|thumb|200px|Circumvallate Papillae]]&lt;br /&gt;
&lt;br /&gt;
[[File:Filiformpapillae.jpg|left|200px|thumb|Foliate Papillae]]&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
'''Function'''&lt;br /&gt;
&lt;br /&gt;
The Tongue has muscular and sensory functions, muscular functions include swallowing and speech where as sensory function involves taste. This section will focus on the sensory functions of the tongue.&lt;br /&gt;
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. [http://www.cf.ac.uk/biosi/staffinfo/jacob/teaching/sensory/taste.html]&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
[[File:Taste_bud_1.jpg|right|thumb|200px|Cross section of a taste bud unit|centre|Cross section of a taste bud unit]]&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
'''Link Between Taste and Smell'''&lt;br /&gt;
&lt;br /&gt;
The pathways of smell and taste are very similar (chemosensation). Pathways both involve the conversion of a dissolved chemical stimulus transformed into a electrical impulse for interpretation by the brain.	&lt;br /&gt;
Taste and smell overlap when humans experience flavour, flavour involves an interaction of taste, smell, texture and temperature, where taste is only a portion of this interaction. when the brain interprets a flavour, contribution from other senses has a significant role in identification. In conclusion Taste and Smell in combination with other senses help develop a sensory interpretation called flavour.[http://www.entnet.org/HealthInformation/smellTaste.cfm]&lt;br /&gt;
[[File:Human smelling.jpg|500px|centre]]&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
== Human Weekly Development - Two Prominent Studies ==&lt;br /&gt;
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. &lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
The findings of these two studies are summarized in the table below. The figures provided relate to the images on their respective research papers.&lt;br /&gt;
&lt;br /&gt;
# [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] &lt;br /&gt;
# [http://chemse.oxfordjournals.org/content/22/6/601.long Scanning electron microscopical studies of developing gustatory papillae in humans, 1997]  &lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
===Timeline of Developmental Processes of Human Taste Buds===&lt;br /&gt;
{| cellpadding=5 style=&amp;quot;border:1px solid #BBB&amp;quot;&lt;br /&gt;
|- bgcolor=&amp;quot;#89CFF0&amp;quot;&lt;br /&gt;
|'''Postovulatory Week'''||'''Description'''&lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#BCD4E6&amp;quot;&lt;br /&gt;
|'''Week 6''' ||&lt;br /&gt;
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. &amp;lt;ref name=&amp;quot;PMID9455607&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;9455607&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#89CFF0&amp;quot;&lt;br /&gt;
| '''Weeks 6 to 7'''|| &lt;br /&gt;
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. &amp;lt;ref name=PMID8955790/&amp;gt;&lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#BCD4E6&amp;quot;&lt;br /&gt;
| '''Week 7 '''||&lt;br /&gt;
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.  &amp;lt;ref name=PMID9455607/&amp;gt; &lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#89CFF0&amp;quot;&lt;br /&gt;
| ''' Week 8  ''' ||&lt;br /&gt;
* The taste bud primordium are still differentiated, elongated epithelial cells, resting on a slightly developed core of young dermal papilla.&lt;br /&gt;
* 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. &lt;br /&gt;
* Ciliated cells also appear around the 8th week, however the significance of these cells which are scattered randomly across the lingual surface remains unclear. &amp;lt;ref name=PMID8955790/&amp;gt; &lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#BCD4E6&amp;quot;&lt;br /&gt;
|'''  Week 9''' ||&lt;br /&gt;
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). &amp;lt;ref name=PMID9455607/&amp;gt;&lt;br /&gt;
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|- bgcolor=&amp;quot;#89CFF0&amp;quot;&lt;br /&gt;
|'''  Weeks 10-11''' ||&lt;br /&gt;
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). &amp;lt;ref name=PMID8955790/&amp;gt; &lt;br /&gt;
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|- bgcolor=&amp;quot;#BCD4E6&amp;quot;&lt;br /&gt;
|''' Week 12 ''' ||&lt;br /&gt;
Taste bud cells are more clearly differentiated into epithelial cell types II and III. &amp;lt;ref name=PMID8955790/&amp;gt; &lt;br /&gt;
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|- bgcolor=&amp;quot;#89CFF0&amp;quot;&lt;br /&gt;
|''' Weeks 12-13  ''' ||&lt;br /&gt;
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). &amp;lt;ref name=PMID8955790/&amp;gt; &lt;br /&gt;
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|- bgcolor=&amp;quot;#BCD4E6&amp;quot;&lt;br /&gt;
|''' Weeks 14 -15 ''' ||&lt;br /&gt;
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. &amp;lt;ref name=PMID8955790/&amp;gt; &lt;br /&gt;
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==Abnormalities==&lt;br /&gt;
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It should be mentioned that gustatory abnormalities have not been widely researched. Most research conducted in this field has been conducted through animal testing on mice and this is the basis of information provided below. &lt;br /&gt;
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===Knocking out P2X Receptors===&lt;br /&gt;
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[[File:Image of taste being evoked by visualising ATP release.jpeg|Left|thumb|200px|Evoking taste - ATP release in tongue]]&lt;br /&gt;
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The sensation of taste is made through neurotransmitters. But what happens when there is a disruption in this 'transmission', either through not releasing neurotransmitter or by a reduction in receptor number? Huang, 2008 &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;21940456&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; use the the premise that P2X receptors are essential in taste transduction and that their absence would lead to the inability to taste. &lt;br /&gt;
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This team used to the neurotransmitter ATP, as a quantitative measure of gustatory sensation and taste. ATP is only one neurotransmitter that is involved in taste transduction among others including ''&amp;quot;acetylcholine, glutamate, norepinephrine (NE), serotonin (5-HT), γ-aminobutyric acid (GABA) and a number of peptides.&amp;quot;''&lt;br /&gt;
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This was done by using a comparison of wild type (WT) and double knockout (DKO) mice. P2X receptors, namely 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. A tastant was administered to mucosal lingual epithelium the tongue of the nice and collected. The release of ATP was measured using luciferase and IHC (Immunohisto Chemistry).&lt;br /&gt;
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It should be noted that the taste buds in DKO are functional, but are not stimulated by the administration of tastants. &lt;br /&gt;
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The transmission of release of ATP is secreted through gap junction hemichannels (pannexin 1 gap junction).&lt;br /&gt;
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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.&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;21940456&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
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===FGF signalling and genes===&lt;br /&gt;
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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 (see image under 'Structure of the tongue').&lt;br /&gt;
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By knocking out ''Spry'' genes using mice which had both ''Spry1'' and ''Spry2'' knocked out showed that the number of CVP doubled. However, when Fibroblast [[#Glossary |'''Growth Factor''']] gene (&amp;quot;Fgf10&amp;quot;) 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 &amp;quot;Fgf10&amp;quot; to limit the size of the CVP progenitor placode. Exclusive expression of ''Fgf10'' in the [[#Glossary |'''mesenchyme''']] is necessary for the formation of CVP. &lt;br /&gt;
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{|&lt;br /&gt;
| [[File:Figure 1 Spry1-2.jpeg|160px|]]&lt;br /&gt;
| [[File:CVP of WT(top) and DKO(bottom) mice with H&amp;amp;E and SEM.png]]&lt;br /&gt;
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|-&lt;br /&gt;
| &amp;lt;center&amp;gt;[[Figure 1 Spry1-2.jpeg]]&amp;lt;/center&amp;gt;&lt;br /&gt;
| &amp;lt;center&amp;gt;[[CVP of WT(top) and DKO(bottom) mice with H&amp;amp;E and SEM.png]]&amp;lt;/center&amp;gt;&lt;br /&gt;
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|}&lt;br /&gt;
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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).&lt;br /&gt;
&lt;br /&gt;
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).&lt;br /&gt;
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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''&amp;amp; ''Spry 1&amp;amp;2''work antagonistically through receptor tyrosine kinase (RTK) signalling.&lt;br /&gt;
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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.&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;21655085&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
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==Gustatory System==&lt;br /&gt;
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[[Image:Taste qualities.gif|thumb|The five basic tastes]]&lt;br /&gt;
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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.&lt;br /&gt;
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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.&amp;lt;ref name=PMID20696704&amp;gt;&amp;lt;pubmed&amp;gt;20696704&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
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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 &amp;lt;ref name=PMID20696704/&amp;gt; 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.&lt;br /&gt;
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===Cell Biology===&lt;br /&gt;
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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.&lt;br /&gt;
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====Type II receptors====&lt;br /&gt;
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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:&lt;br /&gt;
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# Stimulates gustatory nerve afferents which project to gustatory nuclei  in the spinal cord&lt;br /&gt;
# Excites Type III presynaptic nerve fibers to release serotonin. &lt;br /&gt;
# Has a positive feedback effect on type II receptor cells, increasing the level of ATP production.&lt;br /&gt;
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        &lt;br /&gt;
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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.&lt;br /&gt;
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==Taste Map==&lt;br /&gt;
[[Image:Taste map.png|thumb|left|250px|Obsolete idea of the tongue map]]&lt;br /&gt;
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.&lt;br /&gt;
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===Neural Pathways===&lt;br /&gt;
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'''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''. &lt;br /&gt;
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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:  &lt;br /&gt;
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* ''Facial nerve n''. -  carries taste information from the anterior 2/3 of the tongue.&lt;br /&gt;
* ''Hypoglossal n.'' - carries taste information from the posterior 1/3 of the tongue.&lt;br /&gt;
* ''Vagus n''. - carries taste information from the palate&lt;br /&gt;
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'''Second order neurons''' - From the NTS second order neurons carry taste information to the Ventral posteromedial (VPM) nucleus in the thalamus.&amp;lt;ref name=PMID21885776/&amp;gt;&lt;br /&gt;
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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.  &lt;br /&gt;
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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.&lt;br /&gt;
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===Cortical Areas===&lt;br /&gt;
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[[Image:Primary gustatory cortex.png|thumb|Primary gustatory cortex]]&lt;br /&gt;
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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)&amp;lt;ref name=PMID22245354&amp;gt;&amp;lt;pubmed&amp;gt;22245354&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;, with the secondary taste cortex in the caudolateral orbitofrontal cortex.&amp;lt;ref name=PMID21305668&amp;gt;&amp;lt;pubmed&amp;gt;21305668&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;  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.&amp;lt;ref name=PMID21885776&amp;gt;&amp;lt;pubmed&amp;gt;21885776&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; These findings lend weight to the idea that there is only one receptor for each taste quality.&lt;br /&gt;
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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).&amp;lt;ref name=PMID21885776/&amp;gt; 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&lt;br /&gt;
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===Neuronal Development===&lt;br /&gt;
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The gustatory system must not be solely thought of as being comprised of simply the tongue and palate. The types of neurons which carry taste information to the brain are also pivotal in constructing the expression of taste qualities.&lt;br /&gt;
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The two main gustatory neurons which develop are the geniculate ganglion and the petrosal ganglion. These are the visceral sensory ganglion of cranial nerves VII (Facial) and  IX (Hypoglossal) respectively which carry taste information from the tongue to the nucleus tractus solitarius. They arise at the posterior placodal region from the epibranchial placodes, a thickening of ectoderm. The first epibranchial placode gives rise to the geniculate ganglion and the second to the petrosal ganglion.&lt;br /&gt;
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The molecular basis for gustatory neuron formation is not completely understood though there are a number of transcription factors which are thought to play an important role in firstly, placode formation and secondly, neuron differentiation.&lt;br /&gt;
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*Six1/2, Six1/5 and Eya – transcription factors which cause differentiation of epibranchial placodes into the petrosal and geniculate ganglion.&lt;br /&gt;
*Bone morphogenic Protein 7 (BMP7) – a signal arising from the pharyngeal pouch which is believed to induce epibranchial placode formation. May not be solely responsible for this process, current research has been inconclusive as to how it may work with other proteins of the same family.&lt;br /&gt;
*NGN2 - Following the initial differentiation of the placodes, further differentiation occurs to form neuroblasts. NGN2 causes the delamination and migration of these neuroblasts, which subsequently migrate and fuse to form neurons.&lt;br /&gt;
*Phox2b – maintains the structural integrity of neurons. Knockout of these genes in mice causes marked atrophy of the petrosal and geniculate ganglia.&lt;br /&gt;
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The neurons involved in the gustatory system are overproduced and thus in the embryonic stage, undergo programmed cell death (apoptosis). The total amount of neurons in the geniculate ganglion, appears to be quite stable over the embryonic stages. This suggests, unlike the petrosal ganglion, the levels of neuroblast proliferation and apoptosis are fairly similar. The factors which regulate these processes remains unclear. It is posited that neurotrophins BDNF, NT4/5 and NT3 may regulate neuronal survival whilst also playing a part in axon growth from the sensory ganglion. More research is required to discern the exact individual functions of each of the neurotrophins.&lt;br /&gt;
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==Current Research==&lt;br /&gt;
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[[File:Mousetounge histologicalstain.jpg|right|thumb|200px|Image shows histological stains of a mice tongue showing dysplasia]]&lt;br /&gt;
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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. &lt;br /&gt;
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.&lt;br /&gt;
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'''Synergistic relationships of Six Genes '''&lt;br /&gt;
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In an animal study using mice by Suzuki Y, Ikeda K, Kawakami K.(2011)  Firstly nominating &amp;quot;[[#Glossary |'''Six Genes''']]&amp;quot; as a major component in [[#Glossary |'''gustatory ''']] development, stating that deficiencies in certain Six genes (specifically Six1 &amp;amp; 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 &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;21978088&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
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[[File:Abnormal of tongue.jpg|thumb|200px|Image shows an example of tongue abnormalities, this is called &amp;quot;double tongue&amp;quot; each side has independent movement!]]&lt;br /&gt;
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'''Neural Crest responsibilities '''&lt;br /&gt;
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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 &amp;quot;[[#Glossary |'''epithelium''']]&amp;quot; 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.&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;22659543&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
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'''Augmentation of Endoderm'''&lt;br /&gt;
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In an animal study conducted by Rothova M, Thompson H, Lickert H, Tucker AS.(2012) exploring the historically debated issue of &amp;quot;[[#Glossary |'''endoderm''']]&amp;quot; contribution to tongue development showed promising evidence that position of taste buds are patterned by the border of &amp;quot;[[#Glossary |'''ectoderm''']]&amp;quot; and endoderm derivative epithelium. This study was accomplished via microscopic examination of previously stained specimens. Concluding endoderm has direct influence on gustatory development &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;22581563&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
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'''Changes in Taste Cells over time'''&lt;br /&gt;
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Research by &lt;br /&gt;
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.  &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;22643728&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
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'''Shh key component of taste bud proginators'''&lt;br /&gt;
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A [[#Glossary |'''tamoxifen''']] treatment which suppresses &amp;quot;[[#Glossary |'''Sonic hedgehog''']]&amp;quot; (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.&lt;br /&gt;
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 &amp;quot;Axiocam CCD camera and Axioplan fluorescence microscope with Axiovision software&amp;quot; a study by Harlow, Yang, Williams, Barlow (2011)&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;PMC2674259&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
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'''WNT family exhibit various roles'''&lt;br /&gt;
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The WNT gene family has a function of directing work antagonistically through receptor tyrosine kinase (RTK) signaling. However, the deletion of Sprouty Homolog 2 (Spry2) led to the increase of chimaeric virus particles (CVPs) and a significant decrease in number of fungiform papillae. In contrast, the absence of Fibroblast growth factor 10 (Fgf10) in conjunction with 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. 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. &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;PMC2768563&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
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[[File:Developing_tongue_histology_001.jpg|right|thumb|200px|HIstological stain of a developing rat tongue]]&lt;br /&gt;
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==Glossary==&lt;br /&gt;
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* '''Circumvallate papillae''' - papillae that contain taste buds, that help form the Sulcus terminalis&lt;br /&gt;
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* '''Ectoderm'''- outer germ layer of embryo&lt;br /&gt;
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* '''Endoderm''' - inner germ layer of embryo&lt;br /&gt;
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* '''Epithelium''' - basic animal tissue that is composed of tightly packed cells, usually covering the outer portion of organs&lt;br /&gt;
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* '''Exocystosis''' - movement of contents out of cell&lt;br /&gt;
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* '''Filiform papillae''' - numerous papillae that do not contain taste buds&lt;br /&gt;
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* '''Foliate papillae''' - papillae that contain taste buds&lt;br /&gt;
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* '''Fungiform papillae''' - papillae that contain taste buds&lt;br /&gt;
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* '''Ganglia''' - the accumulation of a nerve cell body&lt;br /&gt;
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* '''Growth factor''' - a substance that stimulates the growth of cells&lt;br /&gt;
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* '''Gustatory''' - anything that relates to the taste sense&lt;br /&gt;
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* '''Hydrolysis''' - breakdown of a chemical when it reacts with water&lt;br /&gt;
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* '''Mesoderm''' - middle germ layer of embryo&lt;br /&gt;
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* '''Mesenchyme''' - multipotential cells&lt;br /&gt;
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* '''Neural crest''' - a part of the ectoderm found on both sides of the neural tube&lt;br /&gt;
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* '''Neuron''' - most simplistic unit of the nervous system&lt;br /&gt;
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* '''Neurotransmitter''' - chemicals which allow the passing of signals from neuron to neuron via connecting part (synapse) &lt;br /&gt;
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* '''Papillae''' - small rough surface projection&lt;br /&gt;
&lt;br /&gt;
* '''Six genes''' - a family of genes&lt;br /&gt;
&lt;br /&gt;
* '''Sonic hedgehog (Shh)''' - signalling protein involved in normal development&lt;br /&gt;
&lt;br /&gt;
* '''Sulcus terminalis''' - describes a physical transition point separating the anterior 2/3 of the tongue from the posterior 1/3&lt;br /&gt;
&lt;br /&gt;
* '''Tamoxifen''' - hormonal altering drug&lt;br /&gt;
&lt;br /&gt;
* '''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).&lt;br /&gt;
&lt;br /&gt;
* '''Type II taste cells''' - Receptor cells acting as primary detectors of sweet, bitter or umami taste.&lt;br /&gt;
&lt;br /&gt;
* '''Type III taste cells''' - Presynaptic cells that respond to sweet, salty, sour, bitter and umami compounds.&lt;br /&gt;
&lt;br /&gt;
== References ==&lt;br /&gt;
&amp;lt;references/&amp;gt;&lt;br /&gt;
&lt;br /&gt;
==External Links==&lt;br /&gt;
{{External Links}}&lt;br /&gt;
&lt;br /&gt;
1.[http://www.surgicalneurologyint.com/article.asp?issn=2152-7806;year=2012;volume=3;issue=1;spage=23;epage=23;aulast=Manjila]&lt;br /&gt;
&lt;br /&gt;
2.[http://embryology.med.unsw.edu.au/embryology/index.php?title=2012_Group_Project_4]&lt;br /&gt;
&lt;br /&gt;
3.[http://www.webmd.com/oral-health/picture-of-the-tongue]&lt;br /&gt;
&lt;br /&gt;
4.[http://www.tutorvista.com/content/biology/biology-iv/nervous-coordination/tongue-structure.php#parts-of-tongue]&lt;br /&gt;
&lt;br /&gt;
5.[http://www.cf.ac.uk/biosi/staffinfo/jacob/teaching/sensory/taste.html]&lt;br /&gt;
&lt;br /&gt;
--[[User:Z8600021|Mark Hill]] 00:19, 5 October 2012 (EST) There should be text with these links.&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
--[[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.&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
----&lt;br /&gt;
&lt;br /&gt;
{{2012Projects}}&lt;/div&gt;</summary>
		<author><name>Z3330795</name></author>
	</entry>
	<entry>
		<id>https://embryology.med.unsw.edu.au/embryology/index.php?title=2012_Group_Project_3&amp;diff=106007</id>
		<title>2012 Group Project 3</title>
		<link rel="alternate" type="text/html" href="https://embryology.med.unsw.edu.au/embryology/index.php?title=2012_Group_Project_3&amp;diff=106007"/>
		<updated>2012-10-05T00:24:05Z</updated>

		<summary type="html">&lt;p&gt;Z3330795: /* Current Research */&lt;/p&gt;
&lt;hr /&gt;
&lt;div&gt;=Taste Development=&lt;br /&gt;
&lt;br /&gt;
You are out to dinner and your meal arrives in front of you, the aromas and the presentation of your food strikes you immediately. Half way through, the waiter returns and asks “How does your meal taste?”  The answer is not as simple as one might think. Why does the meal taste pleasant? How do we experience different tastes? In the following page, we aim to discern how exactly one would answer these questions by looking at the embryological development of the taste system from week to week. &lt;br /&gt;
&lt;br /&gt;
Taste is a complex sensory system and its precise workings are to this day not fully understood. What makes it so complicated is the interaction between the structure of tongue and taste buds and how this contributes to the representation of taste qualities (salty, bitter, sweet, sour and umami) in the brain. We will also look at some current research on animal models being undertaken to evaluate the role of specific genes in the development of sensory structures. By looking at the taste system’s genetic basis, we now have a greater understanding of the abnormalities that may occur during development and a direction to pursue in future research to attempt to fill in the gaps of scientific knowledge.&lt;br /&gt;
&lt;br /&gt;
[[File:Baby tongue.jpg|centre|500px]]&lt;br /&gt;
&lt;br /&gt;
==History of Discoveries==&lt;br /&gt;
&lt;br /&gt;
{| cellpadding=5 style=&amp;quot;border:1px solid #BBB&amp;quot;&lt;br /&gt;
|- bgcolor=&amp;quot;#faecc8&amp;quot;&lt;br /&gt;
|''' Date'''|| '''Significant Discovery'''&lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#faf6ed&amp;quot;&lt;br /&gt;
|'''350BC'''&lt;br /&gt;
|| Aristotle writes about the basic tastes, sweet and bitter. He also notes that it can be modified by salty and acidic. &amp;lt;ref name=&amp;quot;PMID22717400&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;22717400&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#faecc8&amp;quot;&lt;br /&gt;
|'''1901'''&lt;br /&gt;
|| D. Hanig publishes a paper describing taste sensitivity in different regions of the tongue. &lt;br /&gt;
''Interesting fact:'' The modern concept of a 'tongue map' is a misinterpretation of this study. &amp;lt;ref name=&amp;quot;PMID22717400&amp;quot;/&amp;gt;&lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#faf6ed&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''1908'''&lt;br /&gt;
|Kikunae Ikeda, a professor of the Tokyo Imperial University, discovered and identified the fifth basic taste: umami (savouriness), made palatable by glutamate.  &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;12438213&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
[http://chemse.oxfordjournals.org/content/27/9/847.long New Seasonings]&lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#faecc8&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''1931-32'''&lt;br /&gt;
| A chemist named Arthur Fox and his college noted that they had different sensitivities to the bitter tasting Phenylthiocarbamide (PTC).&amp;lt;ref&amp;gt;Blakeslee AF, Fox AL. Our different taste worlds. J Hered. 1932;23:97–107.&amp;lt;/ref&amp;gt; Geneticists later confirm these findings, and discover that non-tasting is a recessive genetic trait. &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;17782493&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/pubmed/17782493 Inherited taste deficiency] &lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#faf6ed&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''1965'''&lt;br /&gt;
|Farbman's study of the developing taste but in rat fungiform papilla was significant in increasing our understanding of taste bud development. &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;14300090&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
[http://www.sciencedirect.com/science/article/pii/0012160665900400 Electron microscope study of the developing taste bud in rat fungiform papilla.]&lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#faecc8&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''1992'''&lt;br /&gt;
|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. &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;1608467 &amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
[http://www.nature.com/nature/journal/v357/n6379/abs/357563a0.html Gustducin is a taste-cell-specific G protein closely related to the transducins]&lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#faf6ed&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''1995'''&lt;br /&gt;
|Barlow et al. experimented with Axolotl salamanders and concluded that taste buds from this species arise exclusively from epithelial tissue, &amp;quot;oropharyngeal [[#Glossary |'''epithelium''']]&amp;quot;. &amp;lt;ref name=&amp;quot;PMID17826760&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;17826760&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/pubmed/17826760 Embryonic origin of gustatory cranial sensory neurons] &lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#faecc8&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''1996'''&lt;br /&gt;
| 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 &amp;quot;at least dual function of embryonic/fetal taste buds&amp;quot;, including non-gustatory, paracrine functions prior to the 14th week and gustatory after the 14th week. &amp;lt;ref name=&amp;quot;PMID8955790&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;8955790&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/pubmed/8955790 Embryonic and early fetal development of human taste buds: a transmission electron microscopical study]&lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#faf6ed&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''2000'''&lt;br /&gt;
|Chandrashekar, J. et al. discover the first taste sonsors, the T2R bitter taste receptors. &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;10761935&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
[http://www.sciencedirect.com/science/article/pii/S0092867400807060 T2Rs Function as Bitter Taste Receptors]&lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#faecc8&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''2001'''&lt;br /&gt;
|Nelson, G. et al. discover the sweet receptor: a combination of T1R2 and T1R3. &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;11509186&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/pubmed/11509186?dopt=Abstract&amp;amp;holding=npg Mammalian sweet taste receptors.]&lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#faf6ed&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''2002'''&lt;br /&gt;
|Nelson G. et al. discover the amino acid (umami) taste receptor: a combination of T1R1 and T1R3 identified.  &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;11894099&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/pubmed/11894099?dopt=Abstract&amp;amp;holding=npg An amino-acid taste receptor]&lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#faecc8&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''2005'''&lt;br /&gt;
|Dyer, J. et al. discover sweet taste receptors in the GI tract. &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;17855558&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1986582/ Sweet taste signaling in the gut]&lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#faf6ed&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''2006'''&lt;br /&gt;
|Huang, A. L et al. discover cells for sour taste, identified by PKD2L1 (a polycystic kidney disease-like ion channel). &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;16929298&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1571047/ The Cells and Logic for Mammalian Sour Taste detection]&lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#faecc8&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''2007'''&lt;br /&gt;
|Harlow DE, Barlow LA of the University of Colorado Denver Health Sciences Center provide evidence of the &amp;quot;embryonic origin of gustatory cranial sensory neurons&amp;quot;. &amp;lt;ref name=&amp;quot;PMID17826760&amp;quot;/&amp;gt;&lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/pubmed/17826760 Embryonic origin of gustatory cranial sensory neurons.]&lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#faf6ed&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''2009'''&lt;br /&gt;
|A study by Hevezi P et al, presents &amp;quot;the first comprehensive characterization of gene expression in primate taste buds&amp;quot;, as opposed to previous studies which focused on rodents. &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;19636377&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/pubmed/19636377 Genome-wide analysis of gene expression in primate taste buds reveals links to diverse processes]&lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#faecc8&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''2010'''&lt;br /&gt;
|Chandrashekar, J. et al. identify epithelial sodium channel (ENaC) as the sodium-salt taste receptor. &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;20107438&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/pubmed/20107438?dopt=Abstract&amp;amp;holding=npg The cells and peripheral representation of sodium taste in mice]&lt;br /&gt;
|}&lt;br /&gt;
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&lt;br /&gt;
&lt;br /&gt;
==Adult Tongue and Taste Buds – Structure and Function==&lt;br /&gt;
&lt;br /&gt;
'''Structure'''&lt;br /&gt;
&lt;br /&gt;
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.  &lt;br /&gt;
&lt;br /&gt;
[http://www.webmd.com/oral-health/picture-of-the-tongue] &lt;br /&gt;
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''''The image below is a simplistic diagram of the surface of the tongue showing the locations of the different papillae and other important features'''&lt;br /&gt;
&lt;br /&gt;
{|&lt;br /&gt;
| [[Image:Drawing of Tongue.png|centre|500px]]&lt;br /&gt;
&lt;br /&gt;
[[File:Taste_pathway.jpg|right|thumb|200px|Simplistic Pathway of Taste]]&lt;br /&gt;
&lt;br /&gt;
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&lt;br /&gt;
&lt;br /&gt;
'''Papillae'''&lt;br /&gt;
&lt;br /&gt;
There are 4 types of papillae on the tongue.&lt;br /&gt;
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.[http://www.tutorvista.com/content/biology/biology-iv/nervous-coordination/tongue-structure.php#parts-of-tongue]&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
[[File:Papillae.jpg|Left|thumb|200px|Close up of Human Tongue Papillae]]&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
[[File:Fungiformpapillae.jpg|left|thumb|200px|Fungiform Papillae]]&lt;br /&gt;
&lt;br /&gt;
[[File:Circumvallatepapillae.jpg |left|thumb|200px|Circumvallate Papillae]]&lt;br /&gt;
&lt;br /&gt;
[[File:Filiformpapillae.jpg|left|200px|thumb|Foliate Papillae]]&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
'''Function'''&lt;br /&gt;
&lt;br /&gt;
The Tongue has muscular and sensory functions, muscular functions include swallowing and speech where as sensory function involves taste. This section will focus on the sensory functions of the tongue.&lt;br /&gt;
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. [http://www.cf.ac.uk/biosi/staffinfo/jacob/teaching/sensory/taste.html]&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
[[File:Taste_bud_1.jpg|right|thumb|200px|Cross section of a taste bud unit|centre|Cross section of a taste bud unit]]&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
'''Link Between Taste and Smell'''&lt;br /&gt;
&lt;br /&gt;
The pathways of smell and taste are very similar (chemosensation). Pathways both involve the conversion of a dissolved chemical stimulus transformed into a electrical impulse for interpretation by the brain.	&lt;br /&gt;
Taste and smell overlap when humans experience flavour, flavour involves an interaction of taste, smell, texture and temperature, where taste is only a portion of this interaction. when the brain interprets a flavour, contribution from other senses has a significant role in identification. In conclusion Taste and Smell in combination with other senses help develop a sensory interpretation called flavour.[http://www.entnet.org/HealthInformation/smellTaste.cfm]&lt;br /&gt;
[[File:Human smelling.jpg|500px|centre]]&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
== Human Weekly Development - Two Prominent Studies ==&lt;br /&gt;
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. &lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
The findings of these two studies are summarized in the table below. The figures provided relate to the images on their respective research papers.&lt;br /&gt;
&lt;br /&gt;
# [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] &lt;br /&gt;
# [http://chemse.oxfordjournals.org/content/22/6/601.long Scanning electron microscopical studies of developing gustatory papillae in humans, 1997]  &lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
===Timeline of Developmental Processes of Human Taste Buds===&lt;br /&gt;
{| cellpadding=5 style=&amp;quot;border:1px solid #BBB&amp;quot;&lt;br /&gt;
|- bgcolor=&amp;quot;#89CFF0&amp;quot;&lt;br /&gt;
|'''Postovulatory Week'''||'''Description'''&lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#BCD4E6&amp;quot;&lt;br /&gt;
|'''Week 6''' ||&lt;br /&gt;
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. &amp;lt;ref name=&amp;quot;PMID9455607&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;9455607&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#89CFF0&amp;quot;&lt;br /&gt;
| '''Weeks 6 to 7'''|| &lt;br /&gt;
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. &amp;lt;ref name=PMID8955790/&amp;gt;&lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#BCD4E6&amp;quot;&lt;br /&gt;
| '''Week 7 '''||&lt;br /&gt;
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.  &amp;lt;ref name=PMID9455607/&amp;gt; &lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#89CFF0&amp;quot;&lt;br /&gt;
| ''' Week 8  ''' ||&lt;br /&gt;
* The taste bud primordium are still differentiated, elongated epithelial cells, resting on a slightly developed core of young dermal papilla.&lt;br /&gt;
* 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. &lt;br /&gt;
* Ciliated cells also appear around the 8th week, however the significance of these cells which are scattered randomly across the lingual surface remains unclear. &amp;lt;ref name=PMID8955790/&amp;gt; &lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#BCD4E6&amp;quot;&lt;br /&gt;
|'''  Week 9''' ||&lt;br /&gt;
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). &amp;lt;ref name=PMID9455607/&amp;gt;&lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#89CFF0&amp;quot;&lt;br /&gt;
|'''  Weeks 10-11''' ||&lt;br /&gt;
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). &amp;lt;ref name=PMID8955790/&amp;gt; &lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#BCD4E6&amp;quot;&lt;br /&gt;
|''' Week 12 ''' ||&lt;br /&gt;
Taste bud cells are more clearly differentiated into epithelial cell types II and III. &amp;lt;ref name=PMID8955790/&amp;gt; &lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#89CFF0&amp;quot;&lt;br /&gt;
|''' Weeks 12-13  ''' ||&lt;br /&gt;
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). &amp;lt;ref name=PMID8955790/&amp;gt; &lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#BCD4E6&amp;quot;&lt;br /&gt;
|''' Weeks 14 -15 ''' ||&lt;br /&gt;
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. &amp;lt;ref name=PMID8955790/&amp;gt; &lt;br /&gt;
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==Abnormalities==&lt;br /&gt;
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It should be mentioned that gustatory abnormalities have not been widely researched. Most research conducted in this field has been conducted through animal testing on mice and this is the basis of information provided below. &lt;br /&gt;
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===Knocking out P2X Receptors===&lt;br /&gt;
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[[File:Image of taste being evoked by visualising ATP release.jpeg|Left|thumb|200px|Evoking taste - ATP release in tongue]]&lt;br /&gt;
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The sensation of taste is made through neurotransmitters. But what happens when there is a disruption in this 'transmission', either through not releasing neurotransmitter or by a reduction in receptor number? Huang, 2008 &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;21940456&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; use the the premise that P2X receptors are essential in taste transduction and that their absence would lead to the inability to taste. &lt;br /&gt;
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This team used to the neurotransmitter ATP, as a quantitative measure of gustatory sensation and taste. ATP is only one neurotransmitter that is involved in taste transduction among others including ''&amp;quot;acetylcholine, glutamate, norepinephrine (NE), serotonin (5-HT), γ-aminobutyric acid (GABA) and a number of peptides.&amp;quot;''&lt;br /&gt;
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This was done by using a comparison of wild type (WT) and double knockout (DKO) mice. P2X receptors, namely 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. A tastant was administered to mucosal lingual epithelium the tongue of the nice and collected. The release of ATP was measured using luciferase and IHC (Immunohisto Chemistry).&lt;br /&gt;
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It should be noted that the taste buds in DKO are functional, but are not stimulated by the administration of tastants. &lt;br /&gt;
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The transmission of release of ATP is secreted through gap junction hemichannels (pannexin 1 gap junction).&lt;br /&gt;
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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.&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;21940456&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
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===FGF signalling and genes===&lt;br /&gt;
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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 (see image under 'Structure of the tongue').&lt;br /&gt;
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By knocking out ''Spry'' genes using mice which had both ''Spry1'' and ''Spry2'' knocked out showed that the number of CVP doubled. However, when Fibroblast [[#Glossary |'''Growth Factor''']] gene (&amp;quot;Fgf10&amp;quot;) 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 &amp;quot;Fgf10&amp;quot; to limit the size of the CVP progenitor placode. Exclusive expression of ''Fgf10'' in the [[#Glossary |'''mesenchyme''']] is necessary for the formation of CVP. &lt;br /&gt;
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{|&lt;br /&gt;
| [[File:Figure 1 Spry1-2.jpeg|160px|]]&lt;br /&gt;
| [[File:CVP of WT(top) and DKO(bottom) mice with H&amp;amp;E and SEM.png]]&lt;br /&gt;
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| &amp;lt;center&amp;gt;[[Figure 1 Spry1-2.jpeg]]&amp;lt;/center&amp;gt;&lt;br /&gt;
| &amp;lt;center&amp;gt;[[CVP of WT(top) and DKO(bottom) mice with H&amp;amp;E and SEM.png]]&amp;lt;/center&amp;gt;&lt;br /&gt;
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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).&lt;br /&gt;
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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).&lt;br /&gt;
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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''&amp;amp; ''Spry 1&amp;amp;2''work antagonistically through receptor tyrosine kinase (RTK) signalling.&lt;br /&gt;
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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.&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;21655085&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
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==Gustatory System==&lt;br /&gt;
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[[Image:Taste qualities.gif|thumb|The five basic tastes]]&lt;br /&gt;
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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.&lt;br /&gt;
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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.&amp;lt;ref name=PMID20696704&amp;gt;&amp;lt;pubmed&amp;gt;20696704&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
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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 &amp;lt;ref name=PMID20696704/&amp;gt; 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.&lt;br /&gt;
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===Cell Biology===&lt;br /&gt;
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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.&lt;br /&gt;
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====Type II receptors====&lt;br /&gt;
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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:&lt;br /&gt;
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# Stimulates gustatory nerve afferents which project to gustatory nuclei  in the spinal cord&lt;br /&gt;
# Excites Type III presynaptic nerve fibers to release serotonin. &lt;br /&gt;
# Has a positive feedback effect on type II receptor cells, increasing the level of ATP production.&lt;br /&gt;
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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.&lt;br /&gt;
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==Taste Map==&lt;br /&gt;
[[Image:Taste map.png|thumb|left|250px|Obsolete idea of the tongue map]]&lt;br /&gt;
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.&lt;br /&gt;
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===Neural Pathways===&lt;br /&gt;
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'''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''. &lt;br /&gt;
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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:  &lt;br /&gt;
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* ''Facial nerve n''. -  carries taste information from the anterior 2/3 of the tongue.&lt;br /&gt;
* ''Hypoglossal n.'' - carries taste information from the posterior 1/3 of the tongue.&lt;br /&gt;
* ''Vagus n''. - carries taste information from the palate&lt;br /&gt;
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'''Second order neurons''' - From the NTS second order neurons carry taste information to the Ventral posteromedial (VPM) nucleus in the thalamus.&amp;lt;ref name=PMID21885776/&amp;gt;&lt;br /&gt;
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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.  &lt;br /&gt;
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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.&lt;br /&gt;
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===Cortical Areas===&lt;br /&gt;
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[[Image:Primary gustatory cortex.png|thumb|Primary gustatory cortex]]&lt;br /&gt;
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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)&amp;lt;ref name=PMID22245354&amp;gt;&amp;lt;pubmed&amp;gt;22245354&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;, with the secondary taste cortex in the caudolateral orbitofrontal cortex.&amp;lt;ref name=PMID21305668&amp;gt;&amp;lt;pubmed&amp;gt;21305668&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;  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.&amp;lt;ref name=PMID21885776&amp;gt;&amp;lt;pubmed&amp;gt;21885776&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; These findings lend weight to the idea that there is only one receptor for each taste quality.&lt;br /&gt;
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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).&amp;lt;ref name=PMID21885776/&amp;gt; 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&lt;br /&gt;
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===Neuronal Development===&lt;br /&gt;
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The gustatory system must not be solely thought of as being comprised of simply the tongue and palate. The types of neurons which carry taste information to the brain are also pivotal in constructing the expression of taste qualities.&lt;br /&gt;
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The two main gustatory neurons which develop are the geniculate ganglion and the petrosal ganglion. These are the visceral sensory ganglion of cranial nerves VII (Facial) and  IX (Hypoglossal) respectively which carry taste information from the tongue to the nucleus tractus solitarius. They arise at the posterior placodal region from the epibranchial placodes, a thickening of ectoderm. The first epibranchial placode gives rise to the geniculate ganglion and the second to the petrosal ganglion.&lt;br /&gt;
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The molecular basis for gustatory neuron formation is not completely understood though there are a number of transcription factors which are thought to play an important role in firstly, placode formation and secondly, neuron differentiation.&lt;br /&gt;
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*Six1/2, Six1/5 and Eya – transcription factors which cause differentiation of epibranchial placodes into the petrosal and geniculate ganglion.&lt;br /&gt;
*Bone morphogenic Protein 7 (BMP7) – a signal arising from the pharyngeal pouch which is believed to induce epibranchial placode formation. May not be solely responsible for this process, current research has been inconclusive as to how it may work with other proteins of the same family.&lt;br /&gt;
*NGN2 - Following the initial differentiation of the placodes, further differentiation occurs to form neuroblasts. NGN2 causes the delamination and migration of these neuroblasts, which subsequently migrate and fuse to form neurons.&lt;br /&gt;
*Phox2b – maintains the structural integrity of neurons. Knockout of these genes in mice causes marked atrophy of the petrosal and geniculate ganglia.&lt;br /&gt;
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The neurons involved in the gustatory system are overproduced and thus in the embryonic stage, undergo programmed cell death (apoptosis). The total amount of neurons in the geniculate ganglion, appears to be quite stable over the embryonic stages. This suggests, unlike the petrosal ganglion, the levels of neuroblast proliferation and apoptosis are fairly similar. The factors which regulate these processes remains unclear. It is posited that neurotrophins BDNF, NT4/5 and NT3 may regulate neuronal survival whilst also playing a part in axon growth from the sensory ganglion. More research is required to discern the exact individual functions of each of the neurotrophins.&lt;br /&gt;
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==Current Research==&lt;br /&gt;
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[[File:Mousetounge histologicalstain.jpg|right|thumb|200px|Image shows histological stains of a mice tongue showing dysplasia]]&lt;br /&gt;
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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. &lt;br /&gt;
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.&lt;br /&gt;
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'''Synergistic relationships of Six Genes '''&lt;br /&gt;
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In an animal study using mice by Suzuki Y, Ikeda K, Kawakami K.(2011)  Firstly nominating &amp;quot;[[#Glossary |'''Six Genes''']]&amp;quot; as a major component in [[#Glossary |'''gustatory ''']] development, stating that deficiencies in certain Six genes (specifically Six1 &amp;amp; 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 &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;21978088&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
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[[File:Abnormal of tongue.jpg|thumb|200px|Image shows an example of tongue abnormalities, this is called &amp;quot;double tongue&amp;quot; each side has independent movement!]]&lt;br /&gt;
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'''Neural Crest responsibilities '''&lt;br /&gt;
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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.&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;22659543&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
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'''Augmentation of Endoderm'''&lt;br /&gt;
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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 &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;22581563&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
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'''Changes in Taste Cells over time'''&lt;br /&gt;
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Research by &lt;br /&gt;
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.  &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;22643728&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
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'''Shh key component of taste bud proginators'''&lt;br /&gt;
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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.&lt;br /&gt;
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 &amp;quot;Axiocam CCD camera and Axioplan fluorescence microscope with Axiovision software&amp;quot; a study by Harlow, Yang, Williams, Barlow (2011)&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;PMC2674259&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
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'''WNT family exhibit various roles'''&lt;br /&gt;
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The WNT gene family has a function of signaling work antagonistically through receptor tyrosine kinase (RTK) signaling. However, the deletion of Sprouty Homolog 2 (Spry2) led to the increase of chimaeric virus particles (CVPs) and a significant decrease in number of fungiform papillae. In contrast, the absence of Fibroblast growth factor 10 (Fgf10) in conjunction with 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. 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. &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;PMC2768563&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
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[[File:Developing_tongue_histology_001.jpg|right|thumb|200px|HIstological stain of a developing rat tongue]]&lt;br /&gt;
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==Glossary==&lt;br /&gt;
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* '''Circumvallate papillae''' - papillae that contain taste buds, that help form the Sulcus terminalis&lt;br /&gt;
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* '''Ectoderm'''- outer germ layer of embryo&lt;br /&gt;
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* '''Endoderm''' - inner germ layer of embryo&lt;br /&gt;
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* '''Epithelium''' - basic animal tissue that is composed of tightly packed cells, usually covering the outer portion of organs&lt;br /&gt;
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* '''Exocystosis''' - movement of contents out of cell&lt;br /&gt;
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* '''Filiform papillae''' - numerous papillae that do not contain taste buds&lt;br /&gt;
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* '''Foliate papillae''' - papillae that contain taste buds&lt;br /&gt;
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* '''Fungiform papillae''' - papillae that contain taste buds&lt;br /&gt;
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* '''Ganglia''' - the accumulation of a nerve cell body&lt;br /&gt;
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* '''Growth factor''' - a substance that stimulates the growth of cells&lt;br /&gt;
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* '''Gustatory''' - anything that relates to the taste sense&lt;br /&gt;
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* '''Hydrolysis''' - breakdown of a chemical when it reacts with water&lt;br /&gt;
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* '''Mesoderm''' - middle germ layer of embryo&lt;br /&gt;
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* '''Mesenchyme''' - multipotential cells&lt;br /&gt;
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* '''Neural crest''' - a part of the ectoderm found on both sides of the neural tube&lt;br /&gt;
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* '''Neuron''' - most simplistic unit of the nervous system&lt;br /&gt;
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* '''Neurotransmitter''' - chemicals which allow the passing of signals from neuron to neuron via connecting part (synapse) &lt;br /&gt;
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* '''Papillae''' - small rough surface projection&lt;br /&gt;
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* '''Six genes''' - a family of genes&lt;br /&gt;
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* '''Sonic hedgehog (Shh)''' - signalling protein involved in normal development&lt;br /&gt;
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* '''Sulcus terminalis''' - describes a physical transition point separating the anterior 2/3 of the tongue from the posterior 1/3&lt;br /&gt;
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* '''Tamoxifen''' - hormonal altering drug&lt;br /&gt;
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* '''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).&lt;br /&gt;
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* '''Type II taste cells''' - Receptor cells acting as primary detectors of sweet, bitter or umami taste.&lt;br /&gt;
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* '''Type III taste cells''' - Presynaptic cells that respond to sweet, salty, sour, bitter and umami compounds.&lt;br /&gt;
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== References ==&lt;br /&gt;
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==External Links==&lt;br /&gt;
{{External Links}}&lt;br /&gt;
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1.[http://www.surgicalneurologyint.com/article.asp?issn=2152-7806;year=2012;volume=3;issue=1;spage=23;epage=23;aulast=Manjila]&lt;br /&gt;
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2.[http://embryology.med.unsw.edu.au/embryology/index.php?title=2012_Group_Project_4]&lt;br /&gt;
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3.[http://www.webmd.com/oral-health/picture-of-the-tongue]&lt;br /&gt;
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4.[http://www.tutorvista.com/content/biology/biology-iv/nervous-coordination/tongue-structure.php#parts-of-tongue]&lt;br /&gt;
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5.[http://www.cf.ac.uk/biosi/staffinfo/jacob/teaching/sensory/taste.html]&lt;br /&gt;
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--[[User:Z8600021|Mark Hill]] 00:19, 5 October 2012 (EST) There should be text with these links.&lt;br /&gt;
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--[[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.&lt;br /&gt;
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----&lt;br /&gt;
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{{2012Projects}}&lt;/div&gt;</summary>
		<author><name>Z3330795</name></author>
	</entry>
	<entry>
		<id>https://embryology.med.unsw.edu.au/embryology/index.php?title=2012_Group_Project_3&amp;diff=105387</id>
		<title>2012 Group Project 3</title>
		<link rel="alternate" type="text/html" href="https://embryology.med.unsw.edu.au/embryology/index.php?title=2012_Group_Project_3&amp;diff=105387"/>
		<updated>2012-10-03T01:55:07Z</updated>

		<summary type="html">&lt;p&gt;Z3330795: /* Glossary */&lt;/p&gt;
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&lt;div&gt;=Taste Development=&lt;br /&gt;
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You are out to dinner and your meal arrives in front of you, the aromas and the presentation of your food strikes you immediately. Half way through, the waiter returns and asks “How does your meal taste?”  The answer is not as simple as one might think. Why does the meal taste pleasant? How do we experience different tastes? In the following page, we aim to discern how exactly one would answer these questions by looking at the embryological development of the taste system from week to week. &lt;br /&gt;
&lt;br /&gt;
Taste is a complex sensory system and its precise workings are to this day not fully understood. What makes it so complicated is the interaction between the structure of tongue and taste buds and how this contributes to the representation of taste qualities (salty, bitter, sweet, sour and umami) in the brain. We will also look at some current research on animal models being undertaken to evaluate the role of specific genes in the development of sensory structures. By looking at the taste system’s genetic basis, we now have a greater understanding of the abnormalities that may occur during development and a direction to pursue in future research to attempt to fill in the gaps of scientific knowledge.&lt;br /&gt;
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[[File:Baby tongue.jpg|centre|500px]]&lt;br /&gt;
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==History of Discoveries==&lt;br /&gt;
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{| cellpadding=5 style=&amp;quot;border:1px solid #BBB&amp;quot;&lt;br /&gt;
|- bgcolor=&amp;quot;#faecc8&amp;quot;&lt;br /&gt;
|''' Date'''|| '''Significant Discovery'''&lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#faf6ed&amp;quot;&lt;br /&gt;
|'''350BC'''&lt;br /&gt;
|| Aristotle writes about the basic tastes, sweet and bitter. He also notes that it can be modified by salty and acidic. &amp;lt;ref name=&amp;quot;PMID22717400&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;22717400&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#faecc8&amp;quot;&lt;br /&gt;
|'''1901'''&lt;br /&gt;
|| D. Hanig publishes a paper describing taste sensitivity in different regions of the tongue. &lt;br /&gt;
''Interesting fact:'' The modern concept of a 'tongue map' is a misinterpretation of this study. &amp;lt;ref name=&amp;quot;PMID22717400&amp;quot;/&amp;gt;&lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#faf6ed&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''1908'''&lt;br /&gt;
|Kikunae Ikeda, a professor of the Tokyo Imperial University, discovered and identified the fifth basic taste: umami (savouriness), made palatable by glutamate.  &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;12438213&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
[http://chemse.oxfordjournals.org/content/27/9/847.long New Seasonings]&lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#faecc8&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''1931-32'''&lt;br /&gt;
| A chemist named Arthur Fox and his college noted that they had different sensitivities to the bitter tasting Phenylthiocarbamide (PTC).&amp;lt;ref&amp;gt;Blakeslee AF, Fox AL. Our different taste worlds. J Hered. 1932;23:97–107.&amp;lt;/ref&amp;gt; Geneticists later confirm these findings, and discover that non-tasting is a recessive genetic trait. &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;17782493&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/pubmed/17782493 Inherited taste deficiency] &lt;br /&gt;
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|- bgcolor=&amp;quot;#faf6ed&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''1965'''&lt;br /&gt;
|Farbman's study of the developing taste but in rat fungiform papilla was significant in increasing our understanding of taste bud development. &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;14300090&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
[http://www.sciencedirect.com/science/article/pii/0012160665900400 Electron microscope study of the developing taste bud in rat fungiform papilla.]&lt;br /&gt;
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|- bgcolor=&amp;quot;#faecc8&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''1992'''&lt;br /&gt;
|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. &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;1608467 &amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
[http://www.nature.com/nature/journal/v357/n6379/abs/357563a0.html Gustducin is a taste-cell-specific G protein closely related to the transducins]&lt;br /&gt;
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|- bgcolor=&amp;quot;#faf6ed&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''1995'''&lt;br /&gt;
|Barlow et al. experimented with Axolotl salamanders and concluded that taste buds from this species arise exclusively from epithelial tissue, &amp;quot;oropharyngeal [[#Glossary |'''epithelium''']]&amp;quot;. &amp;lt;ref name=&amp;quot;PMID17826760&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;17826760&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/pubmed/17826760 Embryonic origin of gustatory cranial sensory neurons] &lt;br /&gt;
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|- bgcolor=&amp;quot;#faecc8&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''1996'''&lt;br /&gt;
| 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 &amp;quot;at least dual function of embryonic/fetal taste buds&amp;quot;, including non-gustatory, paracrine functions prior to the 14th week and gustatory after the 14th week. &amp;lt;ref name=&amp;quot;PMID8955790&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;8955790&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/pubmed/8955790 Embryonic and early fetal development of human taste buds: a transmission electron microscopical study]&lt;br /&gt;
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|- bgcolor=&amp;quot;#faf6ed&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''2000'''&lt;br /&gt;
|Chandrashekar, J. et al. discover the first taste sonsors, the T2R bitter taste receptors. &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;10761935&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
[http://www.sciencedirect.com/science/article/pii/S0092867400807060 T2Rs Function as Bitter Taste Receptors]&lt;br /&gt;
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|- bgcolor=&amp;quot;#faecc8&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''2001'''&lt;br /&gt;
|Nelson, G. et al. discover the sweet receptor: a combination of T1R2 and T1R3. &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;11509186&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/pubmed/11509186?dopt=Abstract&amp;amp;holding=npg Mammalian sweet taste receptors.]&lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#faf6ed&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''2002'''&lt;br /&gt;
|Nelson G. et al. discover the amino acid (umami) taste receptor: a combination of T1R1 and T1R3 identified.  &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;11894099&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/pubmed/11894099?dopt=Abstract&amp;amp;holding=npg An amino-acid taste receptor]&lt;br /&gt;
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|- bgcolor=&amp;quot;#faecc8&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''2005'''&lt;br /&gt;
|Dyer, J. et al. discover sweet taste receptors in the GI tract. &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;17855558&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1986582/ Sweet taste signaling in the gut]&lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#faf6ed&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''2006'''&lt;br /&gt;
|Huang, A. L et al. discover cells for sour taste, identified by PKD2L1 (a polycystic kidney disease-like ion channel). &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;16929298&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1571047/ The Cells and Logic for Mammalian Sour Taste detection]&lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#faecc8&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''2007'''&lt;br /&gt;
|Harlow DE, Barlow LA of the University of Colorado Denver Health Sciences Center provide evidence of the &amp;quot;embryonic origin of gustatory cranial sensory neurons&amp;quot;. &amp;lt;ref name=&amp;quot;PMID17826760&amp;quot;/&amp;gt;&lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/pubmed/17826760 Embryonic origin of gustatory cranial sensory neurons.]&lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#faf6ed&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''2009'''&lt;br /&gt;
|A study by Hevezi P et al, presents &amp;quot;the first comprehensive characterization of gene expression in primate taste buds&amp;quot;, as opposed to previous studies which focused on rodents. &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;19636377&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/pubmed/19636377 Genome-wide analysis of gene expression in primate taste buds reveals links to diverse processes]&lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#faecc8&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''2010'''&lt;br /&gt;
|Chandrashekar, J. et al. identify epithelial sodium channel (ENaC) as the sodium-salt taste receptor. &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;20107438&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/pubmed/20107438?dopt=Abstract&amp;amp;holding=npg The cells and peripheral representation of sodium taste in mice]&lt;br /&gt;
|}&lt;br /&gt;
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==Adult Tongue and Taste Buds – Structure and Function==&lt;br /&gt;
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'''Structure'''&lt;br /&gt;
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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.  &lt;br /&gt;
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[http://www.webmd.com/oral-health/picture-of-the-tongue] &lt;br /&gt;
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''''The image below is a simplistic diagram of the surface of the tongue showing the locations of the different papillae and other important features'''&lt;br /&gt;
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{|&lt;br /&gt;
| [[Image:Drawing of Tongue.png|centre|500px]]&lt;br /&gt;
&lt;br /&gt;
[[File:Taste_pathway.jpg|right|thumb|200px|Simplistic Pathway of Taste]]&lt;br /&gt;
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'''Papillae'''&lt;br /&gt;
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There are 4 types of papillae on the tongue.&lt;br /&gt;
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.[http://www.tutorvista.com/content/biology/biology-iv/nervous-coordination/tongue-structure.php#parts-of-tongue]&lt;br /&gt;
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[[File:Papillae.jpg|Left|thumb|200px|Close up of Human Tongue Papillae]]&lt;br /&gt;
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[[File:Fungiformpapillae.jpg|left|thumb|200px|Fungiform Papillae]]&lt;br /&gt;
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[[File:Circumvallatepapillae.jpg |left|thumb|200px|Circumvallate Papillae]]&lt;br /&gt;
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[[File:Filiformpapillae.jpg|left|200px|thumb|Foliate Papillae]]&lt;br /&gt;
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'''Function'''&lt;br /&gt;
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The Tongue has muscular and sensory functions, muscular functions include swallowing and speech where as sensory function involves taste. This section will focus on the sensory functions of the tongue.&lt;br /&gt;
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. [http://www.cf.ac.uk/biosi/staffinfo/jacob/teaching/sensory/taste.html]&lt;br /&gt;
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[[File:Taste_bud_1.jpg|right|thumb|200px|Cross section of a taste bud unit|centre|Cross section of a taste bud unit]]&lt;br /&gt;
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'''Link Between Taste and Smell'''&lt;br /&gt;
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The pathways of smell and taste are very similar (chemosensation). Pathways both involve the conversion of a dissolved chemical stimulus transformed into a electrical impulse for interpretation by the brain.	&lt;br /&gt;
Taste and smell overlap when humans experience flavour, flavour involves an interaction of taste, smell, texture and temperature, where taste is only a portion of this interaction. when the brain interprets a flavour, contribution from other senses has a significant role in identification. In conclusion Taste and Smell in combination with other senses help develop a sensory interpretation called flavour.[http://www.entnet.org/HealthInformation/smellTaste.cfm]&lt;br /&gt;
[[File:Human smelling.jpg|500px|centre]]&lt;br /&gt;
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== Human Weekly Development - Two Prominent Studies ==&lt;br /&gt;
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. &lt;br /&gt;
&lt;br /&gt;
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The findings of these two studies are summarized in the table below. The figures provided relate to the images on their respective research papers.&lt;br /&gt;
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# [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] &lt;br /&gt;
# [http://chemse.oxfordjournals.org/content/22/6/601.long Scanning electron microscopical studies of developing gustatory papillae in humans, 1997]  &lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
===Timeline of Developmental Processes of Human Taste Buds===&lt;br /&gt;
{| cellpadding=5 style=&amp;quot;border:1px solid #BBB&amp;quot;&lt;br /&gt;
|- bgcolor=&amp;quot;#89CFF0&amp;quot;&lt;br /&gt;
|'''Postovulatory Week'''||'''Description'''&lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#BCD4E6&amp;quot;&lt;br /&gt;
|'''Week 6''' ||&lt;br /&gt;
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. &amp;lt;ref name=&amp;quot;PMID9455607&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;9455607&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#89CFF0&amp;quot;&lt;br /&gt;
| '''Weeks 6 to 7'''|| &lt;br /&gt;
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. &amp;lt;ref name=PMID8955790/&amp;gt;&lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#BCD4E6&amp;quot;&lt;br /&gt;
| '''Week 7 '''||&lt;br /&gt;
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.  &amp;lt;ref name=PMID9455607/&amp;gt; &lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#89CFF0&amp;quot;&lt;br /&gt;
| ''' Week 8  ''' ||&lt;br /&gt;
* The taste bud primordium are still differentiated, elongated epithelial cells, resting on a slightly developed core of young dermal papilla.&lt;br /&gt;
* 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. &lt;br /&gt;
* Ciliated cells also appear around the 8th week, however the significance of these cells which are scattered randomly across the lingual surface remains unclear. &amp;lt;ref name=PMID8955790/&amp;gt; &lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#BCD4E6&amp;quot;&lt;br /&gt;
|'''  Week 9''' ||&lt;br /&gt;
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). &amp;lt;ref name=PMID9455607/&amp;gt;&lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#89CFF0&amp;quot;&lt;br /&gt;
|'''  Weeks 10-11''' ||&lt;br /&gt;
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). &amp;lt;ref name=PMID8955790/&amp;gt; &lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#BCD4E6&amp;quot;&lt;br /&gt;
|''' Week 12 ''' ||&lt;br /&gt;
Taste bud cells are more clearly differentiated into epithelial cell types II and III. &amp;lt;ref name=PMID8955790/&amp;gt; &lt;br /&gt;
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|- bgcolor=&amp;quot;#89CFF0&amp;quot;&lt;br /&gt;
|''' Weeks 12-13  ''' ||&lt;br /&gt;
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). &amp;lt;ref name=PMID8955790/&amp;gt; &lt;br /&gt;
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|- bgcolor=&amp;quot;#BCD4E6&amp;quot;&lt;br /&gt;
|''' Weeks 14 -15 ''' ||&lt;br /&gt;
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. &amp;lt;ref name=PMID8955790/&amp;gt; &lt;br /&gt;
|}&lt;br /&gt;
&lt;br /&gt;
==Abnormalities==&lt;br /&gt;
&lt;br /&gt;
It should be mentioned that gustatory abnormalities have not been widely researched. Most research conducted in this field has been conducted through animal testing on mice and this is the basis of information provided below. &lt;br /&gt;
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===Knocking out P2X Receptors===&lt;br /&gt;
&lt;br /&gt;
[[File:Image of taste being evoked by visualising ATP release.jpeg|Left|thumb|200px|Evoking taste - ATP release in tongue]]&lt;br /&gt;
&lt;br /&gt;
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. &lt;br /&gt;
&lt;br /&gt;
It should be noted that the taste buds in DKO are functional, but are not stimulated by the administration of tastants. &lt;br /&gt;
&lt;br /&gt;
The transmission of release of ATP is secretion through gap junction hemichannels (pannexin 1 gap junction).&lt;br /&gt;
&lt;br /&gt;
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.&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;21940456&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
===FGF signalling and genes===&lt;br /&gt;
&lt;br /&gt;
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.&lt;br /&gt;
&lt;br /&gt;
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 (&amp;quot;Fgf10&amp;quot;) 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 &amp;quot;Fgf10&amp;quot; to limit the size of the CVP progenitor placode. Exclusive expression of ''Fgf10'' in the [[#Glossary |'''mesenchyme''']] is necessary for the formation of CVP. &lt;br /&gt;
&lt;br /&gt;
'''This image shows the CVP stained with H&amp;amp;E and scanned by Scanning Electron Microscope (SEM)'''&lt;br /&gt;
[[File:CVP of WT(top) and DKO(bottom) mice with H&amp;amp;E and SEM.png]]&lt;br /&gt;
&lt;br /&gt;
'''This image shows the location of the CVP and the increased number in DKO mice by SEM'''&lt;br /&gt;
[[File:Mouse circumvallate papilla 01.jpg|300px]]&lt;br /&gt;
&lt;br /&gt;
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).&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
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).&lt;br /&gt;
&lt;br /&gt;
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''&amp;amp; ''Spry 1&amp;amp;2''work antagonistically through receptor tyrosine kinase (RTK)signalling.&lt;br /&gt;
&lt;br /&gt;
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.&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;21655085&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
==Gustatory System==&lt;br /&gt;
&lt;br /&gt;
[[Image:Taste qualities.gif|thumb|The five basic tastes]]&lt;br /&gt;
&lt;br /&gt;
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.&lt;br /&gt;
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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.&amp;lt;ref name=PMID20696704&amp;gt;&amp;lt;pubmed&amp;gt;20696704&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
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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 &amp;lt;ref name=PMID20696704/&amp;gt; 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.&lt;br /&gt;
&lt;br /&gt;
===Cell Biology===&lt;br /&gt;
&lt;br /&gt;
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.&lt;br /&gt;
&lt;br /&gt;
====Type II receptors====&lt;br /&gt;
&lt;br /&gt;
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:&lt;br /&gt;
&lt;br /&gt;
# Stimulates gustatory nerve afferents which project to gustatory nuclei  in the spinal cord&lt;br /&gt;
# Excites Type III presynaptic nerve fibers to release serotonin. &lt;br /&gt;
# Has a positive feedback effect on type II receptor cells, increasing the level of ATP production.&lt;br /&gt;
&lt;br /&gt;
        &lt;br /&gt;
&lt;br /&gt;
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.&lt;br /&gt;
&lt;br /&gt;
==Taste Map==&lt;br /&gt;
[[Image:Taste map.png|thumb|left|250px|Obsolete idea of the tongue map]]&lt;br /&gt;
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.&lt;br /&gt;
&lt;br /&gt;
===Neural Pathways===&lt;br /&gt;
&lt;br /&gt;
'''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''. &lt;br /&gt;
&lt;br /&gt;
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:  &lt;br /&gt;
&lt;br /&gt;
* ''Facial nerve n''. -  carries taste information from the anterior 2/3 of the tongue.&lt;br /&gt;
* ''Hypoglossal n.'' - carries taste information from the posterior 1/3 of the tongue.&lt;br /&gt;
* ''Vagus n''. - carries taste information from the palate&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
'''Second order neurons''' - From the NTS second order neurons carry taste information to the Ventral posteromedial (VPM) nucleus in the thalamus.&amp;lt;ref name=PMID21885776/&amp;gt;&lt;br /&gt;
&lt;br /&gt;
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.  &lt;br /&gt;
&lt;br /&gt;
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.&lt;br /&gt;
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===Cortical Areas===&lt;br /&gt;
&lt;br /&gt;
[[Image:Primary gustatory cortex.png|thumb|Primary gustatory cortex]]&lt;br /&gt;
&lt;br /&gt;
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)&amp;lt;ref name=PMID22245354&amp;gt;&amp;lt;pubmed&amp;gt;22245354&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;, with the secondary taste cortex in the caudolateral orbitofrontal cortex.&amp;lt;ref name=PMID21305668&amp;gt;&amp;lt;pubmed&amp;gt;21305668&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;  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.&amp;lt;ref name=PMID21885776&amp;gt;&amp;lt;pubmed&amp;gt;21885776&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; These findings lend weight to the idea that there is only one receptor for each taste quality.&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
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).&amp;lt;ref name=PMID21885776/&amp;gt; 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&lt;br /&gt;
&lt;br /&gt;
===Neuronal Development===&lt;br /&gt;
&lt;br /&gt;
The gustatory system must not be solely thought of as being comprised of simply the tongue and palate. The types of neurons which carry taste information to the brain are also pivotal in constructing the expression of taste qualities.&lt;br /&gt;
&lt;br /&gt;
The two main gustatory neurons which develop are the geniculate ganglion and the petrosal ganglion. These are the visceral sensory ganglion of cranial nerves VII (Facial) and  IX (Hypoglossal) respectively which carry taste information from the tongue to the nucleus tractus solitarius. They arise at the posterior placodal region from the epibranchial placodes, a thickening of ectoderm. The first epibranchial placode gives rise to the geniculate ganglion and the second to the petrosal ganglion.&lt;br /&gt;
&lt;br /&gt;
The molecular basis for gustatory neuron formation is not completely understood though there are a number of transcription factors which are thought to play an important role in firstly, placode formation and secondly, neuron differentiation.&lt;br /&gt;
&lt;br /&gt;
*Six1/2, Six1/5 and Eya – transcription factors which cause differentiation of epibranchial placodes into the petrosal and geniculate ganglion.&lt;br /&gt;
*Bone morphogenic Protein 7 (BMP7) – a signal arising from the pharyngeal pouch which is believed to induce epibranchial placode formation. May not be solely responsible for this process, current research has been inconclusive as to how it may work with other proteins of the same family.&lt;br /&gt;
*NGN2 - Following the initial differentiation of the placodes, further differentiation occurs to form neuroblasts. NGN2 causes the delamination and migration of these neuroblasts, which subsequently migrate and fuse to form neurons.&lt;br /&gt;
*Phox2b – maintains the structural integrity of neurons. Knockout of these genes in mice causes marked atrophy of the petrosal and geniculate ganglia.&lt;br /&gt;
&lt;br /&gt;
The neurons involved in the gustatory system are overproduced and thus in the embryonic stage, undergo programmed cell death (apoptosis). The total amount of neurons in the geniculate ganglion, appears to be quite stable over the embryonic stages. This suggests, unlike the petrosal ganglion, the levels of neuroblast proliferation and apoptosis are fairly similar. The factors which regulate these processes remains unclear. It is posited that neurotrophins BDNF, NT4/5 and NT3 may regulate neuronal survival whilst also playing a part in axon growth from the sensory ganglion. More research is required to discern the exact individual functions of each of the neurotrophins.&lt;br /&gt;
&lt;br /&gt;
==Current Research==&lt;br /&gt;
&lt;br /&gt;
[[File:Mousetounge histologicalstain.jpg|right|thumb|200px|Image shows histological stains of a mice tongue showing dysplasia]]&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
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. &lt;br /&gt;
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.&lt;br /&gt;
&lt;br /&gt;
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&lt;br /&gt;
'''Synergistic relationships of Six Genes '''&lt;br /&gt;
&lt;br /&gt;
In an animal study using mice by Suzuki Y, Ikeda K, Kawakami K.(2011)  Firstly nominating &amp;quot;[[#Glossary |'''Six Genes''']]&amp;quot; as a major component in [[#Glossary |'''gustatory ''']] development, stating that deficiencies in certain Six genes (specifically Six1 &amp;amp; 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 &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;21978088&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
[[File:Abnormal of tongue.jpg|thumb|200px|Image shows an example of tongue abnormalities, this is called &amp;quot;double tongue&amp;quot; each side has independent movement!]]&lt;br /&gt;
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'''Neural Crest responsibilities '''&lt;br /&gt;
&lt;br /&gt;
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.&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;22659543&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
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'''Augmentation of Endoderm'''&lt;br /&gt;
&lt;br /&gt;
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 &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;22581563&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
&lt;br /&gt;
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'''Changes in Taste Cells over time'''&lt;br /&gt;
&lt;br /&gt;
Research by &lt;br /&gt;
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.  &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;22643728&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
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'''Shh key component of taste bud proginators'''&lt;br /&gt;
&lt;br /&gt;
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.&lt;br /&gt;
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 &amp;quot;Axiocam CCD camera and Axioplan fluorescence microscope with Axiovision software&amp;quot; a study by Harlow, Yang, Williams, Barlow (2011)&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;PMC2674259&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
'''WNT family exhibit various roles'''&lt;br /&gt;
&lt;br /&gt;
 &lt;br /&gt;
The WNT gene family has a function of signaling work antagonistically through receptor tyrosine kinase (RTK) signaling. However, the deletion of Sprouty Homolog 2 (Spry2) led to the increase of chimaeric virus particles (CVPs) and a significant decrease in number of fungiform papillae. In contrast, the absence of Fibroblast growth factor 10 (Fgf10) in conjunction with 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. 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. &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;PMC2768563&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
[[File:Developing_tongue_histology_001.jpg|right|thumb|200px|HIstological stain of a developing rat tongue]]&lt;br /&gt;
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&lt;br /&gt;
'''Controversial Research - Not Ectodermal Origin'''&lt;br /&gt;
&lt;br /&gt;
==Glossary==&lt;br /&gt;
&lt;br /&gt;
* '''Circumvallate papillae''' - papillae that contain taste buds, that help form the Sulcus terminalis&lt;br /&gt;
&lt;br /&gt;
* '''Ectoderm'''- outer germ layer of embryo&lt;br /&gt;
&lt;br /&gt;
* '''Endoderm''' - inner germ layer of embryo&lt;br /&gt;
&lt;br /&gt;
* '''Epithelium''' - basic animal tissue that is composed of tightly packed cells, usually covering the outer portion of organs&lt;br /&gt;
&lt;br /&gt;
* '''Exocystosis''' - movement of contents out of cell&lt;br /&gt;
&lt;br /&gt;
* '''Filiform papillae''' - numerous papillae that do not contain taste buds&lt;br /&gt;
&lt;br /&gt;
* '''Foliate papillae''' - papillae that contain taste buds&lt;br /&gt;
&lt;br /&gt;
* '''Fungiform papillae''' - papillae that contain taste buds&lt;br /&gt;
&lt;br /&gt;
* '''Ganglia''' - the accumulation of a nerve cell body&lt;br /&gt;
&lt;br /&gt;
* '''Growth factor''' - a substance that stimulates the growth of cells&lt;br /&gt;
&lt;br /&gt;
* '''Gustatory''' - anything that relates to the taste sense&lt;br /&gt;
&lt;br /&gt;
* '''Hydrolysis''' - breakdown of a chemical when it reacts with water&lt;br /&gt;
&lt;br /&gt;
* '''Mesoderm''' - middle germ layer of embryo&lt;br /&gt;
&lt;br /&gt;
* '''Mesenchyme''' - multipotential cells&lt;br /&gt;
&lt;br /&gt;
* '''Neural crest''' - a part of the ectoderm found on both sides of the neural tube&lt;br /&gt;
&lt;br /&gt;
* '''Neuron''' - most simplistic unit of the nervous system&lt;br /&gt;
&lt;br /&gt;
* '''Neurotransmitter''' - chemicals which allow the passing of signals from neuron to neuron via connecting part (synapse) &lt;br /&gt;
&lt;br /&gt;
* '''Papillae''' - small rough surface projection&lt;br /&gt;
&lt;br /&gt;
* '''Six genes''' - a family of genes&lt;br /&gt;
&lt;br /&gt;
* '''Sonic hedgehog (Shh)''' - signalling protein involved in normal development&lt;br /&gt;
&lt;br /&gt;
* '''Sulcus terminalis''' - describes a physical transition point separating the anterior 2/3 of the tongue from the posterior 1/3&lt;br /&gt;
&lt;br /&gt;
* '''Tamoxifen''' - hormonal altering drug&lt;br /&gt;
&lt;br /&gt;
* '''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).&lt;br /&gt;
&lt;br /&gt;
* '''Type II taste cells''' - Receptor cells acting as primary detectors of sweet, bitter or umami taste.&lt;br /&gt;
&lt;br /&gt;
* '''Type III taste cells''' - Presynaptic cells that respond to sweet, salty, sour, bitter and umami compounds.&lt;br /&gt;
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== References ==&lt;br /&gt;
&amp;lt;references/&amp;gt;&lt;br /&gt;
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==External Links==&lt;br /&gt;
{{External Links}}&lt;br /&gt;
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1.[http://www.surgicalneurologyint.com/article.asp?issn=2152-7806;year=2012;volume=3;issue=1;spage=23;epage=23;aulast=Manjila]&lt;br /&gt;
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2.[http://embryology.med.unsw.edu.au/embryology/index.php?title=2012_Group_Project_4]&lt;br /&gt;
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3.[http://www.webmd.com/oral-health/picture-of-the-tongue]&lt;br /&gt;
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4.[http://www.tutorvista.com/content/biology/biology-iv/nervous-coordination/tongue-structure.php#parts-of-tongue]&lt;br /&gt;
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5.[http://www.cf.ac.uk/biosi/staffinfo/jacob/teaching/sensory/taste.html]&lt;br /&gt;
&lt;br /&gt;
--[[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.&lt;br /&gt;
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{{2012Projects}}&lt;/div&gt;</summary>
		<author><name>Z3330795</name></author>
	</entry>
	<entry>
		<id>https://embryology.med.unsw.edu.au/embryology/index.php?title=2012_Group_Project_3&amp;diff=105381</id>
		<title>2012 Group Project 3</title>
		<link rel="alternate" type="text/html" href="https://embryology.med.unsw.edu.au/embryology/index.php?title=2012_Group_Project_3&amp;diff=105381"/>
		<updated>2012-10-03T01:50:03Z</updated>

		<summary type="html">&lt;p&gt;Z3330795: /* Taste Development */&lt;/p&gt;
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&lt;div&gt;=Taste Development=&lt;br /&gt;
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You are out to dinner and your meal arrives in front of you, the aromas and the presentation of your food strikes you immediately. Half way through, the waiter returns and asks “How does your meal taste?”  The answer is not as simple as one might think. Why does the meal taste pleasant? How do we experience different tastes? In the following page, we aim to discern how exactly one would answer these questions by looking at the embryological development of the taste system from week to week. &lt;br /&gt;
&lt;br /&gt;
Taste is a complex sensory system and its precise workings are to this day not fully understood. What makes it so complicated is the interaction between the structure of tongue and taste buds and how this contributes to the representation of taste qualities (salty, bitter, sweet, sour and umami) in the brain. We will also look at some current research on animal models being undertaken to evaluate the role of specific genes in the development of sensory structures. By looking at the taste system’s genetic basis, we now have a greater understanding of the abnormalities that may occur during development and a direction to pursue in future research to attempt to fill in the gaps of scientific knowledge.&lt;br /&gt;
&lt;br /&gt;
[[File:Baby tongue.jpg|centre|500px]]&lt;br /&gt;
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==History of Discoveries==&lt;br /&gt;
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{| cellpadding=5 style=&amp;quot;border:1px solid #BBB&amp;quot;&lt;br /&gt;
|- bgcolor=&amp;quot;#faecc8&amp;quot;&lt;br /&gt;
|''' Date'''|| '''Significant Discovery'''&lt;br /&gt;
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|- bgcolor=&amp;quot;#faf6ed&amp;quot;&lt;br /&gt;
|'''350BC'''&lt;br /&gt;
|| Aristotle writes about the basic tastes, sweet and bitter. He also notes that it can be modified by salty and acidic. &amp;lt;ref name=&amp;quot;PMID22717400&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;22717400&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
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|- bgcolor=&amp;quot;#faecc8&amp;quot;&lt;br /&gt;
|'''1901'''&lt;br /&gt;
|| D. Hanig publishes a paper describing taste sensitivity in different regions of the tongue. &lt;br /&gt;
''Interesting fact:'' The modern concept of a 'tongue map' is a misinterpretation of this study. &amp;lt;ref name=&amp;quot;PMID22717400&amp;quot;/&amp;gt;&lt;br /&gt;
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|- bgcolor=&amp;quot;#faf6ed&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''1908'''&lt;br /&gt;
|Kikunae Ikeda, a professor of the Tokyo Imperial University, discovered and identified the fifth basic taste: umami (savouriness), made palatable by glutamate.  &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;12438213&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
[http://chemse.oxfordjournals.org/content/27/9/847.long New Seasonings]&lt;br /&gt;
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|- bgcolor=&amp;quot;#faecc8&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''1931-32'''&lt;br /&gt;
| A chemist named Arthur Fox and his college noted that they had different sensitivities to the bitter tasting Phenylthiocarbamide (PTC).&amp;lt;ref&amp;gt;Blakeslee AF, Fox AL. Our different taste worlds. J Hered. 1932;23:97–107.&amp;lt;/ref&amp;gt; Geneticists later confirm these findings, and discover that non-tasting is a recessive genetic trait. &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;17782493&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/pubmed/17782493 Inherited taste deficiency] &lt;br /&gt;
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|- bgcolor=&amp;quot;#faf6ed&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''1965'''&lt;br /&gt;
|Farbman's study of the developing taste but in rat fungiform papilla was significant in increasing our understanding of taste bud development. &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;14300090&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
[http://www.sciencedirect.com/science/article/pii/0012160665900400 Electron microscope study of the developing taste bud in rat fungiform papilla.]&lt;br /&gt;
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|- bgcolor=&amp;quot;#faecc8&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''1992'''&lt;br /&gt;
|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. &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;1608467 &amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
[http://www.nature.com/nature/journal/v357/n6379/abs/357563a0.html Gustducin is a taste-cell-specific G protein closely related to the transducins]&lt;br /&gt;
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|- bgcolor=&amp;quot;#faf6ed&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''1995'''&lt;br /&gt;
|Barlow et al. experimented with Axolotl salamanders and concluded that taste buds from this species arise exclusively from epithelial tissue, &amp;quot;oropharyngeal [[#Glossary |'''epithelium''']]&amp;quot;. &amp;lt;ref name=&amp;quot;PMID17826760&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;17826760&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/pubmed/17826760 Embryonic origin of gustatory cranial sensory neurons] &lt;br /&gt;
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|- bgcolor=&amp;quot;#faecc8&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''1996'''&lt;br /&gt;
| 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 &amp;quot;at least dual function of embryonic/fetal taste buds&amp;quot;, including non-gustatory, paracrine functions prior to the 14th week and gustatory after the 14th week. &amp;lt;ref name=&amp;quot;PMID8955790&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;8955790&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/pubmed/8955790 Embryonic and early fetal development of human taste buds: a transmission electron microscopical study]&lt;br /&gt;
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|- bgcolor=&amp;quot;#faf6ed&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''2000'''&lt;br /&gt;
|Chandrashekar, J. et al. discover the first taste sonsors, the T2R bitter taste receptors. &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;10761935&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
[http://www.sciencedirect.com/science/article/pii/S0092867400807060 T2Rs Function as Bitter Taste Receptors]&lt;br /&gt;
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|- bgcolor=&amp;quot;#faecc8&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''2001'''&lt;br /&gt;
|Nelson, G. et al. discover the sweet receptor: a combination of T1R2 and T1R3. &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;11509186&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/pubmed/11509186?dopt=Abstract&amp;amp;holding=npg Mammalian sweet taste receptors.]&lt;br /&gt;
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|- bgcolor=&amp;quot;#faf6ed&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''2002'''&lt;br /&gt;
|Nelson G. et al. discover the amino acid (umami) taste receptor: a combination of T1R1 and T1R3 identified.  &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;11894099&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/pubmed/11894099?dopt=Abstract&amp;amp;holding=npg An amino-acid taste receptor]&lt;br /&gt;
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|- bgcolor=&amp;quot;#faecc8&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''2005'''&lt;br /&gt;
|Dyer, J. et al. discover sweet taste receptors in the GI tract. &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;17855558&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1986582/ Sweet taste signaling in the gut]&lt;br /&gt;
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|- bgcolor=&amp;quot;#faf6ed&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''2006'''&lt;br /&gt;
|Huang, A. L et al. discover cells for sour taste, identified by PKD2L1 (a polycystic kidney disease-like ion channel). &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;16929298&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1571047/ The Cells and Logic for Mammalian Sour Taste detection]&lt;br /&gt;
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|- bgcolor=&amp;quot;#faecc8&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''2007'''&lt;br /&gt;
|Harlow DE, Barlow LA of the University of Colorado Denver Health Sciences Center provide evidence of the &amp;quot;embryonic origin of gustatory cranial sensory neurons&amp;quot;. &amp;lt;ref name=&amp;quot;PMID17826760&amp;quot;/&amp;gt;&lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/pubmed/17826760 Embryonic origin of gustatory cranial sensory neurons.]&lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#faf6ed&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''2009'''&lt;br /&gt;
|A study by Hevezi P et al, presents &amp;quot;the first comprehensive characterization of gene expression in primate taste buds&amp;quot;, as opposed to previous studies which focused on rodents. &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;19636377&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/pubmed/19636377 Genome-wide analysis of gene expression in primate taste buds reveals links to diverse processes]&lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#faecc8&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''2010'''&lt;br /&gt;
|Chandrashekar, J. et al. identify epithelial sodium channel (ENaC) as the sodium-salt taste receptor. &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;20107438&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/pubmed/20107438?dopt=Abstract&amp;amp;holding=npg The cells and peripheral representation of sodium taste in mice]&lt;br /&gt;
|}&lt;br /&gt;
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==Adult Tongue and Taste Buds – Structure and Function==&lt;br /&gt;
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'''Structure'''&lt;br /&gt;
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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.  &lt;br /&gt;
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[http://www.webmd.com/oral-health/picture-of-the-tongue] &lt;br /&gt;
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''''The image below is a simplistic diagram of the surface of the tongue showing the locations of the different papillae and other important features'''&lt;br /&gt;
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{|&lt;br /&gt;
| [[Image:Drawing of Tongue.png|centre|500px]]&lt;br /&gt;
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[[File:Taste_pathway.jpg|right|thumb|200px|Simplistic Pathway of Taste]]&lt;br /&gt;
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'''Papillae'''&lt;br /&gt;
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There are 4 types of papillae on the tongue.&lt;br /&gt;
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.[http://www.tutorvista.com/content/biology/biology-iv/nervous-coordination/tongue-structure.php#parts-of-tongue]&lt;br /&gt;
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[[File:Papillae.jpg|Left|thumb|200px|Close up of Human Tongue Papillae]]&lt;br /&gt;
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[[File:Fungiformpapillae.jpg|left|thumb|200px|Fungiform Papillae]]&lt;br /&gt;
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[[File:Circumvallatepapillae.jpg |left|thumb|200px|Circumvallate Papillae]]&lt;br /&gt;
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[[File:Filiformpapillae.jpg|left|200px|thumb|Foliate Papillae]]&lt;br /&gt;
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'''Function'''&lt;br /&gt;
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The Tongue has muscular and sensory functions, muscular functions include swallowing and speech where as sensory function involves taste. This section will focus on the sensory functions of the tongue.&lt;br /&gt;
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. [http://www.cf.ac.uk/biosi/staffinfo/jacob/teaching/sensory/taste.html]&lt;br /&gt;
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[[File:Taste_bud_1.jpg|right|thumb|200px|Cross section of a taste bud unit|centre|Cross section of a taste bud unit]]&lt;br /&gt;
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'''Link Between Taste and Smell'''&lt;br /&gt;
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The pathways of smell and taste are very similar (chemosensation). Pathways both involve the conversion of a dissolved chemical stimulus transformed into a electrical impulse for interpretation by the brain.	&lt;br /&gt;
Taste and smell overlap when humans experience flavour, flavour involves an interaction of taste, smell, texture and temperature, where taste is only a portion of this interaction. when the brain interprets a flavour, contribution from other senses has a significant role in identification. In conclusion Taste and Smell in combination with other senses help develop a sensory interpretation called flavour.[http://www.entnet.org/HealthInformation/smellTaste.cfm]&lt;br /&gt;
[[File:Human smelling.jpg|500px|centre]]&lt;br /&gt;
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== Human Weekly Development - Two Prominent Studies ==&lt;br /&gt;
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. &lt;br /&gt;
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The findings of these two studies are summarized in the table below. The figures provided relate to the images on their respective research papers.&lt;br /&gt;
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# [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] &lt;br /&gt;
# [http://chemse.oxfordjournals.org/content/22/6/601.long Scanning electron microscopical studies of developing gustatory papillae in humans, 1997]  &lt;br /&gt;
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===Timeline of Developmental Processes of Human Taste Buds===&lt;br /&gt;
{| cellpadding=5 style=&amp;quot;border:1px solid #BBB&amp;quot;&lt;br /&gt;
|- bgcolor=&amp;quot;#89CFF0&amp;quot;&lt;br /&gt;
|'''Postovulatory Week'''||'''Description'''&lt;br /&gt;
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|- bgcolor=&amp;quot;#BCD4E6&amp;quot;&lt;br /&gt;
|'''Week 6''' ||&lt;br /&gt;
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. &amp;lt;ref name=&amp;quot;PMID9455607&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;9455607&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
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|- bgcolor=&amp;quot;#89CFF0&amp;quot;&lt;br /&gt;
| '''Weeks 6 to 7'''|| &lt;br /&gt;
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. &amp;lt;ref name=PMID8955790/&amp;gt;&lt;br /&gt;
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|- bgcolor=&amp;quot;#BCD4E6&amp;quot;&lt;br /&gt;
| '''Week 7 '''||&lt;br /&gt;
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.  &amp;lt;ref name=PMID9455607/&amp;gt; &lt;br /&gt;
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|- bgcolor=&amp;quot;#89CFF0&amp;quot;&lt;br /&gt;
| ''' Week 8  ''' ||&lt;br /&gt;
* The taste bud primordium are still differentiated, elongated epithelial cells, resting on a slightly developed core of young dermal papilla.&lt;br /&gt;
* 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. &lt;br /&gt;
* Ciliated cells also appear around the 8th week, however the significance of these cells which are scattered randomly across the lingual surface remains unclear. &amp;lt;ref name=PMID8955790/&amp;gt; &lt;br /&gt;
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|- bgcolor=&amp;quot;#BCD4E6&amp;quot;&lt;br /&gt;
|'''  Week 9''' ||&lt;br /&gt;
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). &amp;lt;ref name=PMID9455607/&amp;gt;&lt;br /&gt;
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|- bgcolor=&amp;quot;#89CFF0&amp;quot;&lt;br /&gt;
|'''  Weeks 10-11''' ||&lt;br /&gt;
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). &amp;lt;ref name=PMID8955790/&amp;gt; &lt;br /&gt;
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|- bgcolor=&amp;quot;#BCD4E6&amp;quot;&lt;br /&gt;
|''' Week 12 ''' ||&lt;br /&gt;
Taste bud cells are more clearly differentiated into epithelial cell types II and III. &amp;lt;ref name=PMID8955790/&amp;gt; &lt;br /&gt;
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|- bgcolor=&amp;quot;#89CFF0&amp;quot;&lt;br /&gt;
|''' Weeks 12-13  ''' ||&lt;br /&gt;
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). &amp;lt;ref name=PMID8955790/&amp;gt; &lt;br /&gt;
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|- bgcolor=&amp;quot;#BCD4E6&amp;quot;&lt;br /&gt;
|''' Weeks 14 -15 ''' ||&lt;br /&gt;
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. &amp;lt;ref name=PMID8955790/&amp;gt; &lt;br /&gt;
|}&lt;br /&gt;
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==Abnormalities==&lt;br /&gt;
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It should be mentioned that gustatory abnormalities have not been widely researched. Most research conducted in this field has been conducted through animal testing on mice and this is the basis of information provided below. &lt;br /&gt;
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===Knocking out P2X Receptors===&lt;br /&gt;
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[[File:Image of taste being evoked by visualising ATP release.jpeg|Left|thumb|200px|Evoking taste - ATP release in tongue]]&lt;br /&gt;
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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. &lt;br /&gt;
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It should be noted that the taste buds in DKO are functional, but are not stimulated by the administration of tastants. &lt;br /&gt;
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The transmission of release of ATP is secretion through gap junction hemichannels (pannexin 1 gap junction).&lt;br /&gt;
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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.&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;21940456&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
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===FGF signalling and genes===&lt;br /&gt;
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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.&lt;br /&gt;
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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 (&amp;quot;Fgf10&amp;quot;) 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 &amp;quot;Fgf10&amp;quot; to limit the size of the CVP progenitor placode. Exclusive expression of ''Fgf10'' in the [[#Glossary |'''mesenchyme''']] is necessary for the formation of CVP. &lt;br /&gt;
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'''This image shows the CVP stained with H&amp;amp;E and scanned by Scanning Electron Microscope (SEM)'''&lt;br /&gt;
[[File:CVP of WT(top) and DKO(bottom) mice with H&amp;amp;E and SEM.png]]&lt;br /&gt;
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'''This image shows the location of the CVP and the increased number in DKO mice by SEM'''&lt;br /&gt;
[[File:Mouse circumvallate papilla 01.jpg|300px]]&lt;br /&gt;
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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).&lt;br /&gt;
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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).&lt;br /&gt;
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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''&amp;amp; ''Spry 1&amp;amp;2''work antagonistically through receptor tyrosine kinase (RTK)signalling.&lt;br /&gt;
&lt;br /&gt;
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.&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;21655085&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
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==Gustatory System==&lt;br /&gt;
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[[Image:Taste qualities.gif|thumb|The five basic tastes]]&lt;br /&gt;
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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.&lt;br /&gt;
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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.&amp;lt;ref name=PMID20696704&amp;gt;&amp;lt;pubmed&amp;gt;20696704&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
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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 &amp;lt;ref name=PMID20696704/&amp;gt; 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.&lt;br /&gt;
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===Cell Biology===&lt;br /&gt;
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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.&lt;br /&gt;
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====Type II receptors====&lt;br /&gt;
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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:&lt;br /&gt;
&lt;br /&gt;
# Stimulates gustatory nerve afferents which project to gustatory nuclei  in the spinal cord&lt;br /&gt;
# Excites Type III presynaptic nerve fibers to release serotonin. &lt;br /&gt;
# Has a positive feedback effect on type II receptor cells, increasing the level of ATP production.&lt;br /&gt;
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        &lt;br /&gt;
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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.&lt;br /&gt;
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==Taste Map==&lt;br /&gt;
[[Image:Taste map.png|thumb|left|250px|Obsolete idea of the tongue map]]&lt;br /&gt;
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.&lt;br /&gt;
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===Neural Pathways===&lt;br /&gt;
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'''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''. &lt;br /&gt;
&lt;br /&gt;
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:  &lt;br /&gt;
&lt;br /&gt;
* ''Facial nerve n''. -  carries taste information from the anterior 2/3 of the tongue.&lt;br /&gt;
* ''Hypoglossal n.'' - carries taste information from the posterior 1/3 of the tongue.&lt;br /&gt;
* ''Vagus n''. - carries taste information from the palate&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
'''Second order neurons''' - From the NTS second order neurons carry taste information to the Ventral posteromedial (VPM) nucleus in the thalamus.&amp;lt;ref name=PMID21885776/&amp;gt;&lt;br /&gt;
&lt;br /&gt;
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.  &lt;br /&gt;
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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.&lt;br /&gt;
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===Cortical Areas===&lt;br /&gt;
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[[Image:Primary gustatory cortex.png|thumb|Primary gustatory cortex]]&lt;br /&gt;
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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)&amp;lt;ref name=PMID22245354&amp;gt;&amp;lt;pubmed&amp;gt;22245354&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;, with the secondary taste cortex in the caudolateral orbitofrontal cortex.&amp;lt;ref name=PMID21305668&amp;gt;&amp;lt;pubmed&amp;gt;21305668&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;  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.&amp;lt;ref name=PMID21885776&amp;gt;&amp;lt;pubmed&amp;gt;21885776&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; These findings lend weight to the idea that there is only one receptor for each taste quality.&lt;br /&gt;
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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).&amp;lt;ref name=PMID21885776/&amp;gt; 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&lt;br /&gt;
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===Neuronal Development===&lt;br /&gt;
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The gustatory system must not be solely thought of as being comprised of simply the tongue and palate. The types of neurons which carry taste information to the brain are also pivotal in constructing the expression of taste qualities.&lt;br /&gt;
&lt;br /&gt;
The two main gustatory neurons which develop are the geniculate ganglion and the petrosal ganglion. These are the visceral sensory ganglion of cranial nerves VII (Facial) and  IX (Hypoglossal) respectively which carry taste information from the tongue to the nucleus tractus solitarius. They arise at the posterior placodal region from the epibranchial placodes, a thickening of ectoderm. The first epibranchial placode gives rise to the geniculate ganglion and the second to the petrosal ganglion.&lt;br /&gt;
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The molecular basis for gustatory neuron formation is not completely understood though there are a number of transcription factors which are thought to play an important role in firstly, placode formation and secondly, neuron differentiation.&lt;br /&gt;
&lt;br /&gt;
*Six1/2, Six1/5 and Eya – transcription factors which cause differentiation of epibranchial placodes into the petrosal and geniculate ganglion.&lt;br /&gt;
*Bone morphogenic Protein 7 (BMP7) – a signal arising from the pharyngeal pouch which is believed to induce epibranchial placode formation. May not be solely responsible for this process, current research has been inconclusive as to how it may work with other proteins of the same family.&lt;br /&gt;
*NGN2 - Following the initial differentiation of the placodes, further differentiation occurs to form neuroblasts. NGN2 causes the delamination and migration of these neuroblasts, which subsequently migrate and fuse to form neurons.&lt;br /&gt;
*Phox2b – maintains the structural integrity of neurons. Knockout of these genes in mice causes marked atrophy of the petrosal and geniculate ganglia.&lt;br /&gt;
&lt;br /&gt;
The neurons involved in the gustatory system are overproduced and thus in the embryonic stage, undergo programmed cell death (apoptosis). The total amount of neurons in the geniculate ganglion, appears to be quite stable over the embryonic stages. This suggests, unlike the petrosal ganglion, the levels of neuroblast proliferation and apoptosis are fairly similar. The factors which regulate these processes remains unclear. It is posited that neurotrophins BDNF, NT4/5 and NT3 may regulate neuronal survival whilst also playing a part in axon growth from the sensory ganglion. More research is required to discern the exact individual functions of each of the neurotrophins.&lt;br /&gt;
&lt;br /&gt;
==Current Research==&lt;br /&gt;
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[[File:Mousetounge histologicalstain.jpg|right|thumb|200px|Image shows histological stains of a mice tongue showing dysplasia]]&lt;br /&gt;
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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. &lt;br /&gt;
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.&lt;br /&gt;
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'''Synergistic relationships of Six Genes '''&lt;br /&gt;
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In an animal study using mice by Suzuki Y, Ikeda K, Kawakami K.(2011)  Firstly nominating &amp;quot;[[#Glossary |'''Six Genes''']]&amp;quot; as a major component in [[#Glossary |'''gustatory ''']] development, stating that deficiencies in certain Six genes (specifically Six1 &amp;amp; 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 &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;21978088&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
[[File:Abnormal of tongue.jpg|thumb|200px|Image shows an example of tongue abnormalities, this is called &amp;quot;double tongue&amp;quot; each side has independent movement!]]&lt;br /&gt;
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'''Neural Crest responsibilities '''&lt;br /&gt;
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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.&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;22659543&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
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'''Augmentation of Endoderm'''&lt;br /&gt;
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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 &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;22581563&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
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'''Changes in Taste Cells over time'''&lt;br /&gt;
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Research by &lt;br /&gt;
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.  &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;22643728&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
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'''Shh key component of taste bud proginators'''&lt;br /&gt;
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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.&lt;br /&gt;
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 &amp;quot;Axiocam CCD camera and Axioplan fluorescence microscope with Axiovision software&amp;quot; a study by Harlow, Yang, Williams, Barlow (2011)&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;PMC2674259&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
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'''WNT family exhibit various roles'''&lt;br /&gt;
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 &lt;br /&gt;
The WNT gene family has a function of signaling work antagonistically through receptor tyrosine kinase (RTK) signaling. However, the deletion of Sprouty Homolog 2 (Spry2) led to the increase of chimaeric virus particles (CVPs) and a significant decrease in number of fungiform papillae. In contrast, the absence of Fibroblast growth factor 10 (Fgf10) in conjunction with 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. 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. &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;PMC2768563&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
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[[File:Developing_tongue_histology_001.jpg|right|thumb|200px|HIstological stain of a developing rat tongue]]&lt;br /&gt;
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'''Controversial Research - Not Ectodermal Origin'''&lt;br /&gt;
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==Glossary==&lt;br /&gt;
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* '''Circumvallate papillae''' - &lt;br /&gt;
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* '''Ectoderm'''- outer germ layer of embryo&lt;br /&gt;
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* '''Endoderm''' - inner germ layer of embryo&lt;br /&gt;
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* '''Epithelium''' - basic animal tissue that is composed of tightly packed cells, usually covering the outer portion of organs&lt;br /&gt;
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* '''Exocystosis''' - movement of contents out of cell&lt;br /&gt;
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* '''Filiform papillae''' - &lt;br /&gt;
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* '''Foliate papillae''' - &lt;br /&gt;
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* '''Fungiform papillae''' - &lt;br /&gt;
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* '''Ganglia''' - the accumulation of a nerve cell body&lt;br /&gt;
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* '''Growth factor''' - a substance that stimulates the growth of cells&lt;br /&gt;
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* '''Gustatory''' - anything that relates to the taste sense&lt;br /&gt;
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* '''Hydrolysis''' - breakdown of a chemical when it reacts with water&lt;br /&gt;
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* '''Mesoderm''' - middle germ layer of embryo&lt;br /&gt;
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* '''Mesenchyme''' - multipotential cells&lt;br /&gt;
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* '''Neural crest''' - a part of the ectoderm found on both sides of the neural tube&lt;br /&gt;
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* '''Neuron''' - most simplistic unit of the nervous system&lt;br /&gt;
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* '''Neurotransmitter''' - chemicals which allow the passing of signals from neuron to neuron via connecting part (synapse) &lt;br /&gt;
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* '''Papillae''' - small rough surface projection&lt;br /&gt;
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* '''Six genes''' - a family of genes&lt;br /&gt;
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* '''Sonic hedgehog (Shh)''' - signalling protein involved in normal development&lt;br /&gt;
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* '''Sulcus terminalis''' - describes a physical transition point separating the anterior 2/3 of the tongue from the posterior 1/3&lt;br /&gt;
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* '''Tamoxifen''' - hormonal altering drug&lt;br /&gt;
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* '''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).&lt;br /&gt;
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* '''Type II taste cells''' - Receptor cells acting as primary detectors of sweet, bitter or umami taste.&lt;br /&gt;
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* '''Type III taste cells''' - Presynaptic cells that respond to sweet, salty, sour, bitter and umami compounds.&lt;br /&gt;
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== References ==&lt;br /&gt;
&amp;lt;references/&amp;gt;&lt;br /&gt;
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==External Links==&lt;br /&gt;
{{External Links}}&lt;br /&gt;
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1.[http://www.surgicalneurologyint.com/article.asp?issn=2152-7806;year=2012;volume=3;issue=1;spage=23;epage=23;aulast=Manjila]&lt;br /&gt;
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2.[http://embryology.med.unsw.edu.au/embryology/index.php?title=2012_Group_Project_4]&lt;br /&gt;
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3.[http://www.webmd.com/oral-health/picture-of-the-tongue]&lt;br /&gt;
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4.[http://www.tutorvista.com/content/biology/biology-iv/nervous-coordination/tongue-structure.php#parts-of-tongue]&lt;br /&gt;
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5.[http://www.cf.ac.uk/biosi/staffinfo/jacob/teaching/sensory/taste.html]&lt;br /&gt;
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--[[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.&lt;br /&gt;
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{{2012Projects}}&lt;/div&gt;</summary>
		<author><name>Z3330795</name></author>
	</entry>
	<entry>
		<id>https://embryology.med.unsw.edu.au/embryology/index.php?title=2012_Group_Project_3&amp;diff=105378</id>
		<title>2012 Group Project 3</title>
		<link rel="alternate" type="text/html" href="https://embryology.med.unsw.edu.au/embryology/index.php?title=2012_Group_Project_3&amp;diff=105378"/>
		<updated>2012-10-03T01:48:35Z</updated>

		<summary type="html">&lt;p&gt;Z3330795: /* Taste Development */&lt;/p&gt;
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&lt;div&gt;=Taste Development=&lt;br /&gt;
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You are out to dinner and your meal arrives in front of you, the aromas and the presentation of your food strikes you immediately. Half way through, the waiter returns and asks “How does your meal taste?”  The answer is not as simple as one might think. Why does the meal taste pleasant? How do we experience different tastes? In the following page, we aim to discern how exactly one would answer these questions by looking at the embryological development of the taste system from week to week. &lt;br /&gt;
&lt;br /&gt;
Taste is a complex sensory system and its precise workings are to this day not fully understood. What makes it so complicated is the interaction between the structure of tongue and taste buds and how this contributes to the representation of taste qualities (salty, bitter, sweet, sour and umami) in the brain. We will also look at some current research on animal models being undertaken to evaluate the role of specific genes in the development of sensory structures. By looking at the taste system’s genetic basis, we now have a greater understanding of the abnormalities that may occur during development and a direction to pursue in future research to attempt to fill in the gaps of scientific knowledge.&lt;br /&gt;
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[[File:Baby tongue.jpg]]&lt;br /&gt;
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==History of Discoveries==&lt;br /&gt;
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{| cellpadding=5 style=&amp;quot;border:1px solid #BBB&amp;quot;&lt;br /&gt;
|- bgcolor=&amp;quot;#faecc8&amp;quot;&lt;br /&gt;
|''' Date'''|| '''Significant Discovery'''&lt;br /&gt;
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|- bgcolor=&amp;quot;#faf6ed&amp;quot;&lt;br /&gt;
|'''350BC'''&lt;br /&gt;
|| Aristotle writes about the basic tastes, sweet and bitter. He also notes that it can be modified by salty and acidic. &amp;lt;ref name=&amp;quot;PMID22717400&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;22717400&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#faecc8&amp;quot;&lt;br /&gt;
|'''1901'''&lt;br /&gt;
|| D. Hanig publishes a paper describing taste sensitivity in different regions of the tongue. &lt;br /&gt;
''Interesting fact:'' The modern concept of a 'tongue map' is a misinterpretation of this study. &amp;lt;ref name=&amp;quot;PMID22717400&amp;quot;/&amp;gt;&lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#faf6ed&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''1908'''&lt;br /&gt;
|Kikunae Ikeda, a professor of the Tokyo Imperial University, discovered and identified the fifth basic taste: umami (savouriness), made palatable by glutamate.  &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;12438213&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
[http://chemse.oxfordjournals.org/content/27/9/847.long New Seasonings]&lt;br /&gt;
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|- bgcolor=&amp;quot;#faecc8&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''1931-32'''&lt;br /&gt;
| A chemist named Arthur Fox and his college noted that they had different sensitivities to the bitter tasting Phenylthiocarbamide (PTC).&amp;lt;ref&amp;gt;Blakeslee AF, Fox AL. Our different taste worlds. J Hered. 1932;23:97–107.&amp;lt;/ref&amp;gt; Geneticists later confirm these findings, and discover that non-tasting is a recessive genetic trait. &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;17782493&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/pubmed/17782493 Inherited taste deficiency] &lt;br /&gt;
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|- bgcolor=&amp;quot;#faf6ed&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''1965'''&lt;br /&gt;
|Farbman's study of the developing taste but in rat fungiform papilla was significant in increasing our understanding of taste bud development. &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;14300090&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
[http://www.sciencedirect.com/science/article/pii/0012160665900400 Electron microscope study of the developing taste bud in rat fungiform papilla.]&lt;br /&gt;
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|- bgcolor=&amp;quot;#faecc8&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''1992'''&lt;br /&gt;
|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. &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;1608467 &amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
[http://www.nature.com/nature/journal/v357/n6379/abs/357563a0.html Gustducin is a taste-cell-specific G protein closely related to the transducins]&lt;br /&gt;
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|- bgcolor=&amp;quot;#faf6ed&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''1995'''&lt;br /&gt;
|Barlow et al. experimented with Axolotl salamanders and concluded that taste buds from this species arise exclusively from epithelial tissue, &amp;quot;oropharyngeal [[#Glossary |'''epithelium''']]&amp;quot;. &amp;lt;ref name=&amp;quot;PMID17826760&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;17826760&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/pubmed/17826760 Embryonic origin of gustatory cranial sensory neurons] &lt;br /&gt;
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|- bgcolor=&amp;quot;#faecc8&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''1996'''&lt;br /&gt;
| 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 &amp;quot;at least dual function of embryonic/fetal taste buds&amp;quot;, including non-gustatory, paracrine functions prior to the 14th week and gustatory after the 14th week. &amp;lt;ref name=&amp;quot;PMID8955790&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;8955790&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/pubmed/8955790 Embryonic and early fetal development of human taste buds: a transmission electron microscopical study]&lt;br /&gt;
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|- bgcolor=&amp;quot;#faf6ed&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''2000'''&lt;br /&gt;
|Chandrashekar, J. et al. discover the first taste sonsors, the T2R bitter taste receptors. &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;10761935&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
[http://www.sciencedirect.com/science/article/pii/S0092867400807060 T2Rs Function as Bitter Taste Receptors]&lt;br /&gt;
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|- bgcolor=&amp;quot;#faecc8&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''2001'''&lt;br /&gt;
|Nelson, G. et al. discover the sweet receptor: a combination of T1R2 and T1R3. &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;11509186&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/pubmed/11509186?dopt=Abstract&amp;amp;holding=npg Mammalian sweet taste receptors.]&lt;br /&gt;
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|- bgcolor=&amp;quot;#faf6ed&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''2002'''&lt;br /&gt;
|Nelson G. et al. discover the amino acid (umami) taste receptor: a combination of T1R1 and T1R3 identified.  &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;11894099&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/pubmed/11894099?dopt=Abstract&amp;amp;holding=npg An amino-acid taste receptor]&lt;br /&gt;
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|- bgcolor=&amp;quot;#faecc8&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''2005'''&lt;br /&gt;
|Dyer, J. et al. discover sweet taste receptors in the GI tract. &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;17855558&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1986582/ Sweet taste signaling in the gut]&lt;br /&gt;
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|- bgcolor=&amp;quot;#faf6ed&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''2006'''&lt;br /&gt;
|Huang, A. L et al. discover cells for sour taste, identified by PKD2L1 (a polycystic kidney disease-like ion channel). &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;16929298&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1571047/ The Cells and Logic for Mammalian Sour Taste detection]&lt;br /&gt;
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|- bgcolor=&amp;quot;#faecc8&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''2007'''&lt;br /&gt;
|Harlow DE, Barlow LA of the University of Colorado Denver Health Sciences Center provide evidence of the &amp;quot;embryonic origin of gustatory cranial sensory neurons&amp;quot;. &amp;lt;ref name=&amp;quot;PMID17826760&amp;quot;/&amp;gt;&lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/pubmed/17826760 Embryonic origin of gustatory cranial sensory neurons.]&lt;br /&gt;
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|- bgcolor=&amp;quot;#faf6ed&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''2009'''&lt;br /&gt;
|A study by Hevezi P et al, presents &amp;quot;the first comprehensive characterization of gene expression in primate taste buds&amp;quot;, as opposed to previous studies which focused on rodents. &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;19636377&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/pubmed/19636377 Genome-wide analysis of gene expression in primate taste buds reveals links to diverse processes]&lt;br /&gt;
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|- bgcolor=&amp;quot;#faecc8&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''2010'''&lt;br /&gt;
|Chandrashekar, J. et al. identify epithelial sodium channel (ENaC) as the sodium-salt taste receptor. &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;20107438&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/pubmed/20107438?dopt=Abstract&amp;amp;holding=npg The cells and peripheral representation of sodium taste in mice]&lt;br /&gt;
|}&lt;br /&gt;
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==Adult Tongue and Taste Buds – Structure and Function==&lt;br /&gt;
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'''Structure'''&lt;br /&gt;
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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.  &lt;br /&gt;
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[http://www.webmd.com/oral-health/picture-of-the-tongue] &lt;br /&gt;
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''''The image below is a simplistic diagram of the surface of the tongue showing the locations of the different papillae and other important features'''&lt;br /&gt;
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{|&lt;br /&gt;
| [[Image:Drawing of Tongue.png|centre|500px]]&lt;br /&gt;
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[[File:Taste_pathway.jpg|right|thumb|200px|Simplistic Pathway of Taste]]&lt;br /&gt;
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'''Papillae'''&lt;br /&gt;
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There are 4 types of papillae on the tongue.&lt;br /&gt;
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.[http://www.tutorvista.com/content/biology/biology-iv/nervous-coordination/tongue-structure.php#parts-of-tongue]&lt;br /&gt;
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[[File:Papillae.jpg|Left|thumb|200px|Close up of Human Tongue Papillae]]&lt;br /&gt;
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[[File:Fungiformpapillae.jpg|left|thumb|200px|Fungiform Papillae]]&lt;br /&gt;
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[[File:Circumvallatepapillae.jpg |left|thumb|200px|Circumvallate Papillae]]&lt;br /&gt;
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[[File:Filiformpapillae.jpg|left|200px|thumb|Foliate Papillae]]&lt;br /&gt;
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'''Function'''&lt;br /&gt;
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The Tongue has muscular and sensory functions, muscular functions include swallowing and speech where as sensory function involves taste. This section will focus on the sensory functions of the tongue.&lt;br /&gt;
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. [http://www.cf.ac.uk/biosi/staffinfo/jacob/teaching/sensory/taste.html]&lt;br /&gt;
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[[File:Taste_bud_1.jpg|right|thumb|200px|Cross section of a taste bud unit|centre|Cross section of a taste bud unit]]&lt;br /&gt;
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'''Link Between Taste and Smell'''&lt;br /&gt;
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The pathways of smell and taste are very similar (chemosensation). Pathways both involve the conversion of a dissolved chemical stimulus transformed into a electrical impulse for interpretation by the brain.	&lt;br /&gt;
Taste and smell overlap when humans experience flavour, flavour involves an interaction of taste, smell, texture and temperature, where taste is only a portion of this interaction. when the brain interprets a flavour, contribution from other senses has a significant role in identification. In conclusion Taste and Smell in combination with other senses help develop a sensory interpretation called flavour.[http://www.entnet.org/HealthInformation/smellTaste.cfm]&lt;br /&gt;
[[File:Human smelling.jpg|500px|centre]]&lt;br /&gt;
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== Human Weekly Development - Two Prominent Studies ==&lt;br /&gt;
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. &lt;br /&gt;
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The findings of these two studies are summarized in the table below. The figures provided relate to the images on their respective research papers.&lt;br /&gt;
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# [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] &lt;br /&gt;
# [http://chemse.oxfordjournals.org/content/22/6/601.long Scanning electron microscopical studies of developing gustatory papillae in humans, 1997]  &lt;br /&gt;
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===Timeline of Developmental Processes of Human Taste Buds===&lt;br /&gt;
{| cellpadding=5 style=&amp;quot;border:1px solid #BBB&amp;quot;&lt;br /&gt;
|- bgcolor=&amp;quot;#89CFF0&amp;quot;&lt;br /&gt;
|'''Postovulatory Week'''||'''Description'''&lt;br /&gt;
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|- bgcolor=&amp;quot;#BCD4E6&amp;quot;&lt;br /&gt;
|'''Week 6''' ||&lt;br /&gt;
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. &amp;lt;ref name=&amp;quot;PMID9455607&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;9455607&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
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|- bgcolor=&amp;quot;#89CFF0&amp;quot;&lt;br /&gt;
| '''Weeks 6 to 7'''|| &lt;br /&gt;
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. &amp;lt;ref name=PMID8955790/&amp;gt;&lt;br /&gt;
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|- bgcolor=&amp;quot;#BCD4E6&amp;quot;&lt;br /&gt;
| '''Week 7 '''||&lt;br /&gt;
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.  &amp;lt;ref name=PMID9455607/&amp;gt; &lt;br /&gt;
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|- bgcolor=&amp;quot;#89CFF0&amp;quot;&lt;br /&gt;
| ''' Week 8  ''' ||&lt;br /&gt;
* The taste bud primordium are still differentiated, elongated epithelial cells, resting on a slightly developed core of young dermal papilla.&lt;br /&gt;
* 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. &lt;br /&gt;
* Ciliated cells also appear around the 8th week, however the significance of these cells which are scattered randomly across the lingual surface remains unclear. &amp;lt;ref name=PMID8955790/&amp;gt; &lt;br /&gt;
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|- bgcolor=&amp;quot;#BCD4E6&amp;quot;&lt;br /&gt;
|'''  Week 9''' ||&lt;br /&gt;
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). &amp;lt;ref name=PMID9455607/&amp;gt;&lt;br /&gt;
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|- bgcolor=&amp;quot;#89CFF0&amp;quot;&lt;br /&gt;
|'''  Weeks 10-11''' ||&lt;br /&gt;
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). &amp;lt;ref name=PMID8955790/&amp;gt; &lt;br /&gt;
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|- bgcolor=&amp;quot;#BCD4E6&amp;quot;&lt;br /&gt;
|''' Week 12 ''' ||&lt;br /&gt;
Taste bud cells are more clearly differentiated into epithelial cell types II and III. &amp;lt;ref name=PMID8955790/&amp;gt; &lt;br /&gt;
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|- bgcolor=&amp;quot;#89CFF0&amp;quot;&lt;br /&gt;
|''' Weeks 12-13  ''' ||&lt;br /&gt;
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). &amp;lt;ref name=PMID8955790/&amp;gt; &lt;br /&gt;
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|- bgcolor=&amp;quot;#BCD4E6&amp;quot;&lt;br /&gt;
|''' Weeks 14 -15 ''' ||&lt;br /&gt;
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. &amp;lt;ref name=PMID8955790/&amp;gt; &lt;br /&gt;
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==Abnormalities==&lt;br /&gt;
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It should be mentioned that gustatory abnormalities have not been widely researched. Most research conducted in this field has been conducted through animal testing on mice and this is the basis of information provided below. &lt;br /&gt;
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===Knocking out P2X Receptors===&lt;br /&gt;
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[[File:Image of taste being evoked by visualising ATP release.jpeg|Left|thumb|200px|Evoking taste - ATP release in tongue]]&lt;br /&gt;
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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. &lt;br /&gt;
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It should be noted that the taste buds in DKO are functional, but are not stimulated by the administration of tastants. &lt;br /&gt;
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The transmission of release of ATP is secretion through gap junction hemichannels (pannexin 1 gap junction).&lt;br /&gt;
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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.&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;21940456&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
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===FGF signalling and genes===&lt;br /&gt;
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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.&lt;br /&gt;
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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 (&amp;quot;Fgf10&amp;quot;) 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 &amp;quot;Fgf10&amp;quot; to limit the size of the CVP progenitor placode. Exclusive expression of ''Fgf10'' in the [[#Glossary |'''mesenchyme''']] is necessary for the formation of CVP. &lt;br /&gt;
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'''This image shows the CVP stained with H&amp;amp;E and scanned by Scanning Electron Microscope (SEM)'''&lt;br /&gt;
[[File:CVP of WT(top) and DKO(bottom) mice with H&amp;amp;E and SEM.png]]&lt;br /&gt;
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'''This image shows the location of the CVP and the increased number in DKO mice by SEM'''&lt;br /&gt;
[[File:Mouse circumvallate papilla 01.jpg|300px]]&lt;br /&gt;
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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).&lt;br /&gt;
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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).&lt;br /&gt;
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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''&amp;amp; ''Spry 1&amp;amp;2''work antagonistically through receptor tyrosine kinase (RTK)signalling.&lt;br /&gt;
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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.&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;21655085&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
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==Gustatory System==&lt;br /&gt;
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[[Image:Taste qualities.gif|thumb|The five basic tastes]]&lt;br /&gt;
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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.&lt;br /&gt;
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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.&amp;lt;ref name=PMID20696704&amp;gt;&amp;lt;pubmed&amp;gt;20696704&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
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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 &amp;lt;ref name=PMID20696704/&amp;gt; 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.&lt;br /&gt;
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===Cell Biology===&lt;br /&gt;
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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.&lt;br /&gt;
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====Type II receptors====&lt;br /&gt;
&lt;br /&gt;
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:&lt;br /&gt;
&lt;br /&gt;
# Stimulates gustatory nerve afferents which project to gustatory nuclei  in the spinal cord&lt;br /&gt;
# Excites Type III presynaptic nerve fibers to release serotonin. &lt;br /&gt;
# Has a positive feedback effect on type II receptor cells, increasing the level of ATP production.&lt;br /&gt;
&lt;br /&gt;
        &lt;br /&gt;
&lt;br /&gt;
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.&lt;br /&gt;
&lt;br /&gt;
==Taste Map==&lt;br /&gt;
[[Image:Taste map.png|thumb|left|250px|Obsolete idea of the tongue map]]&lt;br /&gt;
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.&lt;br /&gt;
&lt;br /&gt;
===Neural Pathways===&lt;br /&gt;
&lt;br /&gt;
'''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''. &lt;br /&gt;
&lt;br /&gt;
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:  &lt;br /&gt;
&lt;br /&gt;
* ''Facial nerve n''. -  carries taste information from the anterior 2/3 of the tongue.&lt;br /&gt;
* ''Hypoglossal n.'' - carries taste information from the posterior 1/3 of the tongue.&lt;br /&gt;
* ''Vagus n''. - carries taste information from the palate&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
'''Second order neurons''' - From the NTS second order neurons carry taste information to the Ventral posteromedial (VPM) nucleus in the thalamus.&amp;lt;ref name=PMID21885776/&amp;gt;&lt;br /&gt;
&lt;br /&gt;
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.  &lt;br /&gt;
&lt;br /&gt;
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.&lt;br /&gt;
&lt;br /&gt;
===Cortical Areas===&lt;br /&gt;
&lt;br /&gt;
[[Image:Primary gustatory cortex.png|thumb|Primary gustatory cortex]]&lt;br /&gt;
&lt;br /&gt;
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)&amp;lt;ref name=PMID22245354&amp;gt;&amp;lt;pubmed&amp;gt;22245354&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;, with the secondary taste cortex in the caudolateral orbitofrontal cortex.&amp;lt;ref name=PMID21305668&amp;gt;&amp;lt;pubmed&amp;gt;21305668&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;  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.&amp;lt;ref name=PMID21885776&amp;gt;&amp;lt;pubmed&amp;gt;21885776&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; These findings lend weight to the idea that there is only one receptor for each taste quality.&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
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).&amp;lt;ref name=PMID21885776/&amp;gt; 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&lt;br /&gt;
&lt;br /&gt;
===Neuronal Development===&lt;br /&gt;
&lt;br /&gt;
The gustatory system must not be solely thought of as being comprised of simply the tongue and palate. The types of neurons which carry taste information to the brain are also pivotal in constructing the expression of taste qualities.&lt;br /&gt;
&lt;br /&gt;
The two main gustatory neurons which develop are the geniculate ganglion and the petrosal ganglion. These are the visceral sensory ganglion of cranial nerves VII (Facial) and  IX (Hypoglossal) respectively which carry taste information from the tongue to the nucleus tractus solitarius. They arise at the posterior placodal region from the epibranchial placodes, a thickening of ectoderm. The first epibranchial placode gives rise to the geniculate ganglion and the second to the petrosal ganglion.&lt;br /&gt;
&lt;br /&gt;
The molecular basis for gustatory neuron formation is not completely understood though there are a number of transcription factors which are thought to play an important role in firstly, placode formation and secondly, neuron differentiation.&lt;br /&gt;
&lt;br /&gt;
*Six1/2, Six1/5 and Eya – transcription factors which cause differentiation of epibranchial placodes into the petrosal and geniculate ganglion.&lt;br /&gt;
*Bone morphogenic Protein 7 (BMP7) – a signal arising from the pharyngeal pouch which is believed to induce epibranchial placode formation. May not be solely responsible for this process, current research has been inconclusive as to how it may work with other proteins of the same family.&lt;br /&gt;
*NGN2 - Following the initial differentiation of the placodes, further differentiation occurs to form neuroblasts. NGN2 causes the delamination and migration of these neuroblasts, which subsequently migrate and fuse to form neurons.&lt;br /&gt;
*Phox2b – maintains the structural integrity of neurons. Knockout of these genes in mice causes marked atrophy of the petrosal and geniculate ganglia.&lt;br /&gt;
&lt;br /&gt;
The neurons involved in the gustatory system are overproduced and thus in the embryonic stage, undergo programmed cell death (apoptosis). The total amount of neurons in the geniculate ganglion, appears to be quite stable over the embryonic stages. This suggests, unlike the petrosal ganglion, the levels of neuroblast proliferation and apoptosis are fairly similar. The factors which regulate these processes remains unclear. It is posited that neurotrophins BDNF, NT4/5 and NT3 may regulate neuronal survival whilst also playing a part in axon growth from the sensory ganglion. More research is required to discern the exact individual functions of each of the neurotrophins.&lt;br /&gt;
&lt;br /&gt;
==Current Research==&lt;br /&gt;
&lt;br /&gt;
[[File:Mousetounge histologicalstain.jpg|right|thumb|200px|Image shows histological stains of a mice tongue showing dysplasia]]&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
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. &lt;br /&gt;
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.&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
'''Synergistic relationships of Six Genes '''&lt;br /&gt;
&lt;br /&gt;
In an animal study using mice by Suzuki Y, Ikeda K, Kawakami K.(2011)  Firstly nominating &amp;quot;[[#Glossary |'''Six Genes''']]&amp;quot; as a major component in [[#Glossary |'''gustatory ''']] development, stating that deficiencies in certain Six genes (specifically Six1 &amp;amp; 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 &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;21978088&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
[[File:Abnormal of tongue.jpg|thumb|200px|Image shows an example of tongue abnormalities, this is called &amp;quot;double tongue&amp;quot; each side has independent movement!]]&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
'''Neural Crest responsibilities '''&lt;br /&gt;
&lt;br /&gt;
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.&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;22659543&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
'''Augmentation of Endoderm'''&lt;br /&gt;
&lt;br /&gt;
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 &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;22581563&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
'''Changes in Taste Cells over time'''&lt;br /&gt;
&lt;br /&gt;
Research by &lt;br /&gt;
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.  &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;22643728&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
'''Shh key component of taste bud proginators'''&lt;br /&gt;
&lt;br /&gt;
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.&lt;br /&gt;
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 &amp;quot;Axiocam CCD camera and Axioplan fluorescence microscope with Axiovision software&amp;quot; a study by Harlow, Yang, Williams, Barlow (2011)&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;PMC2674259&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
'''WNT family exhibit various roles'''&lt;br /&gt;
&lt;br /&gt;
 &lt;br /&gt;
The WNT gene family has a function of signaling work antagonistically through receptor tyrosine kinase (RTK) signaling. However, the deletion of Sprouty Homolog 2 (Spry2) led to the increase of chimaeric virus particles (CVPs) and a significant decrease in number of fungiform papillae. In contrast, the absence of Fibroblast growth factor 10 (Fgf10) in conjunction with 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. 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. &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;PMC2768563&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
[[File:Developing_tongue_histology_001.jpg|right|thumb|200px|HIstological stain of a developing rat tongue]]&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
'''Controversial Research - Not Ectodermal Origin'''&lt;br /&gt;
&lt;br /&gt;
==Glossary==&lt;br /&gt;
&lt;br /&gt;
* '''Circumvallate papillae''' - &lt;br /&gt;
&lt;br /&gt;
* '''Ectoderm'''- outer germ layer of embryo&lt;br /&gt;
&lt;br /&gt;
* '''Endoderm''' - inner germ layer of embryo&lt;br /&gt;
&lt;br /&gt;
* '''Epithelium''' - basic animal tissue that is composed of tightly packed cells, usually covering the outer portion of organs&lt;br /&gt;
&lt;br /&gt;
* '''Exocystosis''' - movement of contents out of cell&lt;br /&gt;
&lt;br /&gt;
* '''Filiform papillae''' - &lt;br /&gt;
&lt;br /&gt;
* '''Foliate papillae''' - &lt;br /&gt;
&lt;br /&gt;
* '''Fungiform papillae''' - &lt;br /&gt;
&lt;br /&gt;
* '''Ganglia''' - the accumulation of a nerve cell body&lt;br /&gt;
&lt;br /&gt;
* '''Growth factor''' - a substance that stimulates the growth of cells&lt;br /&gt;
&lt;br /&gt;
* '''Gustatory''' - anything that relates to the taste sense&lt;br /&gt;
&lt;br /&gt;
* '''Hydrolysis''' - breakdown of a chemical when it reacts with water&lt;br /&gt;
&lt;br /&gt;
* '''Mesoderm''' - middle germ layer of embryo&lt;br /&gt;
&lt;br /&gt;
* '''Mesenchyme''' - multipotential cells&lt;br /&gt;
&lt;br /&gt;
* '''Neural crest''' - a part of the ectoderm found on both sides of the neural tube&lt;br /&gt;
&lt;br /&gt;
* '''Neuron''' - most simplistic unit of the nervous system&lt;br /&gt;
&lt;br /&gt;
* '''Neurotransmitter''' - chemicals which allow the passing of signals from neuron to neuron via connecting part (synapse) &lt;br /&gt;
&lt;br /&gt;
* '''Papillae''' - small rough surface projection&lt;br /&gt;
&lt;br /&gt;
* '''Six genes''' - a family of genes&lt;br /&gt;
&lt;br /&gt;
* '''Sonic hedgehog (Shh)''' - signalling protein involved in normal development&lt;br /&gt;
&lt;br /&gt;
* '''Sulcus terminalis''' - describes a physical transition point separating the anterior 2/3 of the tongue from the posterior 1/3&lt;br /&gt;
&lt;br /&gt;
* '''Tamoxifen''' - hormonal altering drug&lt;br /&gt;
&lt;br /&gt;
* '''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).&lt;br /&gt;
&lt;br /&gt;
* '''Type II taste cells''' - Receptor cells acting as primary detectors of sweet, bitter or umami taste.&lt;br /&gt;
&lt;br /&gt;
* '''Type III taste cells''' - Presynaptic cells that respond to sweet, salty, sour, bitter and umami compounds.&lt;br /&gt;
&lt;br /&gt;
== References ==&lt;br /&gt;
&amp;lt;references/&amp;gt;&lt;br /&gt;
&lt;br /&gt;
==External Links==&lt;br /&gt;
{{External Links}}&lt;br /&gt;
&lt;br /&gt;
1.[http://www.surgicalneurologyint.com/article.asp?issn=2152-7806;year=2012;volume=3;issue=1;spage=23;epage=23;aulast=Manjila]&lt;br /&gt;
&lt;br /&gt;
2.[http://embryology.med.unsw.edu.au/embryology/index.php?title=2012_Group_Project_4]&lt;br /&gt;
&lt;br /&gt;
3.[http://www.webmd.com/oral-health/picture-of-the-tongue]&lt;br /&gt;
&lt;br /&gt;
4.[http://www.tutorvista.com/content/biology/biology-iv/nervous-coordination/tongue-structure.php#parts-of-tongue]&lt;br /&gt;
&lt;br /&gt;
5.[http://www.cf.ac.uk/biosi/staffinfo/jacob/teaching/sensory/taste.html]&lt;br /&gt;
&lt;br /&gt;
--[[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.&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
----&lt;br /&gt;
&lt;br /&gt;
{{2012Projects}}&lt;/div&gt;</summary>
		<author><name>Z3330795</name></author>
	</entry>
	<entry>
		<id>https://embryology.med.unsw.edu.au/embryology/index.php?title=File:Baby_tongue.jpg&amp;diff=105375</id>
		<title>File:Baby tongue.jpg</title>
		<link rel="alternate" type="text/html" href="https://embryology.med.unsw.edu.au/embryology/index.php?title=File:Baby_tongue.jpg&amp;diff=105375"/>
		<updated>2012-10-03T01:47:30Z</updated>

		<summary type="html">&lt;p&gt;Z3330795: (Student Image|2012)

== Human infant with developed tongue ==

This image is for the purpose of drawing readers to our page as the picture is interesting.

== Original text ==

This photo was taken on May 11, 2008 using a Canon EOS Digital Rebel XT. 

th&lt;/p&gt;
&lt;hr /&gt;
&lt;div&gt;(Student Image|2012)&lt;br /&gt;
&lt;br /&gt;
== Human infant with developed tongue ==&lt;br /&gt;
&lt;br /&gt;
This image is for the purpose of drawing readers to our page as the picture is interesting.&lt;br /&gt;
&lt;br /&gt;
== Original text ==&lt;br /&gt;
&lt;br /&gt;
This photo was taken on May 11, 2008 using a Canon EOS Digital Rebel XT. &lt;br /&gt;
&lt;br /&gt;
the henry leo&lt;br /&gt;
&lt;br /&gt;
http://www.flickr.com/photos/xtop/2485737687/&lt;br /&gt;
&lt;br /&gt;
== Copyright Information ==&lt;br /&gt;
&lt;br /&gt;
You are free:&lt;br /&gt;
to Share — to copy, distribute and transmit the work to Remix — to adapt the work &lt;br /&gt;
&lt;br /&gt;
Under the following conditions:&lt;br /&gt;
Attribution — You must attribute the work in the manner specified by the author or licensor (but not in any way that suggests that they endorse you or your use of the work). &lt;br /&gt;
&lt;br /&gt;
Attribute this work: &lt;br /&gt;
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What does &amp;quot;Attribute this work&amp;quot; mean? &lt;br /&gt;
The page you came from contained embedded licensing metadata, including how the creator wishes to be attributed for re-use. You can use the HTML here to cite the work. Doing so will also include metadata on your page so that others can find the original work as well. Noncommercial — You may not use this work for commercial purposes.&lt;/div&gt;</summary>
		<author><name>Z3330795</name></author>
	</entry>
	<entry>
		<id>https://embryology.med.unsw.edu.au/embryology/index.php?title=File:Abnormal_of_tongue.jpg&amp;diff=105351</id>
		<title>File:Abnormal of tongue.jpg</title>
		<link rel="alternate" type="text/html" href="https://embryology.med.unsw.edu.au/embryology/index.php?title=File:Abnormal_of_tongue.jpg&amp;diff=105351"/>
		<updated>2012-10-03T01:24:09Z</updated>

		<summary type="html">&lt;p&gt;Z3330795: &lt;/p&gt;
&lt;hr /&gt;
&lt;div&gt;{Student image||2012} &lt;br /&gt;
&lt;br /&gt;
== Tongue Abnormality ==&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
eleven-year-old African-American female patient with tongue and facial abnormalities.&lt;br /&gt;
&lt;br /&gt;
== Original Text ==&lt;br /&gt;
Figure 1: Demonstration of facial abnormalities (a) full body view showing scoliosis, frontal view demonstrating hypertelorism and cleft lip and image of mouth showing supernumerary teeth (b) demonstration of independent movement of double tongues: right tongue withdrawn while left protrudes&lt;br /&gt;
&lt;br /&gt;
== Copyright Information ==&lt;br /&gt;
&lt;br /&gt;
© 2012 Manjila et al; This is an open-access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.&lt;br /&gt;
&lt;br /&gt;
DOI: 10.4103/2152-7806.92939&lt;/div&gt;</summary>
		<author><name>Z3330795</name></author>
	</entry>
	<entry>
		<id>https://embryology.med.unsw.edu.au/embryology/index.php?title=2012_Group_Project_3&amp;diff=105349</id>
		<title>2012 Group Project 3</title>
		<link rel="alternate" type="text/html" href="https://embryology.med.unsw.edu.au/embryology/index.php?title=2012_Group_Project_3&amp;diff=105349"/>
		<updated>2012-10-03T01:23:05Z</updated>

		<summary type="html">&lt;p&gt;Z3330795: /* Current Research */&lt;/p&gt;
&lt;hr /&gt;
&lt;div&gt;=Taste Development=&lt;br /&gt;
&lt;br /&gt;
You are out to dinner and your meal arrives in front of you, the aromas and the presentation of your food strikes you immediately. Half way through, the waiter returns and asks “How does your meal taste?”  The answer is not as simple as one might think. Why does the meal taste pleasant? How do we experience different tastes? In the following page, we aim to discern how exactly one would answer these questions by looking at the embryological development of the taste system from week to week. &lt;br /&gt;
&lt;br /&gt;
Taste is a complex sensory system and its precise workings are to this day not fully understood. What makes it so complicated is the interaction between the structure of tongue and taste buds and how this contributes to the representation of taste qualities (salty, bitter, sweet, sour and umami) in the brain. We will also look at some current research on animal models being undertaken to evaluate the role of specific genes in the development of sensory structures. By looking at the taste system’s genetic basis, we now have a greater understanding of the abnormalities that may occur during development and a direction to pursue in future research to attempt to fill in the gaps of scientific knowledge.&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
==History of Discoveries==&lt;br /&gt;
&lt;br /&gt;
{| cellpadding=5 style=&amp;quot;border:1px solid #BBB&amp;quot;&lt;br /&gt;
|- bgcolor=&amp;quot;#faecc8&amp;quot;&lt;br /&gt;
|''' Date'''|| '''Significant Discovery'''&lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#faf6ed&amp;quot;&lt;br /&gt;
|'''350BC'''&lt;br /&gt;
|| Aristotle writes about the basic tastes, sweet and bitter. He also notes that it can be modified by salty and acidic. &amp;lt;ref name=&amp;quot;PMID22717400&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;22717400&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#faecc8&amp;quot;&lt;br /&gt;
|'''1901'''&lt;br /&gt;
|| D. Hanig publishes a paper describing taste sensitivity in different regions of the tongue. &lt;br /&gt;
''Interesting fact:'' The modern concept of a 'tongue map' is a misinterpretation of this study. &amp;lt;ref name=&amp;quot;PMID22717400&amp;quot;/&amp;gt;&lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#faf6ed&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''1908'''&lt;br /&gt;
|Kikunae Ikeda, a professor of the Tokyo Imperial University, discovered and identified the fifth basic taste: umami (savouriness), made palatable by glutamate.  &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;12438213&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
[http://chemse.oxfordjournals.org/content/27/9/847.long New Seasonings]&lt;br /&gt;
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|- bgcolor=&amp;quot;#faecc8&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''1931-32'''&lt;br /&gt;
| A chemist named Arthur Fox and his college noted that they had different sensitivities to the bitter tasting Phenylthiocarbamide (PTC).&amp;lt;ref&amp;gt;Blakeslee AF, Fox AL. Our different taste worlds. J Hered. 1932;23:97–107.&amp;lt;/ref&amp;gt; Geneticists later confirm these findings, and discover that non-tasting is a recessive genetic trait. &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;17782493&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/pubmed/17782493 Inherited taste deficiency] &lt;br /&gt;
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|- bgcolor=&amp;quot;#faf6ed&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''1965'''&lt;br /&gt;
|Farbman's study of the developing taste but in rat fungiform papilla was significant in increasing our understanding of taste bud development. &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;14300090&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
[http://www.sciencedirect.com/science/article/pii/0012160665900400 Electron microscope study of the developing taste bud in rat fungiform papilla.]&lt;br /&gt;
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|- bgcolor=&amp;quot;#faecc8&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''1992'''&lt;br /&gt;
|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. &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;1608467 &amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
[http://www.nature.com/nature/journal/v357/n6379/abs/357563a0.html Gustducin is a taste-cell-specific G protein closely related to the transducins]&lt;br /&gt;
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|- bgcolor=&amp;quot;#faf6ed&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''1995'''&lt;br /&gt;
|Barlow et al. experimented with Axolotl salamanders and concluded that taste buds from this species arise exclusively from epithelial tissue, &amp;quot;oropharyngeal [[#Glossary |'''epithelium''']]&amp;quot;. &amp;lt;ref name=&amp;quot;PMID17826760&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;17826760&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/pubmed/17826760 Embryonic origin of gustatory cranial sensory neurons] &lt;br /&gt;
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|- bgcolor=&amp;quot;#faecc8&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''1996'''&lt;br /&gt;
| 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 &amp;quot;at least dual function of embryonic/fetal taste buds&amp;quot;, including non-gustatory, paracrine functions prior to the 14th week and gustatory after the 14th week. &amp;lt;ref name=&amp;quot;PMID8955790&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;8955790&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/pubmed/8955790 Embryonic and early fetal development of human taste buds: a transmission electron microscopical study]&lt;br /&gt;
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|- bgcolor=&amp;quot;#faf6ed&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''2000'''&lt;br /&gt;
|Chandrashekar, J. et al. discover the first taste sonsors, the T2R bitter taste receptors. &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;10761935&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
[http://www.sciencedirect.com/science/article/pii/S0092867400807060 T2Rs Function as Bitter Taste Receptors]&lt;br /&gt;
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|- bgcolor=&amp;quot;#faecc8&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''2001'''&lt;br /&gt;
|Nelson, G. et al. discover the sweet receptor: a combination of T1R2 and T1R3. &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;11509186&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/pubmed/11509186?dopt=Abstract&amp;amp;holding=npg Mammalian sweet taste receptors.]&lt;br /&gt;
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|- bgcolor=&amp;quot;#faf6ed&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''2002'''&lt;br /&gt;
|Nelson G. et al. discover the amino acid (umami) taste receptor: a combination of T1R1 and T1R3 identified.  &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;11894099&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/pubmed/11894099?dopt=Abstract&amp;amp;holding=npg An amino-acid taste receptor]&lt;br /&gt;
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|- bgcolor=&amp;quot;#faecc8&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''2005'''&lt;br /&gt;
|Dyer, J. et al. discover sweet taste receptors in the GI tract. &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;17855558&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1986582/ Sweet taste signaling in the gut]&lt;br /&gt;
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|- bgcolor=&amp;quot;#faf6ed&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''2006'''&lt;br /&gt;
|Huang, A. L et al. discover cells for sour taste, identified by PKD2L1 (a polycystic kidney disease-like ion channel). &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;16929298&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1571047/ The Cells and Logic for Mammalian Sour Taste detection]&lt;br /&gt;
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|- bgcolor=&amp;quot;#faecc8&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''2007'''&lt;br /&gt;
|Harlow DE, Barlow LA of the University of Colorado Denver Health Sciences Center provide evidence of the &amp;quot;embryonic origin of gustatory cranial sensory neurons&amp;quot;. &amp;lt;ref name=&amp;quot;PMID17826760&amp;quot;/&amp;gt;&lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/pubmed/17826760 Embryonic origin of gustatory cranial sensory neurons.]&lt;br /&gt;
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|- bgcolor=&amp;quot;#faf6ed&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''2009'''&lt;br /&gt;
|A study by Hevezi P et al, presents &amp;quot;the first comprehensive characterization of gene expression in primate taste buds&amp;quot;, as opposed to previous studies which focused on rodents. &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;19636377&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/pubmed/19636377 Genome-wide analysis of gene expression in primate taste buds reveals links to diverse processes]&lt;br /&gt;
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|- bgcolor=&amp;quot;#faecc8&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''2010'''&lt;br /&gt;
|Chandrashekar, J. et al. identify epithelial sodium channel (ENaC) as the sodium-salt taste receptor. &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;20107438&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/pubmed/20107438?dopt=Abstract&amp;amp;holding=npg The cells and peripheral representation of sodium taste in mice]&lt;br /&gt;
|}&lt;br /&gt;
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==Adult Tongue and Taste Buds – Structure and Function==&lt;br /&gt;
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'''Structure'''&lt;br /&gt;
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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.  &lt;br /&gt;
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[http://www.webmd.com/oral-health/picture-of-the-tongue] &lt;br /&gt;
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''''The image below is a simplistic diagram of the surface of the tongue showing the locations of the different papillae and other important features'''&lt;br /&gt;
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{|&lt;br /&gt;
| [[Image:Drawing of Tongue.png|centre|500px]]&lt;br /&gt;
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[[File:Taste_pathway.jpg|right|thumb|200px|Simplistic Pathway of Taste]]&lt;br /&gt;
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'''Papillae'''&lt;br /&gt;
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There are 4 types of papillae on the tongue.&lt;br /&gt;
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.[http://www.tutorvista.com/content/biology/biology-iv/nervous-coordination/tongue-structure.php#parts-of-tongue]&lt;br /&gt;
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[[File:Papillae.jpg|Left|thumb|200px|Close up of Human Tongue Papillae]]&lt;br /&gt;
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[[File:Fungiformpapillae.jpg|left|thumb|200px|Fungiform Papillae]]&lt;br /&gt;
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[[File:Circumvallatepapillae.jpg |left|thumb|200px|Circumvallate Papillae]]&lt;br /&gt;
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[[File:Filiformpapillae.jpg|left|200px|thumb|Foliate Papillae]]&lt;br /&gt;
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'''Function'''&lt;br /&gt;
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The Tongue has muscular and sensory functions, muscular functions include swallowing and speech where as sensory function involves taste. This section will focus on the sensory functions of the tongue.&lt;br /&gt;
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. [http://www.cf.ac.uk/biosi/staffinfo/jacob/teaching/sensory/taste.html]&lt;br /&gt;
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[[File:Taste_bud_1.jpg|right|thumb|200px|Cross section of a taste bud unit|centre|Cross section of a taste bud unit]]&lt;br /&gt;
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'''Link Between Taste and Smell'''&lt;br /&gt;
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The pathways of smell and taste are very similar (chemosensation). Pathways both involve the conversion of a dissolved chemical stimulus transformed into a electrical impulse for interpretation by the brain.	&lt;br /&gt;
Taste and smell overlap when humans experience flavour, flavour involves an interaction of taste, smell, texture and temperature, where taste is only a portion of this interaction. when the brain interprets a flavour, contribution from other senses has a significant role in identification. In conclusion Taste and Smell in combination with other senses help develop a sensory interpretation called flavour.[http://www.entnet.org/HealthInformation/smellTaste.cfm]&lt;br /&gt;
[[File:Human smelling.jpg|500px|centre]]&lt;br /&gt;
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== Human Weekly Development - Two Prominent Studies ==&lt;br /&gt;
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. &lt;br /&gt;
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The findings of these two studies are summarized in the table below. The figures provided relate to the images on their respective research papers.&lt;br /&gt;
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# [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] &lt;br /&gt;
# [http://chemse.oxfordjournals.org/content/22/6/601.long Scanning electron microscopical studies of developing gustatory papillae in humans, 1997]  &lt;br /&gt;
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===Timeline of Developmental Processes of Human Taste Buds===&lt;br /&gt;
{| cellpadding=5 style=&amp;quot;border:1px solid #BBB&amp;quot;&lt;br /&gt;
|- bgcolor=&amp;quot;#89CFF0&amp;quot;&lt;br /&gt;
|'''Postovulatory Week'''||'''Description'''&lt;br /&gt;
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|- bgcolor=&amp;quot;#BCD4E6&amp;quot;&lt;br /&gt;
|'''Week 6''' ||&lt;br /&gt;
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. &amp;lt;ref name=&amp;quot;PMID9455607&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;9455607&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
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|- bgcolor=&amp;quot;#89CFF0&amp;quot;&lt;br /&gt;
| '''Weeks 6 to 7'''|| &lt;br /&gt;
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. &amp;lt;ref name=PMID8955790/&amp;gt;&lt;br /&gt;
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|- bgcolor=&amp;quot;#BCD4E6&amp;quot;&lt;br /&gt;
| '''Week 7 '''||&lt;br /&gt;
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.  &amp;lt;ref name=PMID9455607/&amp;gt; &lt;br /&gt;
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|- bgcolor=&amp;quot;#89CFF0&amp;quot;&lt;br /&gt;
| ''' Week 8  ''' ||&lt;br /&gt;
* The taste bud primordium are still differentiated, elongated epithelial cells, resting on a slightly developed core of young dermal papilla.&lt;br /&gt;
* 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. &lt;br /&gt;
* Ciliated cells also appear around the 8th week, however the significance of these cells which are scattered randomly across the lingual surface remains unclear. &amp;lt;ref name=PMID8955790/&amp;gt; &lt;br /&gt;
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|- bgcolor=&amp;quot;#BCD4E6&amp;quot;&lt;br /&gt;
|'''  Week 9''' ||&lt;br /&gt;
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). &amp;lt;ref name=PMID9455607/&amp;gt;&lt;br /&gt;
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|- bgcolor=&amp;quot;#89CFF0&amp;quot;&lt;br /&gt;
|'''  Weeks 10-11''' ||&lt;br /&gt;
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). &amp;lt;ref name=PMID8955790/&amp;gt; &lt;br /&gt;
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|- bgcolor=&amp;quot;#BCD4E6&amp;quot;&lt;br /&gt;
|''' Week 12 ''' ||&lt;br /&gt;
Taste bud cells are more clearly differentiated into epithelial cell types II and III. &amp;lt;ref name=PMID8955790/&amp;gt; &lt;br /&gt;
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|- bgcolor=&amp;quot;#89CFF0&amp;quot;&lt;br /&gt;
|''' Weeks 12-13  ''' ||&lt;br /&gt;
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). &amp;lt;ref name=PMID8955790/&amp;gt; &lt;br /&gt;
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|- bgcolor=&amp;quot;#BCD4E6&amp;quot;&lt;br /&gt;
|''' Weeks 14 -15 ''' ||&lt;br /&gt;
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. &amp;lt;ref name=PMID8955790/&amp;gt; &lt;br /&gt;
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==Abnormalities==&lt;br /&gt;
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It should be mentioned that gustatory abnormalities have not been widely researched. Most research conducted in this field has been conducted through animal testing on mice and this is the basis of information provided below. &lt;br /&gt;
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===Knocking out P2X Receptors===&lt;br /&gt;
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[[File:Image of taste being evoked by visualising ATP release.jpeg|Left|thumb|200px|Evoking taste - ATP release in tongue]]&lt;br /&gt;
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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. &lt;br /&gt;
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It should be noted that the taste buds in DKO are functional, but are not stimulated by the administration of tastants. &lt;br /&gt;
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The transmission of release of ATP is secretion through gap junction hemichannels (pannexin 1 gap junction).&lt;br /&gt;
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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.&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;21940456&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
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===FGF signalling and genes===&lt;br /&gt;
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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.&lt;br /&gt;
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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 (&amp;quot;Fgf10&amp;quot;) 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 &amp;quot;Fgf10&amp;quot; to limit the size of the CVP progenitor placode. Exclusive expression of ''Fgf10'' in the [[#Glossary |'''mesenchyme''']] is necessary for the formation of CVP. &lt;br /&gt;
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'''This image shows the CVP stained with H&amp;amp;E and scanned by Scanning Electron Microscope (SEM)'''&lt;br /&gt;
[[File:CVP of WT(top) and DKO(bottom) mice with H&amp;amp;E and SEM.png]]&lt;br /&gt;
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'''This image shows the location of the CVP and the increased number in DKO mice by SEM'''&lt;br /&gt;
[[File:Mouse circumvallate papilla 01.jpg|300px]]&lt;br /&gt;
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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).&lt;br /&gt;
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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).&lt;br /&gt;
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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''&amp;amp; ''Spry 1&amp;amp;2''work antagonistically through receptor tyrosine kinase (RTK)signalling.&lt;br /&gt;
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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.&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;21655085&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
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==Gustatory System==&lt;br /&gt;
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[[Image:Taste qualities.gif|thumb|The five basic tastes]]&lt;br /&gt;
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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.&lt;br /&gt;
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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.&amp;lt;ref name=PMID20696704&amp;gt;&amp;lt;pubmed&amp;gt;20696704&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
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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 &amp;lt;ref name=PMID20696704/&amp;gt; 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.&lt;br /&gt;
&lt;br /&gt;
===Cell Biology===&lt;br /&gt;
&lt;br /&gt;
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.&lt;br /&gt;
&lt;br /&gt;
====Type II receptors====&lt;br /&gt;
&lt;br /&gt;
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:&lt;br /&gt;
&lt;br /&gt;
# Stimulates gustatory nerve afferents which project to gustatory nuclei  in the spinal cord&lt;br /&gt;
# Excites Type III presynaptic nerve fibers to release serotonin. &lt;br /&gt;
# Has a positive feedback effect on type II receptor cells, increasing the level of ATP production.&lt;br /&gt;
&lt;br /&gt;
        &lt;br /&gt;
&lt;br /&gt;
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.&lt;br /&gt;
&lt;br /&gt;
==Taste Map==&lt;br /&gt;
[[Image:Taste map.png|thumb|left|250px|Obsolete idea of the tongue map]]&lt;br /&gt;
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.&lt;br /&gt;
&lt;br /&gt;
===Neural Pathways===&lt;br /&gt;
&lt;br /&gt;
'''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''. &lt;br /&gt;
&lt;br /&gt;
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:  &lt;br /&gt;
&lt;br /&gt;
* ''Facial nerve n''. -  carries taste information from the anterior 2/3 of the tongue.&lt;br /&gt;
* ''Hypoglossal n.'' - carries taste information from the posterior 1/3 of the tongue.&lt;br /&gt;
* ''Vagus n''. - carries taste information from the palate&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
'''Second order neurons''' - From the NTS second order neurons carry taste information to the Ventral posteromedial (VPM) nucleus in the thalamus.&amp;lt;ref name=PMID21885776/&amp;gt;&lt;br /&gt;
&lt;br /&gt;
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.  &lt;br /&gt;
&lt;br /&gt;
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.&lt;br /&gt;
&lt;br /&gt;
===Cortical Areas===&lt;br /&gt;
&lt;br /&gt;
[[Image:Primary gustatory cortex.png|thumb|Primary gustatory cortex]]&lt;br /&gt;
&lt;br /&gt;
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)&amp;lt;ref name=PMID22245354&amp;gt;&amp;lt;pubmed&amp;gt;22245354&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;, with the secondary taste cortex in the caudolateral orbitofrontal cortex.&amp;lt;ref name=PMID21305668&amp;gt;&amp;lt;pubmed&amp;gt;21305668&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;  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.&amp;lt;ref name=PMID21885776&amp;gt;&amp;lt;pubmed&amp;gt;21885776&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; These findings lend weight to the idea that there is only one receptor for each taste quality.&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
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).&amp;lt;ref name=PMID21885776/&amp;gt; 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&lt;br /&gt;
&lt;br /&gt;
===Neuronal Development===&lt;br /&gt;
&lt;br /&gt;
The gustatory system must not be solely thought of as being comprised of simply the tongue and palate. The types of neurons which carry taste information to the brain are also pivotal in constructing the expression of taste qualities.&lt;br /&gt;
&lt;br /&gt;
The two main gustatory neurons which develop are the geniculate ganglion and the petrosal ganglion. These are the visceral sensory ganglion of cranial nerves VII (Facial) and  IX (Hypoglossal) respectively which carry taste information from the tongue to the nucleus tractus solitarius. They arise at the posterior placodal region from the epibranchial placodes, a thickening of ectoderm. The first epibranchial placode gives rise to the geniculate ganglion and the second to the petrosal ganglion.&lt;br /&gt;
&lt;br /&gt;
The molecular basis for gustatory neuron formation is not completely understood though there are a number of transcription factors which are thought to play an important role in firstly, placode formation and secondly, neuron differentiation.&lt;br /&gt;
&lt;br /&gt;
*Six1/2, Six1/5 and Eya – transcription factors which cause differentiation of epibranchial placodes into the petrosal and geniculate ganglion.&lt;br /&gt;
*Bone morphogenic Protein 7 (BMP7) – a signal arising from the pharyngeal pouch which is believed to induce epibranchial placode formation. May not be solely responsible for this process, current research has been inconclusive as to how it may work with other proteins of the same family.&lt;br /&gt;
*NGN2 - Following the initial differentiation of the placodes, further differentiation occurs to form neuroblasts. NGN2 causes the delamination and migration of these neuroblasts, which subsequently migrate and fuse to form neurons.&lt;br /&gt;
*Phox2b – maintains the structural integrity of neurons. Knockout of these genes in mice causes marked atrophy of the petrosal and geniculate ganglia.&lt;br /&gt;
&lt;br /&gt;
The neurons involved in the gustatory system are overproduced and thus in the embryonic stage, undergo programmed cell death (apoptosis). The total amount of neurons in the geniculate ganglion, appears to be quite stable over the embryonic stages. This suggests, unlike the petrosal ganglion, the levels of neuroblast proliferation and apoptosis are fairly similar. The factors which regulate these processes remains unclear. It is posited that neurotrophins BDNF, NT4/5 and NT3 may regulate neuronal survival whilst also playing a part in axon growth from the sensory ganglion. More research is required to discern the exact individual functions of each of the neurotrophins.&lt;br /&gt;
&lt;br /&gt;
==Current Research==&lt;br /&gt;
&lt;br /&gt;
[[File:Mousetounge histologicalstain.jpg|right|thumb|200px|Image shows histological stains of a mice tongue showing dysplasia]]&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
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. &lt;br /&gt;
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.&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
'''Synergistic relationships of Six Genes '''&lt;br /&gt;
&lt;br /&gt;
In an animal study using mice by Suzuki Y, Ikeda K, Kawakami K.(2011)  Firstly nominating &amp;quot;[[#Glossary |'''Six Genes''']]&amp;quot; as a major component in [[#Glossary |'''gustatory ''']] development, stating that deficiencies in certain Six genes (specifically Six1 &amp;amp; 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 &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;21978088&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
[[File:Abnormal of tongue.jpg|thumb|200px|Image shows an example of tongue abnormalities, this is called &amp;quot;double tongue&amp;quot; each side has independent movement!]]&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
'''Neural Crest responsibilities '''&lt;br /&gt;
&lt;br /&gt;
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.&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;22659543&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
'''Augmentation of Endoderm'''&lt;br /&gt;
&lt;br /&gt;
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 &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;22581563&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
'''Changes in Taste Cells over time'''&lt;br /&gt;
&lt;br /&gt;
Research by &lt;br /&gt;
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.  &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;22643728&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
'''Shh key component of taste bud proginators'''&lt;br /&gt;
&lt;br /&gt;
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.&lt;br /&gt;
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 &amp;quot;Axiocam CCD camera and Axioplan fluorescence microscope with Axiovision software&amp;quot; a study by Harlow, Yang, Williams, Barlow (2011)&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;PMC2674259&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
'''WNT family exhibit various roles'''&lt;br /&gt;
&lt;br /&gt;
 &lt;br /&gt;
The WNT gene family has a function of signaling work antagonistically through receptor tyrosine kinase (RTK) signaling. However, the deletion of Sprouty Homolog 2 (Spry2) led to the increase of chimaeric virus particles (CVPs) and a significant decrease in number of fungiform papillae. In contrast, the absence of Fibroblast growth factor 10 (Fgf10) in conjunction with 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. 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. &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;PMC2768563&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
[[File:Developing_tongue_histology_001.jpg|right|thumb|200px|HIstological stain of a developing rat tongue]]&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
'''Controversial Research - Not Ectodermal Origin'''&lt;br /&gt;
&lt;br /&gt;
==Glossary==&lt;br /&gt;
&lt;br /&gt;
* '''Circumvallate papillae''' - &lt;br /&gt;
&lt;br /&gt;
* '''Ectoderm'''- outer germ layer of embryo&lt;br /&gt;
&lt;br /&gt;
* '''Endoderm''' - inner germ layer of embryo&lt;br /&gt;
&lt;br /&gt;
* '''Epithelium''' - basic animal tissue that is composed of tightly packed cells, usually covering the outer portion of organs&lt;br /&gt;
&lt;br /&gt;
* '''Exocystosis''' - movement of contents out of cell&lt;br /&gt;
&lt;br /&gt;
* '''Filiform papillae''' - &lt;br /&gt;
&lt;br /&gt;
* '''Foliate papillae''' - &lt;br /&gt;
&lt;br /&gt;
* '''Fungiform papillae''' - &lt;br /&gt;
&lt;br /&gt;
* '''Ganglia''' - the accumulation of a nerve cell body&lt;br /&gt;
&lt;br /&gt;
* '''Growth factor''' - a substance that stimulates the growth of cells&lt;br /&gt;
&lt;br /&gt;
* '''Gustatory''' - anything that relates to the taste sense&lt;br /&gt;
&lt;br /&gt;
* '''Hydrolysis''' - breakdown of a chemical when it reacts with water&lt;br /&gt;
&lt;br /&gt;
* '''Mesoderm''' - middle germ layer of embryo&lt;br /&gt;
&lt;br /&gt;
* '''Mesenchyme''' - multipotential cells&lt;br /&gt;
&lt;br /&gt;
* '''Neural crest''' - a part of the ectoderm found on both sides of the neural tube&lt;br /&gt;
&lt;br /&gt;
* '''Neuron''' - most simplistic unit of the nervous system&lt;br /&gt;
&lt;br /&gt;
* '''Neurotransmitter''' - chemicals which allow the passing of signals from neuron to neuron via connecting part (synapse) &lt;br /&gt;
&lt;br /&gt;
* '''Papillae''' - small rough surface projection&lt;br /&gt;
&lt;br /&gt;
* '''Six genes''' - a family of genes&lt;br /&gt;
&lt;br /&gt;
* '''Sonic hedgehog (Shh)''' - signalling protein involved in normal development&lt;br /&gt;
&lt;br /&gt;
* '''Sulcus terminalis''' - describes a physical transition point separating the anterior 2/3 of the tongue from the posterior 1/3&lt;br /&gt;
&lt;br /&gt;
* '''Tamoxifen''' - hormonal altering drug&lt;br /&gt;
&lt;br /&gt;
* '''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).&lt;br /&gt;
&lt;br /&gt;
* '''Type II taste cells''' - Receptor cells acting as primary detectors of sweet, bitter or umami taste.&lt;br /&gt;
&lt;br /&gt;
* '''Type III taste cells''' - Presynaptic cells that respond to sweet, salty, sour, bitter and umami compounds.&lt;br /&gt;
&lt;br /&gt;
== References ==&lt;br /&gt;
&amp;lt;references/&amp;gt;&lt;br /&gt;
&lt;br /&gt;
==External Links==&lt;br /&gt;
{{External Links}}&lt;br /&gt;
&lt;br /&gt;
1.[http://www.surgicalneurologyint.com/article.asp?issn=2152-7806;year=2012;volume=3;issue=1;spage=23;epage=23;aulast=Manjila]&lt;br /&gt;
&lt;br /&gt;
2.[http://embryology.med.unsw.edu.au/embryology/index.php?title=2012_Group_Project_4]&lt;br /&gt;
&lt;br /&gt;
3.[http://www.webmd.com/oral-health/picture-of-the-tongue]&lt;br /&gt;
&lt;br /&gt;
4.[http://www.tutorvista.com/content/biology/biology-iv/nervous-coordination/tongue-structure.php#parts-of-tongue]&lt;br /&gt;
&lt;br /&gt;
5.[http://www.cf.ac.uk/biosi/staffinfo/jacob/teaching/sensory/taste.html]&lt;br /&gt;
&lt;br /&gt;
--[[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.&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
----&lt;br /&gt;
&lt;br /&gt;
{{2012Projects}}&lt;/div&gt;</summary>
		<author><name>Z3330795</name></author>
	</entry>
	<entry>
		<id>https://embryology.med.unsw.edu.au/embryology/index.php?title=File:Mousetounge_histologicalstain.jpg&amp;diff=105341</id>
		<title>File:Mousetounge histologicalstain.jpg</title>
		<link rel="alternate" type="text/html" href="https://embryology.med.unsw.edu.au/embryology/index.php?title=File:Mousetounge_histologicalstain.jpg&amp;diff=105341"/>
		<updated>2012-10-03T01:19:52Z</updated>

		<summary type="html">&lt;p&gt;Z3330795: &lt;/p&gt;
&lt;hr /&gt;
&lt;div&gt;{Student image||2012} &lt;br /&gt;
&lt;br /&gt;
== Mouse Tongue, Histological Stain ==&lt;br /&gt;
&lt;br /&gt;
Histological examination is a technique used to examine specimen features in a thorough, specific manner. Structures under histological veiw are easily identifiable and differences and abnormalities can easily be noted. This image was uploaded not to highlight any aspect of taste or tongue development, yet to give an example of contempory techniques used in research.&lt;br /&gt;
&lt;br /&gt;
== Original text ==&lt;br /&gt;
&lt;br /&gt;
Fig 2 Histological findings of tongue in mice treated with 4NQO during 16 weeks. a Normal tongue with no histopathological changes 24 weeks after starting the experiment. b Mild dysplasia after 24 weeks. c Moderate dysplasia after 28 weeks. d Severe dysplasia after 28 weeks. e Invasive squamous cell carcinoma after 32 weeks. Original magnification ×10&lt;br /&gt;
by Schoop, Remilio A. L.; Noteborn, Mathieu H. M.; Baatenburg de Jong, Robert J. Journal: Journal of Molecular Histology Vol. 40 Issue 3 DOI: 10.1007/s10735-009-9228-z Published: 2009-10-27 Institution(s): Leiden University Medical Center, Leiden University, Erasmus Medical Center&lt;br /&gt;
&lt;br /&gt;
http://www.springerimages.com/Images/LifeSciences/1-10.1007_s10735-009-9228-z-1&lt;br /&gt;
&lt;br /&gt;
== Copyright Information ==&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
This image is copyrighted by The Author(s). This image is published with open access and made available for noncommercial purposes. For more information on what you are allowed to do with this image, please see the Creative Commons pages.&lt;br /&gt;
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You are free:&lt;br /&gt;
to Share — to copy, distribute and transmit the work to Remix — to adapt the work &lt;br /&gt;
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Under the following conditions:&lt;br /&gt;
Attribution — You must attribute the work in the manner specified by the author or licensor (but not in any way that suggests that they endorse you or your use of the work). &lt;br /&gt;
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Attribute this work: &lt;br /&gt;
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What does &amp;quot;Attribute this work&amp;quot; mean? &lt;br /&gt;
The page you came from contained embedded licensing metadata, including how the creator wishes to be attributed for re-use. You can use the HTML here to cite the work. Doing so will also include metadata on your page so that others can find the original work as well. Noncommercial — You may not use this work for commercial purposes.&lt;/div&gt;</summary>
		<author><name>Z3330795</name></author>
	</entry>
	<entry>
		<id>https://embryology.med.unsw.edu.au/embryology/index.php?title=File:Mousetounge_histologicalstain.jpg&amp;diff=105338</id>
		<title>File:Mousetounge histologicalstain.jpg</title>
		<link rel="alternate" type="text/html" href="https://embryology.med.unsw.edu.au/embryology/index.php?title=File:Mousetounge_histologicalstain.jpg&amp;diff=105338"/>
		<updated>2012-10-03T01:19:18Z</updated>

		<summary type="html">&lt;p&gt;Z3330795: &lt;/p&gt;
&lt;hr /&gt;
&lt;div&gt;{Student image||2012} &lt;br /&gt;
&lt;br /&gt;
== Mouse Tongue, Histological Stain ==&lt;br /&gt;
&lt;br /&gt;
Histological examination is a technique used to examine specimen features in a thorough, specific manner. Structures under histological veiw are easily identifiable and differences and abnormalities can easily be noted. This image was uploaded not to highlight any aspect of taste or tongue development, yet to give an example of contempory techniques used in research.&lt;br /&gt;
&lt;br /&gt;
== Original text ==&lt;br /&gt;
&lt;br /&gt;
Fig 2 Histological findings of tongue in mice treated with 4NQO during 16 weeks. a Normal tongue with no histopathological changes 24 weeks after starting the experiment. b Mild dysplasia after 24 weeks. c Moderate dysplasia after 28 weeks. d Severe dysplasia after 28 weeks. e Invasive squamous cell carcinoma after 32 weeks. Original magnification ×10&lt;br /&gt;
by Schoop, Remilio A. L.; Noteborn, Mathieu H. M.; Baatenburg de Jong, Robert J. Journal: Journal of Molecular Histology Vol. 40 Issue 3 DOI: 10.1007/s10735-009-9228-z Published: 2009-10-27 Institution(s): Leiden University Medical Center, Leiden University, Erasmus Medical Center&lt;br /&gt;
&lt;br /&gt;
http://www.springerimages.com/Images/LifeSciences/1-10.1007_s10735-009-9228-z-1&lt;br /&gt;
&lt;br /&gt;
== Copyright Information ==&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
This image is copyrighted by The Author(s). This image is published with open access and made available for noncommercial purposes. For more information on what you are allowed to do with this image, please see the Creative Commons pages.&lt;/div&gt;</summary>
		<author><name>Z3330795</name></author>
	</entry>
	<entry>
		<id>https://embryology.med.unsw.edu.au/embryology/index.php?title=File:Human_smelling.jpg&amp;diff=105332</id>
		<title>File:Human smelling.jpg</title>
		<link rel="alternate" type="text/html" href="https://embryology.med.unsw.edu.au/embryology/index.php?title=File:Human_smelling.jpg&amp;diff=105332"/>
		<updated>2012-10-03T01:16:10Z</updated>

		<summary type="html">&lt;p&gt;Z3330795: &lt;/p&gt;
&lt;hr /&gt;
&lt;div&gt;{Student image||2012} &lt;br /&gt;
&lt;br /&gt;
== Human Smelling a flower ==&lt;br /&gt;
&lt;br /&gt;
A purely decorative image of a human lady using her sense of smell, reinforcing that there is interaction between senses.&lt;br /&gt;
&lt;br /&gt;
== Original text and file name ==&lt;br /&gt;
Smelling Colours&lt;br /&gt;
&lt;br /&gt;
== Copyright information ==&lt;br /&gt;
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Attribution — You must attribute Smelling Colors to tali bamba (with link).&lt;br /&gt;
&lt;br /&gt;
Direct links are required and they are seen below:&lt;br /&gt;
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&amp;lt;div xmlns:cc=&amp;quot;http://creativecommons.org/ns#&amp;quot; xmlns:dct=&amp;quot;http://purl.org/dc/terms/&amp;quot; about=&amp;quot;http://images.cdn.fotopedia.com/flickr-3941398946-hd.jpg&amp;quot;&amp;gt;&amp;lt;span property=&amp;quot;dct:title&amp;quot;&amp;gt;Smelling Colors&amp;lt;/span&amp;gt; (&amp;lt;a rel=&amp;quot;cc:attributionURL&amp;quot; property=&amp;quot;cc:attributionName&amp;quot; href=&amp;quot;http://www.fotopedia.com/users/talibamba&amp;quot;&amp;gt;tali bamba&amp;lt;/a&amp;gt;) / &amp;lt;a rel=&amp;quot;license&amp;quot; href=&amp;quot;http://creativecommons.org/licenses/by-nd/2.0/&amp;quot;&amp;gt;CC BY-ND 2.0&amp;lt;/a&amp;gt;&amp;lt;/div&amp;gt;&lt;br /&gt;
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No Derivative Works — You may not alter, transform, or build upon this work.&lt;/div&gt;</summary>
		<author><name>Z3330795</name></author>
	</entry>
	<entry>
		<id>https://embryology.med.unsw.edu.au/embryology/index.php?title=File:Papillae.jpg&amp;diff=105318</id>
		<title>File:Papillae.jpg</title>
		<link rel="alternate" type="text/html" href="https://embryology.med.unsw.edu.au/embryology/index.php?title=File:Papillae.jpg&amp;diff=105318"/>
		<updated>2012-10-03T01:08:15Z</updated>

		<summary type="html">&lt;p&gt;Z3330795: &lt;/p&gt;
&lt;hr /&gt;
&lt;div&gt;{Student image||2012}&lt;br /&gt;
&lt;br /&gt;
== Close up of human tongue ==&lt;br /&gt;
&lt;br /&gt;
This image shows a close up of human tongue, showing papillae(seen as little bumps).This picture is for the purpose to appreciate a macroscopic perspective of the papillae. &lt;br /&gt;
&lt;br /&gt;
== Original text and file name ==&lt;br /&gt;
&lt;br /&gt;
Photo of the day reacion photoblog, &lt;br /&gt;
I had never seen taste buds so closely before. It’s really cool to see all of the little red dots in there,&lt;br /&gt;
January 25, 2007 by Joe Lencioni&lt;br /&gt;
http://shiftingpixel.com/2007/01/25/tongue/&lt;br /&gt;
&lt;br /&gt;
== Copyright Information ==&lt;br /&gt;
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to Share — to copy, distribute and transmit the work&lt;br /&gt;
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	<entry>
		<id>https://embryology.med.unsw.edu.au/embryology/index.php?title=2012_Group_Project_3&amp;diff=105281</id>
		<title>2012 Group Project 3</title>
		<link rel="alternate" type="text/html" href="https://embryology.med.unsw.edu.au/embryology/index.php?title=2012_Group_Project_3&amp;diff=105281"/>
		<updated>2012-10-03T00:45:53Z</updated>

		<summary type="html">&lt;p&gt;Z3330795: /* Adult Tongue and Taste Buds – Structure and Function */&lt;/p&gt;
&lt;hr /&gt;
&lt;div&gt;=Taste Development=&lt;br /&gt;
&lt;br /&gt;
You are out to dinner and your meal arrives in front of you, the aromas and the presentation of your food strikes you immediately. Half way through, the waiter returns and asks “How does your meal taste?”  The answer is not as simple as one might think. Why does the meal taste pleasant? How do we experience different tastes? In the following page, we aim to discern how exactly one would answer these questions by looking at the embryological development of the taste system from week to week. &lt;br /&gt;
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Taste is a complex sensory system and its precise workings are to this day not fully understood. What makes it so complicated is the interaction between the structure of tongue and taste buds and how this contributes to the representation of taste qualities (salty, bitter, sweet, sour and umami) in the brain. We will also look at some current research on animal models being undertaken to evaluate the role of specific genes in the development of sensory structures. By looking at the taste system’s genetic basis, we now have a greater understanding of the abnormalities that may occur during development and a direction to pursue in future research to attempt to fill in the gaps of scientific knowledge.&lt;br /&gt;
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==Adult Tongue and Taste Buds – Structure and Function==&lt;br /&gt;
&lt;br /&gt;
'''Structure'''&lt;br /&gt;
&lt;br /&gt;
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.  &lt;br /&gt;
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[http://www.webmd.com/oral-health/picture-of-the-tongue] &lt;br /&gt;
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''''The image below is a simplistic diagram of the surface of the tongue showing the locations of the different papillae and other important features'''&lt;br /&gt;
&lt;br /&gt;
{|&lt;br /&gt;
| [[Image:Drawing of Tongue.png|centre|500px]]&lt;br /&gt;
&lt;br /&gt;
[[File:Taste_pathway.jpg|right|thumb|200px|Simplistic Pathway of Taste]]&lt;br /&gt;
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'''Papillae'''&lt;br /&gt;
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There are 4 types of papillae on the tongue.&lt;br /&gt;
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.[http://www.tutorvista.com/content/biology/biology-iv/nervous-coordination/tongue-structure.php#parts-of-tongue]&lt;br /&gt;
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[[File:Papillae.jpg|Left|thumb|200px|Close up of Human Tongue Papillae]]&lt;br /&gt;
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[[File:Fungiformpapillae.jpg|left|thumb|200px|Fungiform Papillae]]&lt;br /&gt;
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[[File:Circumvallatepapillae.jpg |left|thumb|200px|Circumvallate Papillae]]&lt;br /&gt;
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[[File:Filiformpapillae.jpg|left|200px|thumb|Foliate Papillae]]&lt;br /&gt;
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'''Function'''&lt;br /&gt;
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The Tongue has muscular and sensory functions, muscular functions include swallowing and speech where as sensory function involves taste. This section will focus on the sensory functions of the tongue.&lt;br /&gt;
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. [http://www.cf.ac.uk/biosi/staffinfo/jacob/teaching/sensory/taste.html]&lt;br /&gt;
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[[File:Taste_bud_1.jpg|right|thumb|200px|Cross section of a taste bud unit|centre|Cross section of a taste bud unit]]&lt;br /&gt;
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'''Link Between Taste and Smell'''&lt;br /&gt;
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The pathways of smell and taste are very similar (chemosensation). Pathways both involve the conversion of a dissolved chemical stimulus transformed into a electrical impulse for interpretation by the brain.	&lt;br /&gt;
Taste and smell overlap when humans experience flavour, flavour involves an interaction of taste, smell, texture and temperature, where taste is only a portion of this interaction. when the brain interprets a flavour, contribution from other senses has a significant role in identification. In conclusion Taste and Smell in combination with other senses help develop a sensory interpretation called flavour.[http://www.entnet.org/HealthInformation/smellTaste.cfm]&lt;br /&gt;
[[File:Human smelling.jpg|500px|centre]]&lt;br /&gt;
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==History of Discoveries==&lt;br /&gt;
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{| cellpadding=5 style=&amp;quot;border:1px solid #BBB&amp;quot;&lt;br /&gt;
|- bgcolor=&amp;quot;#faecc8&amp;quot;&lt;br /&gt;
|''' Date'''|| '''Significant Discovery'''&lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#faf6ed&amp;quot;&lt;br /&gt;
|'''350BC'''&lt;br /&gt;
|| Aristotle writes about the basic tastes, sweet and bitter. He also notes that it can be modified by salty and acidic. &amp;lt;ref name=&amp;quot;PMID22717400&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;22717400&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#faecc8&amp;quot;&lt;br /&gt;
|'''1901'''&lt;br /&gt;
|| D. Hanig publishes a paper describing taste sensitivity in different regions of the tongue. &lt;br /&gt;
''Interesting fact:'' The modern concept of a 'tongue map' is a misinterpretation of this study. &amp;lt;ref name=&amp;quot;PMID22717400&amp;quot;/&amp;gt;&lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#faf6ed&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''1908'''&lt;br /&gt;
|Kikunae Ikeda, a professor of the Tokyo Imperial University, discovered and identified the fifth basic taste: umami (savouriness), made palatable by glutamate.  &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;12438213&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
[http://chemse.oxfordjournals.org/content/27/9/847.long New Seasonings]&lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#faecc8&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''1931-32'''&lt;br /&gt;
| A chemist named Arthur Fox and his college noted that they had different sensitivities to the bitter tasting Phenylthiocarbamide (PTC).&amp;lt;ref&amp;gt;Blakeslee AF, Fox AL. Our different taste worlds. J Hered. 1932;23:97–107.&amp;lt;/ref&amp;gt; Geneticists later confirm these findings, and discover that non-tasting is a recessive genetic trait. &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;17782493&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/pubmed/17782493 Inherited taste deficiency] &lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#faf6ed&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''1965'''&lt;br /&gt;
|Farbman's study of the developing taste but in rat fungiform papilla was significant in increasing our understanding of taste bud development. &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;14300090&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
[http://www.sciencedirect.com/science/article/pii/0012160665900400 Electron microscope study of the developing taste bud in rat fungiform papilla.]&lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#faecc8&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''1992'''&lt;br /&gt;
|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. &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;1608467 &amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
[http://www.nature.com/nature/journal/v357/n6379/abs/357563a0.html Gustducin is a taste-cell-specific G protein closely related to the transducins]&lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#faf6ed&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''1995'''&lt;br /&gt;
|Barlow et al. experimented with Axolotl salamanders and concluded that taste buds from this species arise exclusively from epithelial tissue, &amp;quot;oropharyngeal [[#Glossary |'''epithelium''']]&amp;quot;. &amp;lt;ref name=&amp;quot;PMID17826760&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;17826760&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/pubmed/17826760 Embryonic origin of gustatory cranial sensory neurons] &lt;br /&gt;
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|- bgcolor=&amp;quot;#faecc8&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''1996'''&lt;br /&gt;
| 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 &amp;quot;at least dual function of embryonic/fetal taste buds&amp;quot;, including non-gustatory, paracrine functions prior to the 14th week and gustatory after the 14th week. &amp;lt;ref name=&amp;quot;PMID8955790&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;8955790&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/pubmed/8955790 Embryonic and early fetal development of human taste buds: a transmission electron microscopical study]&lt;br /&gt;
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|- bgcolor=&amp;quot;#faf6ed&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''2000'''&lt;br /&gt;
|Chandrashekar, J. et al. discover the first taste sonsors, the T2R bitter taste receptors. &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;10761935&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
[http://www.sciencedirect.com/science/article/pii/S0092867400807060 T2Rs Function as Bitter Taste Receptors]&lt;br /&gt;
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|- bgcolor=&amp;quot;#faecc8&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''2001'''&lt;br /&gt;
|Nelson, G. et al. discover the sweet receptor: a combination of T1R2 and T1R3. &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;11509186&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/pubmed/11509186?dopt=Abstract&amp;amp;holding=npg Mammalian sweet taste receptors.]&lt;br /&gt;
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|- bgcolor=&amp;quot;#faf6ed&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''2002'''&lt;br /&gt;
|Nelson G. et al. discover the amino acid (umami) taste receptor: a combination of T1R1 and T1R3 identified.  &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;11894099&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/pubmed/11894099?dopt=Abstract&amp;amp;holding=npg An amino-acid taste receptor]&lt;br /&gt;
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|- bgcolor=&amp;quot;#faecc8&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''2005'''&lt;br /&gt;
|Dyer, J. et al. discover sweet taste receptors in the GI tract. &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;17855558&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1986582/ Sweet taste signaling in the gut]&lt;br /&gt;
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|- bgcolor=&amp;quot;#faf6ed&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''2006'''&lt;br /&gt;
|Huang, A. L et al. discover cells for sour taste, identified by PKD2L1 (a polycystic kidney disease-like ion channel). &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;16929298&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1571047/ The Cells and Logic for Mammalian Sour Taste detection]&lt;br /&gt;
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|- bgcolor=&amp;quot;#faecc8&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''2007'''&lt;br /&gt;
|Harlow DE, Barlow LA of the University of Colorado Denver Health Sciences Center provide evidence of the &amp;quot;embryonic origin of gustatory cranial sensory neurons&amp;quot;. &amp;lt;ref name=&amp;quot;PMID17826760&amp;quot;/&amp;gt;&lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/pubmed/17826760 Embryonic origin of gustatory cranial sensory neurons.]&lt;br /&gt;
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|- bgcolor=&amp;quot;#faf6ed&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''2009'''&lt;br /&gt;
|A study by Hevezi P et al, presents &amp;quot;the first comprehensive characterization of gene expression in primate taste buds&amp;quot;, as opposed to previous studies which focused on rodents. &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;19636377&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/pubmed/19636377 Genome-wide analysis of gene expression in primate taste buds reveals links to diverse processes]&lt;br /&gt;
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|- bgcolor=&amp;quot;#faecc8&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''2010'''&lt;br /&gt;
|Chandrashekar, J. et al. identify epithelial sodium channel (ENaC) as the sodium-salt taste receptor. &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;20107438&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/pubmed/20107438?dopt=Abstract&amp;amp;holding=npg The cells and peripheral representation of sodium taste in mice]&lt;br /&gt;
|}&lt;br /&gt;
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== Human Weekly Development - Two Prominent Studies ==&lt;br /&gt;
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. &lt;br /&gt;
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The findings of these two studies are summarized in the table below. The figures provided relate to the images on their respective research papers.&lt;br /&gt;
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# [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] &lt;br /&gt;
# [http://chemse.oxfordjournals.org/content/22/6/601.long Scanning electron microscopical studies of developing gustatory papillae in humans, 1997]  &lt;br /&gt;
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===Timeline of Developmental Processes of Human Taste Buds===&lt;br /&gt;
{| cellpadding=5 style=&amp;quot;border:1px solid #BBB&amp;quot;&lt;br /&gt;
|- bgcolor=&amp;quot;#89CFF0&amp;quot;&lt;br /&gt;
|'''Postovulatory Week'''||'''Description'''&lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#BCD4E6&amp;quot;&lt;br /&gt;
|'''Week 6''' ||&lt;br /&gt;
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. &amp;lt;ref name=&amp;quot;PMID9455607&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;9455607&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#89CFF0&amp;quot;&lt;br /&gt;
| '''Weeks 6 to 7'''|| &lt;br /&gt;
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. &amp;lt;ref name=PMID8955790/&amp;gt;&lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#BCD4E6&amp;quot;&lt;br /&gt;
| '''Week 7 '''||&lt;br /&gt;
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.  &amp;lt;ref name=PMID9455607/&amp;gt; &lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#89CFF0&amp;quot;&lt;br /&gt;
| ''' Week 8  ''' ||&lt;br /&gt;
* The taste bud primordium are still differentiated, elongated epithelial cells, resting on a slightly developed core of young dermal papilla.&lt;br /&gt;
* 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. &lt;br /&gt;
* Ciliated cells also appear around the 8th week, however the significance of these cells which are scattered randomly across the lingual surface remains unclear. &amp;lt;ref name=PMID8955790/&amp;gt; &lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#BCD4E6&amp;quot;&lt;br /&gt;
|'''  Week 9''' ||&lt;br /&gt;
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). &amp;lt;ref name=PMID9455607/&amp;gt;&lt;br /&gt;
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|- bgcolor=&amp;quot;#89CFF0&amp;quot;&lt;br /&gt;
|'''  Weeks 10-11''' ||&lt;br /&gt;
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). &amp;lt;ref name=PMID8955790/&amp;gt; &lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#BCD4E6&amp;quot;&lt;br /&gt;
|''' Week 12 ''' ||&lt;br /&gt;
Taste bud cells are more clearly differentiated into epithelial cell types II and III. &amp;lt;ref name=PMID8955790/&amp;gt; &lt;br /&gt;
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|- bgcolor=&amp;quot;#89CFF0&amp;quot;&lt;br /&gt;
|''' Weeks 12-13  ''' ||&lt;br /&gt;
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). &amp;lt;ref name=PMID8955790/&amp;gt; &lt;br /&gt;
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|- bgcolor=&amp;quot;#BCD4E6&amp;quot;&lt;br /&gt;
|''' Weeks 14 -15 ''' ||&lt;br /&gt;
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. &amp;lt;ref name=PMID8955790/&amp;gt; &lt;br /&gt;
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==Abnormalities==&lt;br /&gt;
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It should be mentioned that gustatory abnormalities have not been widely researched. Most research conducted in this field has been conducted through animal testing on mice and this is the basis of information provided below. &lt;br /&gt;
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===Knocking out P2X Receptors===&lt;br /&gt;
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[[File:Image of taste being evoked by visualising ATP release.jpeg|Left|thumb|200px|Evoking taste - ATP release in tongue]]&lt;br /&gt;
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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. &lt;br /&gt;
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It should be noted that the taste buds in DKO are functional, but are not stimulated by the administration of tastants. &lt;br /&gt;
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The transmission of release of ATP is secretion through gap junction hemichannels (pannexin 1 gap junction).&lt;br /&gt;
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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.&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;21940456&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
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===FGF signalling and genes===&lt;br /&gt;
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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.&lt;br /&gt;
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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 (&amp;quot;Fgf10&amp;quot;) 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 &amp;quot;Fgf10&amp;quot; to limit the size of the CVP progenitor placode. Exclusive expression of ''Fgf10'' in the [[#Glossary |'''mesenchyme''']] is necessary for the formation of CVP. &lt;br /&gt;
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'''This image shows the CVP stained with H&amp;amp;E and scanned by Scanning Electron Microscope (SEM)'''&lt;br /&gt;
[[File:CVP of WT(top) and DKO(bottom) mice with H&amp;amp;E and SEM.png]]&lt;br /&gt;
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'''This image shows the location of the CVP and the increased number in DKO mice by SEM'''&lt;br /&gt;
[[File:Mouse circumvallate papilla 01.jpg|300px]]&lt;br /&gt;
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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).&lt;br /&gt;
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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).&lt;br /&gt;
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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''&amp;amp; ''Spry 1&amp;amp;2''work antagonistically through receptor tyrosine kinase (RTK)signalling.&lt;br /&gt;
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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.&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;21655085&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
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==Gustatory System==&lt;br /&gt;
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[[Image:Taste qualities.gif|thumb|The five basic tastes]]&lt;br /&gt;
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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.&lt;br /&gt;
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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.&amp;lt;ref name=PMID20696704&amp;gt;&amp;lt;pubmed&amp;gt;20696704&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
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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 &amp;lt;ref name=PMID20696704/&amp;gt; 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.&lt;br /&gt;
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===Cell Biology===&lt;br /&gt;
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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.&lt;br /&gt;
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====Type II receptors====&lt;br /&gt;
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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:&lt;br /&gt;
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# Stimulates gustatory nerve afferents which project to gustatory nuclei  in the spinal cord&lt;br /&gt;
# Excites Type III presynaptic nerve fibers to release serotonin. &lt;br /&gt;
# Has a positive feedback effect on type II receptor cells, increasing the level of ATP production.&lt;br /&gt;
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        &lt;br /&gt;
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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.&lt;br /&gt;
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==Taste Map==&lt;br /&gt;
[[Image:Taste map.png|thumb|left|250px|Obsolete idea of the tongue map]]&lt;br /&gt;
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.&lt;br /&gt;
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===Neural Pathways===&lt;br /&gt;
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'''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''. &lt;br /&gt;
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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:  &lt;br /&gt;
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* ''Facial nerve n''. -  carries taste information from the anterior 2/3 of the tongue.&lt;br /&gt;
* ''Hypoglossal n.'' - carries taste information from the posterior 1/3 of the tongue.&lt;br /&gt;
* ''Vagus n''. - carries taste information from the palate&lt;br /&gt;
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'''Second order neurons''' - From the NTS second order neurons carry taste information to the Ventral posteromedial (VPM) nucleus in the thalamus.&amp;lt;ref name=PMID21885776/&amp;gt;&lt;br /&gt;
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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.  &lt;br /&gt;
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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.&lt;br /&gt;
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===Cortical Areas===&lt;br /&gt;
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[[Image:Primary gustatory cortex.png|thumb|Primary gustatory cortex]]&lt;br /&gt;
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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)&amp;lt;ref name=PMID22245354&amp;gt;&amp;lt;pubmed&amp;gt;22245354&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;, with the secondary taste cortex in the caudolateral orbitofrontal cortex.&amp;lt;ref name=PMID21305668&amp;gt;&amp;lt;pubmed&amp;gt;21305668&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;  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.&amp;lt;ref name=PMID21885776&amp;gt;&amp;lt;pubmed&amp;gt;21885776&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; These findings lend weight to the idea that there is only one receptor for each taste quality.&lt;br /&gt;
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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).&amp;lt;ref name=PMID21885776/&amp;gt; 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&lt;br /&gt;
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===Neuronal Development===&lt;br /&gt;
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The gustatory system must not be solely thought of as being comprised of simply the tongue and palate. The types of neurons which carry taste information to the brain are also pivotal in constructing the expression of taste qualities.&lt;br /&gt;
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The two main gustatory neurons which develop are the geniculate ganglion and the petrosal ganglion. These are the visceral sensory ganglion of cranial nerves VII (Facial) and  IX (Hypoglossal) respectively which carry taste information from the tongue to the nucleus tractus solitarius. They arise at the posterior placodal region from the epibranchial placodes, a thickening of ectoderm. The first epibranchial placode gives rise to the geniculate ganglion and the second to the petrosal ganglion.&lt;br /&gt;
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The molecular basis for gustatory neuron formation is not completely understood though there are a number of transcription factors which are thought to play an important role in firstly, placode formation and secondly, neuron differentiation.&lt;br /&gt;
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*Six1/2, Six1/5 and Eya – transcription factors which cause differentiation of epibranchial placodes into the petrosal and geniculate ganglion.&lt;br /&gt;
*Bone morphogenic Protein 7 (BMP7) – a signal arising from the pharyngeal pouch which is believed to induce epibranchial placode formation. May not be solely responsible for this process, current research has been inconclusive as to how it may work with other proteins of the same family.&lt;br /&gt;
*NGN2 - Following the initial differentiation of the placodes, further differentiation occurs to form neuroblasts. NGN2 causes the delamination and migration of these neuroblasts, which subsequently migrate and fuse to form neurons.&lt;br /&gt;
*Phox2b – maintains the structural integrity of neurons. Knockout of these genes in mice causes marked atrophy of the petrosal and geniculate ganglia.&lt;br /&gt;
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The neurons involved in the gustatory system are overproduced and thus in the embryonic stage, undergo programmed cell death (apoptosis). The total amount of neurons in the geniculate ganglion, appears to be quite stable over the embryonic stages. This suggests, unlike the petrosal ganglion, the levels of neuroblast proliferation and apoptosis are fairly similar. The factors which regulate these processes remains unclear. It is posited that neurotrophins BDNF, NT4/5 and NT3 may regulate neuronal survival whilst also playing a part in axon growth from the sensory ganglion. More research is required to discern the exact individual functions of each of the neurotrophins.&lt;br /&gt;
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==Current Research==&lt;br /&gt;
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[[File:Mousetounge histologicalstain.jpg|right|thumb|200px|Image shows histological stains of a mice tongue showing dysplasia]]&lt;br /&gt;
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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. &lt;br /&gt;
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.&lt;br /&gt;
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'''Synergistic relationships of Six Genes '''&lt;br /&gt;
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In an animal study using mice by Suzuki Y, Ikeda K, Kawakami K.(2011)  Firstly nominating &amp;quot;[[#Glossary |'''Six Genes''']]&amp;quot; as a major component in [[#Glossary |'''gustatory ''']] development, stating that deficiencies in certain Six genes (specifically Six1 &amp;amp; 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 &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;21978088&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
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[[File:Highpowered_microscope.jpg|Left|thumb|200px|Image of a high powered microscope]]&lt;br /&gt;
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'''Neural Crest responsibilities '''&lt;br /&gt;
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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.&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;22659543&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
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'''Augmentation of Endoderm'''&lt;br /&gt;
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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 &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;22581563&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
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'''Changes in Taste Cells over time'''&lt;br /&gt;
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Research by &lt;br /&gt;
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.  &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;22643728&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
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'''Shh key component of taste bud proginators'''&lt;br /&gt;
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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.&lt;br /&gt;
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 &amp;quot;Axiocam CCD camera and Axioplan fluorescence microscope with Axiovision software&amp;quot; a study by Harlow, Yang, Williams, Barlow (2011)&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;PMC2674259&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
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'''WNT family exhibit various roles'''&lt;br /&gt;
&lt;br /&gt;
 [[File:Abnormal of tongue.jpg|thumb|200px|Image shows an example of tongue abnormalities, this is called &amp;quot;double tongue&amp;quot; each side has independent movement!]]&lt;br /&gt;
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The WNT gene family has a function of signaling work antagonistically through receptor tyrosine kinase (RTK) signaling. However, the deletion of Sprouty Homolog 2 (Spry2) led to the increase of chimaeric virus particles (CVPs) and a significant decrease in number of fungiform papillae. In contrast, the absence of Fibroblast growth factor 10 (Fgf10) in conjunction with 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. 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. &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;PMC2768563&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
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[[File:Developing_tongue_histology_001.jpg|right|thumb|200px|HIstological stain of a developing rat tongue]]&lt;br /&gt;
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==Glossary==&lt;br /&gt;
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* '''Circumvallate papillae''' - &lt;br /&gt;
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* '''Ectoderm'''- outer germ layer of embryo&lt;br /&gt;
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* '''Endoderm''' - inner germ layer of embryo&lt;br /&gt;
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* '''Epithelium''' - basic animal tissue that is composed of tightly packed cells, usually covering the outer portion of organs&lt;br /&gt;
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* '''Exocystosis''' - movement of contents out of cell&lt;br /&gt;
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* '''Filiform papillae''' - &lt;br /&gt;
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* '''Foliate papillae''' - &lt;br /&gt;
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* '''Fungiform papillae''' - &lt;br /&gt;
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* '''Ganglia''' - the accumulation of a nerve cell body&lt;br /&gt;
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* '''Growth factor''' - a substance that stimulates the growth of cells&lt;br /&gt;
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* '''Gustatory''' - anything that relates to the taste sense&lt;br /&gt;
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* '''Hydrolysis''' - breakdown of a chemical when it reacts with water&lt;br /&gt;
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* '''Mesoderm''' - middle germ layer of embryo&lt;br /&gt;
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* '''Mesenchyme''' - multipotential cells&lt;br /&gt;
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* '''Neural crest''' - a part of the ectoderm found on both sides of the neural tube&lt;br /&gt;
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* '''Neuron''' - most simplistic unit of the nervous system&lt;br /&gt;
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* '''Neurotransmitter''' - chemicals which allow the passing of signals from neuron to neuron via connecting part (synapse) &lt;br /&gt;
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* '''Papillae''' - small rough surface projection&lt;br /&gt;
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* '''Six genes''' - a family of genes&lt;br /&gt;
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* '''Sonic hedgehog (Shh)''' - signalling protein involved in normal development&lt;br /&gt;
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* '''Sulcus terminalis''' - describes a physical transition point separating the anterior 2/3 of the tongue from the posterior 1/3&lt;br /&gt;
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* '''Tamoxifen''' - hormonal altering drug&lt;br /&gt;
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* '''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).&lt;br /&gt;
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* '''Type II taste cells''' - Receptor cells acting as primary detectors of sweet, bitter or umami taste.&lt;br /&gt;
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* '''Type III taste cells''' - Presynaptic cells that respond to sweet, salty, sour, bitter and umami compounds.&lt;br /&gt;
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== References ==&lt;br /&gt;
&amp;lt;references/&amp;gt;&lt;br /&gt;
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==External Links==&lt;br /&gt;
{{External Links}}&lt;br /&gt;
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1.[http://www.surgicalneurologyint.com/article.asp?issn=2152-7806;year=2012;volume=3;issue=1;spage=23;epage=23;aulast=Manjila]&lt;br /&gt;
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2.[http://embryology.med.unsw.edu.au/embryology/index.php?title=2012_Group_Project_4]&lt;br /&gt;
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3.[http://www.webmd.com/oral-health/picture-of-the-tongue]&lt;br /&gt;
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4.[http://www.tutorvista.com/content/biology/biology-iv/nervous-coordination/tongue-structure.php#parts-of-tongue]&lt;br /&gt;
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5.[http://www.cf.ac.uk/biosi/staffinfo/jacob/teaching/sensory/taste.html]&lt;br /&gt;
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--[[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.&lt;br /&gt;
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{{2012Projects}}&lt;/div&gt;</summary>
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	</entry>
	<entry>
		<id>https://embryology.med.unsw.edu.au/embryology/index.php?title=2012_Group_Project_3&amp;diff=105272</id>
		<title>2012 Group Project 3</title>
		<link rel="alternate" type="text/html" href="https://embryology.med.unsw.edu.au/embryology/index.php?title=2012_Group_Project_3&amp;diff=105272"/>
		<updated>2012-10-03T00:41:18Z</updated>

		<summary type="html">&lt;p&gt;Z3330795: /* External Links */&lt;/p&gt;
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&lt;div&gt;=Taste Development=&lt;br /&gt;
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You are out to dinner and your meal arrives in front of you, the aromas and the presentation of your food strikes you immediately. Half way through, the waiter returns and asks “How does your meal taste?”  The answer is not as simple as one might think. Why does the meal taste pleasant? How do we experience different tastes? In the following page, we aim to discern how exactly one would answer these questions by looking at the embryological development of the taste system from week to week. &lt;br /&gt;
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Taste is a complex sensory system and its precise workings are to this day not fully understood. What makes it so complicated is the interaction between the structure of tongue and taste buds and how this contributes to the representation of taste qualities (salty, bitter, sweet, sour and umami) in the brain. We will also look at some current research on animal models being undertaken to evaluate the role of specific genes in the development of sensory structures. By looking at the taste system’s genetic basis, we now have a greater understanding of the abnormalities that may occur during development and a direction to pursue in future research to attempt to fill in the gaps of scientific knowledge.&lt;br /&gt;
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==Adult Tongue and Taste Buds – Structure and Function==&lt;br /&gt;
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'''Structure'''&lt;br /&gt;
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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.  &lt;br /&gt;
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[http://www.webmd.com/oral-health/picture-of-the-tongue &lt;br /&gt;
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''''The image below is a simplistic diagram of the surface of the tongue showing the locations of the different papillae and other important features'''&lt;br /&gt;
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{|&lt;br /&gt;
| [[Image:Drawing of Tongue.png|centre|500px]]&lt;br /&gt;
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[[File:Taste_pathway.jpg|right|thumb|200px|Simplistic Pathway of Taste]]&lt;br /&gt;
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'''Papillae'''&lt;br /&gt;
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There are 4 types of papillae on the tongue.&lt;br /&gt;
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.[http://www.tutorvista.com/content/biology/biology-iv/nervous-coordination/tongue-structure.php#parts-of-tongue &lt;br /&gt;
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[[File:Papillae.jpg|Left|thumb|200px|Close up of Human Tongue Papillae]]&lt;br /&gt;
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[[File:Fungiformpapillae.jpg|left|thumb|200px|Fungiform Papillae]]&lt;br /&gt;
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[[File:Circumvallatepapillae.jpg |left|thumb|200px|Circumvallate Papillae]]&lt;br /&gt;
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[[File:Filiformpapillae.jpg|left|200px|thumb|Foliate Papillae]]&lt;br /&gt;
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'''Function'''&lt;br /&gt;
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The Tongue has muscular and sensory functions, muscular functions include swallowing and speech where as sensory function involves taste. This section will focus on the sensory functions of the tongue.&lt;br /&gt;
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. [http://www.cf.ac.uk/biosi/staffinfo/jacob/teaching/sensory/taste.html &lt;br /&gt;
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[[File:Taste_bud_1.jpg|right|thumb|200px|Cross section of a taste bud unit|centre|Cross section of a taste bud unit]]&lt;br /&gt;
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'''Link Between Taste and Smell'''&lt;br /&gt;
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The pathways of smell and taste are very similar. Pathways both involve the conversion of a dissolved chemical stimulus transformed into a electrical impulse for interpretation by the brain.	&lt;br /&gt;
Taste and smell overlap when humans experience flavour, flavour involves an interaction of taste, smell, texture and temperature, where taste is only a portion of this interaction. when the brain interprets a flavour, contribution from other senses has a significant role in identification. In conclusion Taste and Smell in combination with other senses help develop a sensory interpretation called flavour.&lt;br /&gt;
[[File:Human smelling.jpg|500px|centre]]&lt;br /&gt;
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==History of Discoveries==&lt;br /&gt;
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{| cellpadding=5 style=&amp;quot;border:1px solid #BBB&amp;quot;&lt;br /&gt;
|- bgcolor=&amp;quot;#faecc8&amp;quot;&lt;br /&gt;
|''' Date'''|| '''Significant Discovery'''&lt;br /&gt;
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|- bgcolor=&amp;quot;#faf6ed&amp;quot;&lt;br /&gt;
|'''350BC'''&lt;br /&gt;
|| Aristotle writes about the basic tastes, sweet and bitter. He also notes that it can be modified by salty and acidic. &amp;lt;ref name=&amp;quot;PMID22717400&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;22717400&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
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|- bgcolor=&amp;quot;#faecc8&amp;quot;&lt;br /&gt;
|'''1901'''&lt;br /&gt;
|| D. Hanig publishes a paper describing taste sensitivity in different regions of the tongue. &lt;br /&gt;
''Interesting fact:'' The modern concept of a 'tongue map' is a misinterpretation of this study. &amp;lt;ref name=&amp;quot;PMID22717400&amp;quot;/&amp;gt;&lt;br /&gt;
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|- bgcolor=&amp;quot;#faf6ed&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''1908'''&lt;br /&gt;
|Kikunae Ikeda, a professor of the Tokyo Imperial University, discovered and identified the fifth basic taste: umami (savouriness), made palatable by glutamate.  &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;12438213&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
[http://chemse.oxfordjournals.org/content/27/9/847.long New Seasonings]&lt;br /&gt;
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|- bgcolor=&amp;quot;#faecc8&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''1931-32'''&lt;br /&gt;
| A chemist named Arthur Fox and his college noted that they had different sensitivities to the bitter tasting Phenylthiocarbamide (PTC).&amp;lt;ref&amp;gt;Blakeslee AF, Fox AL. Our different taste worlds. J Hered. 1932;23:97–107.&amp;lt;/ref&amp;gt; Geneticists later confirm these findings, and discover that non-tasting is a recessive genetic trait. &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;17782493&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/pubmed/17782493 Inherited taste deficiency] &lt;br /&gt;
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|- bgcolor=&amp;quot;#faf6ed&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''1965'''&lt;br /&gt;
|Farbman's study of the developing taste but in rat fungiform papilla was significant in increasing our understanding of taste bud development. &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;14300090&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
[http://www.sciencedirect.com/science/article/pii/0012160665900400 Electron microscope study of the developing taste bud in rat fungiform papilla.]&lt;br /&gt;
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|- bgcolor=&amp;quot;#faecc8&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''1992'''&lt;br /&gt;
|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. &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;1608467 &amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
[http://www.nature.com/nature/journal/v357/n6379/abs/357563a0.html Gustducin is a taste-cell-specific G protein closely related to the transducins]&lt;br /&gt;
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|- bgcolor=&amp;quot;#faf6ed&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''1995'''&lt;br /&gt;
|Barlow et al. experimented with Axolotl salamanders and concluded that taste buds from this species arise exclusively from epithelial tissue, &amp;quot;oropharyngeal [[#Glossary |'''epithelium''']]&amp;quot;. &amp;lt;ref name=&amp;quot;PMID17826760&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;17826760&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/pubmed/17826760 Embryonic origin of gustatory cranial sensory neurons] &lt;br /&gt;
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|- bgcolor=&amp;quot;#faecc8&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''1996'''&lt;br /&gt;
| 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 &amp;quot;at least dual function of embryonic/fetal taste buds&amp;quot;, including non-gustatory, paracrine functions prior to the 14th week and gustatory after the 14th week. &amp;lt;ref name=&amp;quot;PMID8955790&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;8955790&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/pubmed/8955790 Embryonic and early fetal development of human taste buds: a transmission electron microscopical study]&lt;br /&gt;
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|- bgcolor=&amp;quot;#faf6ed&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''2000'''&lt;br /&gt;
|Chandrashekar, J. et al. discover the first taste sonsors, the T2R bitter taste receptors. &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;10761935&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
[http://www.sciencedirect.com/science/article/pii/S0092867400807060 T2Rs Function as Bitter Taste Receptors]&lt;br /&gt;
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|- bgcolor=&amp;quot;#faecc8&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''2001'''&lt;br /&gt;
|Nelson, G. et al. discover the sweet receptor: a combination of T1R2 and T1R3. &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;11509186&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/pubmed/11509186?dopt=Abstract&amp;amp;holding=npg Mammalian sweet taste receptors.]&lt;br /&gt;
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|- bgcolor=&amp;quot;#faf6ed&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''2002'''&lt;br /&gt;
|Nelson G. et al. discover the amino acid (umami) taste receptor: a combination of T1R1 and T1R3 identified.  &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;11894099&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/pubmed/11894099?dopt=Abstract&amp;amp;holding=npg An amino-acid taste receptor]&lt;br /&gt;
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|- bgcolor=&amp;quot;#faecc8&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''2005'''&lt;br /&gt;
|Dyer, J. et al. discover sweet taste receptors in the GI tract. &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;17855558&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1986582/ Sweet taste signaling in the gut]&lt;br /&gt;
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|- bgcolor=&amp;quot;#faf6ed&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''2006'''&lt;br /&gt;
|Huang, A. L et al. discover cells for sour taste, identified by PKD2L1 (a polycystic kidney disease-like ion channel). &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;16929298&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1571047/ The Cells and Logic for Mammalian Sour Taste detection]&lt;br /&gt;
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|- bgcolor=&amp;quot;#faecc8&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''2007'''&lt;br /&gt;
|Harlow DE, Barlow LA of the University of Colorado Denver Health Sciences Center provide evidence of the &amp;quot;embryonic origin of gustatory cranial sensory neurons&amp;quot;. &amp;lt;ref name=&amp;quot;PMID17826760&amp;quot;/&amp;gt;&lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/pubmed/17826760 Embryonic origin of gustatory cranial sensory neurons.]&lt;br /&gt;
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|- bgcolor=&amp;quot;#faf6ed&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''2009'''&lt;br /&gt;
|A study by Hevezi P et al, presents &amp;quot;the first comprehensive characterization of gene expression in primate taste buds&amp;quot;, as opposed to previous studies which focused on rodents. &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;19636377&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/pubmed/19636377 Genome-wide analysis of gene expression in primate taste buds reveals links to diverse processes]&lt;br /&gt;
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|- bgcolor=&amp;quot;#faecc8&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''2010'''&lt;br /&gt;
|Chandrashekar, J. et al. identify epithelial sodium channel (ENaC) as the sodium-salt taste receptor. &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;20107438&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/pubmed/20107438?dopt=Abstract&amp;amp;holding=npg The cells and peripheral representation of sodium taste in mice]&lt;br /&gt;
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== Human Weekly Development - Two Prominent Studies ==&lt;br /&gt;
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. &lt;br /&gt;
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The findings of these two studies are summarized in the table below. The figures provided relate to the images on their respective research papers.&lt;br /&gt;
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# [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] &lt;br /&gt;
# [http://chemse.oxfordjournals.org/content/22/6/601.long Scanning electron microscopical studies of developing gustatory papillae in humans, 1997]  &lt;br /&gt;
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===Timeline of Developmental Processes of Human Taste Buds===&lt;br /&gt;
{| cellpadding=5 style=&amp;quot;border:1px solid #BBB&amp;quot;&lt;br /&gt;
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|'''Postovulatory Week'''||'''Description'''&lt;br /&gt;
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|'''Week 6''' ||&lt;br /&gt;
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. &amp;lt;ref name=&amp;quot;PMID9455607&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;9455607&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
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|- bgcolor=&amp;quot;#89CFF0&amp;quot;&lt;br /&gt;
| '''Weeks 6 to 7'''|| &lt;br /&gt;
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. &amp;lt;ref name=PMID8955790/&amp;gt;&lt;br /&gt;
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|- bgcolor=&amp;quot;#BCD4E6&amp;quot;&lt;br /&gt;
| '''Week 7 '''||&lt;br /&gt;
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.  &amp;lt;ref name=PMID9455607/&amp;gt; &lt;br /&gt;
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|- bgcolor=&amp;quot;#89CFF0&amp;quot;&lt;br /&gt;
| ''' Week 8  ''' ||&lt;br /&gt;
* The taste bud primordium are still differentiated, elongated epithelial cells, resting on a slightly developed core of young dermal papilla.&lt;br /&gt;
* 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. &lt;br /&gt;
* Ciliated cells also appear around the 8th week, however the significance of these cells which are scattered randomly across the lingual surface remains unclear. &amp;lt;ref name=PMID8955790/&amp;gt; &lt;br /&gt;
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|- bgcolor=&amp;quot;#BCD4E6&amp;quot;&lt;br /&gt;
|'''  Week 9''' ||&lt;br /&gt;
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). &amp;lt;ref name=PMID9455607/&amp;gt;&lt;br /&gt;
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|- bgcolor=&amp;quot;#89CFF0&amp;quot;&lt;br /&gt;
|'''  Weeks 10-11''' ||&lt;br /&gt;
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). &amp;lt;ref name=PMID8955790/&amp;gt; &lt;br /&gt;
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|- bgcolor=&amp;quot;#BCD4E6&amp;quot;&lt;br /&gt;
|''' Week 12 ''' ||&lt;br /&gt;
Taste bud cells are more clearly differentiated into epithelial cell types II and III. &amp;lt;ref name=PMID8955790/&amp;gt; &lt;br /&gt;
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|- bgcolor=&amp;quot;#89CFF0&amp;quot;&lt;br /&gt;
|''' Weeks 12-13  ''' ||&lt;br /&gt;
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). &amp;lt;ref name=PMID8955790/&amp;gt; &lt;br /&gt;
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|- bgcolor=&amp;quot;#BCD4E6&amp;quot;&lt;br /&gt;
|''' Weeks 14 -15 ''' ||&lt;br /&gt;
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. &amp;lt;ref name=PMID8955790/&amp;gt; &lt;br /&gt;
|}&lt;br /&gt;
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==Abnormalities==&lt;br /&gt;
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It should be mentioned that gustatory abnormalities have not been widely researched. Most research conducted in this field has been conducted through animal testing on mice and this is the basis of information provided below. &lt;br /&gt;
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===Knocking out P2X Receptors===&lt;br /&gt;
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[[File:Image of taste being evoked by visualising ATP release.jpeg|Left|thumb|200px|Evoking taste - ATP release in tongue]]&lt;br /&gt;
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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. &lt;br /&gt;
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It should be noted that the taste buds in DKO are functional, but are not stimulated by the administration of tastants. &lt;br /&gt;
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The transmission of release of ATP is secretion through gap junction hemichannels (pannexin 1 gap junction).&lt;br /&gt;
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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.&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;21940456&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
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===FGF signalling and genes===&lt;br /&gt;
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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.&lt;br /&gt;
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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 (&amp;quot;Fgf10&amp;quot;) 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 &amp;quot;Fgf10&amp;quot; to limit the size of the CVP progenitor placode. Exclusive expression of ''Fgf10'' in the [[#Glossary |'''mesenchyme''']] is necessary for the formation of CVP. &lt;br /&gt;
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'''This image shows the CVP stained with H&amp;amp;E and scanned by Scanning Electron Microscope (SEM)'''&lt;br /&gt;
[[File:CVP of WT(top) and DKO(bottom) mice with H&amp;amp;E and SEM.png]]&lt;br /&gt;
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'''This image shows the location of the CVP and the increased number in DKO mice by SEM'''&lt;br /&gt;
[[File:Mouse circumvallate papilla 01.jpg|300px]]&lt;br /&gt;
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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).&lt;br /&gt;
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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).&lt;br /&gt;
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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''&amp;amp; ''Spry 1&amp;amp;2''work antagonistically through receptor tyrosine kinase (RTK)signalling.&lt;br /&gt;
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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.&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;21655085&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
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==Gustatory System==&lt;br /&gt;
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[[Image:Taste qualities.gif|thumb|The five basic tastes]]&lt;br /&gt;
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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.&lt;br /&gt;
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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.&amp;lt;ref name=PMID20696704&amp;gt;&amp;lt;pubmed&amp;gt;20696704&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
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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 &amp;lt;ref name=PMID20696704/&amp;gt; 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.&lt;br /&gt;
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===Cell Biology===&lt;br /&gt;
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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.&lt;br /&gt;
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====Type II receptors====&lt;br /&gt;
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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:&lt;br /&gt;
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# Stimulates gustatory nerve afferents which project to gustatory nuclei  in the spinal cord&lt;br /&gt;
# Excites Type III presynaptic nerve fibers to release serotonin. &lt;br /&gt;
# Has a positive feedback effect on type II receptor cells, increasing the level of ATP production.&lt;br /&gt;
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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.&lt;br /&gt;
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==Taste Map==&lt;br /&gt;
[[Image:Taste map.png|thumb|left|250px|Obsolete idea of the tongue map]]&lt;br /&gt;
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.&lt;br /&gt;
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===Neural Pathways===&lt;br /&gt;
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'''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''. &lt;br /&gt;
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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:  &lt;br /&gt;
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* ''Facial nerve n''. -  carries taste information from the anterior 2/3 of the tongue.&lt;br /&gt;
* ''Hypoglossal n.'' - carries taste information from the posterior 1/3 of the tongue.&lt;br /&gt;
* ''Vagus n''. - carries taste information from the palate&lt;br /&gt;
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'''Second order neurons''' - From the NTS second order neurons carry taste information to the Ventral posteromedial (VPM) nucleus in the thalamus.&amp;lt;ref name=PMID21885776/&amp;gt;&lt;br /&gt;
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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.  &lt;br /&gt;
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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.&lt;br /&gt;
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===Cortical Areas===&lt;br /&gt;
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[[Image:Primary gustatory cortex.png|thumb|Primary gustatory cortex]]&lt;br /&gt;
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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)&amp;lt;ref name=PMID22245354&amp;gt;&amp;lt;pubmed&amp;gt;22245354&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;, with the secondary taste cortex in the caudolateral orbitofrontal cortex.&amp;lt;ref name=PMID21305668&amp;gt;&amp;lt;pubmed&amp;gt;21305668&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;  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.&amp;lt;ref name=PMID21885776&amp;gt;&amp;lt;pubmed&amp;gt;21885776&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; These findings lend weight to the idea that there is only one receptor for each taste quality.&lt;br /&gt;
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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).&amp;lt;ref name=PMID21885776/&amp;gt; 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&lt;br /&gt;
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===Neuronal Development===&lt;br /&gt;
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The gustatory system must not be solely thought of as being comprised of simply the tongue and palate. The types of neurons which carry taste information to the brain are also pivotal in constructing the expression of taste qualities.&lt;br /&gt;
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The two main gustatory neurons which develop are the geniculate ganglion and the petrosal ganglion. These are the visceral sensory ganglion of cranial nerves VII (Facial) and  IX (Hypoglossal) respectively which carry taste information from the tongue to the nucleus tractus solitarius. They arise at the posterior placodal region from the epibranchial placodes, a thickening of ectoderm. The first epibranchial placode gives rise to the geniculate ganglion and the second to the petrosal ganglion.&lt;br /&gt;
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The molecular basis for gustatory neuron formation is not completely understood though there are a number of transcription factors which are thought to play an important role in firstly, placode formation and secondly, neuron differentiation.&lt;br /&gt;
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*Six1/2, Six1/5 and Eya – transcription factors which cause differentiation of epibranchial placodes into the petrosal and geniculate ganglion.&lt;br /&gt;
*Bone morphogenic Protein 7 (BMP7) – a signal arising from the pharyngeal pouch which is believed to induce epibranchial placode formation. May not be solely responsible for this process, current research has been inconclusive as to how it may work with other proteins of the same family.&lt;br /&gt;
*NGN2 - Following the initial differentiation of the placodes, further differentiation occurs to form neuroblasts. NGN2 causes the delamination and migration of these neuroblasts, which subsequently migrate and fuse to form neurons.&lt;br /&gt;
*Phox2b – maintains the structural integrity of neurons. Knockout of these genes in mice causes marked atrophy of the petrosal and geniculate ganglia.&lt;br /&gt;
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The neurons involved in the gustatory system are overproduced and thus in the embryonic stage, undergo programmed cell death (apoptosis). The total amount of neurons in the geniculate ganglion, appears to be quite stable over the embryonic stages. This suggests, unlike the petrosal ganglion, the levels of neuroblast proliferation and apoptosis are fairly similar. The factors which regulate these processes remains unclear. It is posited that neurotrophins BDNF, NT4/5 and NT3 may regulate neuronal survival whilst also playing a part in axon growth from the sensory ganglion. More research is required to discern the exact individual functions of each of the neurotrophins.&lt;br /&gt;
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==Current Research==&lt;br /&gt;
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[[File:Mousetounge histologicalstain.jpg|right|thumb|200px|Image shows histological stains of a mice tongue showing dysplasia]]&lt;br /&gt;
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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. &lt;br /&gt;
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.&lt;br /&gt;
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'''Synergistic relationships of Six Genes '''&lt;br /&gt;
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In an animal study using mice by Suzuki Y, Ikeda K, Kawakami K.(2011)  Firstly nominating &amp;quot;[[#Glossary |'''Six Genes''']]&amp;quot; as a major component in [[#Glossary |'''gustatory ''']] development, stating that deficiencies in certain Six genes (specifically Six1 &amp;amp; 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 &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;21978088&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
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[[File:Highpowered_microscope.jpg|Left|thumb|200px|Image of a high powered microscope]]&lt;br /&gt;
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'''Neural Crest responsibilities '''&lt;br /&gt;
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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.&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;22659543&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
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'''Augmentation of Endoderm'''&lt;br /&gt;
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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 &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;22581563&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
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'''Changes in Taste Cells over time'''&lt;br /&gt;
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Research by &lt;br /&gt;
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.  &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;22643728&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
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'''Shh key component of taste bud proginators'''&lt;br /&gt;
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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.&lt;br /&gt;
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 &amp;quot;Axiocam CCD camera and Axioplan fluorescence microscope with Axiovision software&amp;quot; a study by Harlow, Yang, Williams, Barlow (2011)&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;PMC2674259&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
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'''WNT family exhibit various roles'''&lt;br /&gt;
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 [[File:Abnormal of tongue.jpg|thumb|200px|Image shows an example of tongue abnormalities, this is called &amp;quot;double tongue&amp;quot; each side has independent movement!]]&lt;br /&gt;
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The WNT gene family has a function of signaling work antagonistically through receptor tyrosine kinase (RTK) signaling. However, the deletion of Sprouty Homolog 2 (Spry2) led to the increase of chimaeric virus particles (CVPs) and a significant decrease in number of fungiform papillae. In contrast, the absence of Fibroblast growth factor 10 (Fgf10) in conjunction with 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. 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. &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;PMC2768563&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
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[[File:Developing_tongue_histology_001.jpg|right|thumb|200px|HIstological stain of a developing rat tongue]]&lt;br /&gt;
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==Glossary==&lt;br /&gt;
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* '''Circumvallate papillae''' - &lt;br /&gt;
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* '''Ectoderm'''- outer germ layer of embryo&lt;br /&gt;
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* '''Endoderm''' - inner germ layer of embryo&lt;br /&gt;
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* '''Epithelium''' - basic animal tissue that is composed of tightly packed cells, usually covering the outer portion of organs&lt;br /&gt;
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* '''Exocystosis''' - movement of contents out of cell&lt;br /&gt;
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* '''Filiform papillae''' - &lt;br /&gt;
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* '''Foliate papillae''' - &lt;br /&gt;
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* '''Fungiform papillae''' - &lt;br /&gt;
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* '''Ganglia''' - the accumulation of a nerve cell body&lt;br /&gt;
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* '''Growth factor''' - a substance that stimulates the growth of cells&lt;br /&gt;
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* '''Gustatory''' - anything that relates to the taste sense&lt;br /&gt;
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* '''Hydrolysis''' - breakdown of a chemical when it reacts with water&lt;br /&gt;
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* '''Mesoderm''' - middle germ layer of embryo&lt;br /&gt;
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* '''Mesenchyme''' - multipotential cells&lt;br /&gt;
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* '''Neural crest''' - a part of the ectoderm found on both sides of the neural tube&lt;br /&gt;
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* '''Neuron''' - most simplistic unit of the nervous system&lt;br /&gt;
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* '''Neurotransmitter''' - chemicals which allow the passing of signals from neuron to neuron via connecting part (synapse) &lt;br /&gt;
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* '''Papillae''' - small rough surface projection&lt;br /&gt;
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* '''Six genes''' - a family of genes&lt;br /&gt;
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* '''Sonic hedgehog (Shh)''' - signalling protein involved in normal development&lt;br /&gt;
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* '''Sulcus terminalis''' - describes a physical transition point separating the anterior 2/3 of the tongue from the posterior 1/3&lt;br /&gt;
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* '''Tamoxifen''' - hormonal altering drug&lt;br /&gt;
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* '''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).&lt;br /&gt;
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* '''Type II taste cells''' - Receptor cells acting as primary detectors of sweet, bitter or umami taste.&lt;br /&gt;
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* '''Type III taste cells''' - Presynaptic cells that respond to sweet, salty, sour, bitter and umami compounds.&lt;br /&gt;
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== References ==&lt;br /&gt;
&amp;lt;references/&amp;gt;&lt;br /&gt;
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==External Links==&lt;br /&gt;
{{External Links}}&lt;br /&gt;
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1.[http://www.surgicalneurologyint.com/article.asp?issn=2152-7806;year=2012;volume=3;issue=1;spage=23;epage=23;aulast=Manjila]&lt;br /&gt;
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2.[http://embryology.med.unsw.edu.au/embryology/index.php?title=2012_Group_Project_4]&lt;br /&gt;
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3.[http://www.webmd.com/oral-health/picture-of-the-tongue]&lt;br /&gt;
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4.[http://www.tutorvista.com/content/biology/biology-iv/nervous-coordination/tongue-structure.php#parts-of-tongue]&lt;br /&gt;
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5.[http://www.cf.ac.uk/biosi/staffinfo/jacob/teaching/sensory/taste.html]&lt;br /&gt;
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--[[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.&lt;br /&gt;
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{{2012Projects}}&lt;/div&gt;</summary>
		<author><name>Z3330795</name></author>
	</entry>
	<entry>
		<id>https://embryology.med.unsw.edu.au/embryology/index.php?title=2012_Group_Project_3&amp;diff=105268</id>
		<title>2012 Group Project 3</title>
		<link rel="alternate" type="text/html" href="https://embryology.med.unsw.edu.au/embryology/index.php?title=2012_Group_Project_3&amp;diff=105268"/>
		<updated>2012-10-03T00:36:41Z</updated>

		<summary type="html">&lt;p&gt;Z3330795: /* Adult Tongue and Taste Buds – Structure and Function */&lt;/p&gt;
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&lt;div&gt;=Taste Development=&lt;br /&gt;
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You are out to dinner and your meal arrives in front of you, the aromas and the presentation of your food strikes you immediately. Half way through, the waiter returns and asks “How does your meal taste?”  The answer is not as simple as one might think. Why does the meal taste pleasant? How do we experience different tastes? In the following page, we aim to discern how exactly one would answer these questions by looking at the embryological development of the taste system from week to week. &lt;br /&gt;
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Taste is a complex sensory system and its precise workings are to this day not fully understood. What makes it so complicated is the interaction between the structure of tongue and taste buds and how this contributes to the representation of taste qualities (salty, bitter, sweet, sour and umami) in the brain. We will also look at some current research on animal models being undertaken to evaluate the role of specific genes in the development of sensory structures. By looking at the taste system’s genetic basis, we now have a greater understanding of the abnormalities that may occur during development and a direction to pursue in future research to attempt to fill in the gaps of scientific knowledge.&lt;br /&gt;
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==Adult Tongue and Taste Buds – Structure and Function==&lt;br /&gt;
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'''Structure'''&lt;br /&gt;
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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.  &lt;br /&gt;
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[http://www.webmd.com/oral-health/picture-of-the-tongue &lt;br /&gt;
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''''The image below is a simplistic diagram of the surface of the tongue showing the locations of the different papillae and other important features'''&lt;br /&gt;
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{|&lt;br /&gt;
| [[Image:Drawing of Tongue.png|centre|500px]]&lt;br /&gt;
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[[File:Taste_pathway.jpg|right|thumb|200px|Simplistic Pathway of Taste]]&lt;br /&gt;
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'''Papillae'''&lt;br /&gt;
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There are 4 types of papillae on the tongue.&lt;br /&gt;
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.[http://www.tutorvista.com/content/biology/biology-iv/nervous-coordination/tongue-structure.php#parts-of-tongue &lt;br /&gt;
]&lt;br /&gt;
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[[File:Papillae.jpg|Left|thumb|200px|Close up of Human Tongue Papillae]]&lt;br /&gt;
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[[File:Fungiformpapillae.jpg|left|thumb|200px|Fungiform Papillae]]&lt;br /&gt;
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[[File:Circumvallatepapillae.jpg |left|thumb|200px|Circumvallate Papillae]]&lt;br /&gt;
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[[File:Filiformpapillae.jpg|left|200px|thumb|Foliate Papillae]]&lt;br /&gt;
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'''Function'''&lt;br /&gt;
&lt;br /&gt;
The Tongue has muscular and sensory functions, muscular functions include swallowing and speech where as sensory function involves taste. This section will focus on the sensory functions of the tongue.&lt;br /&gt;
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. [http://www.cf.ac.uk/biosi/staffinfo/jacob/teaching/sensory/taste.html &lt;br /&gt;
]&lt;br /&gt;
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[[File:Taste_bud_1.jpg|right|thumb|200px|Cross section of a taste bud unit|centre|Cross section of a taste bud unit]]&lt;br /&gt;
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'''Link Between Taste and Smell'''&lt;br /&gt;
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The pathways of smell and taste are very similar. Pathways both involve the conversion of a dissolved chemical stimulus transformed into a electrical impulse for interpretation by the brain.	&lt;br /&gt;
Taste and smell overlap when humans experience flavour, flavour involves an interaction of taste, smell, texture and temperature, where taste is only a portion of this interaction. when the brain interprets a flavour, contribution from other senses has a significant role in identification. In conclusion Taste and Smell in combination with other senses help develop a sensory interpretation called flavour.&lt;br /&gt;
[[File:Human smelling.jpg|500px|centre]]&lt;br /&gt;
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==History of Discoveries==&lt;br /&gt;
&lt;br /&gt;
{| cellpadding=5 style=&amp;quot;border:1px solid #BBB&amp;quot;&lt;br /&gt;
|- bgcolor=&amp;quot;#faecc8&amp;quot;&lt;br /&gt;
|''' Date'''|| '''Significant Discovery'''&lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#faf6ed&amp;quot;&lt;br /&gt;
|'''350BC'''&lt;br /&gt;
|| Aristotle writes about the basic tastes, sweet and bitter. He also notes that it can be modified by salty and acidic. &amp;lt;ref name=&amp;quot;PMID22717400&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;22717400&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#faecc8&amp;quot;&lt;br /&gt;
|'''1901'''&lt;br /&gt;
|| D. Hanig publishes a paper describing taste sensitivity in different regions of the tongue. &lt;br /&gt;
''Interesting fact:'' The modern concept of a 'tongue map' is a misinterpretation of this study. &amp;lt;ref name=&amp;quot;PMID22717400&amp;quot;/&amp;gt;&lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#faf6ed&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''1908'''&lt;br /&gt;
|Kikunae Ikeda, a professor of the Tokyo Imperial University, discovered and identified the fifth basic taste: umami (savouriness), made palatable by glutamate.  &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;12438213&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
[http://chemse.oxfordjournals.org/content/27/9/847.long New Seasonings]&lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#faecc8&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''1931-32'''&lt;br /&gt;
| A chemist named Arthur Fox and his college noted that they had different sensitivities to the bitter tasting Phenylthiocarbamide (PTC).&amp;lt;ref&amp;gt;Blakeslee AF, Fox AL. Our different taste worlds. J Hered. 1932;23:97–107.&amp;lt;/ref&amp;gt; Geneticists later confirm these findings, and discover that non-tasting is a recessive genetic trait. &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;17782493&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/pubmed/17782493 Inherited taste deficiency] &lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#faf6ed&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''1965'''&lt;br /&gt;
|Farbman's study of the developing taste but in rat fungiform papilla was significant in increasing our understanding of taste bud development. &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;14300090&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
[http://www.sciencedirect.com/science/article/pii/0012160665900400 Electron microscope study of the developing taste bud in rat fungiform papilla.]&lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#faecc8&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''1992'''&lt;br /&gt;
|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. &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;1608467 &amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
[http://www.nature.com/nature/journal/v357/n6379/abs/357563a0.html Gustducin is a taste-cell-specific G protein closely related to the transducins]&lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#faf6ed&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''1995'''&lt;br /&gt;
|Barlow et al. experimented with Axolotl salamanders and concluded that taste buds from this species arise exclusively from epithelial tissue, &amp;quot;oropharyngeal [[#Glossary |'''epithelium''']]&amp;quot;. &amp;lt;ref name=&amp;quot;PMID17826760&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;17826760&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/pubmed/17826760 Embryonic origin of gustatory cranial sensory neurons] &lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#faecc8&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''1996'''&lt;br /&gt;
| 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 &amp;quot;at least dual function of embryonic/fetal taste buds&amp;quot;, including non-gustatory, paracrine functions prior to the 14th week and gustatory after the 14th week. &amp;lt;ref name=&amp;quot;PMID8955790&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;8955790&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/pubmed/8955790 Embryonic and early fetal development of human taste buds: a transmission electron microscopical study]&lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#faf6ed&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''2000'''&lt;br /&gt;
|Chandrashekar, J. et al. discover the first taste sonsors, the T2R bitter taste receptors. &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;10761935&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
[http://www.sciencedirect.com/science/article/pii/S0092867400807060 T2Rs Function as Bitter Taste Receptors]&lt;br /&gt;
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|- bgcolor=&amp;quot;#faecc8&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''2001'''&lt;br /&gt;
|Nelson, G. et al. discover the sweet receptor: a combination of T1R2 and T1R3. &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;11509186&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/pubmed/11509186?dopt=Abstract&amp;amp;holding=npg Mammalian sweet taste receptors.]&lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#faf6ed&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''2002'''&lt;br /&gt;
|Nelson G. et al. discover the amino acid (umami) taste receptor: a combination of T1R1 and T1R3 identified.  &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;11894099&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/pubmed/11894099?dopt=Abstract&amp;amp;holding=npg An amino-acid taste receptor]&lt;br /&gt;
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|- bgcolor=&amp;quot;#faecc8&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''2005'''&lt;br /&gt;
|Dyer, J. et al. discover sweet taste receptors in the GI tract. &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;17855558&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1986582/ Sweet taste signaling in the gut]&lt;br /&gt;
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|- bgcolor=&amp;quot;#faf6ed&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''2006'''&lt;br /&gt;
|Huang, A. L et al. discover cells for sour taste, identified by PKD2L1 (a polycystic kidney disease-like ion channel). &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;16929298&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1571047/ The Cells and Logic for Mammalian Sour Taste detection]&lt;br /&gt;
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|- bgcolor=&amp;quot;#faecc8&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''2007'''&lt;br /&gt;
|Harlow DE, Barlow LA of the University of Colorado Denver Health Sciences Center provide evidence of the &amp;quot;embryonic origin of gustatory cranial sensory neurons&amp;quot;. &amp;lt;ref name=&amp;quot;PMID17826760&amp;quot;/&amp;gt;&lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/pubmed/17826760 Embryonic origin of gustatory cranial sensory neurons.]&lt;br /&gt;
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|- bgcolor=&amp;quot;#faf6ed&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''2009'''&lt;br /&gt;
|A study by Hevezi P et al, presents &amp;quot;the first comprehensive characterization of gene expression in primate taste buds&amp;quot;, as opposed to previous studies which focused on rodents. &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;19636377&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/pubmed/19636377 Genome-wide analysis of gene expression in primate taste buds reveals links to diverse processes]&lt;br /&gt;
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|- bgcolor=&amp;quot;#faecc8&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''2010'''&lt;br /&gt;
|Chandrashekar, J. et al. identify epithelial sodium channel (ENaC) as the sodium-salt taste receptor. &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;20107438&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/pubmed/20107438?dopt=Abstract&amp;amp;holding=npg The cells and peripheral representation of sodium taste in mice]&lt;br /&gt;
|}&lt;br /&gt;
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== Human Weekly Development - Two Prominent Studies ==&lt;br /&gt;
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. &lt;br /&gt;
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The findings of these two studies are summarized in the table below. The figures provided relate to the images on their respective research papers.&lt;br /&gt;
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# [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] &lt;br /&gt;
# [http://chemse.oxfordjournals.org/content/22/6/601.long Scanning electron microscopical studies of developing gustatory papillae in humans, 1997]  &lt;br /&gt;
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===Timeline of Developmental Processes of Human Taste Buds===&lt;br /&gt;
{| cellpadding=5 style=&amp;quot;border:1px solid #BBB&amp;quot;&lt;br /&gt;
|- bgcolor=&amp;quot;#89CFF0&amp;quot;&lt;br /&gt;
|'''Postovulatory Week'''||'''Description'''&lt;br /&gt;
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|- bgcolor=&amp;quot;#BCD4E6&amp;quot;&lt;br /&gt;
|'''Week 6''' ||&lt;br /&gt;
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. &amp;lt;ref name=&amp;quot;PMID9455607&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;9455607&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#89CFF0&amp;quot;&lt;br /&gt;
| '''Weeks 6 to 7'''|| &lt;br /&gt;
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. &amp;lt;ref name=PMID8955790/&amp;gt;&lt;br /&gt;
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|- bgcolor=&amp;quot;#BCD4E6&amp;quot;&lt;br /&gt;
| '''Week 7 '''||&lt;br /&gt;
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.  &amp;lt;ref name=PMID9455607/&amp;gt; &lt;br /&gt;
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|- bgcolor=&amp;quot;#89CFF0&amp;quot;&lt;br /&gt;
| ''' Week 8  ''' ||&lt;br /&gt;
* The taste bud primordium are still differentiated, elongated epithelial cells, resting on a slightly developed core of young dermal papilla.&lt;br /&gt;
* 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. &lt;br /&gt;
* Ciliated cells also appear around the 8th week, however the significance of these cells which are scattered randomly across the lingual surface remains unclear. &amp;lt;ref name=PMID8955790/&amp;gt; &lt;br /&gt;
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|- bgcolor=&amp;quot;#BCD4E6&amp;quot;&lt;br /&gt;
|'''  Week 9''' ||&lt;br /&gt;
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). &amp;lt;ref name=PMID9455607/&amp;gt;&lt;br /&gt;
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|- bgcolor=&amp;quot;#89CFF0&amp;quot;&lt;br /&gt;
|'''  Weeks 10-11''' ||&lt;br /&gt;
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). &amp;lt;ref name=PMID8955790/&amp;gt; &lt;br /&gt;
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|- bgcolor=&amp;quot;#BCD4E6&amp;quot;&lt;br /&gt;
|''' Week 12 ''' ||&lt;br /&gt;
Taste bud cells are more clearly differentiated into epithelial cell types II and III. &amp;lt;ref name=PMID8955790/&amp;gt; &lt;br /&gt;
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|- bgcolor=&amp;quot;#89CFF0&amp;quot;&lt;br /&gt;
|''' Weeks 12-13  ''' ||&lt;br /&gt;
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). &amp;lt;ref name=PMID8955790/&amp;gt; &lt;br /&gt;
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|- bgcolor=&amp;quot;#BCD4E6&amp;quot;&lt;br /&gt;
|''' Weeks 14 -15 ''' ||&lt;br /&gt;
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. &amp;lt;ref name=PMID8955790/&amp;gt; &lt;br /&gt;
|}&lt;br /&gt;
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==Abnormalities==&lt;br /&gt;
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It should be mentioned that gustatory abnormalities have not been widely researched. Most research conducted in this field has been conducted through animal testing on mice and this is the basis of information provided below. &lt;br /&gt;
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===Knocking out P2X Receptors===&lt;br /&gt;
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[[File:Image of taste being evoked by visualising ATP release.jpeg|Left|thumb|200px|Evoking taste - ATP release in tongue]]&lt;br /&gt;
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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. &lt;br /&gt;
&lt;br /&gt;
It should be noted that the taste buds in DKO are functional, but are not stimulated by the administration of tastants. &lt;br /&gt;
&lt;br /&gt;
The transmission of release of ATP is secretion through gap junction hemichannels (pannexin 1 gap junction).&lt;br /&gt;
&lt;br /&gt;
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.&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;21940456&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
===FGF signalling and genes===&lt;br /&gt;
&lt;br /&gt;
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.&lt;br /&gt;
&lt;br /&gt;
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 (&amp;quot;Fgf10&amp;quot;) 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 &amp;quot;Fgf10&amp;quot; to limit the size of the CVP progenitor placode. Exclusive expression of ''Fgf10'' in the [[#Glossary |'''mesenchyme''']] is necessary for the formation of CVP. &lt;br /&gt;
&lt;br /&gt;
'''This image shows the CVP stained with H&amp;amp;E and scanned by Scanning Electron Microscope (SEM)'''&lt;br /&gt;
[[File:CVP of WT(top) and DKO(bottom) mice with H&amp;amp;E and SEM.png]]&lt;br /&gt;
&lt;br /&gt;
'''This image shows the location of the CVP and the increased number in DKO mice by SEM'''&lt;br /&gt;
[[File:Mouse circumvallate papilla 01.jpg|300px]]&lt;br /&gt;
&lt;br /&gt;
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).&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
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).&lt;br /&gt;
&lt;br /&gt;
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''&amp;amp; ''Spry 1&amp;amp;2''work antagonistically through receptor tyrosine kinase (RTK)signalling.&lt;br /&gt;
&lt;br /&gt;
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.&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;21655085&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
==Gustatory System==&lt;br /&gt;
&lt;br /&gt;
[[Image:Taste qualities.gif|thumb|The five basic tastes]]&lt;br /&gt;
&lt;br /&gt;
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.&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
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.&amp;lt;ref name=PMID20696704&amp;gt;&amp;lt;pubmed&amp;gt;20696704&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
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 &amp;lt;ref name=PMID20696704/&amp;gt; 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.&lt;br /&gt;
&lt;br /&gt;
===Cell Biology===&lt;br /&gt;
&lt;br /&gt;
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.&lt;br /&gt;
&lt;br /&gt;
====Type II receptors====&lt;br /&gt;
&lt;br /&gt;
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:&lt;br /&gt;
&lt;br /&gt;
# Stimulates gustatory nerve afferents which project to gustatory nuclei  in the spinal cord&lt;br /&gt;
# Excites Type III presynaptic nerve fibers to release serotonin. &lt;br /&gt;
# Has a positive feedback effect on type II receptor cells, increasing the level of ATP production.&lt;br /&gt;
&lt;br /&gt;
        &lt;br /&gt;
&lt;br /&gt;
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.&lt;br /&gt;
&lt;br /&gt;
==Taste Map==&lt;br /&gt;
[[Image:Taste map.png|thumb|left|250px|Obsolete idea of the tongue map]]&lt;br /&gt;
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.&lt;br /&gt;
&lt;br /&gt;
===Neural Pathways===&lt;br /&gt;
&lt;br /&gt;
'''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''. &lt;br /&gt;
&lt;br /&gt;
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:  &lt;br /&gt;
&lt;br /&gt;
* ''Facial nerve n''. -  carries taste information from the anterior 2/3 of the tongue.&lt;br /&gt;
* ''Hypoglossal n.'' - carries taste information from the posterior 1/3 of the tongue.&lt;br /&gt;
* ''Vagus n''. - carries taste information from the palate&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
'''Second order neurons''' - From the NTS second order neurons carry taste information to the Ventral posteromedial (VPM) nucleus in the thalamus.&amp;lt;ref name=PMID21885776/&amp;gt;&lt;br /&gt;
&lt;br /&gt;
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.  &lt;br /&gt;
&lt;br /&gt;
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.&lt;br /&gt;
&lt;br /&gt;
===Cortical Areas===&lt;br /&gt;
&lt;br /&gt;
[[Image:Primary gustatory cortex.png|thumb|Primary gustatory cortex]]&lt;br /&gt;
&lt;br /&gt;
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)&amp;lt;ref name=PMID22245354&amp;gt;&amp;lt;pubmed&amp;gt;22245354&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;, with the secondary taste cortex in the caudolateral orbitofrontal cortex.&amp;lt;ref name=PMID21305668&amp;gt;&amp;lt;pubmed&amp;gt;21305668&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;  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.&amp;lt;ref name=PMID21885776&amp;gt;&amp;lt;pubmed&amp;gt;21885776&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; These findings lend weight to the idea that there is only one receptor for each taste quality.&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
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).&amp;lt;ref name=PMID21885776/&amp;gt; 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&lt;br /&gt;
&lt;br /&gt;
===Neuronal Development===&lt;br /&gt;
&lt;br /&gt;
The gustatory system must not be solely thought of as being comprised of simply the tongue and palate. The types of neurons which carry taste information to the brain are also pivotal in constructing the expression of taste qualities.&lt;br /&gt;
&lt;br /&gt;
The two main gustatory neurons which develop are the geniculate ganglion and the petrosal ganglion. These are the visceral sensory ganglion of cranial nerves VII (Facial) and  IX (Hypoglossal) respectively which carry taste information from the tongue to the nucleus tractus solitarius. They arise at the posterior placodal region from the epibranchial placodes, a thickening of ectoderm. The first epibranchial placode gives rise to the geniculate ganglion and the second to the petrosal ganglion.&lt;br /&gt;
&lt;br /&gt;
The molecular basis for gustatory neuron formation is not completely understood though there are a number of transcription factors which are thought to play an important role in firstly, placode formation and secondly, neuron differentiation.&lt;br /&gt;
&lt;br /&gt;
*Six1/2, Six1/5 and Eya – transcription factors which cause differentiation of epibranchial placodes into the petrosal and geniculate ganglion.&lt;br /&gt;
*Bone morphogenic Protein 7 (BMP7) – a signal arising from the pharyngeal pouch which is believed to induce epibranchial placode formation. May not be solely responsible for this process, current research has been inconclusive as to how it may work with other proteins of the same family.&lt;br /&gt;
*NGN2 - Following the initial differentiation of the placodes, further differentiation occurs to form neuroblasts. NGN2 causes the delamination and migration of these neuroblasts, which subsequently migrate and fuse to form neurons.&lt;br /&gt;
*Phox2b – maintains the structural integrity of neurons. Knockout of these genes in mice causes marked atrophy of the petrosal and geniculate ganglia.&lt;br /&gt;
&lt;br /&gt;
The neurons involved in the gustatory system are overproduced and thus in the embryonic stage, undergo programmed cell death (apoptosis). The total amount of neurons in the geniculate ganglion, appears to be quite stable over the embryonic stages. This suggests, unlike the petrosal ganglion, the levels of neuroblast proliferation and apoptosis are fairly similar. The factors which regulate these processes remains unclear. It is posited that neurotrophins BDNF, NT4/5 and NT3 may regulate neuronal survival whilst also playing a part in axon growth from the sensory ganglion. More research is required to discern the exact individual functions of each of the neurotrophins.&lt;br /&gt;
&lt;br /&gt;
==Current Research==&lt;br /&gt;
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[[File:Mousetounge histologicalstain.jpg|right|thumb|200px|Image shows histological stains of a mice tongue showing dysplasia]]&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
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. &lt;br /&gt;
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.&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
'''Synergistic relationships of Six Genes '''&lt;br /&gt;
&lt;br /&gt;
In an animal study using mice by Suzuki Y, Ikeda K, Kawakami K.(2011)  Firstly nominating &amp;quot;[[#Glossary |'''Six Genes''']]&amp;quot; as a major component in [[#Glossary |'''gustatory ''']] development, stating that deficiencies in certain Six genes (specifically Six1 &amp;amp; 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 &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;21978088&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
[[File:Highpowered_microscope.jpg|Left|thumb|200px|Image of a high powered microscope]]&lt;br /&gt;
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'''Neural Crest responsibilities '''&lt;br /&gt;
&lt;br /&gt;
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.&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;22659543&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
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'''Augmentation of Endoderm'''&lt;br /&gt;
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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 &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;22581563&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
'''Changes in Taste Cells over time'''&lt;br /&gt;
&lt;br /&gt;
Research by &lt;br /&gt;
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.  &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;22643728&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
&lt;br /&gt;
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'''Shh key component of taste bud proginators'''&lt;br /&gt;
&lt;br /&gt;
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.&lt;br /&gt;
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 &amp;quot;Axiocam CCD camera and Axioplan fluorescence microscope with Axiovision software&amp;quot; a study by Harlow, Yang, Williams, Barlow (2011)&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;PMC2674259&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
'''WNT family exhibit various roles'''&lt;br /&gt;
&lt;br /&gt;
 [[File:Abnormal of tongue.jpg|thumb|200px|Image shows an example of tongue abnormalities, this is called &amp;quot;double tongue&amp;quot; each side has independent movement!]]&lt;br /&gt;
&lt;br /&gt;
The WNT gene family has a function of signaling work antagonistically through receptor tyrosine kinase (RTK) signaling. However, the deletion of Sprouty Homolog 2 (Spry2) led to the increase of chimaeric virus particles (CVPs) and a significant decrease in number of fungiform papillae. In contrast, the absence of Fibroblast growth factor 10 (Fgf10) in conjunction with 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. 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. &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;PMC2768563&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
[[File:Developing_tongue_histology_001.jpg|right|thumb|200px|HIstological stain of a developing rat tongue]]&lt;br /&gt;
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==Glossary==&lt;br /&gt;
&lt;br /&gt;
* '''Circumvallate papillae''' - &lt;br /&gt;
&lt;br /&gt;
* '''Ectoderm'''- outer germ layer of embryo&lt;br /&gt;
&lt;br /&gt;
* '''Endoderm''' - inner germ layer of embryo&lt;br /&gt;
&lt;br /&gt;
* '''Epithelium''' - basic animal tissue that is composed of tightly packed cells, usually covering the outer portion of organs&lt;br /&gt;
&lt;br /&gt;
* '''Exocystosis''' - movement of contents out of cell&lt;br /&gt;
&lt;br /&gt;
* '''Filiform papillae''' - &lt;br /&gt;
&lt;br /&gt;
* '''Foliate papillae''' - &lt;br /&gt;
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* '''Fungiform papillae''' - &lt;br /&gt;
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* '''Ganglia''' - the accumulation of a nerve cell body&lt;br /&gt;
&lt;br /&gt;
* '''Growth factor''' - a substance that stimulates the growth of cells&lt;br /&gt;
&lt;br /&gt;
* '''Gustatory''' - anything that relates to the taste sense&lt;br /&gt;
&lt;br /&gt;
* '''Hydrolysis''' - breakdown of a chemical when it reacts with water&lt;br /&gt;
&lt;br /&gt;
* '''Mesoderm''' - middle germ layer of embryo&lt;br /&gt;
&lt;br /&gt;
* '''Mesenchyme''' - multipotential cells&lt;br /&gt;
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* '''Neural crest''' - a part of the ectoderm found on both sides of the neural tube&lt;br /&gt;
&lt;br /&gt;
* '''Neuron''' - most simplistic unit of the nervous system&lt;br /&gt;
&lt;br /&gt;
* '''Neurotransmitter''' - chemicals which allow the passing of signals from neuron to neuron via connecting part (synapse) &lt;br /&gt;
&lt;br /&gt;
* '''Papillae''' - small rough surface projection&lt;br /&gt;
&lt;br /&gt;
* '''Six genes''' - a family of genes&lt;br /&gt;
&lt;br /&gt;
* '''Sonic hedgehog (Shh)''' - signalling protein involved in normal development&lt;br /&gt;
&lt;br /&gt;
* '''Sulcus terminalis''' - describes a physical transition point separating the anterior 2/3 of the tongue from the posterior 1/3&lt;br /&gt;
&lt;br /&gt;
* '''Tamoxifen''' - hormonal altering drug&lt;br /&gt;
&lt;br /&gt;
* '''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).&lt;br /&gt;
&lt;br /&gt;
* '''Type II taste cells''' - Receptor cells acting as primary detectors of sweet, bitter or umami taste.&lt;br /&gt;
&lt;br /&gt;
* '''Type III taste cells''' - Presynaptic cells that respond to sweet, salty, sour, bitter and umami compounds.&lt;br /&gt;
&lt;br /&gt;
== References ==&lt;br /&gt;
&amp;lt;references/&amp;gt;&lt;br /&gt;
&lt;br /&gt;
==External Links==&lt;br /&gt;
{{External Links}}&lt;br /&gt;
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[http://www.surgicalneurologyint.com/article.asp?issn=2152-7806;year=2012;volume=3;issue=1;spage=23;epage=23;aulast=Manjila]&lt;br /&gt;
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http://embryology.med.unsw.edu.au/embryology/index.php?title=2012_Group_Project_4&lt;br /&gt;
&lt;br /&gt;
http://www.webmd.com/oral-health/picture-of-the-tongue&lt;br /&gt;
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http://www.tutorvista.com/content/biology/biology-iv/nervous-coordination/tongue-structure.php#parts-of-tongue&lt;br /&gt;
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http://www.cf.ac.uk/biosi/staffinfo/jacob/teaching/sensory/taste.html&lt;br /&gt;
&lt;br /&gt;
--[[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.&lt;br /&gt;
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{{2012Projects}}&lt;/div&gt;</summary>
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	</entry>
	<entry>
		<id>https://embryology.med.unsw.edu.au/embryology/index.php?title=File:Abnormal_of_tongue.jpg&amp;diff=105224</id>
		<title>File:Abnormal of tongue.jpg</title>
		<link rel="alternate" type="text/html" href="https://embryology.med.unsw.edu.au/embryology/index.php?title=File:Abnormal_of_tongue.jpg&amp;diff=105224"/>
		<updated>2012-10-03T00:13:40Z</updated>

		<summary type="html">&lt;p&gt;Z3330795: &lt;/p&gt;
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&lt;div&gt;{Student image||2012} &lt;br /&gt;
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eleven-year-old African-American female patient with tongue and facial abnormalities.&lt;br /&gt;
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Figure 1: Demonstration of facial abnormalities (a) full body view showing scoliosis, frontal view demonstrating hypertelorism and cleft lip and image of mouth showing supernumerary teeth (b) demonstration of independent movement of double tongues: right tongue withdrawn while left protrudes&lt;br /&gt;
&lt;br /&gt;
© 2012 Manjila et al; This is an open-access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.&lt;br /&gt;
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DOI: 10.4103/2152-7806.92939&lt;/div&gt;</summary>
		<author><name>Z3330795</name></author>
	</entry>
	<entry>
		<id>https://embryology.med.unsw.edu.au/embryology/index.php?title=File:Highpowered_microscope.jpg&amp;diff=105221</id>
		<title>File:Highpowered microscope.jpg</title>
		<link rel="alternate" type="text/html" href="https://embryology.med.unsw.edu.au/embryology/index.php?title=File:Highpowered_microscope.jpg&amp;diff=105221"/>
		<updated>2012-10-03T00:12:46Z</updated>

		<summary type="html">&lt;p&gt;Z3330795: &lt;/p&gt;
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&lt;div&gt;{Student image||2012} &lt;br /&gt;
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High powered microscopes are a common tool for observing subtle differences between specimens and have been repeatably mentioned as an important tool within current research.&lt;br /&gt;
&lt;br /&gt;
Copyright information:&lt;br /&gt;
&lt;br /&gt;
to copy, distribute, display, and perform the work&lt;br /&gt;
to make derivative works&lt;br /&gt;
Under the following conditions:&lt;br /&gt;
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Attribution — You must give the original author credit.&lt;br /&gt;
Non-Commercial — You may not use this work for commercial purposes.&lt;br /&gt;
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--[[User:Z8600021|Mark Hill]] 00:38, 3 October 2012 (EST) This is not an example of a high powered microscope.&lt;/div&gt;</summary>
		<author><name>Z3330795</name></author>
	</entry>
	<entry>
		<id>https://embryology.med.unsw.edu.au/embryology/index.php?title=File:Mousetounge_histologicalstain.jpg&amp;diff=105218</id>
		<title>File:Mousetounge histologicalstain.jpg</title>
		<link rel="alternate" type="text/html" href="https://embryology.med.unsw.edu.au/embryology/index.php?title=File:Mousetounge_histologicalstain.jpg&amp;diff=105218"/>
		<updated>2012-10-03T00:12:05Z</updated>

		<summary type="html">&lt;p&gt;Z3330795: &lt;/p&gt;
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&lt;div&gt;{Student image||2012} &lt;br /&gt;
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Histological examination is a technique used to examine specimen features in a thorough, specific manner. Structures under histological veiw are easily identifiable and differences and abnormalities can easily be noted. This image was uploaded not to highlight any aspect of taste or tongue development, yet to give an example of contempory techniques used in research.&lt;br /&gt;
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Fig 2 Histological findings of tongue in mice treated with 4NQO during 16 weeks. a Normal tongue with no histopathological changes 24 weeks after starting the experiment. b Mild dysplasia after 24 weeks. c Moderate dysplasia after 28 weeks. d Severe dysplasia after 28 weeks. e Invasive squamous cell carcinoma after 32 weeks. Original magnification ×10&lt;br /&gt;
by Schoop, Remilio A. L.; Noteborn, Mathieu H. M.; Baatenburg de Jong, Robert J. Journal: Journal of Molecular Histology Vol. 40 Issue 3 DOI: 10.1007/s10735-009-9228-z Published: 2009-10-27 Institution(s): Leiden University Medical Center, Leiden University, Erasmus Medical Center&lt;br /&gt;
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This image is copyrighted by The Author(s). This image is published with open access and made available for noncommercial purposes. For more information on what you are allowed to do with this image, please see the Creative Commons pages.&lt;/div&gt;</summary>
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	</entry>
	<entry>
		<id>https://embryology.med.unsw.edu.au/embryology/index.php?title=File:Human_smelling.jpg&amp;diff=105214</id>
		<title>File:Human smelling.jpg</title>
		<link rel="alternate" type="text/html" href="https://embryology.med.unsw.edu.au/embryology/index.php?title=File:Human_smelling.jpg&amp;diff=105214"/>
		<updated>2012-10-03T00:11:28Z</updated>

		<summary type="html">&lt;p&gt;Z3330795: &lt;/p&gt;
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&lt;div&gt;{Student image||2012} &lt;br /&gt;
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A purely decorative image of a human lady using her sense of smell, reinforcing that there is interaction between senses.&lt;br /&gt;
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You are free:&lt;br /&gt;
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&amp;lt;div xmlns:cc=&amp;quot;http://creativecommons.org/ns#&amp;quot; xmlns:dct=&amp;quot;http://purl.org/dc/terms/&amp;quot; about=&amp;quot;http://images.cdn.fotopedia.com/flickr-3941398946-hd.jpg&amp;quot;&amp;gt;&amp;lt;span property=&amp;quot;dct:title&amp;quot;&amp;gt;Smelling Colors&amp;lt;/span&amp;gt; (&amp;lt;a rel=&amp;quot;cc:attributionURL&amp;quot; property=&amp;quot;cc:attributionName&amp;quot; href=&amp;quot;http://www.fotopedia.com/users/talibamba&amp;quot;&amp;gt;tali bamba&amp;lt;/a&amp;gt;) / &amp;lt;a rel=&amp;quot;license&amp;quot; href=&amp;quot;http://creativecommons.org/licenses/by-nd/2.0/&amp;quot;&amp;gt;CC BY-ND 2.0&amp;lt;/a&amp;gt;&amp;lt;/div&amp;gt;&lt;br /&gt;
  &lt;br /&gt;
No Derivative Works — You may not alter, transform, or build upon this work.&lt;/div&gt;</summary>
		<author><name>Z3330795</name></author>
	</entry>
	<entry>
		<id>https://embryology.med.unsw.edu.au/embryology/index.php?title=File:Taste_bud_1.jpg&amp;diff=105212</id>
		<title>File:Taste bud 1.jpg</title>
		<link rel="alternate" type="text/html" href="https://embryology.med.unsw.edu.au/embryology/index.php?title=File:Taste_bud_1.jpg&amp;diff=105212"/>
		<updated>2012-10-03T00:10:52Z</updated>

		<summary type="html">&lt;p&gt;Z3330795: &lt;/p&gt;
&lt;hr /&gt;
&lt;div&gt;{Student image||2012} &lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
This diagram shows a smilpistic pathway from the oral cavity to the brain.&lt;br /&gt;
&lt;br /&gt;
Simplistic , hand drawn diagram by z3330795, who exclusively gives persmission to anyone to use, for any purpose. the image was created by combing existing knowledge with my new understanding of tongue structure and function through extensive research from an endless number of contributiong sources. This image was in no way copied from any existing diagram.&lt;/div&gt;</summary>
		<author><name>Z3330795</name></author>
	</entry>
	<entry>
		<id>https://embryology.med.unsw.edu.au/embryology/index.php?title=File:Taste_bud_1.jpg&amp;diff=105210</id>
		<title>File:Taste bud 1.jpg</title>
		<link rel="alternate" type="text/html" href="https://embryology.med.unsw.edu.au/embryology/index.php?title=File:Taste_bud_1.jpg&amp;diff=105210"/>
		<updated>2012-10-03T00:10:28Z</updated>

		<summary type="html">&lt;p&gt;Z3330795: &lt;/p&gt;
&lt;hr /&gt;
&lt;div&gt;{Student image||2012} &lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
This diagram shows a smilpistic pathway from the oral cavity to the brain.&lt;br /&gt;
&lt;br /&gt;
Simplistic , hand drawn diagram by Jared Berndt, who exclusively gives persmission to anyone to use, for any purpose. the image was created by combing existing knowledge with my new understanding of tongue structure and function through extensive research from an endless number of contributiong sources. This image was in no way copied from any existing diagram.&lt;/div&gt;</summary>
		<author><name>Z3330795</name></author>
	</entry>
	<entry>
		<id>https://embryology.med.unsw.edu.au/embryology/index.php?title=File:Papillae.jpg&amp;diff=105206</id>
		<title>File:Papillae.jpg</title>
		<link rel="alternate" type="text/html" href="https://embryology.med.unsw.edu.au/embryology/index.php?title=File:Papillae.jpg&amp;diff=105206"/>
		<updated>2012-10-03T00:09:41Z</updated>

		<summary type="html">&lt;p&gt;Z3330795: &lt;/p&gt;
&lt;hr /&gt;
&lt;div&gt;{Student image||2012}&lt;br /&gt;
&lt;br /&gt;
This image shows a close up of human tongue, showing papillae(seen as little bumps).&lt;br /&gt;
&lt;br /&gt;
This picture is for the purpose to appreciate a macroscopic perspective of the papillae. &lt;br /&gt;
&lt;br /&gt;
http://shiftingpixel.com/2007/01/25/tongue/&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 2.5 License. Attribution requirements for my work&lt;br /&gt;
&lt;br /&gt;
to Share — to copy, distribute and transmit the work&lt;br /&gt;
to Remix — to adapt the work&lt;br /&gt;
Under the following conditions:&lt;br /&gt;
&lt;br /&gt;
Attribution — You must attribute the work in the manner specified by the author or licensor (but not in any way that suggests that they endorse you or your use of the work).&lt;br /&gt;
Noncommercial — You may not use this work for commercial purposes.&lt;br /&gt;
Share Alike — If you alter, transform, or build upon this work, you may distribute the resulting work only under the same or similar license to this one.&lt;/div&gt;</summary>
		<author><name>Z3330795</name></author>
	</entry>
	<entry>
		<id>https://embryology.med.unsw.edu.au/embryology/index.php?title=File:Filiformpapillae.jpg&amp;diff=105203</id>
		<title>File:Filiformpapillae.jpg</title>
		<link rel="alternate" type="text/html" href="https://embryology.med.unsw.edu.au/embryology/index.php?title=File:Filiformpapillae.jpg&amp;diff=105203"/>
		<updated>2012-10-03T00:08:12Z</updated>

		<summary type="html">&lt;p&gt;Z3330795: &lt;/p&gt;
&lt;hr /&gt;
&lt;div&gt;{Student image||2012} &lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
foliate papillae, very simplistic to give idea of morphology and also the location of the taste buds. &lt;br /&gt;
&lt;br /&gt;
This is a hand drawn diagram by UNSW student z3330795, who gives permission to anyone to reuse this image.&lt;/div&gt;</summary>
		<author><name>Z3330795</name></author>
	</entry>
	<entry>
		<id>https://embryology.med.unsw.edu.au/embryology/index.php?title=File:Circumvallatepapillae.jpg&amp;diff=105201</id>
		<title>File:Circumvallatepapillae.jpg</title>
		<link rel="alternate" type="text/html" href="https://embryology.med.unsw.edu.au/embryology/index.php?title=File:Circumvallatepapillae.jpg&amp;diff=105201"/>
		<updated>2012-10-03T00:07:25Z</updated>

		<summary type="html">&lt;p&gt;Z3330795: &lt;/p&gt;
&lt;hr /&gt;
&lt;div&gt;{Student image||2012} &lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
circumvallate papillae, very simplistic to give idea of morphology and also the location of the taste buds. &lt;br /&gt;
&lt;br /&gt;
This is a hand drawn diagram by UNSW student z3330795, who gives permission to anyone to reuse this image.&lt;/div&gt;</summary>
		<author><name>Z3330795</name></author>
	</entry>
	<entry>
		<id>https://embryology.med.unsw.edu.au/embryology/index.php?title=File:Fungiformpapillae.jpg&amp;diff=105198</id>
		<title>File:Fungiformpapillae.jpg</title>
		<link rel="alternate" type="text/html" href="https://embryology.med.unsw.edu.au/embryology/index.php?title=File:Fungiformpapillae.jpg&amp;diff=105198"/>
		<updated>2012-10-03T00:06:40Z</updated>

		<summary type="html">&lt;p&gt;Z3330795: &lt;/p&gt;
&lt;hr /&gt;
&lt;div&gt;&lt;br /&gt;
{Student image||2012} &lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
fungiform papillae diagram, very simplistic to give idea of morphology and also the location of the taste buds.&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
This is a hand drawn diagram by UNSW student z3330795, who gives permission to anyone to reuse this image.&lt;/div&gt;</summary>
		<author><name>Z3330795</name></author>
	</entry>
	<entry>
		<id>https://embryology.med.unsw.edu.au/embryology/index.php?title=File:Taste_pathway.jpg&amp;diff=105191</id>
		<title>File:Taste pathway.jpg</title>
		<link rel="alternate" type="text/html" href="https://embryology.med.unsw.edu.au/embryology/index.php?title=File:Taste_pathway.jpg&amp;diff=105191"/>
		<updated>2012-10-03T00:05:53Z</updated>

		<summary type="html">&lt;p&gt;Z3330795: &lt;/p&gt;
&lt;hr /&gt;
&lt;div&gt;{Student image||2012}&lt;br /&gt;
&lt;br /&gt;
This is an extremely simplistic break down of the pathway of taste, involving the functional steps, more so an overview of the 4 basic steps involved.&lt;br /&gt;
&lt;br /&gt;
1. The chemicals (food) are absorbed though the taste pores in the oral cavity.&lt;br /&gt;
&lt;br /&gt;
2. the taste cells within the taste buds receive these chemical stimulus and convert into a nerve impulse.&lt;br /&gt;
&lt;br /&gt;
3. this nerve impulse travels from the oral cavity cranial nerves towards the brain.&lt;br /&gt;
&lt;br /&gt;
4 the brain receives impulse for interpretation of taste.&lt;br /&gt;
&lt;br /&gt;
This illustration by z3330795 UNSW student who gives permission to anyone to reuse.&lt;/div&gt;</summary>
		<author><name>Z3330795</name></author>
	</entry>
	<entry>
		<id>https://embryology.med.unsw.edu.au/embryology/index.php?title=User:Z3330795&amp;diff=105185</id>
		<title>User:Z3330795</title>
		<link rel="alternate" type="text/html" href="https://embryology.med.unsw.edu.au/embryology/index.php?title=User:Z3330795&amp;diff=105185"/>
		<updated>2012-10-03T00:04:34Z</updated>

		<summary type="html">&lt;p&gt;Z3330795: /* Lab Attendance */&lt;/p&gt;
&lt;hr /&gt;
&lt;div&gt;==Lab Attendance ==&lt;br /&gt;
Lab 1&lt;br /&gt;
&lt;br /&gt;
Lab 2&lt;br /&gt;
&lt;br /&gt;
Lab 3&lt;br /&gt;
&lt;br /&gt;
Lab 4&lt;br /&gt;
&lt;br /&gt;
Lab 5&lt;br /&gt;
&lt;br /&gt;
Lab 6&lt;br /&gt;
&lt;br /&gt;
Lab 7--[[User:Z3330795|Z3330795]] 10:56, 12 September 2012 (EST)&lt;br /&gt;
--[[User:Z8600021|Mark Hill]] 17:26, 11 September 2012 (EST) You need to use the signature tool to log lab attendance.&lt;br /&gt;
&lt;br /&gt;
Lab 8--'''Z3330795'''  20 September 2012 (EST) this one i put in late, but i did attend just forgot to put it in that day.&lt;br /&gt;
&lt;br /&gt;
lab 9 --[[User:Z3330795|Z3330795]] 09:56, 26 September 2012 (EST)&lt;br /&gt;
&lt;br /&gt;
lab 10 --[[User:Z3330795|Z3330795]] 10:04, 3 October 2012 (EST)&lt;br /&gt;
&lt;br /&gt;
=='''Fertilization'''==&lt;br /&gt;
&lt;br /&gt;
The process in Simple Steps:&lt;br /&gt;
&lt;br /&gt;
Step 1 - Many sperm travel from the Male testes to the Female Egg located in the Fallopian tube.]&lt;br /&gt;
&lt;br /&gt;
Step 2 - Once the sperm reach the egg, many try and &amp;quot;enter&amp;quot; by releasing enzymes breaking down the outer layer of the egg.&lt;br /&gt;
&lt;br /&gt;
Step 3 - Only one sperm can penetrate and once this happens, a chemical reaction occurs &amp;quot;pushing&amp;quot; away any other sperm attempting to penetrate.&lt;br /&gt;
&lt;br /&gt;
'''This now fertilized egg is referred to as a zygote'''&lt;br /&gt;
&lt;br /&gt;
Step 4 - pronuclei of the egg merges with the pronuclei of the sperm resulting in cell division.&lt;br /&gt;
&lt;br /&gt;
Step 5 - days later this zygote is moved along the fallopian tube and is now called a blastocyst.&lt;br /&gt;
&lt;br /&gt;
Step 6 - the blastocyst is embedded in the uterine wall activating the start of pregnancy.&lt;br /&gt;
&lt;br /&gt;
'''References:'''&lt;br /&gt;
http://science.howstuffworks.com/&lt;br /&gt;
&lt;br /&gt;
==&amp;quot;Lab 1 Assessment&amp;quot;==&lt;br /&gt;
&lt;br /&gt;
1.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.&lt;br /&gt;
&lt;br /&gt;
The British scientist Robert Edwards has been researching and devloping IVF since the 1950's, the first successful IVF treatment was in 1978 when the worlds first baby was born from this fertilization technique. Following this success methods have been continually rejuvenated with state of the art techniques and research.&lt;br /&gt;
&lt;br /&gt;
Robert Edwards was the winner of the 2010 Nobel Prize in medicine for his efforts in the development of in-vitro fertilisation (IVF).&lt;br /&gt;
&lt;br /&gt;
[http://www.nobelprize.org/nobel_prizes/medicine/laureates/2010/press.html/]&lt;br /&gt;
&lt;br /&gt;
2.Identify and add a PubMed reference link to a recent paper on fertilisation and describe its key findings (1-2 paragraphs).&lt;br /&gt;
&lt;br /&gt;
This paper is explores the potential of screening sperm before fertilization, to predict fertilization rate depending on the &amp;quot;quality&amp;quot; of the sperm. This technology would be of extreme importance and make the IVF process more efficient.&lt;br /&gt;
&lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/pubmed/22762979]&lt;br /&gt;
&lt;br /&gt;
--[[User:Z8600021|Mark Hill]] 17:30, 11 September 2012 (EST) Question 1 has been answered correctly. Question 2 has been answered, but not in sufficient detail (2 lines) to describe the findings in full and the link is not correctly displayed. You should use just the number as here PMID 22762979 or remove the brackets around your link. You have lost marks for the lack of a full description, not the reference formatting.'''6/10'''&lt;br /&gt;
&lt;br /&gt;
==&amp;quot;Lab 2 Assessment&amp;quot;==&lt;br /&gt;
&lt;br /&gt;
Identify a protein associated with the implantation process, including a brief description of the protein's role.&lt;br /&gt;
&lt;br /&gt;
Chemokines are a protein directly associated with the implantation process. Current research has shown that Chemokines play an executive role within the endometrium, specifically throughout implantation. It has been proven that these proteins direct the invading trophoblasts within the maternal vasculature and decidua. This invading process is critical in early development and chemical signally from these proteins allows precise depth of insertion in preparation of the crucial weeks ahead.&lt;br /&gt;
&lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/pubmed/17495644]&lt;br /&gt;
&lt;br /&gt;
[[File:Sexual_development_of_MYT1_mutants.jpeg]]&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
--[[User:Z8600021|Mark Hill]] 17:38, 11 September 2012 (EST) Question 1 image has been uploaded correctly. In the summary box you have included the citation and copyright information, but not a template indicating that this is a student image. &amp;lt;nowiki&amp;gt;{{Template:Student Image}}&amp;lt;/nowiki&amp;gt;. There is also no legend describing what A, B and C are showing, this could have been derived from teh original figure template. Question 2 protein associated with the implantation, chemokines are a relevant &amp;quot;class of proteins&amp;quot;, not a specific protein and the  article you have selected is a review, not a big issue but you need to also clearly identify that it is a review and not a research article. '''7/10'''&lt;br /&gt;
&lt;br /&gt;
==&amp;quot;Lab 3 Assessment&amp;quot;==&lt;br /&gt;
&lt;br /&gt;
1.Identify the difference between &amp;quot;gestational age&amp;quot; and &amp;quot;post-fertilisation age&amp;quot; and explain why clinically &amp;quot;gestational age&amp;quot; is used in describing human development.&lt;br /&gt;
&lt;br /&gt;
a)&lt;br /&gt;
The overlap and confusion of these terms is very common due to physicians frequently using either one to describe the early stage of pregnancy. Technically there is a distinct difference between the two.&amp;quot;Post-fertilization age&amp;quot; is the time elapsed after egg fertilization, where as &amp;quot;Gestational age&amp;quot;(approximately 2 weeks later) is the time since the mothers last menstrual cycle prior to pregnancy.&lt;br /&gt;
&lt;br /&gt;
[http://www.livestrong.com/article/92683-embryo-fetus-development-stages/]&lt;br /&gt;
&lt;br /&gt;
b)&lt;br /&gt;
In a clinical setting is important to use consistant terminology, “Gestational age” is the preffered term used to describe this early stage of pregnacy for the obvious reason that the average women will know when their last menstral cycle began although she will typically have less certainty surrounding when ovulation occured. The delvery date is a simple caculation given acuracy of the Gestational age.&lt;br /&gt;
&lt;br /&gt;
[http://pediatrics.aappublications.org/content/114/5/1362.full]&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
2. Identify using histological descriptions at least 3 different types of tissues formed from somites&lt;br /&gt;
&lt;br /&gt;
Somites form Cartilage (ribs and vertabrae), skeltal muscle (ribs, limbs and back) and also the dermis of the dorsal skin. The cells of the Somites remain multipotential for a long time during development, therefor somite cells can become any somite structure until maturation where they become commited to form structures repective of their regions.&lt;br /&gt;
&lt;br /&gt;
The Somites have three different regions with different tissue outcomes. The somite cells located closest to neural tube turn into mesenchymal cell (through complex cellular processes) this is portion that become chrondocytes of the cartilage formed.&lt;br /&gt;
The cells in the two lateral portions of the somite structure divide to produce the myoblasts which are muscle precursers cells. This is now a 2 layered segment, the top layer is called dermamyotome, and the lower myotome. Depending on the location of the myoblasts determines their fate (epaxial or hypaxial muscles). the final area is located in the centre of the dermamyotome is called the dermatome, producing connective tissue of mesenchymal origin which will mature and eventually form the tissue of ventrally located skin. &lt;br /&gt;
&lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/books/NBK10085/]&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
--[[User:Z8600021|Mark Hill]] 17:43, 11 September 2012 (EST) Question 1 you have identified the difference between &amp;quot;gestational age&amp;quot; and &amp;quot;post-fertilisation age. Your terminology though is confusing &amp;quot;where as Gestational age (approximately 2 weeks later)&amp;quot;, you should have then said &amp;quot;than Post-fertilization age&amp;quot;. Question 2 you have identified 3 different tissues and the textbook link is appropriate. There are several typos throughout your answer that you should have corrected, I have not removed marks for this, but it suggests to the reader that you have not checked your work. '''9/10'''&lt;br /&gt;
&lt;br /&gt;
==&amp;quot;Lab 4 Assessment&amp;quot;==&lt;br /&gt;
&lt;br /&gt;
1. Identify the 2 invasive prenatal diagnostic techniques related to the placenta and 2 abnormalities that can be identified with these techniques.&lt;br /&gt;
&lt;br /&gt;
a)Fluorescence in-situ hybridization is an invasive technique which analyses fetal blood cells present in maternal blood samples. These cells gain access through placental villi. This test can screen for conditions such as the trisomies and monosomy X.&lt;br /&gt;
&lt;br /&gt;
b)Maternal serum alpha-fetoprotein is an invasive technique that measures the level of alpha-fetoprotein (AFP) in maternal blood, knowing that adults exclusively have albumin in their blood we exploit this technique. Typically the fetus will only release small amounts of AFP going across the placenta into the mother blood, although large amount of AFP in the maternal blood sample can indicate a neural tube defect or spina bifida.&lt;br /&gt;
&lt;br /&gt;
[http://library.med.utah.edu/WebPath/TUTORIAL/PRENATAL/PRENATAL.html]&lt;br /&gt;
&lt;br /&gt;
2. Identify a paper that uses cord stem cells therapeutically and write a brief (2-3 paragraph) description of the paper's findings.&lt;br /&gt;
&lt;br /&gt;
My selected Paper &amp;quot;Stem cell therapies for spinal cord injury.&amp;quot; describes the benefits of use along with its many implications. Spinal Cord injuries(SCI) either complete or incomplete pose a catastrophic stress on the individual both physical and emotional. The possibility of treatment for SCI is an area with enormous potential giving hope to those who are unfortunate enough to come across this terrible injury. &lt;br /&gt;
&lt;br /&gt;
There are currently many implications surrounding stem cell therapy such as tumor formation. The controversy surrounding research in this area is supported by data concluding that there is no way around biological implications caused by treatment.&lt;br /&gt;
&lt;br /&gt;
The basic principle behind stem cell therapy is using multipotential cells to create new and functional tissue, this therapy involves a combination of many complex treatments each addressing different components. Cutting edge research has involved using animal models although these types treatments are still in the development of making safe &amp;amp; ethical therapies that can be used in a clinical setting. As we look to the future of Stem cell therapies there are many more methods being explored for example using induced pluripotent stem cells (force expression of certain genes).&lt;br /&gt;
&lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/pubmed/20551948]&lt;br /&gt;
&lt;br /&gt;
--[[User:Z8600021|Mark Hill]] 17:50, 11 September 2012 (EST) Question 1 Fluorescence in-situ hybridization and Maternal serum alpha-fetoprotein are not an invasive technique, the analysis of fetal cells in maternal blood is exactly the opposite, it is replacing invasive techniques. I think you have misinterpreted what I meant by invasive technique, such as chorionic villi sampling or amniocentesis. Question 2 you have identified a stem cell paper, a review rather than research article. Though I did not specify this in the question I am usually asking for research articles. Your description is sufficient. '''5/10'''&lt;br /&gt;
&lt;br /&gt;
==&amp;quot;Lab 5 Assessment&amp;quot;==&lt;br /&gt;
&lt;br /&gt;
1.&lt;br /&gt;
&lt;br /&gt;
(A) Muscles satellite cells are sometimes reffered to as Myosatellite cells, these cells contain a single lobed nucleus and have tendency to differentiate into a specific cell type, similar to stem cells (mononuclear progenitor cell), they are located on the outer surface of muscle fibres and remain dormant until activation occurs&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
(B)  &lt;br /&gt;
&lt;br /&gt;
&amp;quot;Regeneration of adult skeletal muscle is an asynchronous process requiring the activation, proliferation and fusion of satellite cells, to form new muscle fibres.&amp;quot; Cooper, S. Tajbakhsh, V. Mouly, G. Cossu, M. Buckingham and G. S. Butler-Browne (1999). Satellite cells are responsible for the growth and regeneration of muscle, although there are chemical mediators that activate these cells proven by an experiment by Anderson J, Pilipowicz O.(2002),  concluding Nitric Oxide (in vivo) is required to activate satellite cells and also hepatocyte growth factor (HGF) and Nitric Oxide (NO) also participate in mobilizing satellite cells. Ryuichi Tatsumi, Xiaosong Liu, Antonio Pulido, Mark Morales, Tomowa Sakata, Sharon Dial, Akihito Hattori, Yoshihide Ikeuchi, and Ronald E. Allen (2005) Concluded that when a muscle is stretched beyond resting range Satellite cells are activated. This article also states that when muscle hypertrophy occurs satellites cells are recruited, although what is unsure is the chemical signalling involved. In conclusion 2 actions that activate Satellite cells are stretching and hypertrophy. The passive stretching of skeletal muscles triggers the release  and interaction of chemical mediators HGF and NO, which in turn are responsible for activation of satellite cells. If skeletal muscle receives any form of damage through exercise or injury, satellite cells are activated and are attracted to the site of disturbance. Hernandez and Kravitz (1999)&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
2.&lt;br /&gt;
Burnham, Martin, Stein, Bell, MacLean, Steadward (1997) concluded that after a Spinal Cord Injury (SCI) an individuals muscles fibres will undergo alteration from type 1 slow and type 2 fast, to become type 2 fast glycolytic fibres also known as &amp;quot;fast twitch B&amp;quot; which feature less myoglobin and mitochondria. Roberto Scelsi (2001) reported a change in the muscles fibers and micro vascular change after conducting various invasive tests on a paraplegic individual. These changes have a clear relationship with the time elapsed. Scelsi reported adaption of the muscle fibers after 1 month, although for the changes to be prominent 7-8 months has elapsed. To retard this unnatural transition, therapy must be used within week of the SCI such as, Functional Electrical Stimulation, (FES) is a recognised treatment allowing some kind of stimulation to these unused muscle fibres and could improve function. Christopher and Dana Reeves Foundation (2012)&lt;br /&gt;
&lt;br /&gt;
==&amp;quot; Lab 6 Assessment&amp;quot;==&lt;br /&gt;
&lt;br /&gt;
Vision development review:&lt;br /&gt;
&lt;br /&gt;
The key points are Cleary described and Topics have been divided in an efficient way allowing maximum information and an extensive insight into each of these segments, although at this stage there is not enough detail for each.&lt;br /&gt;
There is a substantial amount of visual stimulus although the quality of these stimuli is questionable. For example the images under the heading “research history” lack proper sized labelling, an individual must click on the each image in order to appreciate it. The initial image needs to decrease in size dramatically as is overwhelming and takes away from the product&lt;br /&gt;
Proper citation is evident however; there is a minority of untidy citations along with no copy write information for a certain image. Significant, deep research is not evident, I believe more research is required; there is a respectable attempt to relate content to learning aims of embryology. Information in the history section is insufficient and perhaps needs to be expanded upon.&lt;br /&gt;
To improve more information on each topic is required, review of visual displays (mainly balancing images between sections some have plenty where as other lack) and copy write information is essential&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
Somatosensory review:&lt;br /&gt;
&lt;br /&gt;
The key points are clearly presented at the top of the page efficiently formatted allowing viewer a perfect insight to the entire pages content. There is a severe lack of visual stimuli; this makes the page present as boring and text heavy. &lt;br /&gt;
Image citation is commendable although throughout the text there is unacceptable links to external sites that are not explained with a messy reference section. The information presented is quite detailed and promotes a significant amount of research and understanding, it is put forward in an excellent matter, sections that could easily be expanded are glossary, and perhaps a section specifically on development. Attempt to relate to the learning aims of embryology are apparent. There is a large amount of information presented in a fantastic way although the lack of visual stimuli takes away from the final product, perhaps a more summarised presentation matter would be appropriate to break up large amount of text; this along with the tidy up of referencing needs to be addressed.&lt;br /&gt;
&lt;br /&gt;
Olfaction review:&lt;br /&gt;
&lt;br /&gt;
Upon first glance of the page you immediately get the impression excellent presentation and a surplus of information. Most topics are well described although the history of discoveries layout is questionable and a table would present at a higher quality.&lt;br /&gt;
It is clear that the group has a high level of understanding through large amount of research; this is then transformed into chunks of knowledge in which are easily digestible for the reader. The page lacks visual encourage, I believe more detail into this would only benefit the page. The glossary could quite easily be expanded many terms throughout the text are absent from this list.&lt;br /&gt;
This page is almost parallel with embryological teaching aims. Citation &amp;amp; referencing is excellent. The way to improve this page would be reducing the weight of the text using innovative ideas to the present information in a more exciting way along side inclusion of more visual stimulus.&lt;br /&gt;
&lt;br /&gt;
Abnormal Vision review:&lt;br /&gt;
&lt;br /&gt;
An excellent straight forward introduction, presentation and layout of the page is questionable perhaps the use of different summary methods would improve this for example dot points along with image choice and size.  A common topic among all groups is to expand the glossary which is easily done and will only improve the finished merchandise. Language used throughout could be less primitive, very simplistic in certain sections. The referencing is satisfactory although external links section has been left out.&lt;br /&gt;
All the information is present although the organisation skills need to be assessed to allow optimum presentation of ideas. The text contains in-depth embryological teachings aims. The page looks promising and editing is the easiest part once corrected I expect a sound result.&lt;br /&gt;
&lt;br /&gt;
Hearing review:&lt;br /&gt;
&lt;br /&gt;
This group successfully energies the audience with a funny picture, along with a great introduction and an interactive writing style from the first paragraph. This page needs to address the reoccurring text to image ratio, allowing the reader more explanation complementing the hard work of explaining concepts. The highlight of this text was the abnormal hearing section which I found to be very interesting along with sound presentation of ideas. The demise of this page is the lack of information in current research and being starved of visual stimuli.&lt;br /&gt;
Overall a good attempt to line up embryological teaching concepts, when these easily addressable points are responded to a commendable finish will be apparent.&lt;br /&gt;
&lt;br /&gt;
==&amp;quot; lab 7 assessment &amp;quot;==&lt;br /&gt;
&lt;br /&gt;
1.&lt;br /&gt;
mutations in GATA6 have been linked to neonates with diabatetes, suggesting that mutations in GATA6 disrupts the development of this endocrine organ. Manipulation of genes using animal models helped provide this evidence.&lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/pubmed/23006330]&lt;br /&gt;
&lt;br /&gt;
2. &lt;br /&gt;
The embryonic tooth is derived from the mesodermal and ectodermal layers. The development of teeth originates when the dental lamina divides rapildly to form the future rows that teeth are located within. Their are enanmal organs present which produce circular outgrowths providing an apropriate site for tooth formation, This organ is also responsible for the complete morphology of the later devloped tooth.&lt;/div&gt;</summary>
		<author><name>Z3330795</name></author>
	</entry>
	<entry>
		<id>https://embryology.med.unsw.edu.au/embryology/index.php?title=User:Z3330795&amp;diff=105179</id>
		<title>User:Z3330795</title>
		<link rel="alternate" type="text/html" href="https://embryology.med.unsw.edu.au/embryology/index.php?title=User:Z3330795&amp;diff=105179"/>
		<updated>2012-10-03T00:02:54Z</updated>

		<summary type="html">&lt;p&gt;Z3330795: /* &amp;quot; lab 7 assessment &amp;quot; */&lt;/p&gt;
&lt;hr /&gt;
&lt;div&gt;==Lab Attendance ==&lt;br /&gt;
Lab 1&lt;br /&gt;
&lt;br /&gt;
Lab 2&lt;br /&gt;
&lt;br /&gt;
Lab 3&lt;br /&gt;
&lt;br /&gt;
Lab 4&lt;br /&gt;
&lt;br /&gt;
Lab 5&lt;br /&gt;
&lt;br /&gt;
Lab 6&lt;br /&gt;
&lt;br /&gt;
Lab 7--[[User:Z3330795|Z3330795]] 10:56, 12 September 2012 (EST)&lt;br /&gt;
--[[User:Z8600021|Mark Hill]] 17:26, 11 September 2012 (EST) You need to use the signature tool to log lab attendance.&lt;br /&gt;
&lt;br /&gt;
Lab 8--'''Z3330795'''  20 September 2012 (EST) this one i put in late, but i did attend just forgot to put it in that day.&lt;br /&gt;
&lt;br /&gt;
lab 9 --[[User:Z3330795|Z3330795]] 09:56, 26 September 2012 (EST)&lt;br /&gt;
&lt;br /&gt;
=='''Fertilization'''==&lt;br /&gt;
&lt;br /&gt;
The process in Simple Steps:&lt;br /&gt;
&lt;br /&gt;
Step 1 - Many sperm travel from the Male testes to the Female Egg located in the Fallopian tube.]&lt;br /&gt;
&lt;br /&gt;
Step 2 - Once the sperm reach the egg, many try and &amp;quot;enter&amp;quot; by releasing enzymes breaking down the outer layer of the egg.&lt;br /&gt;
&lt;br /&gt;
Step 3 - Only one sperm can penetrate and once this happens, a chemical reaction occurs &amp;quot;pushing&amp;quot; away any other sperm attempting to penetrate.&lt;br /&gt;
&lt;br /&gt;
'''This now fertilized egg is referred to as a zygote'''&lt;br /&gt;
&lt;br /&gt;
Step 4 - pronuclei of the egg merges with the pronuclei of the sperm resulting in cell division.&lt;br /&gt;
&lt;br /&gt;
Step 5 - days later this zygote is moved along the fallopian tube and is now called a blastocyst.&lt;br /&gt;
&lt;br /&gt;
Step 6 - the blastocyst is embedded in the uterine wall activating the start of pregnancy.&lt;br /&gt;
&lt;br /&gt;
'''References:'''&lt;br /&gt;
http://science.howstuffworks.com/&lt;br /&gt;
&lt;br /&gt;
==&amp;quot;Lab 1 Assessment&amp;quot;==&lt;br /&gt;
&lt;br /&gt;
1.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.&lt;br /&gt;
&lt;br /&gt;
The British scientist Robert Edwards has been researching and devloping IVF since the 1950's, the first successful IVF treatment was in 1978 when the worlds first baby was born from this fertilization technique. Following this success methods have been continually rejuvenated with state of the art techniques and research.&lt;br /&gt;
&lt;br /&gt;
Robert Edwards was the winner of the 2010 Nobel Prize in medicine for his efforts in the development of in-vitro fertilisation (IVF).&lt;br /&gt;
&lt;br /&gt;
[http://www.nobelprize.org/nobel_prizes/medicine/laureates/2010/press.html/]&lt;br /&gt;
&lt;br /&gt;
2.Identify and add a PubMed reference link to a recent paper on fertilisation and describe its key findings (1-2 paragraphs).&lt;br /&gt;
&lt;br /&gt;
This paper is explores the potential of screening sperm before fertilization, to predict fertilization rate depending on the &amp;quot;quality&amp;quot; of the sperm. This technology would be of extreme importance and make the IVF process more efficient.&lt;br /&gt;
&lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/pubmed/22762979]&lt;br /&gt;
&lt;br /&gt;
--[[User:Z8600021|Mark Hill]] 17:30, 11 September 2012 (EST) Question 1 has been answered correctly. Question 2 has been answered, but not in sufficient detail (2 lines) to describe the findings in full and the link is not correctly displayed. You should use just the number as here PMID 22762979 or remove the brackets around your link. You have lost marks for the lack of a full description, not the reference formatting.'''6/10'''&lt;br /&gt;
&lt;br /&gt;
==&amp;quot;Lab 2 Assessment&amp;quot;==&lt;br /&gt;
&lt;br /&gt;
Identify a protein associated with the implantation process, including a brief description of the protein's role.&lt;br /&gt;
&lt;br /&gt;
Chemokines are a protein directly associated with the implantation process. Current research has shown that Chemokines play an executive role within the endometrium, specifically throughout implantation. It has been proven that these proteins direct the invading trophoblasts within the maternal vasculature and decidua. This invading process is critical in early development and chemical signally from these proteins allows precise depth of insertion in preparation of the crucial weeks ahead.&lt;br /&gt;
&lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/pubmed/17495644]&lt;br /&gt;
&lt;br /&gt;
[[File:Sexual_development_of_MYT1_mutants.jpeg]]&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
--[[User:Z8600021|Mark Hill]] 17:38, 11 September 2012 (EST) Question 1 image has been uploaded correctly. In the summary box you have included the citation and copyright information, but not a template indicating that this is a student image. &amp;lt;nowiki&amp;gt;{{Template:Student Image}}&amp;lt;/nowiki&amp;gt;. There is also no legend describing what A, B and C are showing, this could have been derived from teh original figure template. Question 2 protein associated with the implantation, chemokines are a relevant &amp;quot;class of proteins&amp;quot;, not a specific protein and the  article you have selected is a review, not a big issue but you need to also clearly identify that it is a review and not a research article. '''7/10'''&lt;br /&gt;
&lt;br /&gt;
==&amp;quot;Lab 3 Assessment&amp;quot;==&lt;br /&gt;
&lt;br /&gt;
1.Identify the difference between &amp;quot;gestational age&amp;quot; and &amp;quot;post-fertilisation age&amp;quot; and explain why clinically &amp;quot;gestational age&amp;quot; is used in describing human development.&lt;br /&gt;
&lt;br /&gt;
a)&lt;br /&gt;
The overlap and confusion of these terms is very common due to physicians frequently using either one to describe the early stage of pregnancy. Technically there is a distinct difference between the two.&amp;quot;Post-fertilization age&amp;quot; is the time elapsed after egg fertilization, where as &amp;quot;Gestational age&amp;quot;(approximately 2 weeks later) is the time since the mothers last menstrual cycle prior to pregnancy.&lt;br /&gt;
&lt;br /&gt;
[http://www.livestrong.com/article/92683-embryo-fetus-development-stages/]&lt;br /&gt;
&lt;br /&gt;
b)&lt;br /&gt;
In a clinical setting is important to use consistant terminology, “Gestational age” is the preffered term used to describe this early stage of pregnacy for the obvious reason that the average women will know when their last menstral cycle began although she will typically have less certainty surrounding when ovulation occured. The delvery date is a simple caculation given acuracy of the Gestational age.&lt;br /&gt;
&lt;br /&gt;
[http://pediatrics.aappublications.org/content/114/5/1362.full]&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
2. Identify using histological descriptions at least 3 different types of tissues formed from somites&lt;br /&gt;
&lt;br /&gt;
Somites form Cartilage (ribs and vertabrae), skeltal muscle (ribs, limbs and back) and also the dermis of the dorsal skin. The cells of the Somites remain multipotential for a long time during development, therefor somite cells can become any somite structure until maturation where they become commited to form structures repective of their regions.&lt;br /&gt;
&lt;br /&gt;
The Somites have three different regions with different tissue outcomes. The somite cells located closest to neural tube turn into mesenchymal cell (through complex cellular processes) this is portion that become chrondocytes of the cartilage formed.&lt;br /&gt;
The cells in the two lateral portions of the somite structure divide to produce the myoblasts which are muscle precursers cells. This is now a 2 layered segment, the top layer is called dermamyotome, and the lower myotome. Depending on the location of the myoblasts determines their fate (epaxial or hypaxial muscles). the final area is located in the centre of the dermamyotome is called the dermatome, producing connective tissue of mesenchymal origin which will mature and eventually form the tissue of ventrally located skin. &lt;br /&gt;
&lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/books/NBK10085/]&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
--[[User:Z8600021|Mark Hill]] 17:43, 11 September 2012 (EST) Question 1 you have identified the difference between &amp;quot;gestational age&amp;quot; and &amp;quot;post-fertilisation age. Your terminology though is confusing &amp;quot;where as Gestational age (approximately 2 weeks later)&amp;quot;, you should have then said &amp;quot;than Post-fertilization age&amp;quot;. Question 2 you have identified 3 different tissues and the textbook link is appropriate. There are several typos throughout your answer that you should have corrected, I have not removed marks for this, but it suggests to the reader that you have not checked your work. '''9/10'''&lt;br /&gt;
&lt;br /&gt;
==&amp;quot;Lab 4 Assessment&amp;quot;==&lt;br /&gt;
&lt;br /&gt;
1. Identify the 2 invasive prenatal diagnostic techniques related to the placenta and 2 abnormalities that can be identified with these techniques.&lt;br /&gt;
&lt;br /&gt;
a)Fluorescence in-situ hybridization is an invasive technique which analyses fetal blood cells present in maternal blood samples. These cells gain access through placental villi. This test can screen for conditions such as the trisomies and monosomy X.&lt;br /&gt;
&lt;br /&gt;
b)Maternal serum alpha-fetoprotein is an invasive technique that measures the level of alpha-fetoprotein (AFP) in maternal blood, knowing that adults exclusively have albumin in their blood we exploit this technique. Typically the fetus will only release small amounts of AFP going across the placenta into the mother blood, although large amount of AFP in the maternal blood sample can indicate a neural tube defect or spina bifida.&lt;br /&gt;
&lt;br /&gt;
[http://library.med.utah.edu/WebPath/TUTORIAL/PRENATAL/PRENATAL.html]&lt;br /&gt;
&lt;br /&gt;
2. Identify a paper that uses cord stem cells therapeutically and write a brief (2-3 paragraph) description of the paper's findings.&lt;br /&gt;
&lt;br /&gt;
My selected Paper &amp;quot;Stem cell therapies for spinal cord injury.&amp;quot; describes the benefits of use along with its many implications. Spinal Cord injuries(SCI) either complete or incomplete pose a catastrophic stress on the individual both physical and emotional. The possibility of treatment for SCI is an area with enormous potential giving hope to those who are unfortunate enough to come across this terrible injury. &lt;br /&gt;
&lt;br /&gt;
There are currently many implications surrounding stem cell therapy such as tumor formation. The controversy surrounding research in this area is supported by data concluding that there is no way around biological implications caused by treatment.&lt;br /&gt;
&lt;br /&gt;
The basic principle behind stem cell therapy is using multipotential cells to create new and functional tissue, this therapy involves a combination of many complex treatments each addressing different components. Cutting edge research has involved using animal models although these types treatments are still in the development of making safe &amp;amp; ethical therapies that can be used in a clinical setting. As we look to the future of Stem cell therapies there are many more methods being explored for example using induced pluripotent stem cells (force expression of certain genes).&lt;br /&gt;
&lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/pubmed/20551948]&lt;br /&gt;
&lt;br /&gt;
--[[User:Z8600021|Mark Hill]] 17:50, 11 September 2012 (EST) Question 1 Fluorescence in-situ hybridization and Maternal serum alpha-fetoprotein are not an invasive technique, the analysis of fetal cells in maternal blood is exactly the opposite, it is replacing invasive techniques. I think you have misinterpreted what I meant by invasive technique, such as chorionic villi sampling or amniocentesis. Question 2 you have identified a stem cell paper, a review rather than research article. Though I did not specify this in the question I am usually asking for research articles. Your description is sufficient. '''5/10'''&lt;br /&gt;
&lt;br /&gt;
==&amp;quot;Lab 5 Assessment&amp;quot;==&lt;br /&gt;
&lt;br /&gt;
1.&lt;br /&gt;
&lt;br /&gt;
(A) Muscles satellite cells are sometimes reffered to as Myosatellite cells, these cells contain a single lobed nucleus and have tendency to differentiate into a specific cell type, similar to stem cells (mononuclear progenitor cell), they are located on the outer surface of muscle fibres and remain dormant until activation occurs&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
(B)  &lt;br /&gt;
&lt;br /&gt;
&amp;quot;Regeneration of adult skeletal muscle is an asynchronous process requiring the activation, proliferation and fusion of satellite cells, to form new muscle fibres.&amp;quot; Cooper, S. Tajbakhsh, V. Mouly, G. Cossu, M. Buckingham and G. S. Butler-Browne (1999). Satellite cells are responsible for the growth and regeneration of muscle, although there are chemical mediators that activate these cells proven by an experiment by Anderson J, Pilipowicz O.(2002),  concluding Nitric Oxide (in vivo) is required to activate satellite cells and also hepatocyte growth factor (HGF) and Nitric Oxide (NO) also participate in mobilizing satellite cells. Ryuichi Tatsumi, Xiaosong Liu, Antonio Pulido, Mark Morales, Tomowa Sakata, Sharon Dial, Akihito Hattori, Yoshihide Ikeuchi, and Ronald E. Allen (2005) Concluded that when a muscle is stretched beyond resting range Satellite cells are activated. This article also states that when muscle hypertrophy occurs satellites cells are recruited, although what is unsure is the chemical signalling involved. In conclusion 2 actions that activate Satellite cells are stretching and hypertrophy. The passive stretching of skeletal muscles triggers the release  and interaction of chemical mediators HGF and NO, which in turn are responsible for activation of satellite cells. If skeletal muscle receives any form of damage through exercise or injury, satellite cells are activated and are attracted to the site of disturbance. Hernandez and Kravitz (1999)&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
2.&lt;br /&gt;
Burnham, Martin, Stein, Bell, MacLean, Steadward (1997) concluded that after a Spinal Cord Injury (SCI) an individuals muscles fibres will undergo alteration from type 1 slow and type 2 fast, to become type 2 fast glycolytic fibres also known as &amp;quot;fast twitch B&amp;quot; which feature less myoglobin and mitochondria. Roberto Scelsi (2001) reported a change in the muscles fibers and micro vascular change after conducting various invasive tests on a paraplegic individual. These changes have a clear relationship with the time elapsed. Scelsi reported adaption of the muscle fibers after 1 month, although for the changes to be prominent 7-8 months has elapsed. To retard this unnatural transition, therapy must be used within week of the SCI such as, Functional Electrical Stimulation, (FES) is a recognised treatment allowing some kind of stimulation to these unused muscle fibres and could improve function. Christopher and Dana Reeves Foundation (2012)&lt;br /&gt;
&lt;br /&gt;
==&amp;quot; Lab 6 Assessment&amp;quot;==&lt;br /&gt;
&lt;br /&gt;
Vision development review:&lt;br /&gt;
&lt;br /&gt;
The key points are Cleary described and Topics have been divided in an efficient way allowing maximum information and an extensive insight into each of these segments, although at this stage there is not enough detail for each.&lt;br /&gt;
There is a substantial amount of visual stimulus although the quality of these stimuli is questionable. For example the images under the heading “research history” lack proper sized labelling, an individual must click on the each image in order to appreciate it. The initial image needs to decrease in size dramatically as is overwhelming and takes away from the product&lt;br /&gt;
Proper citation is evident however; there is a minority of untidy citations along with no copy write information for a certain image. Significant, deep research is not evident, I believe more research is required; there is a respectable attempt to relate content to learning aims of embryology. Information in the history section is insufficient and perhaps needs to be expanded upon.&lt;br /&gt;
To improve more information on each topic is required, review of visual displays (mainly balancing images between sections some have plenty where as other lack) and copy write information is essential&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
Somatosensory review:&lt;br /&gt;
&lt;br /&gt;
The key points are clearly presented at the top of the page efficiently formatted allowing viewer a perfect insight to the entire pages content. There is a severe lack of visual stimuli; this makes the page present as boring and text heavy. &lt;br /&gt;
Image citation is commendable although throughout the text there is unacceptable links to external sites that are not explained with a messy reference section. The information presented is quite detailed and promotes a significant amount of research and understanding, it is put forward in an excellent matter, sections that could easily be expanded are glossary, and perhaps a section specifically on development. Attempt to relate to the learning aims of embryology are apparent. There is a large amount of information presented in a fantastic way although the lack of visual stimuli takes away from the final product, perhaps a more summarised presentation matter would be appropriate to break up large amount of text; this along with the tidy up of referencing needs to be addressed.&lt;br /&gt;
&lt;br /&gt;
Olfaction review:&lt;br /&gt;
&lt;br /&gt;
Upon first glance of the page you immediately get the impression excellent presentation and a surplus of information. Most topics are well described although the history of discoveries layout is questionable and a table would present at a higher quality.&lt;br /&gt;
It is clear that the group has a high level of understanding through large amount of research; this is then transformed into chunks of knowledge in which are easily digestible for the reader. The page lacks visual encourage, I believe more detail into this would only benefit the page. The glossary could quite easily be expanded many terms throughout the text are absent from this list.&lt;br /&gt;
This page is almost parallel with embryological teaching aims. Citation &amp;amp; referencing is excellent. The way to improve this page would be reducing the weight of the text using innovative ideas to the present information in a more exciting way along side inclusion of more visual stimulus.&lt;br /&gt;
&lt;br /&gt;
Abnormal Vision review:&lt;br /&gt;
&lt;br /&gt;
An excellent straight forward introduction, presentation and layout of the page is questionable perhaps the use of different summary methods would improve this for example dot points along with image choice and size.  A common topic among all groups is to expand the glossary which is easily done and will only improve the finished merchandise. Language used throughout could be less primitive, very simplistic in certain sections. The referencing is satisfactory although external links section has been left out.&lt;br /&gt;
All the information is present although the organisation skills need to be assessed to allow optimum presentation of ideas. The text contains in-depth embryological teachings aims. The page looks promising and editing is the easiest part once corrected I expect a sound result.&lt;br /&gt;
&lt;br /&gt;
Hearing review:&lt;br /&gt;
&lt;br /&gt;
This group successfully energies the audience with a funny picture, along with a great introduction and an interactive writing style from the first paragraph. This page needs to address the reoccurring text to image ratio, allowing the reader more explanation complementing the hard work of explaining concepts. The highlight of this text was the abnormal hearing section which I found to be very interesting along with sound presentation of ideas. The demise of this page is the lack of information in current research and being starved of visual stimuli.&lt;br /&gt;
Overall a good attempt to line up embryological teaching concepts, when these easily addressable points are responded to a commendable finish will be apparent.&lt;br /&gt;
&lt;br /&gt;
==&amp;quot; lab 7 assessment &amp;quot;==&lt;br /&gt;
&lt;br /&gt;
1.&lt;br /&gt;
mutations in GATA6 have been linked to neonates with diabatetes, suggesting that mutations in GATA6 disrupts the development of this endocrine organ. Manipulation of genes using animal models helped provide this evidence.&lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/pubmed/23006330]&lt;br /&gt;
&lt;br /&gt;
2. &lt;br /&gt;
The embryonic tooth is derived from the mesodermal and ectodermal layers. The development of teeth originates when the dental lamina divides rapildly to form the future rows that teeth are located within. Their are enanmal organs present which produce circular outgrowths providing an apropriate site for tooth formation, This organ is also responsible for the complete morphology of the later devloped tooth.&lt;/div&gt;</summary>
		<author><name>Z3330795</name></author>
	</entry>
	<entry>
		<id>https://embryology.med.unsw.edu.au/embryology/index.php?title=User:Z3330795&amp;diff=105167</id>
		<title>User:Z3330795</title>
		<link rel="alternate" type="text/html" href="https://embryology.med.unsw.edu.au/embryology/index.php?title=User:Z3330795&amp;diff=105167"/>
		<updated>2012-10-02T23:55:46Z</updated>

		<summary type="html">&lt;p&gt;Z3330795: /* &amp;quot; Lab 6 Assessment&amp;quot; */&lt;/p&gt;
&lt;hr /&gt;
&lt;div&gt;==Lab Attendance ==&lt;br /&gt;
Lab 1&lt;br /&gt;
&lt;br /&gt;
Lab 2&lt;br /&gt;
&lt;br /&gt;
Lab 3&lt;br /&gt;
&lt;br /&gt;
Lab 4&lt;br /&gt;
&lt;br /&gt;
Lab 5&lt;br /&gt;
&lt;br /&gt;
Lab 6&lt;br /&gt;
&lt;br /&gt;
Lab 7--[[User:Z3330795|Z3330795]] 10:56, 12 September 2012 (EST)&lt;br /&gt;
--[[User:Z8600021|Mark Hill]] 17:26, 11 September 2012 (EST) You need to use the signature tool to log lab attendance.&lt;br /&gt;
&lt;br /&gt;
Lab 8--'''Z3330795'''  20 September 2012 (EST) this one i put in late, but i did attend just forgot to put it in that day.&lt;br /&gt;
&lt;br /&gt;
lab 9 --[[User:Z3330795|Z3330795]] 09:56, 26 September 2012 (EST)&lt;br /&gt;
&lt;br /&gt;
=='''Fertilization'''==&lt;br /&gt;
&lt;br /&gt;
The process in Simple Steps:&lt;br /&gt;
&lt;br /&gt;
Step 1 - Many sperm travel from the Male testes to the Female Egg located in the Fallopian tube.]&lt;br /&gt;
&lt;br /&gt;
Step 2 - Once the sperm reach the egg, many try and &amp;quot;enter&amp;quot; by releasing enzymes breaking down the outer layer of the egg.&lt;br /&gt;
&lt;br /&gt;
Step 3 - Only one sperm can penetrate and once this happens, a chemical reaction occurs &amp;quot;pushing&amp;quot; away any other sperm attempting to penetrate.&lt;br /&gt;
&lt;br /&gt;
'''This now fertilized egg is referred to as a zygote'''&lt;br /&gt;
&lt;br /&gt;
Step 4 - pronuclei of the egg merges with the pronuclei of the sperm resulting in cell division.&lt;br /&gt;
&lt;br /&gt;
Step 5 - days later this zygote is moved along the fallopian tube and is now called a blastocyst.&lt;br /&gt;
&lt;br /&gt;
Step 6 - the blastocyst is embedded in the uterine wall activating the start of pregnancy.&lt;br /&gt;
&lt;br /&gt;
'''References:'''&lt;br /&gt;
http://science.howstuffworks.com/&lt;br /&gt;
&lt;br /&gt;
==&amp;quot;Lab 1 Assessment&amp;quot;==&lt;br /&gt;
&lt;br /&gt;
1.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.&lt;br /&gt;
&lt;br /&gt;
The British scientist Robert Edwards has been researching and devloping IVF since the 1950's, the first successful IVF treatment was in 1978 when the worlds first baby was born from this fertilization technique. Following this success methods have been continually rejuvenated with state of the art techniques and research.&lt;br /&gt;
&lt;br /&gt;
Robert Edwards was the winner of the 2010 Nobel Prize in medicine for his efforts in the development of in-vitro fertilisation (IVF).&lt;br /&gt;
&lt;br /&gt;
[http://www.nobelprize.org/nobel_prizes/medicine/laureates/2010/press.html/]&lt;br /&gt;
&lt;br /&gt;
2.Identify and add a PubMed reference link to a recent paper on fertilisation and describe its key findings (1-2 paragraphs).&lt;br /&gt;
&lt;br /&gt;
This paper is explores the potential of screening sperm before fertilization, to predict fertilization rate depending on the &amp;quot;quality&amp;quot; of the sperm. This technology would be of extreme importance and make the IVF process more efficient.&lt;br /&gt;
&lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/pubmed/22762979]&lt;br /&gt;
&lt;br /&gt;
--[[User:Z8600021|Mark Hill]] 17:30, 11 September 2012 (EST) Question 1 has been answered correctly. Question 2 has been answered, but not in sufficient detail (2 lines) to describe the findings in full and the link is not correctly displayed. You should use just the number as here PMID 22762979 or remove the brackets around your link. You have lost marks for the lack of a full description, not the reference formatting.'''6/10'''&lt;br /&gt;
&lt;br /&gt;
==&amp;quot;Lab 2 Assessment&amp;quot;==&lt;br /&gt;
&lt;br /&gt;
Identify a protein associated with the implantation process, including a brief description of the protein's role.&lt;br /&gt;
&lt;br /&gt;
Chemokines are a protein directly associated with the implantation process. Current research has shown that Chemokines play an executive role within the endometrium, specifically throughout implantation. It has been proven that these proteins direct the invading trophoblasts within the maternal vasculature and decidua. This invading process is critical in early development and chemical signally from these proteins allows precise depth of insertion in preparation of the crucial weeks ahead.&lt;br /&gt;
&lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/pubmed/17495644]&lt;br /&gt;
&lt;br /&gt;
[[File:Sexual_development_of_MYT1_mutants.jpeg]]&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
--[[User:Z8600021|Mark Hill]] 17:38, 11 September 2012 (EST) Question 1 image has been uploaded correctly. In the summary box you have included the citation and copyright information, but not a template indicating that this is a student image. &amp;lt;nowiki&amp;gt;{{Template:Student Image}}&amp;lt;/nowiki&amp;gt;. There is also no legend describing what A, B and C are showing, this could have been derived from teh original figure template. Question 2 protein associated with the implantation, chemokines are a relevant &amp;quot;class of proteins&amp;quot;, not a specific protein and the  article you have selected is a review, not a big issue but you need to also clearly identify that it is a review and not a research article. '''7/10'''&lt;br /&gt;
&lt;br /&gt;
==&amp;quot;Lab 3 Assessment&amp;quot;==&lt;br /&gt;
&lt;br /&gt;
1.Identify the difference between &amp;quot;gestational age&amp;quot; and &amp;quot;post-fertilisation age&amp;quot; and explain why clinically &amp;quot;gestational age&amp;quot; is used in describing human development.&lt;br /&gt;
&lt;br /&gt;
a)&lt;br /&gt;
The overlap and confusion of these terms is very common due to physicians frequently using either one to describe the early stage of pregnancy. Technically there is a distinct difference between the two.&amp;quot;Post-fertilization age&amp;quot; is the time elapsed after egg fertilization, where as &amp;quot;Gestational age&amp;quot;(approximately 2 weeks later) is the time since the mothers last menstrual cycle prior to pregnancy.&lt;br /&gt;
&lt;br /&gt;
[http://www.livestrong.com/article/92683-embryo-fetus-development-stages/]&lt;br /&gt;
&lt;br /&gt;
b)&lt;br /&gt;
In a clinical setting is important to use consistant terminology, “Gestational age” is the preffered term used to describe this early stage of pregnacy for the obvious reason that the average women will know when their last menstral cycle began although she will typically have less certainty surrounding when ovulation occured. The delvery date is a simple caculation given acuracy of the Gestational age.&lt;br /&gt;
&lt;br /&gt;
[http://pediatrics.aappublications.org/content/114/5/1362.full]&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
2. Identify using histological descriptions at least 3 different types of tissues formed from somites&lt;br /&gt;
&lt;br /&gt;
Somites form Cartilage (ribs and vertabrae), skeltal muscle (ribs, limbs and back) and also the dermis of the dorsal skin. The cells of the Somites remain multipotential for a long time during development, therefor somite cells can become any somite structure until maturation where they become commited to form structures repective of their regions.&lt;br /&gt;
&lt;br /&gt;
The Somites have three different regions with different tissue outcomes. The somite cells located closest to neural tube turn into mesenchymal cell (through complex cellular processes) this is portion that become chrondocytes of the cartilage formed.&lt;br /&gt;
The cells in the two lateral portions of the somite structure divide to produce the myoblasts which are muscle precursers cells. This is now a 2 layered segment, the top layer is called dermamyotome, and the lower myotome. Depending on the location of the myoblasts determines their fate (epaxial or hypaxial muscles). the final area is located in the centre of the dermamyotome is called the dermatome, producing connective tissue of mesenchymal origin which will mature and eventually form the tissue of ventrally located skin. &lt;br /&gt;
&lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/books/NBK10085/]&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
--[[User:Z8600021|Mark Hill]] 17:43, 11 September 2012 (EST) Question 1 you have identified the difference between &amp;quot;gestational age&amp;quot; and &amp;quot;post-fertilisation age. Your terminology though is confusing &amp;quot;where as Gestational age (approximately 2 weeks later)&amp;quot;, you should have then said &amp;quot;than Post-fertilization age&amp;quot;. Question 2 you have identified 3 different tissues and the textbook link is appropriate. There are several typos throughout your answer that you should have corrected, I have not removed marks for this, but it suggests to the reader that you have not checked your work. '''9/10'''&lt;br /&gt;
&lt;br /&gt;
==&amp;quot;Lab 4 Assessment&amp;quot;==&lt;br /&gt;
&lt;br /&gt;
1. Identify the 2 invasive prenatal diagnostic techniques related to the placenta and 2 abnormalities that can be identified with these techniques.&lt;br /&gt;
&lt;br /&gt;
a)Fluorescence in-situ hybridization is an invasive technique which analyses fetal blood cells present in maternal blood samples. These cells gain access through placental villi. This test can screen for conditions such as the trisomies and monosomy X.&lt;br /&gt;
&lt;br /&gt;
b)Maternal serum alpha-fetoprotein is an invasive technique that measures the level of alpha-fetoprotein (AFP) in maternal blood, knowing that adults exclusively have albumin in their blood we exploit this technique. Typically the fetus will only release small amounts of AFP going across the placenta into the mother blood, although large amount of AFP in the maternal blood sample can indicate a neural tube defect or spina bifida.&lt;br /&gt;
&lt;br /&gt;
[http://library.med.utah.edu/WebPath/TUTORIAL/PRENATAL/PRENATAL.html]&lt;br /&gt;
&lt;br /&gt;
2. Identify a paper that uses cord stem cells therapeutically and write a brief (2-3 paragraph) description of the paper's findings.&lt;br /&gt;
&lt;br /&gt;
My selected Paper &amp;quot;Stem cell therapies for spinal cord injury.&amp;quot; describes the benefits of use along with its many implications. Spinal Cord injuries(SCI) either complete or incomplete pose a catastrophic stress on the individual both physical and emotional. The possibility of treatment for SCI is an area with enormous potential giving hope to those who are unfortunate enough to come across this terrible injury. &lt;br /&gt;
&lt;br /&gt;
There are currently many implications surrounding stem cell therapy such as tumor formation. The controversy surrounding research in this area is supported by data concluding that there is no way around biological implications caused by treatment.&lt;br /&gt;
&lt;br /&gt;
The basic principle behind stem cell therapy is using multipotential cells to create new and functional tissue, this therapy involves a combination of many complex treatments each addressing different components. Cutting edge research has involved using animal models although these types treatments are still in the development of making safe &amp;amp; ethical therapies that can be used in a clinical setting. As we look to the future of Stem cell therapies there are many more methods being explored for example using induced pluripotent stem cells (force expression of certain genes).&lt;br /&gt;
&lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/pubmed/20551948]&lt;br /&gt;
&lt;br /&gt;
--[[User:Z8600021|Mark Hill]] 17:50, 11 September 2012 (EST) Question 1 Fluorescence in-situ hybridization and Maternal serum alpha-fetoprotein are not an invasive technique, the analysis of fetal cells in maternal blood is exactly the opposite, it is replacing invasive techniques. I think you have misinterpreted what I meant by invasive technique, such as chorionic villi sampling or amniocentesis. Question 2 you have identified a stem cell paper, a review rather than research article. Though I did not specify this in the question I am usually asking for research articles. Your description is sufficient. '''5/10'''&lt;br /&gt;
&lt;br /&gt;
==&amp;quot;Lab 5 Assessment&amp;quot;==&lt;br /&gt;
&lt;br /&gt;
1.&lt;br /&gt;
&lt;br /&gt;
(A) Muscles satellite cells are sometimes reffered to as Myosatellite cells, these cells contain a single lobed nucleus and have tendency to differentiate into a specific cell type, similar to stem cells (mononuclear progenitor cell), they are located on the outer surface of muscle fibres and remain dormant until activation occurs&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
(B)  &lt;br /&gt;
&lt;br /&gt;
&amp;quot;Regeneration of adult skeletal muscle is an asynchronous process requiring the activation, proliferation and fusion of satellite cells, to form new muscle fibres.&amp;quot; Cooper, S. Tajbakhsh, V. Mouly, G. Cossu, M. Buckingham and G. S. Butler-Browne (1999). Satellite cells are responsible for the growth and regeneration of muscle, although there are chemical mediators that activate these cells proven by an experiment by Anderson J, Pilipowicz O.(2002),  concluding Nitric Oxide (in vivo) is required to activate satellite cells and also hepatocyte growth factor (HGF) and Nitric Oxide (NO) also participate in mobilizing satellite cells. Ryuichi Tatsumi, Xiaosong Liu, Antonio Pulido, Mark Morales, Tomowa Sakata, Sharon Dial, Akihito Hattori, Yoshihide Ikeuchi, and Ronald E. Allen (2005) Concluded that when a muscle is stretched beyond resting range Satellite cells are activated. This article also states that when muscle hypertrophy occurs satellites cells are recruited, although what is unsure is the chemical signalling involved. In conclusion 2 actions that activate Satellite cells are stretching and hypertrophy. The passive stretching of skeletal muscles triggers the release  and interaction of chemical mediators HGF and NO, which in turn are responsible for activation of satellite cells. If skeletal muscle receives any form of damage through exercise or injury, satellite cells are activated and are attracted to the site of disturbance. Hernandez and Kravitz (1999)&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
2.&lt;br /&gt;
Burnham, Martin, Stein, Bell, MacLean, Steadward (1997) concluded that after a Spinal Cord Injury (SCI) an individuals muscles fibres will undergo alteration from type 1 slow and type 2 fast, to become type 2 fast glycolytic fibres also known as &amp;quot;fast twitch B&amp;quot; which feature less myoglobin and mitochondria. Roberto Scelsi (2001) reported a change in the muscles fibers and micro vascular change after conducting various invasive tests on a paraplegic individual. These changes have a clear relationship with the time elapsed. Scelsi reported adaption of the muscle fibers after 1 month, although for the changes to be prominent 7-8 months has elapsed. To retard this unnatural transition, therapy must be used within week of the SCI such as, Functional Electrical Stimulation, (FES) is a recognised treatment allowing some kind of stimulation to these unused muscle fibres and could improve function. Christopher and Dana Reeves Foundation (2012)&lt;br /&gt;
&lt;br /&gt;
==&amp;quot; Lab 6 Assessment&amp;quot;==&lt;br /&gt;
&lt;br /&gt;
Vision development review:&lt;br /&gt;
&lt;br /&gt;
The key points are Cleary described and Topics have been divided in an efficient way allowing maximum information and an extensive insight into each of these segments, although at this stage there is not enough detail for each.&lt;br /&gt;
There is a substantial amount of visual stimulus although the quality of these stimuli is questionable. For example the images under the heading “research history” lack proper sized labelling, an individual must click on the each image in order to appreciate it. The initial image needs to decrease in size dramatically as is overwhelming and takes away from the product&lt;br /&gt;
Proper citation is evident however; there is a minority of untidy citations along with no copy write information for a certain image. Significant, deep research is not evident, I believe more research is required; there is a respectable attempt to relate content to learning aims of embryology. Information in the history section is insufficient and perhaps needs to be expanded upon.&lt;br /&gt;
To improve more information on each topic is required, review of visual displays (mainly balancing images between sections some have plenty where as other lack) and copy write information is essential&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
Somatosensory review:&lt;br /&gt;
&lt;br /&gt;
The key points are clearly presented at the top of the page efficiently formatted allowing viewer a perfect insight to the entire pages content. There is a severe lack of visual stimuli; this makes the page present as boring and text heavy. &lt;br /&gt;
Image citation is commendable although throughout the text there is unacceptable links to external sites that are not explained with a messy reference section. The information presented is quite detailed and promotes a significant amount of research and understanding, it is put forward in an excellent matter, sections that could easily be expanded are glossary, and perhaps a section specifically on development. Attempt to relate to the learning aims of embryology are apparent. There is a large amount of information presented in a fantastic way although the lack of visual stimuli takes away from the final product, perhaps a more summarised presentation matter would be appropriate to break up large amount of text; this along with the tidy up of referencing needs to be addressed.&lt;br /&gt;
&lt;br /&gt;
Olfaction review:&lt;br /&gt;
&lt;br /&gt;
Upon first glance of the page you immediately get the impression excellent presentation and a surplus of information. Most topics are well described although the history of discoveries layout is questionable and a table would present at a higher quality.&lt;br /&gt;
It is clear that the group has a high level of understanding through large amount of research; this is then transformed into chunks of knowledge in which are easily digestible for the reader. The page lacks visual encourage, I believe more detail into this would only benefit the page. The glossary could quite easily be expanded many terms throughout the text are absent from this list.&lt;br /&gt;
This page is almost parallel with embryological teaching aims. Citation &amp;amp; referencing is excellent. The way to improve this page would be reducing the weight of the text using innovative ideas to the present information in a more exciting way along side inclusion of more visual stimulus.&lt;br /&gt;
&lt;br /&gt;
Abnormal Vision review:&lt;br /&gt;
&lt;br /&gt;
An excellent straight forward introduction, presentation and layout of the page is questionable perhaps the use of different summary methods would improve this for example dot points along with image choice and size.  A common topic among all groups is to expand the glossary which is easily done and will only improve the finished merchandise. Language used throughout could be less primitive, very simplistic in certain sections. The referencing is satisfactory although external links section has been left out.&lt;br /&gt;
All the information is present although the organisation skills need to be assessed to allow optimum presentation of ideas. The text contains in-depth embryological teachings aims. The page looks promising and editing is the easiest part once corrected I expect a sound result.&lt;br /&gt;
&lt;br /&gt;
Hearing review:&lt;br /&gt;
&lt;br /&gt;
This group successfully energies the audience with a funny picture, along with a great introduction and an interactive writing style from the first paragraph. This page needs to address the reoccurring text to image ratio, allowing the reader more explanation complementing the hard work of explaining concepts. The highlight of this text was the abnormal hearing section which I found to be very interesting along with sound presentation of ideas. The demise of this page is the lack of information in current research and being starved of visual stimuli.&lt;br /&gt;
Overall a good attempt to line up embryological teaching concepts, when these easily addressable points are responded to a commendable finish will be apparent.&lt;br /&gt;
&lt;br /&gt;
==&amp;quot; lab 7 assessment &amp;quot;==&lt;br /&gt;
&lt;br /&gt;
2. &lt;br /&gt;
The embryonic tooth is derived from the mesodermal and ectodermal layers. The development of teeth originates when the dental lamina divides rapildly to form the future rows that teeth are located within. Their are enanmal organs present which produce circular outgrowths providing an apropriate site for tooth formation, This organ is also responsible for the complete morphology of the later devloped tooth.&lt;/div&gt;</summary>
		<author><name>Z3330795</name></author>
	</entry>
	<entry>
		<id>https://embryology.med.unsw.edu.au/embryology/index.php?title=2012_Group_Project_3&amp;diff=105137</id>
		<title>2012 Group Project 3</title>
		<link rel="alternate" type="text/html" href="https://embryology.med.unsw.edu.au/embryology/index.php?title=2012_Group_Project_3&amp;diff=105137"/>
		<updated>2012-10-02T23:26:48Z</updated>

		<summary type="html">&lt;p&gt;Z3330795: /* Adult Tongue and Taste Buds – Structure and Function */&lt;/p&gt;
&lt;hr /&gt;
&lt;div&gt;=Taste Development=&lt;br /&gt;
&lt;br /&gt;
You are out to dinner and your meal arrives in front of you, the aromas and the presentation of your food strikes you immediately. Half way through, the waiter returns and asks “How does your meal taste?”  The answer is not as simple as one might think. Why does the meal taste pleasant? How do we experience different tastes? In the following page, we aim to discern how exactly one would answer these questions by looking at the embryological development of the taste system from week to week. &lt;br /&gt;
&lt;br /&gt;
Taste is a complex sensory system and its precise workings are to this day not fully understood. What makes it so complicated is the interaction between the structure of tongue and taste buds and how this contributes to the representation of taste qualities (salty, bitter, sweet, sour and umami) in the brain. We will also look at some current research on animal models being undertaken to evaluate the role of specific genes in the development of sensory structures. By looking at the taste system’s genetic basis, we now have a greater understanding of the abnormalities that may occur during development and a direction to pursue in future research to attempt to fill in the gaps of scientific knowledge.&lt;br /&gt;
&lt;br /&gt;
==Adult Tongue and Taste Buds – Structure and Function==&lt;br /&gt;
&lt;br /&gt;
'''Structure'''&lt;br /&gt;
&lt;br /&gt;
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.  &lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
''''The image below is a simplistic diagram of the surface of the tongue showing the locations of the different papillae and other important features'''&lt;br /&gt;
&lt;br /&gt;
{|&lt;br /&gt;
| [[Image:Drawing of Tongue.png|centre|500px]]&lt;br /&gt;
&lt;br /&gt;
[[File:Taste_pathway.jpg|right|thumb|200px|Simplistic Pathway of Taste]]&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
'''Papillae'''&lt;br /&gt;
&lt;br /&gt;
There are 4 types of papillae on the tongue.&lt;br /&gt;
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. &lt;br /&gt;
&lt;br /&gt;
[[File:Papillae.jpg|Left|thumb|200px|Close up of Human Tongue Papillae]]&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
[[File:Fungiformpapillae.jpg|left|thumb|200px|Fungiform Papillae]]&lt;br /&gt;
&lt;br /&gt;
[[File:Circumvallatepapillae.jpg |left|thumb|200px|Circumvallate Papillae]]&lt;br /&gt;
&lt;br /&gt;
[[File:Filiformpapillae.jpg|left|200px|thumb|Foliate Papillae]]&lt;br /&gt;
&lt;br /&gt;
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&lt;br /&gt;
'''Function'''&lt;br /&gt;
&lt;br /&gt;
The Tongue has muscular and sensory functions, muscular functions include swallowing and speech where as sensory function involves taste. This section will focus on the sensory functions of the tongue.&lt;br /&gt;
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.&lt;br /&gt;
&lt;br /&gt;
[[File:Taste_bud_1.jpg|right|thumb|200px|Cross section of a taste bud unit|centre|Cross section of a taste bud unit]]&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
'''Link Between Taste and Smell'''&lt;br /&gt;
&lt;br /&gt;
The pathways of smell and taste are very similar. Pathways both involve the conversion of a dissolved chemical stimulus transformed into a electrical impulse for interpretation by the brain.	&lt;br /&gt;
Taste and smell overlap when humans experience flavour, flavour involves an interaction of taste, smell, texture and temperature, where taste is only a portion of this interaction. when the brain interprets a flavour, contribution from other senses has a significant role in identification. In conclusion Taste and Smell in combination with other senses help develop a sensory interpretation called flavour.&lt;br /&gt;
[[File:Human smelling.jpg|500px|centre]]&lt;br /&gt;
&lt;br /&gt;
==History of Discoveries==&lt;br /&gt;
&lt;br /&gt;
{| cellpadding=5 style=&amp;quot;border:1px solid #BBB&amp;quot;&lt;br /&gt;
|- bgcolor=&amp;quot;#faecc8&amp;quot;&lt;br /&gt;
|''' Date'''|| '''Significant Discovery'''&lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#faf6ed&amp;quot;&lt;br /&gt;
|'''350BC'''&lt;br /&gt;
|| Aristotle writes about the basic tastes, sweet and bitter. He also notes that it can be modified by salty and acidic. &amp;lt;ref name=&amp;quot;PMID22717400&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;22717400&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#faecc8&amp;quot;&lt;br /&gt;
|'''1901'''&lt;br /&gt;
|| D. Hanig publishes a paper describing taste sensitivity in different regions of the tongue. &lt;br /&gt;
''Interesting fact:'' The modern concept of a 'tongue map' is a misinterpretation of this study. &amp;lt;ref name=&amp;quot;PMID22717400&amp;quot;/&amp;gt;&lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#faf6ed&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''1908'''&lt;br /&gt;
|Kikunae Ikeda, a professor of the Tokyo Imperial University, discovered and identified the fifth basic taste: umami (savouriness), made palatable by glutamate.  &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;12438213&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
[http://chemse.oxfordjournals.org/content/27/9/847.long New Seasonings]&lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#faecc8&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''1931-32'''&lt;br /&gt;
| A chemist named Arthur Fox and his college noted that they had different sensitivities to the bitter tasting Phenylthiocarbamide (PTC).&amp;lt;ref&amp;gt;Blakeslee AF, Fox AL. Our different taste worlds. J Hered. 1932;23:97–107.&amp;lt;/ref&amp;gt; Geneticists later confirm these findings, and discover that non-tasting is a recessive genetic trait. &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;17782493&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/pubmed/17782493 Inherited taste deficiency] &lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#faf6ed&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''1965'''&lt;br /&gt;
|Farbman's study of the developing taste but in rat fungiform papilla was significant in increasing our understanding of taste bud development. &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;14300090&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
[http://www.sciencedirect.com/science/article/pii/0012160665900400 Electron microscope study of the developing taste bud in rat fungiform papilla.]&lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#faecc8&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''1992'''&lt;br /&gt;
|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. &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;1608467 &amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
[http://www.nature.com/nature/journal/v357/n6379/abs/357563a0.html Gustducin is a taste-cell-specific G protein closely related to the transducins]&lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#faf6ed&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''1995'''&lt;br /&gt;
|Barlow et al. experimented with Axolotl salamanders and concluded that taste buds from this species arise exclusively from epithelial tissue, &amp;quot;oropharyngeal [[#Glossary |'''epithelium''']]&amp;quot;. &amp;lt;ref name=&amp;quot;PMID17826760&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;17826760&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/pubmed/17826760 Embryonic origin of gustatory cranial sensory neurons] &lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#faecc8&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''1996'''&lt;br /&gt;
| 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 &amp;quot;at least dual function of embryonic/fetal taste buds&amp;quot;, including non-gustatory, paracrine functions prior to the 14th week and gustatory after the 14th week. &amp;lt;ref name=&amp;quot;PMID8955790&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;8955790&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/pubmed/8955790 Embryonic and early fetal development of human taste buds: a transmission electron microscopical study]&lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#faf6ed&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''2000'''&lt;br /&gt;
|Chandrashekar, J. et al. discover the first taste sonsors, the T2R bitter taste receptors. &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;10761935&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
[http://www.sciencedirect.com/science/article/pii/S0092867400807060 T2Rs Function as Bitter Taste Receptors]&lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#faecc8&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''2001'''&lt;br /&gt;
|Nelson, G. et al. discover the sweet receptor: a combination of T1R2 and T1R3. &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;11509186&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/pubmed/11509186?dopt=Abstract&amp;amp;holding=npg Mammalian sweet taste receptors.]&lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#faf6ed&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''2002'''&lt;br /&gt;
|Nelson G. et al. discover the amino acid (umami) taste receptor: a combination of T1R1 and T1R3 identified.  &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;11894099&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/pubmed/11894099?dopt=Abstract&amp;amp;holding=npg An amino-acid taste receptor]&lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#faecc8&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''2005'''&lt;br /&gt;
|Dyer, J. et al. discover sweet taste receptors in the GI tract. &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;17855558&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1986582/ Sweet taste signaling in the gut]&lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#faf6ed&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''2006'''&lt;br /&gt;
|Huang, A. L et al. discover cells for sour taste, identified by PKD2L1 (a polycystic kidney disease-like ion channel). &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;16929298&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1571047/ The Cells and Logic for Mammalian Sour Taste detection]&lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#faecc8&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''2007'''&lt;br /&gt;
|Harlow DE, Barlow LA of the University of Colorado Denver Health Sciences Center provide evidence of the &amp;quot;embryonic origin of gustatory cranial sensory neurons&amp;quot;. &amp;lt;ref name=&amp;quot;PMID17826760&amp;quot;/&amp;gt;&lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/pubmed/17826760 Embryonic origin of gustatory cranial sensory neurons.]&lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#faf6ed&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''2009'''&lt;br /&gt;
|A study by Hevezi P et al, presents &amp;quot;the first comprehensive characterization of gene expression in primate taste buds&amp;quot;, as opposed to previous studies which focused on rodents. &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;19636377&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/pubmed/19636377 Genome-wide analysis of gene expression in primate taste buds reveals links to diverse processes]&lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#faecc8&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''2010'''&lt;br /&gt;
|Chandrashekar, J. et al. identify epithelial sodium channel (ENaC) as the sodium-salt taste receptor. &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;20107438&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/pubmed/20107438?dopt=Abstract&amp;amp;holding=npg The cells and peripheral representation of sodium taste in mice]&lt;br /&gt;
|}&lt;br /&gt;
&lt;br /&gt;
== Human Weekly Development - Two Prominent Studies ==&lt;br /&gt;
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. &lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
The findings of these two studies are summarized in the table below. The figures provided relate to the images on their respective research papers.&lt;br /&gt;
&lt;br /&gt;
# [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] &lt;br /&gt;
# [http://chemse.oxfordjournals.org/content/22/6/601.long Scanning electron microscopical studies of developing gustatory papillae in humans, 1997]  &lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
===Timeline of Developmental Processes of Human Taste Buds===&lt;br /&gt;
{| cellpadding=5 style=&amp;quot;border:1px solid #BBB&amp;quot;&lt;br /&gt;
|- bgcolor=&amp;quot;#89CFF0&amp;quot;&lt;br /&gt;
|'''Postovulatory Week'''||'''Description'''&lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#BCD4E6&amp;quot;&lt;br /&gt;
|'''Week 6''' ||&lt;br /&gt;
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. &amp;lt;ref name=&amp;quot;PMID9455607&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;9455607&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#89CFF0&amp;quot;&lt;br /&gt;
| '''Weeks 6 to 7'''|| &lt;br /&gt;
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. &amp;lt;ref name=PMID8955790/&amp;gt;&lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#BCD4E6&amp;quot;&lt;br /&gt;
| '''Week 7 '''||&lt;br /&gt;
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.  &amp;lt;ref name=PMID9455607/&amp;gt; &lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#89CFF0&amp;quot;&lt;br /&gt;
| ''' Week 8  ''' ||&lt;br /&gt;
* The taste bud primordium are still differentiated, elongated epithelial cells, resting on a slightly developed core of young dermal papilla.&lt;br /&gt;
* 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. &lt;br /&gt;
* Ciliated cells also appear around the 8th week, however the significance of these cells which are scattered randomly across the lingual surface remains unclear. &amp;lt;ref name=PMID8955790/&amp;gt; &lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#BCD4E6&amp;quot;&lt;br /&gt;
|'''  Week 9''' ||&lt;br /&gt;
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). &amp;lt;ref name=PMID9455607/&amp;gt;&lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#89CFF0&amp;quot;&lt;br /&gt;
|'''  Weeks 10-11''' ||&lt;br /&gt;
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). &amp;lt;ref name=PMID8955790/&amp;gt; &lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#BCD4E6&amp;quot;&lt;br /&gt;
|''' Week 12 ''' ||&lt;br /&gt;
Taste bud cells are more clearly differentiated into epithelial cell types II and III. &amp;lt;ref name=PMID8955790/&amp;gt; &lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#89CFF0&amp;quot;&lt;br /&gt;
|''' Weeks 12-13  ''' ||&lt;br /&gt;
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). &amp;lt;ref name=PMID8955790/&amp;gt; &lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#BCD4E6&amp;quot;&lt;br /&gt;
|''' Weeks 14 -15 ''' ||&lt;br /&gt;
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. &amp;lt;ref name=PMID8955790/&amp;gt; &lt;br /&gt;
|}&lt;br /&gt;
&lt;br /&gt;
==Abnormalities==&lt;br /&gt;
&lt;br /&gt;
It should be mentioned that gustatory abnormalities have not been widely researched. Most research conducted in this field has been conducted through animal testing on mice and this is the basis of information provided below. &lt;br /&gt;
&lt;br /&gt;
===Knocking out P2X Receptors===&lt;br /&gt;
&lt;br /&gt;
[[File:Image of taste being evoked by visualising ATP release.jpeg|Left|thumb|200px|Evoking taste - ATP release in tongue]]&lt;br /&gt;
&lt;br /&gt;
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. &lt;br /&gt;
&lt;br /&gt;
It should be noted that the taste buds in DKO are functional, but are not stimulated by the administration of tastants. &lt;br /&gt;
&lt;br /&gt;
The transmission of release of ATP is secretion through gap junction hemichannels (pannexin 1 gap junction).&lt;br /&gt;
&lt;br /&gt;
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.&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;21940456&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
===FGF signalling and genes===&lt;br /&gt;
&lt;br /&gt;
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.&lt;br /&gt;
&lt;br /&gt;
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 (&amp;quot;Fgf10&amp;quot;) 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 &amp;quot;Fgf10&amp;quot; to limit the size of the CVP progenitor placode. Exclusive expression of ''Fgf10'' in the [[#Glossary |'''mesenchyme''']] is necessary for the formation of CVP. &lt;br /&gt;
&lt;br /&gt;
'''This image shows the CVP stained with H&amp;amp;E and scanned by Scanning Electron Microscope (SEM)'''&lt;br /&gt;
[[File:CVP of WT(top) and DKO(bottom) mice with H&amp;amp;E and SEM.png]]&lt;br /&gt;
&lt;br /&gt;
'''This image shows the location of the CVP and the increased number in DKO mice by SEM'''&lt;br /&gt;
[[File:Mouse circumvallate papilla 01.jpg|300px]]&lt;br /&gt;
&lt;br /&gt;
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).&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
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).&lt;br /&gt;
&lt;br /&gt;
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''&amp;amp; ''Spry 1&amp;amp;2''work antagonistically through receptor tyrosine kinase (RTK)signalling.&lt;br /&gt;
&lt;br /&gt;
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.&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;21655085&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
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==Gustatory System==&lt;br /&gt;
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[[Image:Taste qualities.gif|thumb|The five basic tastes]]&lt;br /&gt;
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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.&lt;br /&gt;
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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.&amp;lt;ref name=PMID20696704&amp;gt;&amp;lt;pubmed&amp;gt;20696704&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
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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 &amp;lt;ref name=PMID20696704/&amp;gt; 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.&lt;br /&gt;
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===Cell Biology===&lt;br /&gt;
&lt;br /&gt;
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.&lt;br /&gt;
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====Type II receptors====&lt;br /&gt;
&lt;br /&gt;
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:&lt;br /&gt;
&lt;br /&gt;
# Stimulates gustatory nerve afferents which project to gustatory nuclei  in the spinal cord&lt;br /&gt;
# Excites Type III presynaptic nerve fibers to release serotonin. &lt;br /&gt;
# Has a positive feedback effect on type II receptor cells, increasing the level of ATP production.&lt;br /&gt;
&lt;br /&gt;
        &lt;br /&gt;
&lt;br /&gt;
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.&lt;br /&gt;
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==Taste Map==&lt;br /&gt;
[[Image:Taste map.png|thumb|left|250px|Obsolete idea of the tongue map]]&lt;br /&gt;
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.&lt;br /&gt;
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===Neural Pathways===&lt;br /&gt;
&lt;br /&gt;
'''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''. &lt;br /&gt;
&lt;br /&gt;
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:  &lt;br /&gt;
&lt;br /&gt;
* ''Facial nerve n''. -  carries taste information from the anterior 2/3 of the tongue.&lt;br /&gt;
* ''Hypoglossal n.'' - carries taste information from the posterior 1/3 of the tongue.&lt;br /&gt;
* ''Vagus n''. - carries taste information from the palate&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
'''Second order neurons''' - From the NTS second order neurons carry taste information to the Ventral posteromedial (VPM) nucleus in the thalamus.&amp;lt;ref name=PMID21885776/&amp;gt;&lt;br /&gt;
&lt;br /&gt;
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.  &lt;br /&gt;
&lt;br /&gt;
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.&lt;br /&gt;
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===Cortical Areas===&lt;br /&gt;
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[[Image:Primary gustatory cortex.png|thumb|Primary gustatory cortex]]&lt;br /&gt;
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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)&amp;lt;ref name=PMID22245354&amp;gt;&amp;lt;pubmed&amp;gt;22245354&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;, with the secondary taste cortex in the caudolateral orbitofrontal cortex.&amp;lt;ref name=PMID21305668&amp;gt;&amp;lt;pubmed&amp;gt;21305668&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;  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.&amp;lt;ref name=PMID21885776&amp;gt;&amp;lt;pubmed&amp;gt;21885776&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; These findings lend weight to the idea that there is only one receptor for each taste quality.&lt;br /&gt;
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&lt;br /&gt;
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).&amp;lt;ref name=PMID21885776/&amp;gt; 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&lt;br /&gt;
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&lt;br /&gt;
==Current Research==&lt;br /&gt;
&lt;br /&gt;
[[File:Mousetounge histologicalstain.jpg|right|thumb|200px|Image shows histological stains of a mice tongue showing dysplasia]]&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
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. &lt;br /&gt;
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.&lt;br /&gt;
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&lt;br /&gt;
'''Synergistic relationships of Six Genes '''&lt;br /&gt;
&lt;br /&gt;
In an animal study using mice by Suzuki Y, Ikeda K, Kawakami K.(2011)  Firstly nominating &amp;quot;[[#Glossary |'''Six Genes''']]&amp;quot; as a major component in [[#Glossary |'''gustatory ''']] development, stating that deficiencies in certain Six genes (specifically Six1 &amp;amp; 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 &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;21978088&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
[[File:Highpowered_microscope.jpg|Left|thumb|200px|Image of a high powered microscope]]&lt;br /&gt;
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'''Neural Crest responsibilities '''&lt;br /&gt;
&lt;br /&gt;
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.&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;22659543&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
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&lt;br /&gt;
'''Augmentation of Endoderm'''&lt;br /&gt;
&lt;br /&gt;
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 &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;22581563&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
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&lt;br /&gt;
'''Changes in Taste Cells over time'''&lt;br /&gt;
&lt;br /&gt;
Research by &lt;br /&gt;
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.  &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;22643728&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
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'''Shh key component of taste bud proginators'''&lt;br /&gt;
&lt;br /&gt;
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.&lt;br /&gt;
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 &amp;quot;Axiocam CCD camera and Axioplan fluorescence microscope with Axiovision software&amp;quot; a study by Harlow, Yang, Williams, Barlow (2011)&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;PMC2674259&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
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'''WNT family exhibit various roles'''&lt;br /&gt;
&lt;br /&gt;
 [[File:Abnormal of tongue.jpg|thumb|200px|Image shows an example of tongue abnormalities, this is called &amp;quot;double tongue&amp;quot; each side has independent movement!]]&lt;br /&gt;
&lt;br /&gt;
The WNT gene family has a function of signaling work antagonistically through receptor tyrosine kinase (RTK) signaling. However, the deletion of Sprouty Homolog 2 (Spry2) led to the increase of chimaeric virus particles (CVPs) and a significant decrease in number of fungiform papillae. In contrast, the absence of Fibroblast growth factor 10 (Fgf10) in conjunction with 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. 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. &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;PMC2768563&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
[[File:Developing_tongue_histology_001.jpg|right|thumb|200px|HIstological stain of a developing rat tongue]]&lt;br /&gt;
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==Glossary==&lt;br /&gt;
&lt;br /&gt;
* '''Circumvallate papillae''' - &lt;br /&gt;
&lt;br /&gt;
* '''Ectoderm'''- outer germ layer of embryo&lt;br /&gt;
&lt;br /&gt;
* '''Endoderm''' - inner germ layer of embryo&lt;br /&gt;
&lt;br /&gt;
* '''Epithelium''' - basic animal tissue that is composed of tightly packed cells, usually covering the outer portion of organs&lt;br /&gt;
&lt;br /&gt;
* '''Exocystosis''' - movement of contents out of cell&lt;br /&gt;
&lt;br /&gt;
* '''Filiform papillae''' - &lt;br /&gt;
&lt;br /&gt;
* '''Foliate papillae''' - &lt;br /&gt;
&lt;br /&gt;
* '''Fungiform papillae''' - &lt;br /&gt;
&lt;br /&gt;
* '''Ganglia''' - the accumulation of a nerve cell body&lt;br /&gt;
&lt;br /&gt;
* '''Growth factor''' - a substance that stimulates the growth of cells&lt;br /&gt;
&lt;br /&gt;
* '''Gustatory''' - anything that relates to the taste sense&lt;br /&gt;
&lt;br /&gt;
* '''Hydrolysis''' - breakdown of a chemical when it reacts with water&lt;br /&gt;
&lt;br /&gt;
* '''Mesoderm''' - middle germ layer of embryo&lt;br /&gt;
&lt;br /&gt;
* '''Mesenchyme''' - multipotential cells&lt;br /&gt;
&lt;br /&gt;
* '''Neural crest''' - a part of the ectoderm found on both sides of the neural tube&lt;br /&gt;
&lt;br /&gt;
* '''Neuron''' - most simplistic unit of the nervous system&lt;br /&gt;
&lt;br /&gt;
* '''Neurotransmitter''' - chemicals which allow the passing of signals from neuron to neuron via connecting part (synapse) &lt;br /&gt;
&lt;br /&gt;
* '''Papillae''' - small rough surface projection&lt;br /&gt;
&lt;br /&gt;
* '''Six genes''' - a family of genes&lt;br /&gt;
&lt;br /&gt;
* '''Sonic hedgehog (Shh)''' - signalling protein involved in normal development&lt;br /&gt;
&lt;br /&gt;
* '''Sulcus terminalis''' - describes a physical transition point separating the anterior 2/3 of the tongue from the posterior 1/3&lt;br /&gt;
&lt;br /&gt;
* '''Tamoxifen''' - hormonal altering drug&lt;br /&gt;
&lt;br /&gt;
* '''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).&lt;br /&gt;
&lt;br /&gt;
* '''Type II taste cells''' - Receptor cells acting as primary detectors of sweet, bitter or umami taste.&lt;br /&gt;
&lt;br /&gt;
* '''Type III taste cells''' - Presynaptic cells that respond to sweet, salty, sour, bitter and umami compounds.&lt;br /&gt;
&lt;br /&gt;
== References ==&lt;br /&gt;
&amp;lt;references/&amp;gt;&lt;br /&gt;
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==External Links==&lt;br /&gt;
{{External Links}}&lt;br /&gt;
&lt;br /&gt;
[http://www.surgicalneurologyint.com/article.asp?issn=2152-7806;year=2012;volume=3;issue=1;spage=23;epage=23;aulast=Manjila]&lt;br /&gt;
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http://embryology.med.unsw.edu.au/embryology/index.php?title=2012_Group_Project_4&lt;br /&gt;
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http://www.webmd.com/oral-health/picture-of-the-tongue&lt;br /&gt;
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http://www.tutorvista.com/content/biology/biology-iv/nervous-coordination/tongue-structure.php#parts-of-tongue&lt;br /&gt;
&lt;br /&gt;
http://www.cf.ac.uk/biosi/staffinfo/jacob/teaching/sensory/taste.html&lt;br /&gt;
&lt;br /&gt;
--[[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.&lt;br /&gt;
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----&lt;br /&gt;
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{{2012Projects}}&lt;/div&gt;</summary>
		<author><name>Z3330795</name></author>
	</entry>
	<entry>
		<id>https://embryology.med.unsw.edu.au/embryology/index.php?title=2012_Group_Project_3&amp;diff=105133</id>
		<title>2012 Group Project 3</title>
		<link rel="alternate" type="text/html" href="https://embryology.med.unsw.edu.au/embryology/index.php?title=2012_Group_Project_3&amp;diff=105133"/>
		<updated>2012-10-02T23:25:09Z</updated>

		<summary type="html">&lt;p&gt;Z3330795: /* Adult Tongue and Taste Buds – Structure and Function */&lt;/p&gt;
&lt;hr /&gt;
&lt;div&gt;=Taste Development=&lt;br /&gt;
&lt;br /&gt;
You are out to dinner and your meal arrives in front of you, the aromas and the presentation of your food strikes you immediately. Half way through, the waiter returns and asks “How does your meal taste?”  The answer is not as simple as one might think. Why does the meal taste pleasant? How do we experience different tastes? In the following page, we aim to discern how exactly one would answer these questions by looking at the embryological development of the taste system from week to week. &lt;br /&gt;
&lt;br /&gt;
Taste is a complex sensory system and its precise workings are to this day not fully understood. What makes it so complicated is the interaction between the structure of tongue and taste buds and how this contributes to the representation of taste qualities (salty, bitter, sweet, sour and umami) in the brain. We will also look at some current research on animal models being undertaken to evaluate the role of specific genes in the development of sensory structures. By looking at the taste system’s genetic basis, we now have a greater understanding of the abnormalities that may occur during development and a direction to pursue in future research to attempt to fill in the gaps of scientific knowledge.&lt;br /&gt;
&lt;br /&gt;
==Adult Tongue and Taste Buds – Structure and Function==&lt;br /&gt;
&lt;br /&gt;
'''Structure'''&lt;br /&gt;
&lt;br /&gt;
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.  &amp;lt;ref name=http://www.webmd.com/oral-health/picture-of-the-tongue &amp;lt;ref&amp;gt;&lt;br /&gt;
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''''The image below is a simplistic diagram of the surface of the tongue showing the locations of the different papillae and other important features'''&lt;br /&gt;
&lt;br /&gt;
{|&lt;br /&gt;
| [[Image:Drawing of Tongue.png|centre|500px]]&lt;br /&gt;
&lt;br /&gt;
[[File:Taste_pathway.jpg|right|thumb|200px|Simplistic Pathway of Taste]]&lt;br /&gt;
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&lt;br /&gt;
'''Papillae'''&lt;br /&gt;
&lt;br /&gt;
There are 4 types of papillae on the tongue.&lt;br /&gt;
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. &lt;br /&gt;
&lt;br /&gt;
[[File:Papillae.jpg|Left|thumb|200px|Close up of Human Tongue Papillae]]&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
[[File:Fungiformpapillae.jpg|left|thumb|200px|Fungiform Papillae]]&lt;br /&gt;
&lt;br /&gt;
[[File:Circumvallatepapillae.jpg |left|thumb|200px|Circumvallate Papillae]]&lt;br /&gt;
&lt;br /&gt;
[[File:Filiformpapillae.jpg|left|200px|thumb|Foliate Papillae]]&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
'''Function'''&lt;br /&gt;
&lt;br /&gt;
The Tongue has muscular and sensory functions, muscular functions include swallowing and speech where as sensory function involves taste. This section will focus on the sensory functions of the tongue.&lt;br /&gt;
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.&lt;br /&gt;
&lt;br /&gt;
[[File:Taste_bud_1.jpg|right|thumb|200px|Cross section of a taste bud unit|centre|Cross section of a taste bud unit]]&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
'''Link Between Taste and Smell'''&lt;br /&gt;
&lt;br /&gt;
The pathways of smell and taste are very similar. Pathways both involve the conversion of a dissolved chemical stimulus transformed into a electrical impulse for interpretation by the brain.	&lt;br /&gt;
Taste and smell overlap when humans experience flavour, flavour involves an interaction of taste, smell, texture and temperature, where taste is only a portion of this interaction. when the brain interprets a flavour, contribution from other senses has a significant role in identification. In conclusion Taste and Smell in combination with other senses help develop a sensory interpretation called flavour.&lt;br /&gt;
[[File:Human smelling.jpg|500px|centre]]&lt;br /&gt;
&lt;br /&gt;
==History of Discoveries==&lt;br /&gt;
&lt;br /&gt;
{| cellpadding=5 style=&amp;quot;border:1px solid #BBB&amp;quot;&lt;br /&gt;
|- bgcolor=&amp;quot;#faecc8&amp;quot;&lt;br /&gt;
|''' Date'''|| '''Significant Discovery'''&lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#faf6ed&amp;quot;&lt;br /&gt;
|'''350BC'''&lt;br /&gt;
|| Aristotle writes about the basic tastes, sweet and bitter. He also notes that it can be modified by salty and acidic. &amp;lt;ref name=&amp;quot;PMID22717400&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;22717400&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#faecc8&amp;quot;&lt;br /&gt;
|'''1901'''&lt;br /&gt;
|| D. Hanig publishes a paper describing taste sensitivity in different regions of the tongue. &lt;br /&gt;
''Interesting fact:'' The modern concept of a 'tongue map' is a misinterpretation of this study. &amp;lt;ref name=&amp;quot;PMID22717400&amp;quot;/&amp;gt;&lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#faf6ed&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''1908'''&lt;br /&gt;
|Kikunae Ikeda, a professor of the Tokyo Imperial University, discovered and identified the fifth basic taste: umami (savouriness), made palatable by glutamate.  &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;12438213&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
[http://chemse.oxfordjournals.org/content/27/9/847.long New Seasonings]&lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#faecc8&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''1931-32'''&lt;br /&gt;
| A chemist named Arthur Fox and his college noted that they had different sensitivities to the bitter tasting Phenylthiocarbamide (PTC).&amp;lt;ref&amp;gt;Blakeslee AF, Fox AL. Our different taste worlds. J Hered. 1932;23:97–107.&amp;lt;/ref&amp;gt; Geneticists later confirm these findings, and discover that non-tasting is a recessive genetic trait. &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;17782493&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/pubmed/17782493 Inherited taste deficiency] &lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#faf6ed&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''1965'''&lt;br /&gt;
|Farbman's study of the developing taste but in rat fungiform papilla was significant in increasing our understanding of taste bud development. &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;14300090&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
[http://www.sciencedirect.com/science/article/pii/0012160665900400 Electron microscope study of the developing taste bud in rat fungiform papilla.]&lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#faecc8&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''1992'''&lt;br /&gt;
|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. &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;1608467 &amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
[http://www.nature.com/nature/journal/v357/n6379/abs/357563a0.html Gustducin is a taste-cell-specific G protein closely related to the transducins]&lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#faf6ed&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''1995'''&lt;br /&gt;
|Barlow et al. experimented with Axolotl salamanders and concluded that taste buds from this species arise exclusively from epithelial tissue, &amp;quot;oropharyngeal [[#Glossary |'''epithelium''']]&amp;quot;. &amp;lt;ref name=&amp;quot;PMID17826760&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;17826760&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/pubmed/17826760 Embryonic origin of gustatory cranial sensory neurons] &lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#faecc8&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''1996'''&lt;br /&gt;
| 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 &amp;quot;at least dual function of embryonic/fetal taste buds&amp;quot;, including non-gustatory, paracrine functions prior to the 14th week and gustatory after the 14th week. &amp;lt;ref name=&amp;quot;PMID8955790&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;8955790&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/pubmed/8955790 Embryonic and early fetal development of human taste buds: a transmission electron microscopical study]&lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#faf6ed&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''2000'''&lt;br /&gt;
|Chandrashekar, J. et al. discover the first taste sonsors, the T2R bitter taste receptors. &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;10761935&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
[http://www.sciencedirect.com/science/article/pii/S0092867400807060 T2Rs Function as Bitter Taste Receptors]&lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#faecc8&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''2001'''&lt;br /&gt;
|Nelson, G. et al. discover the sweet receptor: a combination of T1R2 and T1R3. &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;11509186&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/pubmed/11509186?dopt=Abstract&amp;amp;holding=npg Mammalian sweet taste receptors.]&lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#faf6ed&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''2002'''&lt;br /&gt;
|Nelson G. et al. discover the amino acid (umami) taste receptor: a combination of T1R1 and T1R3 identified.  &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;11894099&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/pubmed/11894099?dopt=Abstract&amp;amp;holding=npg An amino-acid taste receptor]&lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#faecc8&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''2005'''&lt;br /&gt;
|Dyer, J. et al. discover sweet taste receptors in the GI tract. &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;17855558&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1986582/ Sweet taste signaling in the gut]&lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#faf6ed&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''2006'''&lt;br /&gt;
|Huang, A. L et al. discover cells for sour taste, identified by PKD2L1 (a polycystic kidney disease-like ion channel). &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;16929298&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1571047/ The Cells and Logic for Mammalian Sour Taste detection]&lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#faecc8&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''2007'''&lt;br /&gt;
|Harlow DE, Barlow LA of the University of Colorado Denver Health Sciences Center provide evidence of the &amp;quot;embryonic origin of gustatory cranial sensory neurons&amp;quot;. &amp;lt;ref name=&amp;quot;PMID17826760&amp;quot;/&amp;gt;&lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/pubmed/17826760 Embryonic origin of gustatory cranial sensory neurons.]&lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#faf6ed&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''2009'''&lt;br /&gt;
|A study by Hevezi P et al, presents &amp;quot;the first comprehensive characterization of gene expression in primate taste buds&amp;quot;, as opposed to previous studies which focused on rodents. &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;19636377&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/pubmed/19636377 Genome-wide analysis of gene expression in primate taste buds reveals links to diverse processes]&lt;br /&gt;
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|- bgcolor=&amp;quot;#faecc8&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''2010'''&lt;br /&gt;
|Chandrashekar, J. et al. identify epithelial sodium channel (ENaC) as the sodium-salt taste receptor. &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;20107438&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/pubmed/20107438?dopt=Abstract&amp;amp;holding=npg The cells and peripheral representation of sodium taste in mice]&lt;br /&gt;
|}&lt;br /&gt;
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== Human Weekly Development - Two Prominent Studies ==&lt;br /&gt;
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. &lt;br /&gt;
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The findings of these two studies are summarized in the table below. The figures provided relate to the images on their respective research papers.&lt;br /&gt;
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# [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] &lt;br /&gt;
# [http://chemse.oxfordjournals.org/content/22/6/601.long Scanning electron microscopical studies of developing gustatory papillae in humans, 1997]  &lt;br /&gt;
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===Timeline of Developmental Processes of Human Taste Buds===&lt;br /&gt;
{| cellpadding=5 style=&amp;quot;border:1px solid #BBB&amp;quot;&lt;br /&gt;
|- bgcolor=&amp;quot;#89CFF0&amp;quot;&lt;br /&gt;
|'''Postovulatory Week'''||'''Description'''&lt;br /&gt;
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|- bgcolor=&amp;quot;#BCD4E6&amp;quot;&lt;br /&gt;
|'''Week 6''' ||&lt;br /&gt;
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. &amp;lt;ref name=&amp;quot;PMID9455607&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;9455607&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
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|- bgcolor=&amp;quot;#89CFF0&amp;quot;&lt;br /&gt;
| '''Weeks 6 to 7'''|| &lt;br /&gt;
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. &amp;lt;ref name=PMID8955790/&amp;gt;&lt;br /&gt;
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|- bgcolor=&amp;quot;#BCD4E6&amp;quot;&lt;br /&gt;
| '''Week 7 '''||&lt;br /&gt;
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.  &amp;lt;ref name=PMID9455607/&amp;gt; &lt;br /&gt;
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|- bgcolor=&amp;quot;#89CFF0&amp;quot;&lt;br /&gt;
| ''' Week 8  ''' ||&lt;br /&gt;
* The taste bud primordium are still differentiated, elongated epithelial cells, resting on a slightly developed core of young dermal papilla.&lt;br /&gt;
* 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. &lt;br /&gt;
* Ciliated cells also appear around the 8th week, however the significance of these cells which are scattered randomly across the lingual surface remains unclear. &amp;lt;ref name=PMID8955790/&amp;gt; &lt;br /&gt;
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|- bgcolor=&amp;quot;#BCD4E6&amp;quot;&lt;br /&gt;
|'''  Week 9''' ||&lt;br /&gt;
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). &amp;lt;ref name=PMID9455607/&amp;gt;&lt;br /&gt;
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|- bgcolor=&amp;quot;#89CFF0&amp;quot;&lt;br /&gt;
|'''  Weeks 10-11''' ||&lt;br /&gt;
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). &amp;lt;ref name=PMID8955790/&amp;gt; &lt;br /&gt;
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|- bgcolor=&amp;quot;#BCD4E6&amp;quot;&lt;br /&gt;
|''' Week 12 ''' ||&lt;br /&gt;
Taste bud cells are more clearly differentiated into epithelial cell types II and III. &amp;lt;ref name=PMID8955790/&amp;gt; &lt;br /&gt;
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|- bgcolor=&amp;quot;#89CFF0&amp;quot;&lt;br /&gt;
|''' Weeks 12-13  ''' ||&lt;br /&gt;
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). &amp;lt;ref name=PMID8955790/&amp;gt; &lt;br /&gt;
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|- bgcolor=&amp;quot;#BCD4E6&amp;quot;&lt;br /&gt;
|''' Weeks 14 -15 ''' ||&lt;br /&gt;
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. &amp;lt;ref name=PMID8955790/&amp;gt; &lt;br /&gt;
|}&lt;br /&gt;
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==Abnormalities==&lt;br /&gt;
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It should be mentioned that gustatory abnormalities have not been widely researched. Most research conducted in this field has been conducted through animal testing on mice and this is the basis of information provided below. &lt;br /&gt;
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===Knocking out P2X Receptors===&lt;br /&gt;
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[[File:Image of taste being evoked by visualising ATP release.jpeg|Left|thumb|200px|Evoking taste - ATP release in tongue]]&lt;br /&gt;
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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. &lt;br /&gt;
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It should be noted that the taste buds in DKO are functional, but are not stimulated by the administration of tastants. &lt;br /&gt;
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The transmission of release of ATP is secretion through gap junction hemichannels (pannexin 1 gap junction).&lt;br /&gt;
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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.&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;21940456&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
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===FGF signalling and genes===&lt;br /&gt;
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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.&lt;br /&gt;
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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 (&amp;quot;Fgf10&amp;quot;) 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 &amp;quot;Fgf10&amp;quot; to limit the size of the CVP progenitor placode. Exclusive expression of ''Fgf10'' in the [[#Glossary |'''mesenchyme''']] is necessary for the formation of CVP. &lt;br /&gt;
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'''This image shows the CVP stained with H&amp;amp;E and scanned by Scanning Electron Microscope (SEM)'''&lt;br /&gt;
[[File:CVP of WT(top) and DKO(bottom) mice with H&amp;amp;E and SEM.png]]&lt;br /&gt;
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'''This image shows the location of the CVP and the increased number in DKO mice by SEM'''&lt;br /&gt;
[[File:Mouse circumvallate papilla 01.jpg|300px]]&lt;br /&gt;
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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).&lt;br /&gt;
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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).&lt;br /&gt;
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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''&amp;amp; ''Spry 1&amp;amp;2''work antagonistically through receptor tyrosine kinase (RTK)signalling.&lt;br /&gt;
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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.&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;21655085&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
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==Gustatory System==&lt;br /&gt;
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[[Image:Taste qualities.gif|thumb|The five basic tastes]]&lt;br /&gt;
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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.&lt;br /&gt;
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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.&amp;lt;ref name=PMID20696704&amp;gt;&amp;lt;pubmed&amp;gt;20696704&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
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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 &amp;lt;ref name=PMID20696704/&amp;gt; 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.&lt;br /&gt;
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===Cell Biology===&lt;br /&gt;
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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.&lt;br /&gt;
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====Type II receptors====&lt;br /&gt;
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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:&lt;br /&gt;
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# Stimulates gustatory nerve afferents which project to gustatory nuclei  in the spinal cord&lt;br /&gt;
# Excites Type III presynaptic nerve fibers to release serotonin. &lt;br /&gt;
# Has a positive feedback effect on type II receptor cells, increasing the level of ATP production.&lt;br /&gt;
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        &lt;br /&gt;
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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.&lt;br /&gt;
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==Taste Map==&lt;br /&gt;
[[Image:Taste map.png|thumb|left|250px|Obsolete idea of the tongue map]]&lt;br /&gt;
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.&lt;br /&gt;
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===Neural Pathways===&lt;br /&gt;
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'''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''. &lt;br /&gt;
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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:  &lt;br /&gt;
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* ''Facial nerve n''. -  carries taste information from the anterior 2/3 of the tongue.&lt;br /&gt;
* ''Hypoglossal n.'' - carries taste information from the posterior 1/3 of the tongue.&lt;br /&gt;
* ''Vagus n''. - carries taste information from the palate&lt;br /&gt;
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'''Second order neurons''' - From the NTS second order neurons carry taste information to the Ventral posteromedial (VPM) nucleus in the thalamus.&amp;lt;ref name=PMID21885776/&amp;gt;&lt;br /&gt;
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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.  &lt;br /&gt;
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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.&lt;br /&gt;
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===Cortical Areas===&lt;br /&gt;
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[[Image:Primary gustatory cortex.png|thumb|Primary gustatory cortex]]&lt;br /&gt;
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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)&amp;lt;ref name=PMID22245354&amp;gt;&amp;lt;pubmed&amp;gt;22245354&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;, with the secondary taste cortex in the caudolateral orbitofrontal cortex.&amp;lt;ref name=PMID21305668&amp;gt;&amp;lt;pubmed&amp;gt;21305668&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;  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.&amp;lt;ref name=PMID21885776&amp;gt;&amp;lt;pubmed&amp;gt;21885776&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; These findings lend weight to the idea that there is only one receptor for each taste quality.&lt;br /&gt;
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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).&amp;lt;ref name=PMID21885776/&amp;gt; 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&lt;br /&gt;
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==Current Research==&lt;br /&gt;
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[[File:Mousetounge histologicalstain.jpg|right|thumb|200px|Image shows histological stains of a mice tongue showing dysplasia]]&lt;br /&gt;
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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. &lt;br /&gt;
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.&lt;br /&gt;
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'''Synergistic relationships of Six Genes '''&lt;br /&gt;
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In an animal study using mice by Suzuki Y, Ikeda K, Kawakami K.(2011)  Firstly nominating &amp;quot;[[#Glossary |'''Six Genes''']]&amp;quot; as a major component in [[#Glossary |'''gustatory ''']] development, stating that deficiencies in certain Six genes (specifically Six1 &amp;amp; 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 &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;21978088&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
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[[File:Highpowered_microscope.jpg|Left|thumb|200px|Image of a high powered microscope]]&lt;br /&gt;
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'''Neural Crest responsibilities '''&lt;br /&gt;
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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.&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;22659543&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
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'''Augmentation of Endoderm'''&lt;br /&gt;
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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 &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;22581563&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
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'''Changes in Taste Cells over time'''&lt;br /&gt;
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Research by &lt;br /&gt;
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.  &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;22643728&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
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'''Shh key component of taste bud proginators'''&lt;br /&gt;
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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.&lt;br /&gt;
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 &amp;quot;Axiocam CCD camera and Axioplan fluorescence microscope with Axiovision software&amp;quot; a study by Harlow, Yang, Williams, Barlow (2011)&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;PMC2674259&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
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'''WNT family exhibit various roles'''&lt;br /&gt;
&lt;br /&gt;
 [[File:Abnormal of tongue.jpg|thumb|200px|Image shows an example of tongue abnormalities, this is called &amp;quot;double tongue&amp;quot; each side has independent movement!]]&lt;br /&gt;
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The WNT gene family has a function of signaling work antagonistically through receptor tyrosine kinase (RTK) signaling. However, the deletion of Sprouty Homolog 2 (Spry2) led to the increase of chimaeric virus particles (CVPs) and a significant decrease in number of fungiform papillae. In contrast, the absence of Fibroblast growth factor 10 (Fgf10) in conjunction with 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. 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. &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;PMC2768563&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
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[[File:Developing_tongue_histology_001.jpg|right|thumb|200px|HIstological stain of a developing rat tongue]]&lt;br /&gt;
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==Glossary==&lt;br /&gt;
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* '''Circumvallate papillae''' - &lt;br /&gt;
&lt;br /&gt;
* '''Ectoderm'''- outer germ layer of embryo&lt;br /&gt;
&lt;br /&gt;
* '''Endoderm''' - inner germ layer of embryo&lt;br /&gt;
&lt;br /&gt;
* '''Epithelium''' - basic animal tissue that is composed of tightly packed cells, usually covering the outer portion of organs&lt;br /&gt;
&lt;br /&gt;
* '''Exocystosis''' - movement of contents out of cell&lt;br /&gt;
&lt;br /&gt;
* '''Filiform papillae''' - &lt;br /&gt;
&lt;br /&gt;
* '''Foliate papillae''' - &lt;br /&gt;
&lt;br /&gt;
* '''Fungiform papillae''' - &lt;br /&gt;
&lt;br /&gt;
* '''Ganglia''' - the accumulation of a nerve cell body&lt;br /&gt;
&lt;br /&gt;
* '''Growth factor''' - a substance that stimulates the growth of cells&lt;br /&gt;
&lt;br /&gt;
* '''Gustatory''' - anything that relates to the taste sense&lt;br /&gt;
&lt;br /&gt;
* '''Hydrolysis''' - breakdown of a chemical when it reacts with water&lt;br /&gt;
&lt;br /&gt;
* '''Mesoderm''' - middle germ layer of embryo&lt;br /&gt;
&lt;br /&gt;
* '''Mesenchyme''' - multipotential cells&lt;br /&gt;
&lt;br /&gt;
* '''Neural crest''' - a part of the ectoderm found on both sides of the neural tube&lt;br /&gt;
&lt;br /&gt;
* '''Neuron''' - most simplistic unit of the nervous system&lt;br /&gt;
&lt;br /&gt;
* '''Neurotransmitter''' - chemicals which allow the passing of signals from neuron to neuron via connecting part (synapse) &lt;br /&gt;
&lt;br /&gt;
* '''Papillae''' - small rough surface projection&lt;br /&gt;
&lt;br /&gt;
* '''Six genes''' - a family of genes&lt;br /&gt;
&lt;br /&gt;
* '''Sonic hedgehog (Shh)''' - signalling protein involved in normal development&lt;br /&gt;
&lt;br /&gt;
* '''Sulcus terminalis''' - describes a physical transition point separating the anterior 2/3 of the tongue from the posterior 1/3&lt;br /&gt;
&lt;br /&gt;
* '''Tamoxifen''' - hormonal altering drug&lt;br /&gt;
&lt;br /&gt;
* '''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).&lt;br /&gt;
&lt;br /&gt;
* '''Type II taste cells''' - Receptor cells acting as primary detectors of sweet, bitter or umami taste.&lt;br /&gt;
&lt;br /&gt;
* '''Type III taste cells''' - Presynaptic cells that respond to sweet, salty, sour, bitter and umami compounds.&lt;br /&gt;
&lt;br /&gt;
== References ==&lt;br /&gt;
&amp;lt;references/&amp;gt;&lt;br /&gt;
&lt;br /&gt;
==External Links==&lt;br /&gt;
{{External Links}}&lt;br /&gt;
&lt;br /&gt;
[http://www.surgicalneurologyint.com/article.asp?issn=2152-7806;year=2012;volume=3;issue=1;spage=23;epage=23;aulast=Manjila]&lt;br /&gt;
&lt;br /&gt;
http://embryology.med.unsw.edu.au/embryology/index.php?title=2012_Group_Project_4&lt;br /&gt;
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http://www.webmd.com/oral-health/picture-of-the-tongue&lt;br /&gt;
&lt;br /&gt;
http://www.tutorvista.com/content/biology/biology-iv/nervous-coordination/tongue-structure.php#parts-of-tongue&lt;br /&gt;
&lt;br /&gt;
http://www.cf.ac.uk/biosi/staffinfo/jacob/teaching/sensory/taste.html&lt;br /&gt;
&lt;br /&gt;
--[[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.&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
----&lt;br /&gt;
&lt;br /&gt;
{{2012Projects}}&lt;/div&gt;</summary>
		<author><name>Z3330795</name></author>
	</entry>
	<entry>
		<id>https://embryology.med.unsw.edu.au/embryology/index.php?title=2012_Group_Project_3&amp;diff=105131</id>
		<title>2012 Group Project 3</title>
		<link rel="alternate" type="text/html" href="https://embryology.med.unsw.edu.au/embryology/index.php?title=2012_Group_Project_3&amp;diff=105131"/>
		<updated>2012-10-02T23:21:44Z</updated>

		<summary type="html">&lt;p&gt;Z3330795: /* Adult Tongue and Taste Buds – Structure and Function */&lt;/p&gt;
&lt;hr /&gt;
&lt;div&gt;=Taste Development=&lt;br /&gt;
&lt;br /&gt;
You are out to dinner and your meal arrives in front of you, the aromas and the presentation of your food strikes you immediately. Half way through, the waiter returns and asks “How does your meal taste?”  The answer is not as simple as one might think. Why does the meal taste pleasant? How do we experience different tastes? In the following page, we aim to discern how exactly one would answer these questions by looking at the embryological development of the taste system from week to week. &lt;br /&gt;
&lt;br /&gt;
Taste is a complex sensory system and its precise workings are to this day not fully understood. What makes it so complicated is the interaction between the structure of tongue and taste buds and how this contributes to the representation of taste qualities (salty, bitter, sweet, sour and umami) in the brain. We will also look at some current research on animal models being undertaken to evaluate the role of specific genes in the development of sensory structures. By looking at the taste system’s genetic basis, we now have a greater understanding of the abnormalities that may occur during development and a direction to pursue in future research to attempt to fill in the gaps of scientific knowledge.&lt;br /&gt;
&lt;br /&gt;
==Adult Tongue and Taste Buds – Structure and Function==&lt;br /&gt;
&lt;br /&gt;
'''Structure'''&lt;br /&gt;
&lt;br /&gt;
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.  &lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
''''The image below is a simplistic diagram of the surface of the tongue showing the locations of the different papillae and other important features'''&lt;br /&gt;
&lt;br /&gt;
{|&lt;br /&gt;
| [[Image:Drawing of Tongue.png|centre|500px]]&lt;br /&gt;
&lt;br /&gt;
[[File:Taste_pathway.jpg|right|thumb|200px|Simplistic Pathway of Taste]]&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
'''Papillae'''&lt;br /&gt;
&lt;br /&gt;
There are 4 types of papillae on the tongue.&lt;br /&gt;
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. &lt;br /&gt;
&lt;br /&gt;
[[File:Papillae.jpg|Left|thumb|200px|Close up of Human Tongue Papillae]]&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
[[File:Fungiformpapillae.jpg|left|thumb|200px|Fungiform Papillae]]&lt;br /&gt;
&lt;br /&gt;
[[File:Circumvallatepapillae.jpg |left|thumb|200px|Circumvallate Papillae]]&lt;br /&gt;
&lt;br /&gt;
[[File:Filiformpapillae.jpg|left|200px|thumb|Foliate Papillae]]&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
'''Function'''&lt;br /&gt;
&lt;br /&gt;
The Tongue has muscular and sensory functions, muscular functions include swallowing and speech where as sensory function involves taste. This section will focus on the sensory functions of the tongue.&lt;br /&gt;
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.&lt;br /&gt;
&lt;br /&gt;
[[File:Taste_bud_1.jpg|right|thumb|200px|Cross section of a taste bud unit|centre|Cross section of a taste bud unit]]&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
'''Link Between Taste and Smell'''&lt;br /&gt;
&lt;br /&gt;
The pathways of smell and taste are very similar. Pathways both involve the conversion of a dissolved chemical stimulus transformed into a electrical impulse for interpretation by the brain.	&lt;br /&gt;
Taste and smell overlap when humans experience flavour, flavour involves an interaction of taste, smell, texture and temperature, where taste is only a portion of this interaction. when the brain interprets a flavour, contribution from other senses has a significant role in identification. In conclusion Taste and Smell in combination with other senses help develop a sensory interpretation called flavour.&lt;br /&gt;
[[File:Human smelling.jpg|500px|centre]]&lt;br /&gt;
&lt;br /&gt;
==History of Discoveries==&lt;br /&gt;
&lt;br /&gt;
{| cellpadding=5 style=&amp;quot;border:1px solid #BBB&amp;quot;&lt;br /&gt;
|- bgcolor=&amp;quot;#faecc8&amp;quot;&lt;br /&gt;
|''' Date'''|| '''Significant Discovery'''&lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#faf6ed&amp;quot;&lt;br /&gt;
|'''350BC'''&lt;br /&gt;
|| Aristotle writes about the basic tastes, sweet and bitter. He also notes that it can be modified by salty and acidic. &amp;lt;ref name=&amp;quot;PMID22717400&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;22717400&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#faecc8&amp;quot;&lt;br /&gt;
|'''1901'''&lt;br /&gt;
|| D. Hanig publishes a paper describing taste sensitivity in different regions of the tongue. &lt;br /&gt;
''Interesting fact:'' The modern concept of a 'tongue map' is a misinterpretation of this study. &amp;lt;ref name=&amp;quot;PMID22717400&amp;quot;/&amp;gt;&lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#faf6ed&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''1908'''&lt;br /&gt;
|Kikunae Ikeda, a professor of the Tokyo Imperial University, discovered and identified the fifth basic taste: umami (savouriness), made palatable by glutamate.  &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;12438213&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
[http://chemse.oxfordjournals.org/content/27/9/847.long New Seasonings]&lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#faecc8&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''1931-32'''&lt;br /&gt;
| A chemist named Arthur Fox and his college noted that they had different sensitivities to the bitter tasting Phenylthiocarbamide (PTC).&amp;lt;ref&amp;gt;Blakeslee AF, Fox AL. Our different taste worlds. J Hered. 1932;23:97–107.&amp;lt;/ref&amp;gt; Geneticists later confirm these findings, and discover that non-tasting is a recessive genetic trait. &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;17782493&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/pubmed/17782493 Inherited taste deficiency] &lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#faf6ed&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''1965'''&lt;br /&gt;
|Farbman's study of the developing taste but in rat fungiform papilla was significant in increasing our understanding of taste bud development. &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;14300090&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
[http://www.sciencedirect.com/science/article/pii/0012160665900400 Electron microscope study of the developing taste bud in rat fungiform papilla.]&lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#faecc8&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''1992'''&lt;br /&gt;
|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. &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;1608467 &amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
[http://www.nature.com/nature/journal/v357/n6379/abs/357563a0.html Gustducin is a taste-cell-specific G protein closely related to the transducins]&lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#faf6ed&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''1995'''&lt;br /&gt;
|Barlow et al. experimented with Axolotl salamanders and concluded that taste buds from this species arise exclusively from epithelial tissue, &amp;quot;oropharyngeal [[#Glossary |'''epithelium''']]&amp;quot;. &amp;lt;ref name=&amp;quot;PMID17826760&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;17826760&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/pubmed/17826760 Embryonic origin of gustatory cranial sensory neurons] &lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#faecc8&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''1996'''&lt;br /&gt;
| 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 &amp;quot;at least dual function of embryonic/fetal taste buds&amp;quot;, including non-gustatory, paracrine functions prior to the 14th week and gustatory after the 14th week. &amp;lt;ref name=&amp;quot;PMID8955790&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;8955790&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/pubmed/8955790 Embryonic and early fetal development of human taste buds: a transmission electron microscopical study]&lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#faf6ed&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''2000'''&lt;br /&gt;
|Chandrashekar, J. et al. discover the first taste sonsors, the T2R bitter taste receptors. &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;10761935&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
[http://www.sciencedirect.com/science/article/pii/S0092867400807060 T2Rs Function as Bitter Taste Receptors]&lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#faecc8&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''2001'''&lt;br /&gt;
|Nelson, G. et al. discover the sweet receptor: a combination of T1R2 and T1R3. &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;11509186&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/pubmed/11509186?dopt=Abstract&amp;amp;holding=npg Mammalian sweet taste receptors.]&lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#faf6ed&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''2002'''&lt;br /&gt;
|Nelson G. et al. discover the amino acid (umami) taste receptor: a combination of T1R1 and T1R3 identified.  &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;11894099&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/pubmed/11894099?dopt=Abstract&amp;amp;holding=npg An amino-acid taste receptor]&lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#faecc8&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''2005'''&lt;br /&gt;
|Dyer, J. et al. discover sweet taste receptors in the GI tract. &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;17855558&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1986582/ Sweet taste signaling in the gut]&lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#faf6ed&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''2006'''&lt;br /&gt;
|Huang, A. L et al. discover cells for sour taste, identified by PKD2L1 (a polycystic kidney disease-like ion channel). &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;16929298&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1571047/ The Cells and Logic for Mammalian Sour Taste detection]&lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#faecc8&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''2007'''&lt;br /&gt;
|Harlow DE, Barlow LA of the University of Colorado Denver Health Sciences Center provide evidence of the &amp;quot;embryonic origin of gustatory cranial sensory neurons&amp;quot;. &amp;lt;ref name=&amp;quot;PMID17826760&amp;quot;/&amp;gt;&lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/pubmed/17826760 Embryonic origin of gustatory cranial sensory neurons.]&lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#faf6ed&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''2009'''&lt;br /&gt;
|A study by Hevezi P et al, presents &amp;quot;the first comprehensive characterization of gene expression in primate taste buds&amp;quot;, as opposed to previous studies which focused on rodents. &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;19636377&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/pubmed/19636377 Genome-wide analysis of gene expression in primate taste buds reveals links to diverse processes]&lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#faecc8&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''2010'''&lt;br /&gt;
|Chandrashekar, J. et al. identify epithelial sodium channel (ENaC) as the sodium-salt taste receptor. &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;20107438&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/pubmed/20107438?dopt=Abstract&amp;amp;holding=npg The cells and peripheral representation of sodium taste in mice]&lt;br /&gt;
|}&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
== Human Weekly Development - Two Prominent Studies ==&lt;br /&gt;
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. &lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
The findings of these two studies are summarized in the table below. The figures provided relate to the images on their respective research papers.&lt;br /&gt;
&lt;br /&gt;
# [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] &lt;br /&gt;
# [http://chemse.oxfordjournals.org/content/22/6/601.long Scanning electron microscopical studies of developing gustatory papillae in humans, 1997]  &lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
===Timeline of Developmental Processes of Human Taste Buds===&lt;br /&gt;
{| cellpadding=5 style=&amp;quot;border:1px solid #BBB&amp;quot;&lt;br /&gt;
|- bgcolor=&amp;quot;#89CFF0&amp;quot;&lt;br /&gt;
|'''Postovulatory Week'''||'''Description'''&lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#BCD4E6&amp;quot;&lt;br /&gt;
|'''Week 6''' ||&lt;br /&gt;
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. &amp;lt;ref name=&amp;quot;PMID9455607&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;9455607&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#89CFF0&amp;quot;&lt;br /&gt;
| '''Weeks 6 to 7'''|| &lt;br /&gt;
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. &amp;lt;ref name=PMID8955790/&amp;gt;&lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#BCD4E6&amp;quot;&lt;br /&gt;
| '''Week 7 '''||&lt;br /&gt;
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.  &amp;lt;ref name=PMID9455607/&amp;gt; &lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#89CFF0&amp;quot;&lt;br /&gt;
| ''' Week 8  ''' ||&lt;br /&gt;
* The taste bud primordium are still differentiated, elongated epithelial cells, resting on a slightly developed core of young dermal papilla.&lt;br /&gt;
* 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. &lt;br /&gt;
* Ciliated cells also appear around the 8th week, however the significance of these cells which are scattered randomly across the lingual surface remains unclear. &amp;lt;ref name=PMID8955790/&amp;gt; &lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#BCD4E6&amp;quot;&lt;br /&gt;
|'''  Week 9''' ||&lt;br /&gt;
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). &amp;lt;ref name=PMID9455607/&amp;gt;&lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#89CFF0&amp;quot;&lt;br /&gt;
|'''  Weeks 10-11''' ||&lt;br /&gt;
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). &amp;lt;ref name=PMID8955790/&amp;gt; &lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#BCD4E6&amp;quot;&lt;br /&gt;
|''' Week 12 ''' ||&lt;br /&gt;
Taste bud cells are more clearly differentiated into epithelial cell types II and III. &amp;lt;ref name=PMID8955790/&amp;gt; &lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#89CFF0&amp;quot;&lt;br /&gt;
|''' Weeks 12-13  ''' ||&lt;br /&gt;
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). &amp;lt;ref name=PMID8955790/&amp;gt; &lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#BCD4E6&amp;quot;&lt;br /&gt;
|''' Weeks 14 -15 ''' ||&lt;br /&gt;
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. &amp;lt;ref name=PMID8955790/&amp;gt; &lt;br /&gt;
|}&lt;br /&gt;
&lt;br /&gt;
==Abnormalities==&lt;br /&gt;
&lt;br /&gt;
It should be mentioned that gustatory abnormalities have not been widely researched. Most research conducted in this field has been conducted through animal testing on mice and this is the basis of information provided below. &lt;br /&gt;
&lt;br /&gt;
===Knocking out P2X Receptors===&lt;br /&gt;
&lt;br /&gt;
[[File:Image of taste being evoked by visualising ATP release.jpeg|Left|thumb|200px|Evoking taste - ATP release in tongue]]&lt;br /&gt;
&lt;br /&gt;
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. &lt;br /&gt;
&lt;br /&gt;
It should be noted that the taste buds in DKO are functional, but are not stimulated by the administration of tastants. &lt;br /&gt;
&lt;br /&gt;
The transmission of release of ATP is secretion through gap junction hemichannels (pannexin 1 gap junction).&lt;br /&gt;
&lt;br /&gt;
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.&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;21940456&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
===FGF signalling and genes===&lt;br /&gt;
&lt;br /&gt;
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.&lt;br /&gt;
&lt;br /&gt;
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 (&amp;quot;Fgf10&amp;quot;) 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 &amp;quot;Fgf10&amp;quot; to limit the size of the CVP progenitor placode. Exclusive expression of ''Fgf10'' in the [[#Glossary |'''mesenchyme''']] is necessary for the formation of CVP. &lt;br /&gt;
&lt;br /&gt;
'''This image shows the CVP stained with H&amp;amp;E and scanned by Scanning Electron Microscope (SEM)'''&lt;br /&gt;
[[File:CVP of WT(top) and DKO(bottom) mice with H&amp;amp;E and SEM.png]]&lt;br /&gt;
&lt;br /&gt;
'''This image shows the location of the CVP and the increased number in DKO mice by SEM'''&lt;br /&gt;
[[File:Mouse circumvallate papilla 01.jpg|300px]]&lt;br /&gt;
&lt;br /&gt;
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).&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
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).&lt;br /&gt;
&lt;br /&gt;
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''&amp;amp; ''Spry 1&amp;amp;2''work antagonistically through receptor tyrosine kinase (RTK)signalling.&lt;br /&gt;
&lt;br /&gt;
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.&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;21655085&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
==Gustatory System==&lt;br /&gt;
&lt;br /&gt;
[[Image:Taste qualities.gif|thumb|The five basic tastes]]&lt;br /&gt;
&lt;br /&gt;
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.&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
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.&amp;lt;ref name=PMID20696704&amp;gt;&amp;lt;pubmed&amp;gt;20696704&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
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 &amp;lt;ref name=PMID20696704/&amp;gt; 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.&lt;br /&gt;
&lt;br /&gt;
===Cell Biology===&lt;br /&gt;
&lt;br /&gt;
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.&lt;br /&gt;
&lt;br /&gt;
====Type II receptors====&lt;br /&gt;
&lt;br /&gt;
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:&lt;br /&gt;
&lt;br /&gt;
# Stimulates gustatory nerve afferents which project to gustatory nuclei  in the spinal cord&lt;br /&gt;
# Excites Type III presynaptic nerve fibers to release serotonin. &lt;br /&gt;
# Has a positive feedback effect on type II receptor cells, increasing the level of ATP production.&lt;br /&gt;
&lt;br /&gt;
        &lt;br /&gt;
&lt;br /&gt;
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.&lt;br /&gt;
&lt;br /&gt;
==Taste Map==&lt;br /&gt;
[[Image:Taste map.png|thumb|left|250px|Obsolete idea of the tongue map]]&lt;br /&gt;
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.&lt;br /&gt;
&lt;br /&gt;
===Neural Pathways===&lt;br /&gt;
&lt;br /&gt;
'''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''. &lt;br /&gt;
&lt;br /&gt;
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:  &lt;br /&gt;
&lt;br /&gt;
* ''Facial nerve n''. -  carries taste information from the anterior 2/3 of the tongue.&lt;br /&gt;
* ''Hypoglossal n.'' - carries taste information from the posterior 1/3 of the tongue.&lt;br /&gt;
* ''Vagus n''. - carries taste information from the palate&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
'''Second order neurons''' - From the NTS second order neurons carry taste information to the Ventral posteromedial (VPM) nucleus in the thalamus.&amp;lt;ref name=PMID21885776/&amp;gt;&lt;br /&gt;
&lt;br /&gt;
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.  &lt;br /&gt;
&lt;br /&gt;
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.&lt;br /&gt;
&lt;br /&gt;
===Cortical Areas===&lt;br /&gt;
&lt;br /&gt;
[[Image:Primary gustatory cortex.png|thumb|Primary gustatory cortex]]&lt;br /&gt;
&lt;br /&gt;
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)&amp;lt;ref name=PMID22245354&amp;gt;&amp;lt;pubmed&amp;gt;22245354&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;, with the secondary taste cortex in the caudolateral orbitofrontal cortex.&amp;lt;ref name=PMID21305668&amp;gt;&amp;lt;pubmed&amp;gt;21305668&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;  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.&amp;lt;ref name=PMID21885776&amp;gt;&amp;lt;pubmed&amp;gt;21885776&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; These findings lend weight to the idea that there is only one receptor for each taste quality.&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
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).&amp;lt;ref name=PMID21885776/&amp;gt; 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&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
==Current Research==&lt;br /&gt;
&lt;br /&gt;
[[File:Mousetounge histologicalstain.jpg|right|thumb|200px|Image shows histological stains of a mice tongue showing dysplasia]]&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
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. &lt;br /&gt;
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.&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
'''Synergistic relationships of Six Genes '''&lt;br /&gt;
&lt;br /&gt;
In an animal study using mice by Suzuki Y, Ikeda K, Kawakami K.(2011)  Firstly nominating &amp;quot;[[#Glossary |'''Six Genes''']]&amp;quot; as a major component in [[#Glossary |'''gustatory ''']] development, stating that deficiencies in certain Six genes (specifically Six1 &amp;amp; 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 &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;21978088&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
[[File:Highpowered_microscope.jpg|Left|thumb|200px|Image of a high powered microscope]]&lt;br /&gt;
&lt;br /&gt;
'''Neural Crest responsibilities '''&lt;br /&gt;
&lt;br /&gt;
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.&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;22659543&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
'''Augmentation of Endoderm'''&lt;br /&gt;
&lt;br /&gt;
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 &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;22581563&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
'''Changes in Taste Cells over time'''&lt;br /&gt;
&lt;br /&gt;
Research by &lt;br /&gt;
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.  &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;22643728&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
'''Shh key component of taste bud proginators'''&lt;br /&gt;
&lt;br /&gt;
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.&lt;br /&gt;
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 &amp;quot;Axiocam CCD camera and Axioplan fluorescence microscope with Axiovision software&amp;quot; a study by Harlow, Yang, Williams, Barlow (2011)&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;PMC2674259&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
'''WNT family exhibit various roles'''&lt;br /&gt;
&lt;br /&gt;
 [[File:Abnormal of tongue.jpg|thumb|200px|Image shows an example of tongue abnormalities, this is called &amp;quot;double tongue&amp;quot; each side has independent movement!]]&lt;br /&gt;
&lt;br /&gt;
The WNT gene family has a function of signaling work antagonistically through receptor tyrosine kinase (RTK) signaling. However, the deletion of Sprouty Homolog 2 (Spry2) led to the increase of chimaeric virus particles (CVPs) and a significant decrease in number of fungiform papillae. In contrast, the absence of Fibroblast growth factor 10 (Fgf10) in conjunction with 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. 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. &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;PMC2768563&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
[[File:Developing_tongue_histology_001.jpg|right|thumb|200px|HIstological stain of a developing rat tongue]]&lt;br /&gt;
&lt;br /&gt;
==Glossary==&lt;br /&gt;
&lt;br /&gt;
* '''Circumvallate papillae''' - &lt;br /&gt;
&lt;br /&gt;
* '''Ectoderm'''- outer germ layer of embryo&lt;br /&gt;
&lt;br /&gt;
* '''Endoderm''' - inner germ layer of embryo&lt;br /&gt;
&lt;br /&gt;
* '''Epithelium''' - basic animal tissue that is composed of tightly packed cells, usually covering the outer portion of organs&lt;br /&gt;
&lt;br /&gt;
* '''Exocystosis''' - movement of contents out of cell&lt;br /&gt;
&lt;br /&gt;
* '''Filiform papillae''' - &lt;br /&gt;
&lt;br /&gt;
* '''Foliate papillae''' - &lt;br /&gt;
&lt;br /&gt;
* '''Fungiform papillae''' - &lt;br /&gt;
&lt;br /&gt;
* '''Ganglia''' - the accumulation of a nerve cell body&lt;br /&gt;
&lt;br /&gt;
* '''Growth factor''' - a substance that stimulates the growth of cells&lt;br /&gt;
&lt;br /&gt;
* '''Gustatory''' - anything that relates to the taste sense&lt;br /&gt;
&lt;br /&gt;
* '''Hydrolysis''' - breakdown of a chemical when it reacts with water&lt;br /&gt;
&lt;br /&gt;
* '''Mesoderm''' - middle germ layer of embryo&lt;br /&gt;
&lt;br /&gt;
* '''Mesenchyme''' - multipotential cells&lt;br /&gt;
&lt;br /&gt;
* '''Neural crest''' - a part of the ectoderm found on both sides of the neural tube&lt;br /&gt;
&lt;br /&gt;
* '''Neuron''' - most simplistic unit of the nervous system&lt;br /&gt;
&lt;br /&gt;
* '''Neurotransmitter''' - chemicals which allow the passing of signals from neuron to neuron via connecting part (synapse) &lt;br /&gt;
&lt;br /&gt;
* '''Papillae''' - small rough surface projection&lt;br /&gt;
&lt;br /&gt;
* '''Six genes''' - a family of genes&lt;br /&gt;
&lt;br /&gt;
* '''Sonic hedgehog (Shh)''' - signalling protein involved in normal development&lt;br /&gt;
&lt;br /&gt;
* '''Sulcus terminalis''' - describes a physical transition point separating the anterior 2/3 of the tongue from the posterior 1/3&lt;br /&gt;
&lt;br /&gt;
* '''Tamoxifen''' - hormonal altering drug&lt;br /&gt;
&lt;br /&gt;
* '''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).&lt;br /&gt;
&lt;br /&gt;
* '''Type II taste cells''' - Receptor cells acting as primary detectors of sweet, bitter or umami taste.&lt;br /&gt;
&lt;br /&gt;
* '''Type III taste cells''' - Presynaptic cells that respond to sweet, salty, sour, bitter and umami compounds.&lt;br /&gt;
&lt;br /&gt;
== References ==&lt;br /&gt;
&amp;lt;references/&amp;gt;&lt;br /&gt;
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==External Links==&lt;br /&gt;
{{External Links}}&lt;br /&gt;
&lt;br /&gt;
[http://www.surgicalneurologyint.com/article.asp?issn=2152-7806;year=2012;volume=3;issue=1;spage=23;epage=23;aulast=Manjila]&lt;br /&gt;
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http://embryology.med.unsw.edu.au/embryology/index.php?title=2012_Group_Project_4&lt;br /&gt;
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http://www.webmd.com/oral-health/picture-of-the-tongue&lt;br /&gt;
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http://www.tutorvista.com/content/biology/biology-iv/nervous-coordination/tongue-structure.php#parts-of-tongue&lt;br /&gt;
&lt;br /&gt;
http://www.cf.ac.uk/biosi/staffinfo/jacob/teaching/sensory/taste.html&lt;br /&gt;
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--[[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.&lt;br /&gt;
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{{2012Projects}}&lt;/div&gt;</summary>
		<author><name>Z3330795</name></author>
	</entry>
	<entry>
		<id>https://embryology.med.unsw.edu.au/embryology/index.php?title=2012_Group_Project_3&amp;diff=105125</id>
		<title>2012 Group Project 3</title>
		<link rel="alternate" type="text/html" href="https://embryology.med.unsw.edu.au/embryology/index.php?title=2012_Group_Project_3&amp;diff=105125"/>
		<updated>2012-10-02T23:09:58Z</updated>

		<summary type="html">&lt;p&gt;Z3330795: /* Current Research */&lt;/p&gt;
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&lt;div&gt;=Taste Development=&lt;br /&gt;
&lt;br /&gt;
You are out to dinner and your meal arrives in front of you, the aromas and the presentation of your food strikes you immediately. Half way through, the waiter returns and asks “How does your meal taste?”  The answer is not as simple as one might think. Why does the meal taste pleasant? How do we experience different tastes? In the following page, we aim to discern how exactly one would answer these questions by looking at the embryological development of the taste system from week to week. &lt;br /&gt;
&lt;br /&gt;
Taste is a complex sensory system and its precise workings are to this day not fully understood. What makes it so complicated is the interaction between the structure of tongue and taste buds and how this contributes to the representation of taste qualities (salty, bitter, sweet, sour and umami) in the brain. We will also look at some current research on animal models being undertaken to evaluate the role of specific genes in the development of sensory structures. By looking at the taste system’s genetic basis, we now have a greater understanding of the abnormalities that may occur during development and a direction to pursue in future research to attempt to fill in the gaps of scientific knowledge.&lt;br /&gt;
&lt;br /&gt;
==Adult Tongue and Taste Buds – Structure and Function==&lt;br /&gt;
&lt;br /&gt;
'''Structure'''&lt;br /&gt;
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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.  &lt;br /&gt;
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''''The image below is a simplistic diagram of the surface of the tongue showing the locations of the different papillae and other important features'''&lt;br /&gt;
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{|&lt;br /&gt;
| [[Image:Drawing of Tongue.png|centre|500px]]&lt;br /&gt;
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'''Papillae'''&lt;br /&gt;
[[File:Papillae.jpg|Left|thumb|200px|Close up of Human Tongue Papillae]]&lt;br /&gt;
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There are 4 types of papillae on the tongue.&lt;br /&gt;
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. &lt;br /&gt;
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[[File:Fungiformpapillae.jpg|Left|thumb|200px|Fungiform Papillae]]&lt;br /&gt;
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[[File:Circumvallatepapillae.jpg |Left|thumb|200px|Circumvallate Papillae]]&lt;br /&gt;
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[[File:Filiformpapillae.jpg|Left|thumb|200px|Foliate Papillae]]&lt;br /&gt;
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'''Function'''&lt;br /&gt;
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The Tongue has muscular and sensory functions, muscular functions include swallowing and speech where as sensory function involves taste. This section will focus on the sensory functions of the tongue.&lt;br /&gt;
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.&lt;br /&gt;
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'''The image below is a simplistic hand-drawn cross section of a taste bud unit (not to scale)'''&lt;br /&gt;
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[[File:Taste_bud_1.jpg|x400px|alt=Cross section of a taste bud unit|centre|Cross section of a taste bud unit]]&lt;br /&gt;
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'''Link Between Taste and Smell'''&lt;br /&gt;
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The pathways of smell and taste are very similar. Pathways both involve the conversion of a dissolved chemical stimulus transformed into a electrical impulse for interpretation by the brain.	&lt;br /&gt;
Taste and smell overlap when humans experience flavour, flavour involves an interaction of taste, smell, texture and temperature, where taste is only a portion of this interaction. when the brain interprets a flavour, contribution from other senses has a significant role in identification. In conclusion Taste and Smell in combination with other senses help develop a sensory interpretation called flavour.&lt;br /&gt;
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[[File:Taste_pathway.jpg|right|thumb|200px|Simplistic Pathway of Taste]]&lt;br /&gt;
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[[File:Human smelling.jpg|500px|centre]]&lt;br /&gt;
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==History of Discoveries==&lt;br /&gt;
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{| cellpadding=5 style=&amp;quot;border:1px solid #BBB&amp;quot;&lt;br /&gt;
|- bgcolor=&amp;quot;#faecc8&amp;quot;&lt;br /&gt;
|''' Date'''|| '''Significant Discovery'''&lt;br /&gt;
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|- bgcolor=&amp;quot;#faf6ed&amp;quot;&lt;br /&gt;
|'''350BC'''&lt;br /&gt;
|| Aristotle writes about the basic tastes, sweet and bitter. He also notes that it can be modified by salty and acidic. &amp;lt;ref name=&amp;quot;PMID22717400&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;22717400&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
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|- bgcolor=&amp;quot;#faecc8&amp;quot;&lt;br /&gt;
|'''1901'''&lt;br /&gt;
|| D. Hanig publishes a paper describing taste sensitivity in different regions of the tongue. &lt;br /&gt;
''Interesting fact:'' The modern concept of a 'tongue map' is a misinterpretation of this study. &amp;lt;ref name=&amp;quot;PMID22717400&amp;quot;/&amp;gt;&lt;br /&gt;
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|- bgcolor=&amp;quot;#faf6ed&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''1908'''&lt;br /&gt;
|Kikunae Ikeda, a professor of the Tokyo Imperial University, discovered and identified the fifth basic taste: umami (savouriness), made palatable by glutamate.  &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;12438213&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
[http://chemse.oxfordjournals.org/content/27/9/847.long New Seasonings]&lt;br /&gt;
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|- bgcolor=&amp;quot;#faecc8&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''1931-32'''&lt;br /&gt;
| A chemist named Arthur Fox and his college noted that they had different sensitivities to the bitter tasting Phenylthiocarbamide (PTC).&amp;lt;ref&amp;gt;Blakeslee AF, Fox AL. Our different taste worlds. J Hered. 1932;23:97–107.&amp;lt;/ref&amp;gt; Geneticists later confirm these findings, and discover that non-tasting is a recessive genetic trait. &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;17782493&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/pubmed/17782493 Inherited taste deficiency] &lt;br /&gt;
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|- bgcolor=&amp;quot;#faf6ed&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''1965'''&lt;br /&gt;
|Farbman's study of the developing taste but in rat fungiform papilla was significant in increasing our understanding of taste bud development. &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;14300090&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
[http://www.sciencedirect.com/science/article/pii/0012160665900400 Electron microscope study of the developing taste bud in rat fungiform papilla.]&lt;br /&gt;
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|- bgcolor=&amp;quot;#faecc8&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''1992'''&lt;br /&gt;
|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. &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;1608467 &amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
[http://www.nature.com/nature/journal/v357/n6379/abs/357563a0.html Gustducin is a taste-cell-specific G protein closely related to the transducins]&lt;br /&gt;
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|- bgcolor=&amp;quot;#faf6ed&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''1995'''&lt;br /&gt;
|Barlow et al. experimented with Axolotl salamanders and concluded that taste buds from this species arise exclusively from epithelial tissue, &amp;quot;oropharyngeal [[#Glossary |'''epithelium''']]&amp;quot;. &amp;lt;ref name=&amp;quot;PMID17826760&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;17826760&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/pubmed/17826760 Embryonic origin of gustatory cranial sensory neurons] &lt;br /&gt;
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|- bgcolor=&amp;quot;#faecc8&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''1996'''&lt;br /&gt;
| 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 &amp;quot;at least dual function of embryonic/fetal taste buds&amp;quot;, including non-gustatory, paracrine functions prior to the 14th week and gustatory after the 14th week. &amp;lt;ref name=&amp;quot;PMID8955790&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;8955790&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/pubmed/8955790 Embryonic and early fetal development of human taste buds: a transmission electron microscopical study]&lt;br /&gt;
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|- bgcolor=&amp;quot;#faf6ed&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''2000'''&lt;br /&gt;
|Chandrashekar, J. et al. discover the first taste sonsors, the T2R bitter taste receptors. &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;10761935&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
[http://www.sciencedirect.com/science/article/pii/S0092867400807060 T2Rs Function as Bitter Taste Receptors]&lt;br /&gt;
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|- bgcolor=&amp;quot;#faecc8&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''2001'''&lt;br /&gt;
|Nelson, G. et al. discover the sweet receptor: a combination of T1R2 and T1R3. &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;11509186&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/pubmed/11509186?dopt=Abstract&amp;amp;holding=npg Mammalian sweet taste receptors.]&lt;br /&gt;
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|- bgcolor=&amp;quot;#faf6ed&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''2002'''&lt;br /&gt;
|Nelson G. et al. discover the amino acid (umami) taste receptor: a combination of T1R1 and T1R3 identified.  &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;11894099&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/pubmed/11894099?dopt=Abstract&amp;amp;holding=npg An amino-acid taste receptor]&lt;br /&gt;
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|- bgcolor=&amp;quot;#faecc8&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''2005'''&lt;br /&gt;
|Dyer, J. et al. discover sweet taste receptors in the GI tract. &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;17855558&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1986582/ Sweet taste signaling in the gut]&lt;br /&gt;
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|- bgcolor=&amp;quot;#faf6ed&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''2006'''&lt;br /&gt;
|Huang, A. L et al. discover cells for sour taste, identified by PKD2L1 (a polycystic kidney disease-like ion channel). &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;16929298&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1571047/ The Cells and Logic for Mammalian Sour Taste detection]&lt;br /&gt;
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|- bgcolor=&amp;quot;#faecc8&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''2007'''&lt;br /&gt;
|Harlow DE, Barlow LA of the University of Colorado Denver Health Sciences Center provide evidence of the &amp;quot;embryonic origin of gustatory cranial sensory neurons&amp;quot;. &amp;lt;ref name=&amp;quot;PMID17826760&amp;quot;/&amp;gt;&lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/pubmed/17826760 Embryonic origin of gustatory cranial sensory neurons.]&lt;br /&gt;
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|- bgcolor=&amp;quot;#faf6ed&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''2009'''&lt;br /&gt;
|A study by Hevezi P et al, presents &amp;quot;the first comprehensive characterization of gene expression in primate taste buds&amp;quot;, as opposed to previous studies which focused on rodents. &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;19636377&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/pubmed/19636377 Genome-wide analysis of gene expression in primate taste buds reveals links to diverse processes]&lt;br /&gt;
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|- bgcolor=&amp;quot;#faecc8&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''2010'''&lt;br /&gt;
|Chandrashekar, J. et al. identify epithelial sodium channel (ENaC) as the sodium-salt taste receptor. &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;20107438&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/pubmed/20107438?dopt=Abstract&amp;amp;holding=npg The cells and peripheral representation of sodium taste in mice]&lt;br /&gt;
|}&lt;br /&gt;
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== Human Weekly Development - Two Prominent Studies ==&lt;br /&gt;
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. &lt;br /&gt;
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The findings of these two studies are summarized in the table below. The figures provided relate to the images on their respective research papers.&lt;br /&gt;
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# [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] &lt;br /&gt;
# [http://chemse.oxfordjournals.org/content/22/6/601.long Scanning electron microscopical studies of developing gustatory papillae in humans, 1997]  &lt;br /&gt;
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===Timeline of Developmental Processes of Human Taste Buds===&lt;br /&gt;
{| cellpadding=5 style=&amp;quot;border:1px solid #BBB&amp;quot;&lt;br /&gt;
|- bgcolor=&amp;quot;#89CFF0&amp;quot;&lt;br /&gt;
|'''Postovulatory Week'''||'''Description'''&lt;br /&gt;
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|- bgcolor=&amp;quot;#BCD4E6&amp;quot;&lt;br /&gt;
|'''Week 6''' ||&lt;br /&gt;
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. &amp;lt;ref name=&amp;quot;PMID9455607&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;9455607&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
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|- bgcolor=&amp;quot;#89CFF0&amp;quot;&lt;br /&gt;
| '''Weeks 6 to 7'''|| &lt;br /&gt;
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. &amp;lt;ref name=PMID8955790/&amp;gt;&lt;br /&gt;
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|- bgcolor=&amp;quot;#BCD4E6&amp;quot;&lt;br /&gt;
| '''Week 7 '''||&lt;br /&gt;
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.  &amp;lt;ref name=PMID9455607/&amp;gt; &lt;br /&gt;
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|- bgcolor=&amp;quot;#89CFF0&amp;quot;&lt;br /&gt;
| ''' Week 8  ''' ||&lt;br /&gt;
* The taste bud primordium are still differentiated, elongated epithelial cells, resting on a slightly developed core of young dermal papilla.&lt;br /&gt;
* 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. &lt;br /&gt;
* Ciliated cells also appear around the 8th week, however the significance of these cells which are scattered randomly across the lingual surface remains unclear. &amp;lt;ref name=PMID8955790/&amp;gt; &lt;br /&gt;
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|- bgcolor=&amp;quot;#BCD4E6&amp;quot;&lt;br /&gt;
|'''  Week 9''' ||&lt;br /&gt;
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). &amp;lt;ref name=PMID9455607/&amp;gt;&lt;br /&gt;
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|- bgcolor=&amp;quot;#89CFF0&amp;quot;&lt;br /&gt;
|'''  Weeks 10-11''' ||&lt;br /&gt;
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). &amp;lt;ref name=PMID8955790/&amp;gt; &lt;br /&gt;
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|- bgcolor=&amp;quot;#BCD4E6&amp;quot;&lt;br /&gt;
|''' Week 12 ''' ||&lt;br /&gt;
Taste bud cells are more clearly differentiated into epithelial cell types II and III. &amp;lt;ref name=PMID8955790/&amp;gt; &lt;br /&gt;
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|''' Weeks 12-13  ''' ||&lt;br /&gt;
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). &amp;lt;ref name=PMID8955790/&amp;gt; &lt;br /&gt;
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|- bgcolor=&amp;quot;#BCD4E6&amp;quot;&lt;br /&gt;
|''' Weeks 14 -15 ''' ||&lt;br /&gt;
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. &amp;lt;ref name=PMID8955790/&amp;gt; &lt;br /&gt;
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==Abnormalities==&lt;br /&gt;
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It should be mentioned that gustatory abnormalities have not been widely researched. Most research conducted in this field has been conducted through animal testing on mice and this is the basis of information provided below. &lt;br /&gt;
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===Knocking out P2X Receptors===&lt;br /&gt;
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[[File:Image of taste being evoked by visualising ATP release.jpeg|Left|thumb|200px|Evoking taste - ATP release in tongue]]&lt;br /&gt;
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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. &lt;br /&gt;
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It should be noted that the taste buds in DKO are functional, but are not stimulated by the administration of tastants. &lt;br /&gt;
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The transmission of release of ATP is secretion through gap junction hemichannels (pannexin 1 gap junction).&lt;br /&gt;
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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.&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;21940456&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
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===FGF signalling and genes===&lt;br /&gt;
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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.&lt;br /&gt;
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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 (&amp;quot;Fgf10&amp;quot;) 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 &amp;quot;Fgf10&amp;quot; to limit the size of the CVP progenitor placode. Exclusive expression of ''Fgf10'' in the [[#Glossary |'''mesenchyme''']] is necessary for the formation of CVP. &lt;br /&gt;
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'''This image shows the CVP stained with H&amp;amp;E and scanned by Scanning Electron Microscope (SEM)'''&lt;br /&gt;
[[File:CVP of WT(top) and DKO(bottom) mice with H&amp;amp;E and SEM.png]]&lt;br /&gt;
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'''This image shows the location of the CVP and the increased number in DKO mice by SEM'''&lt;br /&gt;
[[File:Mouse circumvallate papilla 01.jpg|300px]]&lt;br /&gt;
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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).&lt;br /&gt;
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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).&lt;br /&gt;
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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''&amp;amp; ''Spry 1&amp;amp;2''work antagonistically through receptor tyrosine kinase (RTK)signalling.&lt;br /&gt;
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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.&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;21655085&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
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==Gustatory System==&lt;br /&gt;
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[[Image:Taste qualities.gif|thumb|The five basic tastes]]&lt;br /&gt;
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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.&lt;br /&gt;
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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.&amp;lt;ref name=PMID20696704&amp;gt;&amp;lt;pubmed&amp;gt;20696704&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
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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 &amp;lt;ref name=PMID20696704/&amp;gt; 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.&lt;br /&gt;
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===Cell Biology===&lt;br /&gt;
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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.&lt;br /&gt;
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====Type II receptors====&lt;br /&gt;
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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:&lt;br /&gt;
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# Stimulates gustatory nerve afferents which project to gustatory nuclei  in the spinal cord&lt;br /&gt;
# Excites Type III presynaptic nerve fibers to release serotonin. &lt;br /&gt;
# Has a positive feedback effect on type II receptor cells, increasing the level of ATP production.&lt;br /&gt;
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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.&lt;br /&gt;
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==Taste Map==&lt;br /&gt;
[[Image:Taste map.png|thumb|left|250px|Obsolete idea of the tongue map]]&lt;br /&gt;
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.&lt;br /&gt;
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===Neural Pathways===&lt;br /&gt;
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'''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''. &lt;br /&gt;
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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:  &lt;br /&gt;
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* ''Facial nerve n''. -  carries taste information from the anterior 2/3 of the tongue.&lt;br /&gt;
* ''Hypoglossal n.'' - carries taste information from the posterior 1/3 of the tongue.&lt;br /&gt;
* ''Vagus n''. - carries taste information from the palate&lt;br /&gt;
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'''Second order neurons''' - From the NTS second order neurons carry taste information to the Ventral posteromedial (VPM) nucleus in the thalamus.&amp;lt;ref name=PMID21885776/&amp;gt;&lt;br /&gt;
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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.  &lt;br /&gt;
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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.&lt;br /&gt;
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===Cortical Areas===&lt;br /&gt;
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[[Image:Primary gustatory cortex.png|thumb|Primary gustatory cortex]]&lt;br /&gt;
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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)&amp;lt;ref name=PMID22245354&amp;gt;&amp;lt;pubmed&amp;gt;22245354&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;, with the secondary taste cortex in the caudolateral orbitofrontal cortex.&amp;lt;ref name=PMID21305668&amp;gt;&amp;lt;pubmed&amp;gt;21305668&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;  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.&amp;lt;ref name=PMID21885776&amp;gt;&amp;lt;pubmed&amp;gt;21885776&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; These findings lend weight to the idea that there is only one receptor for each taste quality.&lt;br /&gt;
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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).&amp;lt;ref name=PMID21885776/&amp;gt; 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&lt;br /&gt;
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==Current Research==&lt;br /&gt;
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[[File:Mousetounge histologicalstain.jpg|right|thumb|200px|Image shows histological stains of a mice tongue showing dysplasia]]&lt;br /&gt;
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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. &lt;br /&gt;
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.&lt;br /&gt;
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'''Synergistic relationships of Six Genes '''&lt;br /&gt;
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In an animal study using mice by Suzuki Y, Ikeda K, Kawakami K.(2011)  Firstly nominating &amp;quot;[[#Glossary |'''Six Genes''']]&amp;quot; as a major component in [[#Glossary |'''gustatory ''']] development, stating that deficiencies in certain Six genes (specifically Six1 &amp;amp; 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 &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;21978088&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
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[[File:Highpowered_microscope.jpg|Left|thumb|200px|Image of a high powered microscope]]&lt;br /&gt;
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'''Neural Crest responsibilities '''&lt;br /&gt;
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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.&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;22659543&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
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'''Augmentation of Endoderm'''&lt;br /&gt;
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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 &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;22581563&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
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'''Changes in Taste Cells over time'''&lt;br /&gt;
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Research by &lt;br /&gt;
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.  &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;22643728&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
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'''Shh key component of taste bud proginators'''&lt;br /&gt;
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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.&lt;br /&gt;
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 &amp;quot;Axiocam CCD camera and Axioplan fluorescence microscope with Axiovision software&amp;quot; a study by Harlow, Yang, Williams, Barlow (2011)&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;PMC2674259&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
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'''WNT family exhibit various roles'''&lt;br /&gt;
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 [[File:Abnormal of tongue.jpg|thumb|200px|Image shows an example of tongue abnormalities, this is called &amp;quot;double tongue&amp;quot; each side has independent movement!]]&lt;br /&gt;
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The WNT gene family has a function of signaling work antagonistically through receptor tyrosine kinase (RTK) signaling. However, the deletion of Sprouty Homolog 2 (Spry2) led to the increase of chimaeric virus particles (CVPs) and a significant decrease in number of fungiform papillae. In contrast, the absence of Fibroblast growth factor 10 (Fgf10) in conjunction with 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. 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. &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;PMC2768563&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
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[[File:Developing_tongue_histology_001.jpg|right|thumb|200px|HIstological stain of a developing rat tongue]]&lt;br /&gt;
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==Glossary==&lt;br /&gt;
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* '''Circumvallate papillae''' - &lt;br /&gt;
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* '''Ectoderm'''- outer germ layer of embryo&lt;br /&gt;
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* '''Endoderm''' - inner germ layer of embryo&lt;br /&gt;
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* '''Epithelium''' - basic animal tissue that is composed of tightly packed cells, usually covering the outer portion of organs&lt;br /&gt;
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* '''Exocystosis''' - movement of contents out of cell&lt;br /&gt;
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* '''Filiform papillae''' - &lt;br /&gt;
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* '''Foliate papillae''' - &lt;br /&gt;
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* '''Fungiform papillae''' - &lt;br /&gt;
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* '''Ganglia''' - the accumulation of a nerve cell body&lt;br /&gt;
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* '''Growth factor''' - a substance that stimulates the growth of cells&lt;br /&gt;
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* '''Gustatory''' - anything that relates to the taste sense&lt;br /&gt;
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* '''Hydrolysis''' - breakdown of a chemical when it reacts with water&lt;br /&gt;
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* '''Mesoderm''' - middle germ layer of embryo&lt;br /&gt;
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* '''Mesenchyme''' - multipotential cells&lt;br /&gt;
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* '''Neural crest''' - a part of the ectoderm found on both sides of the neural tube&lt;br /&gt;
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* '''Neuron''' - most simplistic unit of the nervous system&lt;br /&gt;
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* '''Neurotransmitter''' - chemicals which allow the passing of signals from neuron to neuron via connecting part (synapse) &lt;br /&gt;
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* '''Papillae''' - small rough surface projection&lt;br /&gt;
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* '''Six genes''' - a family of genes&lt;br /&gt;
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* '''Sonic hedgehog (Shh)''' - signalling protein involved in normal development&lt;br /&gt;
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* '''Sulcus terminalis''' - describes a physical transition point separating the anterior 2/3 of the tongue from the posterior 1/3&lt;br /&gt;
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* '''Tamoxifen''' - hormonal altering drug&lt;br /&gt;
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* '''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).&lt;br /&gt;
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* '''Type II taste cells''' - Receptor cells acting as primary detectors of sweet, bitter or umami taste.&lt;br /&gt;
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* '''Type III taste cells''' - Presynaptic cells that respond to sweet, salty, sour, bitter and umami compounds.&lt;br /&gt;
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== References ==&lt;br /&gt;
&amp;lt;references/&amp;gt;&lt;br /&gt;
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==External Links==&lt;br /&gt;
{{External Links}}&lt;br /&gt;
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[http://www.surgicalneurologyint.com/article.asp?issn=2152-7806;year=2012;volume=3;issue=1;spage=23;epage=23;aulast=Manjila]&lt;br /&gt;
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http://embryology.med.unsw.edu.au/embryology/index.php?title=2012_Group_Project_4&lt;br /&gt;
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http://www.webmd.com/oral-health/picture-of-the-tongue&lt;br /&gt;
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http://www.tutorvista.com/content/biology/biology-iv/nervous-coordination/tongue-structure.php#parts-of-tongue&lt;br /&gt;
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http://www.cf.ac.uk/biosi/staffinfo/jacob/teaching/sensory/taste.html&lt;br /&gt;
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--[[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.&lt;br /&gt;
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{{2012Projects}}&lt;/div&gt;</summary>
		<author><name>Z3330795</name></author>
	</entry>
	<entry>
		<id>https://embryology.med.unsw.edu.au/embryology/index.php?title=2012_Group_Project_3&amp;diff=105122</id>
		<title>2012 Group Project 3</title>
		<link rel="alternate" type="text/html" href="https://embryology.med.unsw.edu.au/embryology/index.php?title=2012_Group_Project_3&amp;diff=105122"/>
		<updated>2012-10-02T22:33:09Z</updated>

		<summary type="html">&lt;p&gt;Z3330795: /* Adult Tongue and Taste Buds – Structure and Function */&lt;/p&gt;
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&lt;div&gt;=Taste Development=&lt;br /&gt;
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You are out to dinner and your meal arrives in front of you, the aromas and the presentation of your food strikes you immediately. Half way through, the waiter returns and asks “How does your meal taste?”  The answer is not as simple as one might think. Why does the meal taste pleasant? How do we experience different tastes? In the following page, we aim to discern how exactly one would answer these questions by looking at the embryological development of the taste system from week to week. &lt;br /&gt;
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Taste is a complex sensory system and its precise workings are to this day not fully understood. What makes it so complicated is the interaction between the structure of tongue and taste buds and how this contributes to the representation of taste qualities (salty, bitter, sweet, sour and umami) in the brain. We will also look at some current research on animal models being undertaken to evaluate the role of specific genes in the development of sensory structures. By looking at the taste system’s genetic basis, we now have a greater understanding of the abnormalities that may occur during development and a direction to pursue in future research to attempt to fill in the gaps of scientific knowledge.&lt;br /&gt;
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==Adult Tongue and Taste Buds – Structure and Function==&lt;br /&gt;
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'''Structure'''&lt;br /&gt;
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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.  &lt;br /&gt;
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''''The image below is a simplistic diagram of the surface of the tongue showing the locations of the different papillae and other important features'''&lt;br /&gt;
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{|&lt;br /&gt;
| [[Image:Drawing of Tongue.png|centre|500px]]&lt;br /&gt;
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'''Papillae'''&lt;br /&gt;
[[File:Papillae.jpg|Left|thumb|200px|Close up of Human Tongue Papillae]]&lt;br /&gt;
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There are 4 types of papillae on the tongue.&lt;br /&gt;
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. &lt;br /&gt;
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[[File:Fungiformpapillae.jpg|Left|thumb|200px|Fungiform Papillae]]&lt;br /&gt;
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[[File:Circumvallatepapillae.jpg |Left|thumb|200px|Circumvallate Papillae]]&lt;br /&gt;
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[[File:Filiformpapillae.jpg|Left|thumb|200px|Foliate Papillae]]&lt;br /&gt;
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'''Function'''&lt;br /&gt;
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The Tongue has muscular and sensory functions, muscular functions include swallowing and speech where as sensory function involves taste. This section will focus on the sensory functions of the tongue.&lt;br /&gt;
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.&lt;br /&gt;
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'''The image below is a simplistic hand-drawn cross section of a taste bud unit (not to scale)'''&lt;br /&gt;
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[[File:Taste_bud_1.jpg|x400px|alt=Cross section of a taste bud unit|centre|Cross section of a taste bud unit]]&lt;br /&gt;
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'''Link Between Taste and Smell'''&lt;br /&gt;
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The pathways of smell and taste are very similar. Pathways both involve the conversion of a dissolved chemical stimulus transformed into a electrical impulse for interpretation by the brain.	&lt;br /&gt;
Taste and smell overlap when humans experience flavour, flavour involves an interaction of taste, smell, texture and temperature, where taste is only a portion of this interaction. when the brain interprets a flavour, contribution from other senses has a significant role in identification. In conclusion Taste and Smell in combination with other senses help develop a sensory interpretation called flavour.&lt;br /&gt;
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[[File:Taste_pathway.jpg|right|thumb|200px|Simplistic Pathway of Taste]]&lt;br /&gt;
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[[File:Human smelling.jpg|500px|centre]]&lt;br /&gt;
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==History of Discoveries==&lt;br /&gt;
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{| cellpadding=5 style=&amp;quot;border:1px solid #BBB&amp;quot;&lt;br /&gt;
|- bgcolor=&amp;quot;#faecc8&amp;quot;&lt;br /&gt;
|''' Date'''|| '''Significant Discovery'''&lt;br /&gt;
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|- bgcolor=&amp;quot;#faf6ed&amp;quot;&lt;br /&gt;
|'''350BC'''&lt;br /&gt;
|| Aristotle writes about the basic tastes, sweet and bitter. He also notes that it can be modified by salty and acidic. &amp;lt;ref name=&amp;quot;PMID22717400&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;22717400&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
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|- bgcolor=&amp;quot;#faecc8&amp;quot;&lt;br /&gt;
|'''1901'''&lt;br /&gt;
|| D. Hanig publishes a paper describing taste sensitivity in different regions of the tongue. &lt;br /&gt;
''Interesting fact:'' The modern concept of a 'tongue map' is a misinterpretation of this study. &amp;lt;ref name=&amp;quot;PMID22717400&amp;quot;/&amp;gt;&lt;br /&gt;
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|- bgcolor=&amp;quot;#faf6ed&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''1908'''&lt;br /&gt;
|Kikunae Ikeda, a professor of the Tokyo Imperial University, discovered and identified the fifth basic taste: umami (savouriness), made palatable by glutamate.  &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;12438213&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
[http://chemse.oxfordjournals.org/content/27/9/847.long New Seasonings]&lt;br /&gt;
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|- bgcolor=&amp;quot;#faecc8&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''1931-32'''&lt;br /&gt;
| A chemist named Arthur Fox and his college noted that they had different sensitivities to the bitter tasting Phenylthiocarbamide (PTC).&amp;lt;ref&amp;gt;Blakeslee AF, Fox AL. Our different taste worlds. J Hered. 1932;23:97–107.&amp;lt;/ref&amp;gt; Geneticists later confirm these findings, and discover that non-tasting is a recessive genetic trait. &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;17782493&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/pubmed/17782493 Inherited taste deficiency] &lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#faf6ed&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''1965'''&lt;br /&gt;
|Farbman's study of the developing taste but in rat fungiform papilla was significant in increasing our understanding of taste bud development. &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;14300090&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
[http://www.sciencedirect.com/science/article/pii/0012160665900400 Electron microscope study of the developing taste bud in rat fungiform papilla.]&lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#faecc8&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''1992'''&lt;br /&gt;
|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. &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;1608467 &amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
[http://www.nature.com/nature/journal/v357/n6379/abs/357563a0.html Gustducin is a taste-cell-specific G protein closely related to the transducins]&lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#faf6ed&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''1995'''&lt;br /&gt;
|Barlow et al. experimented with Axolotl salamanders and concluded that taste buds from this species arise exclusively from epithelial tissue, &amp;quot;oropharyngeal [[#Glossary |'''epithelium''']]&amp;quot;. &amp;lt;ref name=&amp;quot;PMID17826760&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;17826760&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/pubmed/17826760 Embryonic origin of gustatory cranial sensory neurons] &lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#faecc8&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''1996'''&lt;br /&gt;
| 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 &amp;quot;at least dual function of embryonic/fetal taste buds&amp;quot;, including non-gustatory, paracrine functions prior to the 14th week and gustatory after the 14th week. &amp;lt;ref name=&amp;quot;PMID8955790&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;8955790&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/pubmed/8955790 Embryonic and early fetal development of human taste buds: a transmission electron microscopical study]&lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#faf6ed&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''2000'''&lt;br /&gt;
|Chandrashekar, J. et al. discover the first taste sonsors, the T2R bitter taste receptors. &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;10761935&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
[http://www.sciencedirect.com/science/article/pii/S0092867400807060 T2Rs Function as Bitter Taste Receptors]&lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#faecc8&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''2001'''&lt;br /&gt;
|Nelson, G. et al. discover the sweet receptor: a combination of T1R2 and T1R3. &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;11509186&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/pubmed/11509186?dopt=Abstract&amp;amp;holding=npg Mammalian sweet taste receptors.]&lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#faf6ed&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''2002'''&lt;br /&gt;
|Nelson G. et al. discover the amino acid (umami) taste receptor: a combination of T1R1 and T1R3 identified.  &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;11894099&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/pubmed/11894099?dopt=Abstract&amp;amp;holding=npg An amino-acid taste receptor]&lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#faecc8&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''2005'''&lt;br /&gt;
|Dyer, J. et al. discover sweet taste receptors in the GI tract. &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;17855558&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1986582/ Sweet taste signaling in the gut]&lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#faf6ed&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''2006'''&lt;br /&gt;
|Huang, A. L et al. discover cells for sour taste, identified by PKD2L1 (a polycystic kidney disease-like ion channel). &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;16929298&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1571047/ The Cells and Logic for Mammalian Sour Taste detection]&lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#faecc8&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''2007'''&lt;br /&gt;
|Harlow DE, Barlow LA of the University of Colorado Denver Health Sciences Center provide evidence of the &amp;quot;embryonic origin of gustatory cranial sensory neurons&amp;quot;. &amp;lt;ref name=&amp;quot;PMID17826760&amp;quot;/&amp;gt;&lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/pubmed/17826760 Embryonic origin of gustatory cranial sensory neurons.]&lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#faf6ed&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''2009'''&lt;br /&gt;
|A study by Hevezi P et al, presents &amp;quot;the first comprehensive characterization of gene expression in primate taste buds&amp;quot;, as opposed to previous studies which focused on rodents. &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;19636377&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/pubmed/19636377 Genome-wide analysis of gene expression in primate taste buds reveals links to diverse processes]&lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#faecc8&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''2010'''&lt;br /&gt;
|Chandrashekar, J. et al. identify epithelial sodium channel (ENaC) as the sodium-salt taste receptor. &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;20107438&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/pubmed/20107438?dopt=Abstract&amp;amp;holding=npg The cells and peripheral representation of sodium taste in mice]&lt;br /&gt;
|}&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
== Human Weekly Development - Two Prominent Studies ==&lt;br /&gt;
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. &lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
The findings of these two studies are summarized in the table below. The figures provided relate to the images on their respective research papers.&lt;br /&gt;
&lt;br /&gt;
# [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] &lt;br /&gt;
# [http://chemse.oxfordjournals.org/content/22/6/601.long Scanning electron microscopical studies of developing gustatory papillae in humans, 1997]  &lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
===Timeline of Developmental Processes of Human Taste Buds===&lt;br /&gt;
{| cellpadding=5 style=&amp;quot;border:1px solid #BBB&amp;quot;&lt;br /&gt;
|- bgcolor=&amp;quot;#89CFF0&amp;quot;&lt;br /&gt;
|'''Postovulatory Week'''||'''Description'''&lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#BCD4E6&amp;quot;&lt;br /&gt;
|'''Week 6''' ||&lt;br /&gt;
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. &amp;lt;ref name=&amp;quot;PMID9455607&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;9455607&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#89CFF0&amp;quot;&lt;br /&gt;
| '''Weeks 6 to 7'''|| &lt;br /&gt;
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. &amp;lt;ref name=PMID8955790/&amp;gt;&lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#BCD4E6&amp;quot;&lt;br /&gt;
| '''Week 7 '''||&lt;br /&gt;
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.  &amp;lt;ref name=PMID9455607/&amp;gt; &lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#89CFF0&amp;quot;&lt;br /&gt;
| ''' Week 8  ''' ||&lt;br /&gt;
* The taste bud primordium are still differentiated, elongated epithelial cells, resting on a slightly developed core of young dermal papilla.&lt;br /&gt;
* 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. &lt;br /&gt;
* Ciliated cells also appear around the 8th week, however the significance of these cells which are scattered randomly across the lingual surface remains unclear. &amp;lt;ref name=PMID8955790/&amp;gt; &lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#BCD4E6&amp;quot;&lt;br /&gt;
|'''  Week 9''' ||&lt;br /&gt;
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). &amp;lt;ref name=PMID9455607/&amp;gt;&lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#89CFF0&amp;quot;&lt;br /&gt;
|'''  Weeks 10-11''' ||&lt;br /&gt;
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). &amp;lt;ref name=PMID8955790/&amp;gt; &lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#BCD4E6&amp;quot;&lt;br /&gt;
|''' Week 12 ''' ||&lt;br /&gt;
Taste bud cells are more clearly differentiated into epithelial cell types II and III. &amp;lt;ref name=PMID8955790/&amp;gt; &lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#89CFF0&amp;quot;&lt;br /&gt;
|''' Weeks 12-13  ''' ||&lt;br /&gt;
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). &amp;lt;ref name=PMID8955790/&amp;gt; &lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#BCD4E6&amp;quot;&lt;br /&gt;
|''' Weeks 14 -15 ''' ||&lt;br /&gt;
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. &amp;lt;ref name=PMID8955790/&amp;gt; &lt;br /&gt;
|}&lt;br /&gt;
&lt;br /&gt;
==Abnormalities==&lt;br /&gt;
&lt;br /&gt;
It should be mentioned that gustatory abnormalities have not been widely researched. Most research conducted in this field has been conducted through animal testing on mice and this is the basis of information provided below. &lt;br /&gt;
&lt;br /&gt;
===Knocking out P2X Receptors===&lt;br /&gt;
&lt;br /&gt;
[[File:Image of taste being evoked by visualising ATP release.jpeg|Left|thumb|200px|Evoking taste - ATP release in tongue]]&lt;br /&gt;
&lt;br /&gt;
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. &lt;br /&gt;
&lt;br /&gt;
It should be noted that the taste buds in DKO are functional, but are not stimulated by the administration of tastants. &lt;br /&gt;
&lt;br /&gt;
The transmission of release of ATP is secretion through gap junction hemichannels (pannexin 1 gap junction).&lt;br /&gt;
&lt;br /&gt;
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.&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;21940456&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
===FGF signalling and genes===&lt;br /&gt;
&lt;br /&gt;
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.&lt;br /&gt;
&lt;br /&gt;
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 (&amp;quot;Fgf10&amp;quot;) 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 &amp;quot;Fgf10&amp;quot; to limit the size of the CVP progenitor placode. Exclusive expression of ''Fgf10'' in the [[#Glossary |'''mesenchyme''']] is necessary for the formation of CVP. &lt;br /&gt;
&lt;br /&gt;
'''This image shows the CVP stained with H&amp;amp;E and scanned by Scanning Electron Microscope (SEM)'''&lt;br /&gt;
[[File:CVP of WT(top) and DKO(bottom) mice with H&amp;amp;E and SEM.png]]&lt;br /&gt;
&lt;br /&gt;
'''This image shows the location of the CVP and the increased number in DKO mice by SEM'''&lt;br /&gt;
[[File:Mouse circumvallate papilla 01.jpg|300px]]&lt;br /&gt;
&lt;br /&gt;
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).&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
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).&lt;br /&gt;
&lt;br /&gt;
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''&amp;amp; ''Spry 1&amp;amp;2''work antagonistically through receptor tyrosine kinase (RTK)signalling.&lt;br /&gt;
&lt;br /&gt;
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.&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;21655085&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
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==Gustatory System==&lt;br /&gt;
&lt;br /&gt;
[[Image:Taste qualities.gif|thumb|The five basic tastes]]&lt;br /&gt;
&lt;br /&gt;
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.&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
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.&amp;lt;ref name=PMID20696704&amp;gt;&amp;lt;pubmed&amp;gt;20696704&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
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 &amp;lt;ref name=PMID20696704/&amp;gt; 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.&lt;br /&gt;
&lt;br /&gt;
===Cell Biology===&lt;br /&gt;
&lt;br /&gt;
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.&lt;br /&gt;
&lt;br /&gt;
====Type II receptors====&lt;br /&gt;
&lt;br /&gt;
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:&lt;br /&gt;
&lt;br /&gt;
# Stimulates gustatory nerve afferents which project to gustatory nuclei  in the spinal cord&lt;br /&gt;
# Excites Type III presynaptic nerve fibers to release serotonin. &lt;br /&gt;
# Has a positive feedback effect on type II receptor cells, increasing the level of ATP production.&lt;br /&gt;
&lt;br /&gt;
        &lt;br /&gt;
&lt;br /&gt;
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.&lt;br /&gt;
&lt;br /&gt;
==Taste Map==&lt;br /&gt;
[[Image:Taste map.png|thumb|left|250px|Obsolete idea of the tongue map]]&lt;br /&gt;
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.&lt;br /&gt;
&lt;br /&gt;
===Neural Pathways===&lt;br /&gt;
&lt;br /&gt;
'''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''. &lt;br /&gt;
&lt;br /&gt;
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:  &lt;br /&gt;
&lt;br /&gt;
* ''Facial nerve n''. -  carries taste information from the anterior 2/3 of the tongue.&lt;br /&gt;
* ''Hypoglossal n.'' - carries taste information from the posterior 1/3 of the tongue.&lt;br /&gt;
* ''Vagus n''. - carries taste information from the palate&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
'''Second order neurons''' - From the NTS second order neurons carry taste information to the Ventral posteromedial (VPM) nucleus in the thalamus.&amp;lt;ref name=PMID21885776/&amp;gt;&lt;br /&gt;
&lt;br /&gt;
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.  &lt;br /&gt;
&lt;br /&gt;
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.&lt;br /&gt;
&lt;br /&gt;
===Cortical Areas===&lt;br /&gt;
&lt;br /&gt;
[[Image:Primary gustatory cortex.png|thumb|Primary gustatory cortex]]&lt;br /&gt;
&lt;br /&gt;
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)&amp;lt;ref name=PMID22245354&amp;gt;&amp;lt;pubmed&amp;gt;22245354&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;, with the secondary taste cortex in the caudolateral orbitofrontal cortex.&amp;lt;ref name=PMID21305668&amp;gt;&amp;lt;pubmed&amp;gt;21305668&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;  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.&amp;lt;ref name=PMID21885776&amp;gt;&amp;lt;pubmed&amp;gt;21885776&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; These findings lend weight to the idea that there is only one receptor for each taste quality.&lt;br /&gt;
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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).&amp;lt;ref name=PMID21885776/&amp;gt; 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&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
==Current Research==&lt;br /&gt;
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. &lt;br /&gt;
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.&lt;br /&gt;
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[[File:Mousetounge histologicalstain.jpg|Left|thumb|200px|Image shows histological stains of a mice tongue showing dysplasia]]&lt;br /&gt;
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'''Synergistic relationships of Six Genes '''&lt;br /&gt;
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In an animal study using mice by Suzuki Y, Ikeda K, Kawakami K.(2011)  Firstly nominating &amp;quot;[[#Glossary |'''Six Genes''']]&amp;quot; as a major component in [[#Glossary |'''gustatory ''']] development, stating that deficiencies in certain Six genes (specifically Six1 &amp;amp; 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 &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;21978088&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
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[[File:Highpowered_microscope.jpg|Left|thumb|200px|Image of a high powered microscope]]&lt;br /&gt;
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'''Neural Crest responsibilities '''&lt;br /&gt;
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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.&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;22659543&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
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[[File:Developing_tongue_histology_001.jpg|Left|thumb|200px|HIstological stain of a developing rat tongue]]&lt;br /&gt;
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'''Augmentation of Endoderm'''&lt;br /&gt;
&lt;br /&gt;
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 &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;22581563&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
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'''Changes in Taste Cells over time'''&lt;br /&gt;
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Research by &lt;br /&gt;
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.  &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;22643728&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
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'''Shh key component of taste bud proginators'''&lt;br /&gt;
&lt;br /&gt;
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.&lt;br /&gt;
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 &amp;quot;Axiocam CCD camera and Axioplan fluorescence microscope with Axiovision software&amp;quot; a study by Harlow, Yang, Williams, Barlow (2011)&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;PMC2674259&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
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'''WNT family exhibit various roles'''&lt;br /&gt;
&lt;br /&gt;
 [[File:Abnormal of tongue.jpg|thumb|200px|Image shows an example of tongue abnormalities, this is called &amp;quot;double tongue&amp;quot; each side has independent movement!]]&lt;br /&gt;
&lt;br /&gt;
The WNT gene family has a function of signaling work antagonistically through receptor tyrosine kinase (RTK) signaling. However, the deletion of Sprouty Homolog 2 (Spry2) led to the increase of chimaeric virus particles (CVPs) and a significant decrease in number of fungiform papillae. In contrast, the absence of Fibroblast growth factor 10 (Fgf10) in conjunction with 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. 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. &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;PMC2768563&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
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==Glossary==&lt;br /&gt;
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* '''Circumvallate papillae''' - &lt;br /&gt;
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* '''Ectoderm'''- outer germ layer of embryo&lt;br /&gt;
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* '''Endoderm''' - inner germ layer of embryo&lt;br /&gt;
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* '''Epithelium''' - basic animal tissue that is composed of tightly packed cells, usually covering the outer portion of organs&lt;br /&gt;
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* '''Exocystosis''' - movement of contents out of cell&lt;br /&gt;
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* '''Filiform papillae''' - &lt;br /&gt;
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* '''Foliate papillae''' - &lt;br /&gt;
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* '''Fungiform papillae''' - &lt;br /&gt;
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* '''Ganglia''' - the accumulation of a nerve cell body&lt;br /&gt;
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* '''Growth factor''' - a substance that stimulates the growth of cells&lt;br /&gt;
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* '''Gustatory''' - anything that relates to the taste sense&lt;br /&gt;
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* '''Hydrolysis''' - breakdown of a chemical when it reacts with water&lt;br /&gt;
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* '''Mesoderm''' - middle germ layer of embryo&lt;br /&gt;
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* '''Mesenchyme''' - multipotential cells&lt;br /&gt;
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* '''Neural crest''' - a part of the ectoderm found on both sides of the neural tube&lt;br /&gt;
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* '''Neuron''' - most simplistic unit of the nervous system&lt;br /&gt;
&lt;br /&gt;
* '''Neurotransmitter''' - chemicals which allow the passing of signals from neuron to neuron via connecting part (synapse) &lt;br /&gt;
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* '''Papillae''' - small rough surface projection&lt;br /&gt;
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* '''Six genes''' - a family of genes&lt;br /&gt;
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* '''Sonic hedgehog (Shh)''' - signalling protein involved in normal development&lt;br /&gt;
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* '''Sulcus terminalis''' - describes a physical transition point separating the anterior 2/3 of the tongue from the posterior 1/3&lt;br /&gt;
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* '''Tamoxifen''' - hormonal altering drug&lt;br /&gt;
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* '''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).&lt;br /&gt;
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* '''Type II taste cells''' - Receptor cells acting as primary detectors of sweet, bitter or umami taste.&lt;br /&gt;
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* '''Type III taste cells''' - Presynaptic cells that respond to sweet, salty, sour, bitter and umami compounds.&lt;br /&gt;
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== References ==&lt;br /&gt;
&amp;lt;references/&amp;gt;&lt;br /&gt;
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==External Links==&lt;br /&gt;
{{External Links}}&lt;br /&gt;
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[http://www.surgicalneurologyint.com/article.asp?issn=2152-7806;year=2012;volume=3;issue=1;spage=23;epage=23;aulast=Manjila]&lt;br /&gt;
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http://embryology.med.unsw.edu.au/embryology/index.php?title=2012_Group_Project_4&lt;br /&gt;
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http://www.webmd.com/oral-health/picture-of-the-tongue&lt;br /&gt;
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http://www.tutorvista.com/content/biology/biology-iv/nervous-coordination/tongue-structure.php#parts-of-tongue&lt;br /&gt;
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http://www.cf.ac.uk/biosi/staffinfo/jacob/teaching/sensory/taste.html&lt;br /&gt;
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--[[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.&lt;br /&gt;
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{{2012Projects}}&lt;/div&gt;</summary>
		<author><name>Z3330795</name></author>
	</entry>
	<entry>
		<id>https://embryology.med.unsw.edu.au/embryology/index.php?title=2012_Group_Project_3&amp;diff=105118</id>
		<title>2012 Group Project 3</title>
		<link rel="alternate" type="text/html" href="https://embryology.med.unsw.edu.au/embryology/index.php?title=2012_Group_Project_3&amp;diff=105118"/>
		<updated>2012-10-02T22:25:00Z</updated>

		<summary type="html">&lt;p&gt;Z3330795: /* External Links */&lt;/p&gt;
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&lt;div&gt;=Taste Development=&lt;br /&gt;
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You are out to dinner and your meal arrives in front of you, the aromas and the presentation of your food strikes you immediately. Half way through, the waiter returns and asks “How does your meal taste?”  The answer is not as simple as one might think. Why does the meal taste pleasant? How do we experience different tastes? In the following page, we aim to discern how exactly one would answer these questions by looking at the embryological development of the taste system from week to week. &lt;br /&gt;
&lt;br /&gt;
Taste is a complex sensory system and its precise workings are to this day not fully understood. What makes it so complicated is the interaction between the structure of tongue and taste buds and how this contributes to the representation of taste qualities (salty, bitter, sweet, sour and umami) in the brain. We will also look at some current research on animal models being undertaken to evaluate the role of specific genes in the development of sensory structures. By looking at the taste system’s genetic basis, we now have a greater understanding of the abnormalities that may occur during development and a direction to pursue in future research to attempt to fill in the gaps of scientific knowledge.&lt;br /&gt;
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==Adult Tongue and Taste Buds – Structure and Function==&lt;br /&gt;
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'''Structure'''&lt;br /&gt;
&lt;br /&gt;
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.  &lt;br /&gt;
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''''The image below is a simplistic diagram of the surface of the tongue showing the locations of the different papillae and other important features'''&lt;br /&gt;
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{|&lt;br /&gt;
| [[Image:Drawing of Tongue.png|centre|500px]]&lt;br /&gt;
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'''Papillae'''&lt;br /&gt;
[[File:Papillae.jpg|Left|thumb|200px|Close up of Human Tongue Papillae]]&lt;br /&gt;
&lt;br /&gt;
There are 4 types of papillae on the tongue.&lt;br /&gt;
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. &lt;br /&gt;
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[[File:Fungiformpapillae.jpg|Left|thumb|200px|Fungiform Papillae]]&lt;br /&gt;
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[[File:Circumvallatepapillae.jpg |Left|thumb|200px|Circumvallate Papillae]]&lt;br /&gt;
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[[File:Filiformpapillae.jpg|Left|thumb|200px|Foliate Papillae]]&lt;br /&gt;
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'''Function'''&lt;br /&gt;
&lt;br /&gt;
The Tongue has muscular and sensory functions, muscular functions include swallowing and speech where as sensory function involves taste. This section will focus on the sensory functions of the tongue.&lt;br /&gt;
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.&lt;br /&gt;
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'''The image below is a simplistic hand-drawn cross section of a taste bud unit (not to scale)'''&lt;br /&gt;
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[[File:Taste_bud_1.jpg|x400px|alt=Cross section of a taste bud unit|centre|Cross section of a taste bud unit]]&lt;br /&gt;
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&lt;br /&gt;
'''Link Between Taste and Smell'''&lt;br /&gt;
&lt;br /&gt;
The pathways of smell and taste are very similar. Pathways both involve the conversion of a dissolved chemical stimulus into a nerve impulse for interpretation by the brain.	&lt;br /&gt;
Taste does not necessarily equal flavour, flavour involves an interaction of taste, smell, texture and temperature, where taste is only a portion of this interaction. when the brain interprets a taste, contribution from other senses has a significant role in identification. In conclusion Taste and Smell in combination with other senses help develop a sensory interpretation called flavour.&lt;br /&gt;
&lt;br /&gt;
[[File:Taste_pathway.jpg|right|thumb|200px|Simplistic Pathway of Taste]]&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
[[File:Human smelling.jpg|500px|centre]]&lt;br /&gt;
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==History of Discoveries==&lt;br /&gt;
&lt;br /&gt;
{| cellpadding=5 style=&amp;quot;border:1px solid #BBB&amp;quot;&lt;br /&gt;
|- bgcolor=&amp;quot;#faecc8&amp;quot;&lt;br /&gt;
|''' Date'''|| '''Significant Discovery'''&lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#faf6ed&amp;quot;&lt;br /&gt;
|'''350BC'''&lt;br /&gt;
|| Aristotle writes about the basic tastes, sweet and bitter. He also notes that it can be modified by salty and acidic. &amp;lt;ref name=&amp;quot;PMID22717400&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;22717400&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#faecc8&amp;quot;&lt;br /&gt;
|'''1901'''&lt;br /&gt;
|| D. Hanig publishes a paper describing taste sensitivity in different regions of the tongue. &lt;br /&gt;
''Interesting fact:'' The modern concept of a 'tongue map' is a misinterpretation of this study. &amp;lt;ref name=&amp;quot;PMID22717400&amp;quot;/&amp;gt;&lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#faf6ed&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''1908'''&lt;br /&gt;
|Kikunae Ikeda, a professor of the Tokyo Imperial University, discovered and identified the fifth basic taste: umami (savouriness), made palatable by glutamate.  &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;12438213&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
[http://chemse.oxfordjournals.org/content/27/9/847.long New Seasonings]&lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#faecc8&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''1931-32'''&lt;br /&gt;
| A chemist named Arthur Fox and his college noted that they had different sensitivities to the bitter tasting Phenylthiocarbamide (PTC).&amp;lt;ref&amp;gt;Blakeslee AF, Fox AL. Our different taste worlds. J Hered. 1932;23:97–107.&amp;lt;/ref&amp;gt; Geneticists later confirm these findings, and discover that non-tasting is a recessive genetic trait. &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;17782493&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/pubmed/17782493 Inherited taste deficiency] &lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#faf6ed&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''1965'''&lt;br /&gt;
|Farbman's study of the developing taste but in rat fungiform papilla was significant in increasing our understanding of taste bud development. &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;14300090&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
[http://www.sciencedirect.com/science/article/pii/0012160665900400 Electron microscope study of the developing taste bud in rat fungiform papilla.]&lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#faecc8&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''1992'''&lt;br /&gt;
|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. &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;1608467 &amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
[http://www.nature.com/nature/journal/v357/n6379/abs/357563a0.html Gustducin is a taste-cell-specific G protein closely related to the transducins]&lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#faf6ed&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''1995'''&lt;br /&gt;
|Barlow et al. experimented with Axolotl salamanders and concluded that taste buds from this species arise exclusively from epithelial tissue, &amp;quot;oropharyngeal [[#Glossary |'''epithelium''']]&amp;quot;. &amp;lt;ref name=&amp;quot;PMID17826760&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;17826760&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/pubmed/17826760 Embryonic origin of gustatory cranial sensory neurons] &lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#faecc8&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''1996'''&lt;br /&gt;
| 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 &amp;quot;at least dual function of embryonic/fetal taste buds&amp;quot;, including non-gustatory, paracrine functions prior to the 14th week and gustatory after the 14th week. &amp;lt;ref name=&amp;quot;PMID8955790&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;8955790&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/pubmed/8955790 Embryonic and early fetal development of human taste buds: a transmission electron microscopical study]&lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#faf6ed&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''2000'''&lt;br /&gt;
|Chandrashekar, J. et al. discover the first taste sonsors, the T2R bitter taste receptors. &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;10761935&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
[http://www.sciencedirect.com/science/article/pii/S0092867400807060 T2Rs Function as Bitter Taste Receptors]&lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#faecc8&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''2001'''&lt;br /&gt;
|Nelson, G. et al. discover the sweet receptor: a combination of T1R2 and T1R3. &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;11509186&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/pubmed/11509186?dopt=Abstract&amp;amp;holding=npg Mammalian sweet taste receptors.]&lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#faf6ed&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''2002'''&lt;br /&gt;
|Nelson G. et al. discover the amino acid (umami) taste receptor: a combination of T1R1 and T1R3 identified.  &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;11894099&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/pubmed/11894099?dopt=Abstract&amp;amp;holding=npg An amino-acid taste receptor]&lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#faecc8&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''2005'''&lt;br /&gt;
|Dyer, J. et al. discover sweet taste receptors in the GI tract. &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;17855558&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1986582/ Sweet taste signaling in the gut]&lt;br /&gt;
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|- bgcolor=&amp;quot;#faf6ed&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''2006'''&lt;br /&gt;
|Huang, A. L et al. discover cells for sour taste, identified by PKD2L1 (a polycystic kidney disease-like ion channel). &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;16929298&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1571047/ The Cells and Logic for Mammalian Sour Taste detection]&lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#faecc8&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''2007'''&lt;br /&gt;
|Harlow DE, Barlow LA of the University of Colorado Denver Health Sciences Center provide evidence of the &amp;quot;embryonic origin of gustatory cranial sensory neurons&amp;quot;. &amp;lt;ref name=&amp;quot;PMID17826760&amp;quot;/&amp;gt;&lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/pubmed/17826760 Embryonic origin of gustatory cranial sensory neurons.]&lt;br /&gt;
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|- bgcolor=&amp;quot;#faf6ed&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''2009'''&lt;br /&gt;
|A study by Hevezi P et al, presents &amp;quot;the first comprehensive characterization of gene expression in primate taste buds&amp;quot;, as opposed to previous studies which focused on rodents. &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;19636377&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/pubmed/19636377 Genome-wide analysis of gene expression in primate taste buds reveals links to diverse processes]&lt;br /&gt;
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|- bgcolor=&amp;quot;#faecc8&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''2010'''&lt;br /&gt;
|Chandrashekar, J. et al. identify epithelial sodium channel (ENaC) as the sodium-salt taste receptor. &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;20107438&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/pubmed/20107438?dopt=Abstract&amp;amp;holding=npg The cells and peripheral representation of sodium taste in mice]&lt;br /&gt;
|}&lt;br /&gt;
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== Human Weekly Development - Two Prominent Studies ==&lt;br /&gt;
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. &lt;br /&gt;
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The findings of these two studies are summarized in the table below. The figures provided relate to the images on their respective research papers.&lt;br /&gt;
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# [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] &lt;br /&gt;
# [http://chemse.oxfordjournals.org/content/22/6/601.long Scanning electron microscopical studies of developing gustatory papillae in humans, 1997]  &lt;br /&gt;
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===Timeline of Developmental Processes of Human Taste Buds===&lt;br /&gt;
{| cellpadding=5 style=&amp;quot;border:1px solid #BBB&amp;quot;&lt;br /&gt;
|- bgcolor=&amp;quot;#89CFF0&amp;quot;&lt;br /&gt;
|'''Postovulatory Week'''||'''Description'''&lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#BCD4E6&amp;quot;&lt;br /&gt;
|'''Week 6''' ||&lt;br /&gt;
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. &amp;lt;ref name=&amp;quot;PMID9455607&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;9455607&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#89CFF0&amp;quot;&lt;br /&gt;
| '''Weeks 6 to 7'''|| &lt;br /&gt;
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. &amp;lt;ref name=PMID8955790/&amp;gt;&lt;br /&gt;
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|- bgcolor=&amp;quot;#BCD4E6&amp;quot;&lt;br /&gt;
| '''Week 7 '''||&lt;br /&gt;
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.  &amp;lt;ref name=PMID9455607/&amp;gt; &lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#89CFF0&amp;quot;&lt;br /&gt;
| ''' Week 8  ''' ||&lt;br /&gt;
* The taste bud primordium are still differentiated, elongated epithelial cells, resting on a slightly developed core of young dermal papilla.&lt;br /&gt;
* 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. &lt;br /&gt;
* Ciliated cells also appear around the 8th week, however the significance of these cells which are scattered randomly across the lingual surface remains unclear. &amp;lt;ref name=PMID8955790/&amp;gt; &lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#BCD4E6&amp;quot;&lt;br /&gt;
|'''  Week 9''' ||&lt;br /&gt;
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). &amp;lt;ref name=PMID9455607/&amp;gt;&lt;br /&gt;
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|- bgcolor=&amp;quot;#89CFF0&amp;quot;&lt;br /&gt;
|'''  Weeks 10-11''' ||&lt;br /&gt;
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). &amp;lt;ref name=PMID8955790/&amp;gt; &lt;br /&gt;
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|- bgcolor=&amp;quot;#BCD4E6&amp;quot;&lt;br /&gt;
|''' Week 12 ''' ||&lt;br /&gt;
Taste bud cells are more clearly differentiated into epithelial cell types II and III. &amp;lt;ref name=PMID8955790/&amp;gt; &lt;br /&gt;
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|- bgcolor=&amp;quot;#89CFF0&amp;quot;&lt;br /&gt;
|''' Weeks 12-13  ''' ||&lt;br /&gt;
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). &amp;lt;ref name=PMID8955790/&amp;gt; &lt;br /&gt;
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|- bgcolor=&amp;quot;#BCD4E6&amp;quot;&lt;br /&gt;
|''' Weeks 14 -15 ''' ||&lt;br /&gt;
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. &amp;lt;ref name=PMID8955790/&amp;gt; &lt;br /&gt;
|}&lt;br /&gt;
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==Abnormalities==&lt;br /&gt;
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It should be mentioned that gustatory abnormalities have not been widely researched. Most research conducted in this field has been conducted through animal testing on mice and this is the basis of information provided below. &lt;br /&gt;
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===Knocking out P2X Receptors===&lt;br /&gt;
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[[File:Image of taste being evoked by visualising ATP release.jpeg|Left|thumb|200px|Evoking taste - ATP release in tongue]]&lt;br /&gt;
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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. &lt;br /&gt;
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It should be noted that the taste buds in DKO are functional, but are not stimulated by the administration of tastants. &lt;br /&gt;
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The transmission of release of ATP is secretion through gap junction hemichannels (pannexin 1 gap junction).&lt;br /&gt;
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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.&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;21940456&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
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===FGF signalling and genes===&lt;br /&gt;
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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.&lt;br /&gt;
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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 (&amp;quot;Fgf10&amp;quot;) 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 &amp;quot;Fgf10&amp;quot; to limit the size of the CVP progenitor placode. Exclusive expression of ''Fgf10'' in the [[#Glossary |'''mesenchyme''']] is necessary for the formation of CVP. &lt;br /&gt;
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'''This image shows the CVP stained with H&amp;amp;E and scanned by Scanning Electron Microscope (SEM)'''&lt;br /&gt;
[[File:CVP of WT(top) and DKO(bottom) mice with H&amp;amp;E and SEM.png]]&lt;br /&gt;
&lt;br /&gt;
'''This image shows the location of the CVP and the increased number in DKO mice by SEM'''&lt;br /&gt;
[[File:Mouse circumvallate papilla 01.jpg|300px]]&lt;br /&gt;
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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).&lt;br /&gt;
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&lt;br /&gt;
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).&lt;br /&gt;
&lt;br /&gt;
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''&amp;amp; ''Spry 1&amp;amp;2''work antagonistically through receptor tyrosine kinase (RTK)signalling.&lt;br /&gt;
&lt;br /&gt;
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.&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;21655085&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
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==Gustatory System==&lt;br /&gt;
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[[Image:Taste qualities.gif|thumb|The five basic tastes]]&lt;br /&gt;
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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.&lt;br /&gt;
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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.&amp;lt;ref name=PMID20696704&amp;gt;&amp;lt;pubmed&amp;gt;20696704&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
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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 &amp;lt;ref name=PMID20696704/&amp;gt; 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.&lt;br /&gt;
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===Cell Biology===&lt;br /&gt;
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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.&lt;br /&gt;
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====Type II receptors====&lt;br /&gt;
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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:&lt;br /&gt;
&lt;br /&gt;
# Stimulates gustatory nerve afferents which project to gustatory nuclei  in the spinal cord&lt;br /&gt;
# Excites Type III presynaptic nerve fibers to release serotonin. &lt;br /&gt;
# Has a positive feedback effect on type II receptor cells, increasing the level of ATP production.&lt;br /&gt;
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        &lt;br /&gt;
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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.&lt;br /&gt;
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==Taste Map==&lt;br /&gt;
[[Image:Taste map.png|thumb|left|250px|Obsolete idea of the tongue map]]&lt;br /&gt;
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.&lt;br /&gt;
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===Neural Pathways===&lt;br /&gt;
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'''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''. &lt;br /&gt;
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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:  &lt;br /&gt;
&lt;br /&gt;
* ''Facial nerve n''. -  carries taste information from the anterior 2/3 of the tongue.&lt;br /&gt;
* ''Hypoglossal n.'' - carries taste information from the posterior 1/3 of the tongue.&lt;br /&gt;
* ''Vagus n''. - carries taste information from the palate&lt;br /&gt;
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&lt;br /&gt;
'''Second order neurons''' - From the NTS second order neurons carry taste information to the Ventral posteromedial (VPM) nucleus in the thalamus.&amp;lt;ref name=PMID21885776/&amp;gt;&lt;br /&gt;
&lt;br /&gt;
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.  &lt;br /&gt;
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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.&lt;br /&gt;
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===Cortical Areas===&lt;br /&gt;
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[[Image:Primary gustatory cortex.png|thumb|Primary gustatory cortex]]&lt;br /&gt;
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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)&amp;lt;ref name=PMID22245354&amp;gt;&amp;lt;pubmed&amp;gt;22245354&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;, with the secondary taste cortex in the caudolateral orbitofrontal cortex.&amp;lt;ref name=PMID21305668&amp;gt;&amp;lt;pubmed&amp;gt;21305668&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;  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.&amp;lt;ref name=PMID21885776&amp;gt;&amp;lt;pubmed&amp;gt;21885776&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; These findings lend weight to the idea that there is only one receptor for each taste quality.&lt;br /&gt;
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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).&amp;lt;ref name=PMID21885776/&amp;gt; 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&lt;br /&gt;
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==Current Research==&lt;br /&gt;
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. &lt;br /&gt;
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.&lt;br /&gt;
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[[File:Mousetounge histologicalstain.jpg|Left|thumb|200px|Image shows histological stains of a mice tongue showing dysplasia]]&lt;br /&gt;
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'''Synergistic relationships of Six Genes '''&lt;br /&gt;
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In an animal study using mice by Suzuki Y, Ikeda K, Kawakami K.(2011)  Firstly nominating &amp;quot;[[#Glossary |'''Six Genes''']]&amp;quot; as a major component in [[#Glossary |'''gustatory ''']] development, stating that deficiencies in certain Six genes (specifically Six1 &amp;amp; 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 &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;21978088&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
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[[File:Highpowered_microscope.jpg|Left|thumb|200px|Image of a high powered microscope]]&lt;br /&gt;
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'''Neural Crest responsibilities '''&lt;br /&gt;
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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.&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;22659543&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
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[[File:Developing_tongue_histology_001.jpg|Left|thumb|200px|HIstological stain of a developing rat tongue]]&lt;br /&gt;
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'''Augmentation of Endoderm'''&lt;br /&gt;
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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 &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;22581563&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
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'''Changes in Taste Cells over time'''&lt;br /&gt;
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Research by &lt;br /&gt;
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.  &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;22643728&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
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'''Shh key component of taste bud proginators'''&lt;br /&gt;
&lt;br /&gt;
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.&lt;br /&gt;
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 &amp;quot;Axiocam CCD camera and Axioplan fluorescence microscope with Axiovision software&amp;quot; a study by Harlow, Yang, Williams, Barlow (2011)&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;PMC2674259&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
'''WNT family exhibit various roles'''&lt;br /&gt;
&lt;br /&gt;
 [[File:Abnormal of tongue.jpg|thumb|200px|Image shows an example of tongue abnormalities, this is called &amp;quot;double tongue&amp;quot; each side has independent movement!]]&lt;br /&gt;
&lt;br /&gt;
The WNT gene family has a function of signaling work antagonistically through receptor tyrosine kinase (RTK) signaling. However, the deletion of Sprouty Homolog 2 (Spry2) led to the increase of chimaeric virus particles (CVPs) and a significant decrease in number of fungiform papillae. In contrast, the absence of Fibroblast growth factor 10 (Fgf10) in conjunction with 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. 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. &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;PMC2768563&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
==Glossary==&lt;br /&gt;
&lt;br /&gt;
* '''Circumvallate papillae''' - &lt;br /&gt;
&lt;br /&gt;
* '''Ectoderm'''- outer germ layer of embryo&lt;br /&gt;
&lt;br /&gt;
* '''Endoderm''' - inner germ layer of embryo&lt;br /&gt;
&lt;br /&gt;
* '''Epithelium''' - basic animal tissue that is composed of tightly packed cells, usually covering the outer portion of organs&lt;br /&gt;
&lt;br /&gt;
* '''Exocystosis''' - movement of contents out of cell&lt;br /&gt;
&lt;br /&gt;
* '''Filiform papillae''' - &lt;br /&gt;
&lt;br /&gt;
* '''Foliate papillae''' - &lt;br /&gt;
&lt;br /&gt;
* '''Fungiform papillae''' - &lt;br /&gt;
&lt;br /&gt;
* '''Ganglia''' - the accumulation of a nerve cell body&lt;br /&gt;
&lt;br /&gt;
* '''Growth factor''' - a substance that stimulates the growth of cells&lt;br /&gt;
&lt;br /&gt;
* '''Gustatory''' - anything that relates to the taste sense&lt;br /&gt;
&lt;br /&gt;
* '''Hydrolysis''' - breakdown of a chemical when it reacts with water&lt;br /&gt;
&lt;br /&gt;
* '''Mesoderm''' - middle germ layer of embryo&lt;br /&gt;
&lt;br /&gt;
* '''Mesenchyme''' - multipotential cells&lt;br /&gt;
&lt;br /&gt;
* '''Neural crest''' - a part of the ectoderm found on both sides of the neural tube&lt;br /&gt;
&lt;br /&gt;
* '''Neuron''' - most simplistic unit of the nervous system&lt;br /&gt;
&lt;br /&gt;
* '''Neurotransmitter''' - chemicals which allow the passing of signals from neuron to neuron via connecting part (synapse) &lt;br /&gt;
&lt;br /&gt;
* '''Papillae''' - small rough surface projection&lt;br /&gt;
&lt;br /&gt;
* '''Six genes''' - a family of genes&lt;br /&gt;
&lt;br /&gt;
* '''Sonic hedgehog (Shh)''' - signalling protein involved in normal development&lt;br /&gt;
&lt;br /&gt;
* '''Sulcus terminalis''' - describes a physical transition point separating the anterior 2/3 of the tongue from the posterior 1/3&lt;br /&gt;
&lt;br /&gt;
* '''Tamoxifen''' - hormonal altering drug&lt;br /&gt;
&lt;br /&gt;
* '''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).&lt;br /&gt;
&lt;br /&gt;
* '''Type II taste cells''' - Receptor cells acting as primary detectors of sweet, bitter or umami taste.&lt;br /&gt;
&lt;br /&gt;
* '''Type III taste cells''' - Presynaptic cells that respond to sweet, salty, sour, bitter and umami compounds.&lt;br /&gt;
&lt;br /&gt;
== References ==&lt;br /&gt;
&amp;lt;references/&amp;gt;&lt;br /&gt;
&lt;br /&gt;
==External Links==&lt;br /&gt;
{{External Links}}&lt;br /&gt;
&lt;br /&gt;
[http://www.surgicalneurologyint.com/article.asp?issn=2152-7806;year=2012;volume=3;issue=1;spage=23;epage=23;aulast=Manjila]&lt;br /&gt;
&lt;br /&gt;
http://embryology.med.unsw.edu.au/embryology/index.php?title=2012_Group_Project_4&lt;br /&gt;
&lt;br /&gt;
http://www.webmd.com/oral-health/picture-of-the-tongue&lt;br /&gt;
&lt;br /&gt;
http://www.tutorvista.com/content/biology/biology-iv/nervous-coordination/tongue-structure.php#parts-of-tongue&lt;br /&gt;
&lt;br /&gt;
http://www.cf.ac.uk/biosi/staffinfo/jacob/teaching/sensory/taste.html&lt;br /&gt;
&lt;br /&gt;
--[[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.&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
----&lt;br /&gt;
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{{2012Projects}}&lt;/div&gt;</summary>
		<author><name>Z3330795</name></author>
	</entry>
	<entry>
		<id>https://embryology.med.unsw.edu.au/embryology/index.php?title=2012_Group_Project_3&amp;diff=105117</id>
		<title>2012 Group Project 3</title>
		<link rel="alternate" type="text/html" href="https://embryology.med.unsw.edu.au/embryology/index.php?title=2012_Group_Project_3&amp;diff=105117"/>
		<updated>2012-10-02T22:24:26Z</updated>

		<summary type="html">&lt;p&gt;Z3330795: /* Current Research */&lt;/p&gt;
&lt;hr /&gt;
&lt;div&gt;=Taste Development=&lt;br /&gt;
&lt;br /&gt;
You are out to dinner and your meal arrives in front of you, the aromas and the presentation of your food strikes you immediately. Half way through, the waiter returns and asks “How does your meal taste?”  The answer is not as simple as one might think. Why does the meal taste pleasant? How do we experience different tastes? In the following page, we aim to discern how exactly one would answer these questions by looking at the embryological development of the taste system from week to week. &lt;br /&gt;
&lt;br /&gt;
Taste is a complex sensory system and its precise workings are to this day not fully understood. What makes it so complicated is the interaction between the structure of tongue and taste buds and how this contributes to the representation of taste qualities (salty, bitter, sweet, sour and umami) in the brain. We will also look at some current research on animal models being undertaken to evaluate the role of specific genes in the development of sensory structures. By looking at the taste system’s genetic basis, we now have a greater understanding of the abnormalities that may occur during development and a direction to pursue in future research to attempt to fill in the gaps of scientific knowledge.&lt;br /&gt;
&lt;br /&gt;
==Adult Tongue and Taste Buds – Structure and Function==&lt;br /&gt;
&lt;br /&gt;
'''Structure'''&lt;br /&gt;
&lt;br /&gt;
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.  &lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
''''The image below is a simplistic diagram of the surface of the tongue showing the locations of the different papillae and other important features'''&lt;br /&gt;
&lt;br /&gt;
{|&lt;br /&gt;
| [[Image:Drawing of Tongue.png|centre|500px]]&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
'''Papillae'''&lt;br /&gt;
[[File:Papillae.jpg|Left|thumb|200px|Close up of Human Tongue Papillae]]&lt;br /&gt;
&lt;br /&gt;
There are 4 types of papillae on the tongue.&lt;br /&gt;
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. &lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
[[File:Fungiformpapillae.jpg|Left|thumb|200px|Fungiform Papillae]]&lt;br /&gt;
&lt;br /&gt;
[[File:Circumvallatepapillae.jpg |Left|thumb|200px|Circumvallate Papillae]]&lt;br /&gt;
&lt;br /&gt;
[[File:Filiformpapillae.jpg|Left|thumb|200px|Foliate Papillae]]&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
'''Function'''&lt;br /&gt;
&lt;br /&gt;
The Tongue has muscular and sensory functions, muscular functions include swallowing and speech where as sensory function involves taste. This section will focus on the sensory functions of the tongue.&lt;br /&gt;
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.&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
'''The image below is a simplistic hand-drawn cross section of a taste bud unit (not to scale)'''&lt;br /&gt;
&lt;br /&gt;
[[File:Taste_bud_1.jpg|x400px|alt=Cross section of a taste bud unit|centre|Cross section of a taste bud unit]]&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
'''Link Between Taste and Smell'''&lt;br /&gt;
&lt;br /&gt;
The pathways of smell and taste are very similar. Pathways both involve the conversion of a dissolved chemical stimulus into a nerve impulse for interpretation by the brain.	&lt;br /&gt;
Taste does not necessarily equal flavour, flavour involves an interaction of taste, smell, texture and temperature, where taste is only a portion of this interaction. when the brain interprets a taste, contribution from other senses has a significant role in identification. In conclusion Taste and Smell in combination with other senses help develop a sensory interpretation called flavour.&lt;br /&gt;
&lt;br /&gt;
[[File:Taste_pathway.jpg|right|thumb|200px|Simplistic Pathway of Taste]]&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
[[File:Human smelling.jpg|500px|centre]]&lt;br /&gt;
&lt;br /&gt;
==History of Discoveries==&lt;br /&gt;
&lt;br /&gt;
{| cellpadding=5 style=&amp;quot;border:1px solid #BBB&amp;quot;&lt;br /&gt;
|- bgcolor=&amp;quot;#faecc8&amp;quot;&lt;br /&gt;
|''' Date'''|| '''Significant Discovery'''&lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#faf6ed&amp;quot;&lt;br /&gt;
|'''350BC'''&lt;br /&gt;
|| Aristotle writes about the basic tastes, sweet and bitter. He also notes that it can be modified by salty and acidic. &amp;lt;ref name=&amp;quot;PMID22717400&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;22717400&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#faecc8&amp;quot;&lt;br /&gt;
|'''1901'''&lt;br /&gt;
|| D. Hanig publishes a paper describing taste sensitivity in different regions of the tongue. &lt;br /&gt;
''Interesting fact:'' The modern concept of a 'tongue map' is a misinterpretation of this study. &amp;lt;ref name=&amp;quot;PMID22717400&amp;quot;/&amp;gt;&lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#faf6ed&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''1908'''&lt;br /&gt;
|Kikunae Ikeda, a professor of the Tokyo Imperial University, discovered and identified the fifth basic taste: umami (savouriness), made palatable by glutamate.  &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;12438213&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
[http://chemse.oxfordjournals.org/content/27/9/847.long New Seasonings]&lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#faecc8&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''1931-32'''&lt;br /&gt;
| A chemist named Arthur Fox and his college noted that they had different sensitivities to the bitter tasting Phenylthiocarbamide (PTC).&amp;lt;ref&amp;gt;Blakeslee AF, Fox AL. Our different taste worlds. J Hered. 1932;23:97–107.&amp;lt;/ref&amp;gt; Geneticists later confirm these findings, and discover that non-tasting is a recessive genetic trait. &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;17782493&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/pubmed/17782493 Inherited taste deficiency] &lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#faf6ed&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''1965'''&lt;br /&gt;
|Farbman's study of the developing taste but in rat fungiform papilla was significant in increasing our understanding of taste bud development. &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;14300090&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
[http://www.sciencedirect.com/science/article/pii/0012160665900400 Electron microscope study of the developing taste bud in rat fungiform papilla.]&lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#faecc8&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''1992'''&lt;br /&gt;
|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. &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;1608467 &amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
[http://www.nature.com/nature/journal/v357/n6379/abs/357563a0.html Gustducin is a taste-cell-specific G protein closely related to the transducins]&lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#faf6ed&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''1995'''&lt;br /&gt;
|Barlow et al. experimented with Axolotl salamanders and concluded that taste buds from this species arise exclusively from epithelial tissue, &amp;quot;oropharyngeal [[#Glossary |'''epithelium''']]&amp;quot;. &amp;lt;ref name=&amp;quot;PMID17826760&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;17826760&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/pubmed/17826760 Embryonic origin of gustatory cranial sensory neurons] &lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#faecc8&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''1996'''&lt;br /&gt;
| 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 &amp;quot;at least dual function of embryonic/fetal taste buds&amp;quot;, including non-gustatory, paracrine functions prior to the 14th week and gustatory after the 14th week. &amp;lt;ref name=&amp;quot;PMID8955790&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;8955790&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/pubmed/8955790 Embryonic and early fetal development of human taste buds: a transmission electron microscopical study]&lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#faf6ed&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''2000'''&lt;br /&gt;
|Chandrashekar, J. et al. discover the first taste sonsors, the T2R bitter taste receptors. &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;10761935&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
[http://www.sciencedirect.com/science/article/pii/S0092867400807060 T2Rs Function as Bitter Taste Receptors]&lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#faecc8&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''2001'''&lt;br /&gt;
|Nelson, G. et al. discover the sweet receptor: a combination of T1R2 and T1R3. &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;11509186&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/pubmed/11509186?dopt=Abstract&amp;amp;holding=npg Mammalian sweet taste receptors.]&lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#faf6ed&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''2002'''&lt;br /&gt;
|Nelson G. et al. discover the amino acid (umami) taste receptor: a combination of T1R1 and T1R3 identified.  &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;11894099&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/pubmed/11894099?dopt=Abstract&amp;amp;holding=npg An amino-acid taste receptor]&lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#faecc8&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''2005'''&lt;br /&gt;
|Dyer, J. et al. discover sweet taste receptors in the GI tract. &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;17855558&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1986582/ Sweet taste signaling in the gut]&lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#faf6ed&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''2006'''&lt;br /&gt;
|Huang, A. L et al. discover cells for sour taste, identified by PKD2L1 (a polycystic kidney disease-like ion channel). &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;16929298&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1571047/ The Cells and Logic for Mammalian Sour Taste detection]&lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#faecc8&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''2007'''&lt;br /&gt;
|Harlow DE, Barlow LA of the University of Colorado Denver Health Sciences Center provide evidence of the &amp;quot;embryonic origin of gustatory cranial sensory neurons&amp;quot;. &amp;lt;ref name=&amp;quot;PMID17826760&amp;quot;/&amp;gt;&lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/pubmed/17826760 Embryonic origin of gustatory cranial sensory neurons.]&lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#faf6ed&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''2009'''&lt;br /&gt;
|A study by Hevezi P et al, presents &amp;quot;the first comprehensive characterization of gene expression in primate taste buds&amp;quot;, as opposed to previous studies which focused on rodents. &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;19636377&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/pubmed/19636377 Genome-wide analysis of gene expression in primate taste buds reveals links to diverse processes]&lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#faecc8&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''2010'''&lt;br /&gt;
|Chandrashekar, J. et al. identify epithelial sodium channel (ENaC) as the sodium-salt taste receptor. &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;20107438&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/pubmed/20107438?dopt=Abstract&amp;amp;holding=npg The cells and peripheral representation of sodium taste in mice]&lt;br /&gt;
|}&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
== Human Weekly Development - Two Prominent Studies ==&lt;br /&gt;
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. &lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
The findings of these two studies are summarized in the table below. The figures provided relate to the images on their respective research papers.&lt;br /&gt;
&lt;br /&gt;
# [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] &lt;br /&gt;
# [http://chemse.oxfordjournals.org/content/22/6/601.long Scanning electron microscopical studies of developing gustatory papillae in humans, 1997]  &lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
===Timeline of Developmental Processes of Human Taste Buds===&lt;br /&gt;
{| cellpadding=5 style=&amp;quot;border:1px solid #BBB&amp;quot;&lt;br /&gt;
|- bgcolor=&amp;quot;#89CFF0&amp;quot;&lt;br /&gt;
|'''Postovulatory Week'''||'''Description'''&lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#BCD4E6&amp;quot;&lt;br /&gt;
|'''Week 6''' ||&lt;br /&gt;
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. &amp;lt;ref name=&amp;quot;PMID9455607&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;9455607&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#89CFF0&amp;quot;&lt;br /&gt;
| '''Weeks 6 to 7'''|| &lt;br /&gt;
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. &amp;lt;ref name=PMID8955790/&amp;gt;&lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#BCD4E6&amp;quot;&lt;br /&gt;
| '''Week 7 '''||&lt;br /&gt;
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.  &amp;lt;ref name=PMID9455607/&amp;gt; &lt;br /&gt;
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|- bgcolor=&amp;quot;#89CFF0&amp;quot;&lt;br /&gt;
| ''' Week 8  ''' ||&lt;br /&gt;
* The taste bud primordium are still differentiated, elongated epithelial cells, resting on a slightly developed core of young dermal papilla.&lt;br /&gt;
* 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. &lt;br /&gt;
* Ciliated cells also appear around the 8th week, however the significance of these cells which are scattered randomly across the lingual surface remains unclear. &amp;lt;ref name=PMID8955790/&amp;gt; &lt;br /&gt;
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|- bgcolor=&amp;quot;#BCD4E6&amp;quot;&lt;br /&gt;
|'''  Week 9''' ||&lt;br /&gt;
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). &amp;lt;ref name=PMID9455607/&amp;gt;&lt;br /&gt;
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|- bgcolor=&amp;quot;#89CFF0&amp;quot;&lt;br /&gt;
|'''  Weeks 10-11''' ||&lt;br /&gt;
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). &amp;lt;ref name=PMID8955790/&amp;gt; &lt;br /&gt;
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|- bgcolor=&amp;quot;#BCD4E6&amp;quot;&lt;br /&gt;
|''' Week 12 ''' ||&lt;br /&gt;
Taste bud cells are more clearly differentiated into epithelial cell types II and III. &amp;lt;ref name=PMID8955790/&amp;gt; &lt;br /&gt;
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|- bgcolor=&amp;quot;#89CFF0&amp;quot;&lt;br /&gt;
|''' Weeks 12-13  ''' ||&lt;br /&gt;
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). &amp;lt;ref name=PMID8955790/&amp;gt; &lt;br /&gt;
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|- bgcolor=&amp;quot;#BCD4E6&amp;quot;&lt;br /&gt;
|''' Weeks 14 -15 ''' ||&lt;br /&gt;
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. &amp;lt;ref name=PMID8955790/&amp;gt; &lt;br /&gt;
|}&lt;br /&gt;
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==Abnormalities==&lt;br /&gt;
&lt;br /&gt;
It should be mentioned that gustatory abnormalities have not been widely researched. Most research conducted in this field has been conducted through animal testing on mice and this is the basis of information provided below. &lt;br /&gt;
&lt;br /&gt;
===Knocking out P2X Receptors===&lt;br /&gt;
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[[File:Image of taste being evoked by visualising ATP release.jpeg|Left|thumb|200px|Evoking taste - ATP release in tongue]]&lt;br /&gt;
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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. &lt;br /&gt;
&lt;br /&gt;
It should be noted that the taste buds in DKO are functional, but are not stimulated by the administration of tastants. &lt;br /&gt;
&lt;br /&gt;
The transmission of release of ATP is secretion through gap junction hemichannels (pannexin 1 gap junction).&lt;br /&gt;
&lt;br /&gt;
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.&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;21940456&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
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===FGF signalling and genes===&lt;br /&gt;
&lt;br /&gt;
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.&lt;br /&gt;
&lt;br /&gt;
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 (&amp;quot;Fgf10&amp;quot;) 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 &amp;quot;Fgf10&amp;quot; to limit the size of the CVP progenitor placode. Exclusive expression of ''Fgf10'' in the [[#Glossary |'''mesenchyme''']] is necessary for the formation of CVP. &lt;br /&gt;
&lt;br /&gt;
'''This image shows the CVP stained with H&amp;amp;E and scanned by Scanning Electron Microscope (SEM)'''&lt;br /&gt;
[[File:CVP of WT(top) and DKO(bottom) mice with H&amp;amp;E and SEM.png]]&lt;br /&gt;
&lt;br /&gt;
'''This image shows the location of the CVP and the increased number in DKO mice by SEM'''&lt;br /&gt;
[[File:Mouse circumvallate papilla 01.jpg|300px]]&lt;br /&gt;
&lt;br /&gt;
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).&lt;br /&gt;
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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).&lt;br /&gt;
&lt;br /&gt;
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''&amp;amp; ''Spry 1&amp;amp;2''work antagonistically through receptor tyrosine kinase (RTK)signalling.&lt;br /&gt;
&lt;br /&gt;
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.&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;21655085&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
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==Gustatory System==&lt;br /&gt;
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[[Image:Taste qualities.gif|thumb|The five basic tastes]]&lt;br /&gt;
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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.&lt;br /&gt;
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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.&amp;lt;ref name=PMID20696704&amp;gt;&amp;lt;pubmed&amp;gt;20696704&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
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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 &amp;lt;ref name=PMID20696704/&amp;gt; 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.&lt;br /&gt;
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===Cell Biology===&lt;br /&gt;
&lt;br /&gt;
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.&lt;br /&gt;
&lt;br /&gt;
====Type II receptors====&lt;br /&gt;
&lt;br /&gt;
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:&lt;br /&gt;
&lt;br /&gt;
# Stimulates gustatory nerve afferents which project to gustatory nuclei  in the spinal cord&lt;br /&gt;
# Excites Type III presynaptic nerve fibers to release serotonin. &lt;br /&gt;
# Has a positive feedback effect on type II receptor cells, increasing the level of ATP production.&lt;br /&gt;
&lt;br /&gt;
        &lt;br /&gt;
&lt;br /&gt;
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.&lt;br /&gt;
&lt;br /&gt;
==Taste Map==&lt;br /&gt;
[[Image:Taste map.png|thumb|left|250px|Obsolete idea of the tongue map]]&lt;br /&gt;
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.&lt;br /&gt;
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===Neural Pathways===&lt;br /&gt;
&lt;br /&gt;
'''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''. &lt;br /&gt;
&lt;br /&gt;
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:  &lt;br /&gt;
&lt;br /&gt;
* ''Facial nerve n''. -  carries taste information from the anterior 2/3 of the tongue.&lt;br /&gt;
* ''Hypoglossal n.'' - carries taste information from the posterior 1/3 of the tongue.&lt;br /&gt;
* ''Vagus n''. - carries taste information from the palate&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
'''Second order neurons''' - From the NTS second order neurons carry taste information to the Ventral posteromedial (VPM) nucleus in the thalamus.&amp;lt;ref name=PMID21885776/&amp;gt;&lt;br /&gt;
&lt;br /&gt;
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.  &lt;br /&gt;
&lt;br /&gt;
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.&lt;br /&gt;
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===Cortical Areas===&lt;br /&gt;
&lt;br /&gt;
[[Image:Primary gustatory cortex.png|thumb|Primary gustatory cortex]]&lt;br /&gt;
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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)&amp;lt;ref name=PMID22245354&amp;gt;&amp;lt;pubmed&amp;gt;22245354&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;, with the secondary taste cortex in the caudolateral orbitofrontal cortex.&amp;lt;ref name=PMID21305668&amp;gt;&amp;lt;pubmed&amp;gt;21305668&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;  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.&amp;lt;ref name=PMID21885776&amp;gt;&amp;lt;pubmed&amp;gt;21885776&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; These findings lend weight to the idea that there is only one receptor for each taste quality.&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
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).&amp;lt;ref name=PMID21885776/&amp;gt; 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&lt;br /&gt;
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&lt;br /&gt;
==Current Research==&lt;br /&gt;
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. &lt;br /&gt;
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.&lt;br /&gt;
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[[File:Mousetounge histologicalstain.jpg|Left|thumb|200px|Image shows histological stains of a mice tongue showing dysplasia]]&lt;br /&gt;
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'''Synergistic relationships of Six Genes '''&lt;br /&gt;
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In an animal study using mice by Suzuki Y, Ikeda K, Kawakami K.(2011)  Firstly nominating &amp;quot;[[#Glossary |'''Six Genes''']]&amp;quot; as a major component in [[#Glossary |'''gustatory ''']] development, stating that deficiencies in certain Six genes (specifically Six1 &amp;amp; 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 &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;21978088&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
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[[File:Highpowered_microscope.jpg|Left|thumb|200px|Image of a high powered microscope]]&lt;br /&gt;
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'''Neural Crest responsibilities '''&lt;br /&gt;
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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.&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;22659543&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
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[[File:Developing_tongue_histology_001.jpg|Left|thumb|200px|HIstological stain of a developing rat tongue]]&lt;br /&gt;
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'''Augmentation of Endoderm'''&lt;br /&gt;
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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 &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;22581563&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
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'''Changes in Taste Cells over time'''&lt;br /&gt;
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Research by &lt;br /&gt;
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.  &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;22643728&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
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'''Shh key component of taste bud proginators'''&lt;br /&gt;
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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.&lt;br /&gt;
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 &amp;quot;Axiocam CCD camera and Axioplan fluorescence microscope with Axiovision software&amp;quot; a study by Harlow, Yang, Williams, Barlow (2011)&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;PMC2674259&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
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'''WNT family exhibit various roles'''&lt;br /&gt;
&lt;br /&gt;
 [[File:Abnormal of tongue.jpg|thumb|200px|Image shows an example of tongue abnormalities, this is called &amp;quot;double tongue&amp;quot; each side has independent movement!]]&lt;br /&gt;
&lt;br /&gt;
The WNT gene family has a function of signaling work antagonistically through receptor tyrosine kinase (RTK) signaling. However, the deletion of Sprouty Homolog 2 (Spry2) led to the increase of chimaeric virus particles (CVPs) and a significant decrease in number of fungiform papillae. In contrast, the absence of Fibroblast growth factor 10 (Fgf10) in conjunction with 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. 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. &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;PMC2768563&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
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==Glossary==&lt;br /&gt;
&lt;br /&gt;
* '''Circumvallate papillae''' - &lt;br /&gt;
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* '''Ectoderm'''- outer germ layer of embryo&lt;br /&gt;
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* '''Endoderm''' - inner germ layer of embryo&lt;br /&gt;
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* '''Epithelium''' - basic animal tissue that is composed of tightly packed cells, usually covering the outer portion of organs&lt;br /&gt;
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* '''Exocystosis''' - movement of contents out of cell&lt;br /&gt;
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* '''Filiform papillae''' - &lt;br /&gt;
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* '''Foliate papillae''' - &lt;br /&gt;
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* '''Fungiform papillae''' - &lt;br /&gt;
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* '''Ganglia''' - the accumulation of a nerve cell body&lt;br /&gt;
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* '''Growth factor''' - a substance that stimulates the growth of cells&lt;br /&gt;
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* '''Gustatory''' - anything that relates to the taste sense&lt;br /&gt;
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* '''Hydrolysis''' - breakdown of a chemical when it reacts with water&lt;br /&gt;
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* '''Mesoderm''' - middle germ layer of embryo&lt;br /&gt;
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* '''Mesenchyme''' - multipotential cells&lt;br /&gt;
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* '''Neural crest''' - a part of the ectoderm found on both sides of the neural tube&lt;br /&gt;
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* '''Neuron''' - most simplistic unit of the nervous system&lt;br /&gt;
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* '''Neurotransmitter''' - chemicals which allow the passing of signals from neuron to neuron via connecting part (synapse) &lt;br /&gt;
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* '''Papillae''' - small rough surface projection&lt;br /&gt;
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* '''Six genes''' - a family of genes&lt;br /&gt;
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* '''Sonic hedgehog (Shh)''' - signalling protein involved in normal development&lt;br /&gt;
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* '''Sulcus terminalis''' - describes a physical transition point separating the anterior 2/3 of the tongue from the posterior 1/3&lt;br /&gt;
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* '''Tamoxifen''' - hormonal altering drug&lt;br /&gt;
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* '''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).&lt;br /&gt;
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* '''Type II taste cells''' - Receptor cells acting as primary detectors of sweet, bitter or umami taste.&lt;br /&gt;
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* '''Type III taste cells''' - Presynaptic cells that respond to sweet, salty, sour, bitter and umami compounds.&lt;br /&gt;
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== References ==&lt;br /&gt;
&amp;lt;references/&amp;gt;&lt;br /&gt;
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==External Links==&lt;br /&gt;
{{External Links}}&lt;br /&gt;
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http://embryology.med.unsw.edu.au/embryology/index.php?title=2012_Group_Project_4&lt;br /&gt;
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http://www.webmd.com/oral-health/picture-of-the-tongue&lt;br /&gt;
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http://www.tutorvista.com/content/biology/biology-iv/nervous-coordination/tongue-structure.php#parts-of-tongue&lt;br /&gt;
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http://www.cf.ac.uk/biosi/staffinfo/jacob/teaching/sensory/taste.html&lt;br /&gt;
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--[[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.&lt;br /&gt;
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{{2012Projects}}&lt;/div&gt;</summary>
		<author><name>Z3330795</name></author>
	</entry>
	<entry>
		<id>https://embryology.med.unsw.edu.au/embryology/index.php?title=2012_Group_Project_3&amp;diff=105115</id>
		<title>2012 Group Project 3</title>
		<link rel="alternate" type="text/html" href="https://embryology.med.unsw.edu.au/embryology/index.php?title=2012_Group_Project_3&amp;diff=105115"/>
		<updated>2012-10-02T22:23:03Z</updated>

		<summary type="html">&lt;p&gt;Z3330795: /* Current Research */&lt;/p&gt;
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&lt;div&gt;=Taste Development=&lt;br /&gt;
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You are out to dinner and your meal arrives in front of you, the aromas and the presentation of your food strikes you immediately. Half way through, the waiter returns and asks “How does your meal taste?”  The answer is not as simple as one might think. Why does the meal taste pleasant? How do we experience different tastes? In the following page, we aim to discern how exactly one would answer these questions by looking at the embryological development of the taste system from week to week. &lt;br /&gt;
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Taste is a complex sensory system and its precise workings are to this day not fully understood. What makes it so complicated is the interaction between the structure of tongue and taste buds and how this contributes to the representation of taste qualities (salty, bitter, sweet, sour and umami) in the brain. We will also look at some current research on animal models being undertaken to evaluate the role of specific genes in the development of sensory structures. By looking at the taste system’s genetic basis, we now have a greater understanding of the abnormalities that may occur during development and a direction to pursue in future research to attempt to fill in the gaps of scientific knowledge.&lt;br /&gt;
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==Adult Tongue and Taste Buds – Structure and Function==&lt;br /&gt;
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'''Structure'''&lt;br /&gt;
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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.  &lt;br /&gt;
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''''The image below is a simplistic diagram of the surface of the tongue showing the locations of the different papillae and other important features'''&lt;br /&gt;
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{|&lt;br /&gt;
| [[Image:Drawing of Tongue.png|centre|500px]]&lt;br /&gt;
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'''Papillae'''&lt;br /&gt;
[[File:Papillae.jpg|Left|thumb|200px|Close up of Human Tongue Papillae]]&lt;br /&gt;
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There are 4 types of papillae on the tongue.&lt;br /&gt;
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. &lt;br /&gt;
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[[File:Fungiformpapillae.jpg|Left|thumb|200px|Fungiform Papillae]]&lt;br /&gt;
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[[File:Circumvallatepapillae.jpg |Left|thumb|200px|Circumvallate Papillae]]&lt;br /&gt;
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[[File:Filiformpapillae.jpg|Left|thumb|200px|Foliate Papillae]]&lt;br /&gt;
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'''Function'''&lt;br /&gt;
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The Tongue has muscular and sensory functions, muscular functions include swallowing and speech where as sensory function involves taste. This section will focus on the sensory functions of the tongue.&lt;br /&gt;
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.&lt;br /&gt;
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'''The image below is a simplistic hand-drawn cross section of a taste bud unit (not to scale)'''&lt;br /&gt;
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[[File:Taste_bud_1.jpg|x400px|alt=Cross section of a taste bud unit|centre|Cross section of a taste bud unit]]&lt;br /&gt;
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'''Link Between Taste and Smell'''&lt;br /&gt;
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The pathways of smell and taste are very similar. Pathways both involve the conversion of a dissolved chemical stimulus into a nerve impulse for interpretation by the brain.	&lt;br /&gt;
Taste does not necessarily equal flavour, flavour involves an interaction of taste, smell, texture and temperature, where taste is only a portion of this interaction. when the brain interprets a taste, contribution from other senses has a significant role in identification. In conclusion Taste and Smell in combination with other senses help develop a sensory interpretation called flavour.&lt;br /&gt;
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[[File:Taste_pathway.jpg|right|thumb|200px|Simplistic Pathway of Taste]]&lt;br /&gt;
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[[File:Human smelling.jpg|500px|centre]]&lt;br /&gt;
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==History of Discoveries==&lt;br /&gt;
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{| cellpadding=5 style=&amp;quot;border:1px solid #BBB&amp;quot;&lt;br /&gt;
|- bgcolor=&amp;quot;#faecc8&amp;quot;&lt;br /&gt;
|''' Date'''|| '''Significant Discovery'''&lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#faf6ed&amp;quot;&lt;br /&gt;
|'''350BC'''&lt;br /&gt;
|| Aristotle writes about the basic tastes, sweet and bitter. He also notes that it can be modified by salty and acidic. &amp;lt;ref name=&amp;quot;PMID22717400&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;22717400&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#faecc8&amp;quot;&lt;br /&gt;
|'''1901'''&lt;br /&gt;
|| D. Hanig publishes a paper describing taste sensitivity in different regions of the tongue. &lt;br /&gt;
''Interesting fact:'' The modern concept of a 'tongue map' is a misinterpretation of this study. &amp;lt;ref name=&amp;quot;PMID22717400&amp;quot;/&amp;gt;&lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#faf6ed&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''1908'''&lt;br /&gt;
|Kikunae Ikeda, a professor of the Tokyo Imperial University, discovered and identified the fifth basic taste: umami (savouriness), made palatable by glutamate.  &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;12438213&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
[http://chemse.oxfordjournals.org/content/27/9/847.long New Seasonings]&lt;br /&gt;
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|- bgcolor=&amp;quot;#faecc8&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''1931-32'''&lt;br /&gt;
| A chemist named Arthur Fox and his college noted that they had different sensitivities to the bitter tasting Phenylthiocarbamide (PTC).&amp;lt;ref&amp;gt;Blakeslee AF, Fox AL. Our different taste worlds. J Hered. 1932;23:97–107.&amp;lt;/ref&amp;gt; Geneticists later confirm these findings, and discover that non-tasting is a recessive genetic trait. &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;17782493&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/pubmed/17782493 Inherited taste deficiency] &lt;br /&gt;
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|- bgcolor=&amp;quot;#faf6ed&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''1965'''&lt;br /&gt;
|Farbman's study of the developing taste but in rat fungiform papilla was significant in increasing our understanding of taste bud development. &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;14300090&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
[http://www.sciencedirect.com/science/article/pii/0012160665900400 Electron microscope study of the developing taste bud in rat fungiform papilla.]&lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#faecc8&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''1992'''&lt;br /&gt;
|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. &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;1608467 &amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
[http://www.nature.com/nature/journal/v357/n6379/abs/357563a0.html Gustducin is a taste-cell-specific G protein closely related to the transducins]&lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#faf6ed&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''1995'''&lt;br /&gt;
|Barlow et al. experimented with Axolotl salamanders and concluded that taste buds from this species arise exclusively from epithelial tissue, &amp;quot;oropharyngeal [[#Glossary |'''epithelium''']]&amp;quot;. &amp;lt;ref name=&amp;quot;PMID17826760&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;17826760&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/pubmed/17826760 Embryonic origin of gustatory cranial sensory neurons] &lt;br /&gt;
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|- bgcolor=&amp;quot;#faecc8&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''1996'''&lt;br /&gt;
| 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 &amp;quot;at least dual function of embryonic/fetal taste buds&amp;quot;, including non-gustatory, paracrine functions prior to the 14th week and gustatory after the 14th week. &amp;lt;ref name=&amp;quot;PMID8955790&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;8955790&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/pubmed/8955790 Embryonic and early fetal development of human taste buds: a transmission electron microscopical study]&lt;br /&gt;
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|- bgcolor=&amp;quot;#faf6ed&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''2000'''&lt;br /&gt;
|Chandrashekar, J. et al. discover the first taste sonsors, the T2R bitter taste receptors. &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;10761935&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
[http://www.sciencedirect.com/science/article/pii/S0092867400807060 T2Rs Function as Bitter Taste Receptors]&lt;br /&gt;
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|- bgcolor=&amp;quot;#faecc8&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''2001'''&lt;br /&gt;
|Nelson, G. et al. discover the sweet receptor: a combination of T1R2 and T1R3. &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;11509186&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/pubmed/11509186?dopt=Abstract&amp;amp;holding=npg Mammalian sweet taste receptors.]&lt;br /&gt;
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|- bgcolor=&amp;quot;#faf6ed&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''2002'''&lt;br /&gt;
|Nelson G. et al. discover the amino acid (umami) taste receptor: a combination of T1R1 and T1R3 identified.  &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;11894099&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/pubmed/11894099?dopt=Abstract&amp;amp;holding=npg An amino-acid taste receptor]&lt;br /&gt;
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|- bgcolor=&amp;quot;#faecc8&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''2005'''&lt;br /&gt;
|Dyer, J. et al. discover sweet taste receptors in the GI tract. &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;17855558&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1986582/ Sweet taste signaling in the gut]&lt;br /&gt;
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|- bgcolor=&amp;quot;#faf6ed&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''2006'''&lt;br /&gt;
|Huang, A. L et al. discover cells for sour taste, identified by PKD2L1 (a polycystic kidney disease-like ion channel). &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;16929298&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1571047/ The Cells and Logic for Mammalian Sour Taste detection]&lt;br /&gt;
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|- bgcolor=&amp;quot;#faecc8&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''2007'''&lt;br /&gt;
|Harlow DE, Barlow LA of the University of Colorado Denver Health Sciences Center provide evidence of the &amp;quot;embryonic origin of gustatory cranial sensory neurons&amp;quot;. &amp;lt;ref name=&amp;quot;PMID17826760&amp;quot;/&amp;gt;&lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/pubmed/17826760 Embryonic origin of gustatory cranial sensory neurons.]&lt;br /&gt;
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|- bgcolor=&amp;quot;#faf6ed&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''2009'''&lt;br /&gt;
|A study by Hevezi P et al, presents &amp;quot;the first comprehensive characterization of gene expression in primate taste buds&amp;quot;, as opposed to previous studies which focused on rodents. &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;19636377&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/pubmed/19636377 Genome-wide analysis of gene expression in primate taste buds reveals links to diverse processes]&lt;br /&gt;
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|- bgcolor=&amp;quot;#faecc8&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''2010'''&lt;br /&gt;
|Chandrashekar, J. et al. identify epithelial sodium channel (ENaC) as the sodium-salt taste receptor. &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;20107438&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/pubmed/20107438?dopt=Abstract&amp;amp;holding=npg The cells and peripheral representation of sodium taste in mice]&lt;br /&gt;
|}&lt;br /&gt;
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== Human Weekly Development - Two Prominent Studies ==&lt;br /&gt;
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. &lt;br /&gt;
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The findings of these two studies are summarized in the table below. The figures provided relate to the images on their respective research papers.&lt;br /&gt;
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# [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] &lt;br /&gt;
# [http://chemse.oxfordjournals.org/content/22/6/601.long Scanning electron microscopical studies of developing gustatory papillae in humans, 1997]  &lt;br /&gt;
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===Timeline of Developmental Processes of Human Taste Buds===&lt;br /&gt;
{| cellpadding=5 style=&amp;quot;border:1px solid #BBB&amp;quot;&lt;br /&gt;
|- bgcolor=&amp;quot;#89CFF0&amp;quot;&lt;br /&gt;
|'''Postovulatory Week'''||'''Description'''&lt;br /&gt;
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|- bgcolor=&amp;quot;#BCD4E6&amp;quot;&lt;br /&gt;
|'''Week 6''' ||&lt;br /&gt;
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. &amp;lt;ref name=&amp;quot;PMID9455607&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;9455607&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
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|- bgcolor=&amp;quot;#89CFF0&amp;quot;&lt;br /&gt;
| '''Weeks 6 to 7'''|| &lt;br /&gt;
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. &amp;lt;ref name=PMID8955790/&amp;gt;&lt;br /&gt;
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|- bgcolor=&amp;quot;#BCD4E6&amp;quot;&lt;br /&gt;
| '''Week 7 '''||&lt;br /&gt;
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.  &amp;lt;ref name=PMID9455607/&amp;gt; &lt;br /&gt;
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|- bgcolor=&amp;quot;#89CFF0&amp;quot;&lt;br /&gt;
| ''' Week 8  ''' ||&lt;br /&gt;
* The taste bud primordium are still differentiated, elongated epithelial cells, resting on a slightly developed core of young dermal papilla.&lt;br /&gt;
* 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. &lt;br /&gt;
* Ciliated cells also appear around the 8th week, however the significance of these cells which are scattered randomly across the lingual surface remains unclear. &amp;lt;ref name=PMID8955790/&amp;gt; &lt;br /&gt;
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|- bgcolor=&amp;quot;#BCD4E6&amp;quot;&lt;br /&gt;
|'''  Week 9''' ||&lt;br /&gt;
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). &amp;lt;ref name=PMID9455607/&amp;gt;&lt;br /&gt;
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|- bgcolor=&amp;quot;#89CFF0&amp;quot;&lt;br /&gt;
|'''  Weeks 10-11''' ||&lt;br /&gt;
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). &amp;lt;ref name=PMID8955790/&amp;gt; &lt;br /&gt;
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|- bgcolor=&amp;quot;#BCD4E6&amp;quot;&lt;br /&gt;
|''' Week 12 ''' ||&lt;br /&gt;
Taste bud cells are more clearly differentiated into epithelial cell types II and III. &amp;lt;ref name=PMID8955790/&amp;gt; &lt;br /&gt;
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|- bgcolor=&amp;quot;#89CFF0&amp;quot;&lt;br /&gt;
|''' Weeks 12-13  ''' ||&lt;br /&gt;
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). &amp;lt;ref name=PMID8955790/&amp;gt; &lt;br /&gt;
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|- bgcolor=&amp;quot;#BCD4E6&amp;quot;&lt;br /&gt;
|''' Weeks 14 -15 ''' ||&lt;br /&gt;
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. &amp;lt;ref name=PMID8955790/&amp;gt; &lt;br /&gt;
|}&lt;br /&gt;
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==Abnormalities==&lt;br /&gt;
&lt;br /&gt;
It should be mentioned that gustatory abnormalities have not been widely researched. Most research conducted in this field has been conducted through animal testing on mice and this is the basis of information provided below. &lt;br /&gt;
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===Knocking out P2X Receptors===&lt;br /&gt;
&lt;br /&gt;
[[File:Image of taste being evoked by visualising ATP release.jpeg|Left|thumb|200px|Evoking taste - ATP release in tongue]]&lt;br /&gt;
&lt;br /&gt;
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. &lt;br /&gt;
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It should be noted that the taste buds in DKO are functional, but are not stimulated by the administration of tastants. &lt;br /&gt;
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The transmission of release of ATP is secretion through gap junction hemichannels (pannexin 1 gap junction).&lt;br /&gt;
&lt;br /&gt;
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.&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;21940456&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
===FGF signalling and genes===&lt;br /&gt;
&lt;br /&gt;
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.&lt;br /&gt;
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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 (&amp;quot;Fgf10&amp;quot;) 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 &amp;quot;Fgf10&amp;quot; to limit the size of the CVP progenitor placode. Exclusive expression of ''Fgf10'' in the [[#Glossary |'''mesenchyme''']] is necessary for the formation of CVP. &lt;br /&gt;
&lt;br /&gt;
'''This image shows the CVP stained with H&amp;amp;E and scanned by Scanning Electron Microscope (SEM)'''&lt;br /&gt;
[[File:CVP of WT(top) and DKO(bottom) mice with H&amp;amp;E and SEM.png]]&lt;br /&gt;
&lt;br /&gt;
'''This image shows the location of the CVP and the increased number in DKO mice by SEM'''&lt;br /&gt;
[[File:Mouse circumvallate papilla 01.jpg|300px]]&lt;br /&gt;
&lt;br /&gt;
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).&lt;br /&gt;
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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).&lt;br /&gt;
&lt;br /&gt;
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''&amp;amp; ''Spry 1&amp;amp;2''work antagonistically through receptor tyrosine kinase (RTK)signalling.&lt;br /&gt;
&lt;br /&gt;
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.&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;21655085&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
==Gustatory System==&lt;br /&gt;
&lt;br /&gt;
[[Image:Taste qualities.gif|thumb|The five basic tastes]]&lt;br /&gt;
&lt;br /&gt;
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.&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
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.&amp;lt;ref name=PMID20696704&amp;gt;&amp;lt;pubmed&amp;gt;20696704&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
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 &amp;lt;ref name=PMID20696704/&amp;gt; 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.&lt;br /&gt;
&lt;br /&gt;
===Cell Biology===&lt;br /&gt;
&lt;br /&gt;
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.&lt;br /&gt;
&lt;br /&gt;
====Type II receptors====&lt;br /&gt;
&lt;br /&gt;
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:&lt;br /&gt;
&lt;br /&gt;
# Stimulates gustatory nerve afferents which project to gustatory nuclei  in the spinal cord&lt;br /&gt;
# Excites Type III presynaptic nerve fibers to release serotonin. &lt;br /&gt;
# Has a positive feedback effect on type II receptor cells, increasing the level of ATP production.&lt;br /&gt;
&lt;br /&gt;
        &lt;br /&gt;
&lt;br /&gt;
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.&lt;br /&gt;
&lt;br /&gt;
==Taste Map==&lt;br /&gt;
[[Image:Taste map.png|thumb|left|250px|Obsolete idea of the tongue map]]&lt;br /&gt;
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.&lt;br /&gt;
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===Neural Pathways===&lt;br /&gt;
&lt;br /&gt;
'''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''. &lt;br /&gt;
&lt;br /&gt;
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:  &lt;br /&gt;
&lt;br /&gt;
* ''Facial nerve n''. -  carries taste information from the anterior 2/3 of the tongue.&lt;br /&gt;
* ''Hypoglossal n.'' - carries taste information from the posterior 1/3 of the tongue.&lt;br /&gt;
* ''Vagus n''. - carries taste information from the palate&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
'''Second order neurons''' - From the NTS second order neurons carry taste information to the Ventral posteromedial (VPM) nucleus in the thalamus.&amp;lt;ref name=PMID21885776/&amp;gt;&lt;br /&gt;
&lt;br /&gt;
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.  &lt;br /&gt;
&lt;br /&gt;
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.&lt;br /&gt;
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===Cortical Areas===&lt;br /&gt;
&lt;br /&gt;
[[Image:Primary gustatory cortex.png|thumb|Primary gustatory cortex]]&lt;br /&gt;
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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)&amp;lt;ref name=PMID22245354&amp;gt;&amp;lt;pubmed&amp;gt;22245354&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;, with the secondary taste cortex in the caudolateral orbitofrontal cortex.&amp;lt;ref name=PMID21305668&amp;gt;&amp;lt;pubmed&amp;gt;21305668&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;  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.&amp;lt;ref name=PMID21885776&amp;gt;&amp;lt;pubmed&amp;gt;21885776&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; These findings lend weight to the idea that there is only one receptor for each taste quality.&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
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).&amp;lt;ref name=PMID21885776/&amp;gt; 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&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
==Current Research==&lt;br /&gt;
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. &lt;br /&gt;
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.&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
[[File:Mousetounge histologicalstain.jpg|Left|thumb|200px|Image shows histological stains of a mice tongue showing dysplasia]]&lt;br /&gt;
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'''Synergistic relationships of Six Genes '''&lt;br /&gt;
&lt;br /&gt;
In an animal study using mice by Suzuki Y, Ikeda K, Kawakami K.(2011)  Firstly nominating &amp;quot;[[#Glossary |'''Six Genes''']]&amp;quot; as a major component in [[#Glossary |'''gustatory ''']] development, stating that deficiencies in certain Six genes (specifically Six1 &amp;amp; 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 &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;21978088&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
[[File:Highpowered_microscope.jpg|Left|thumb|200px|Image of a high powered microscope]]&lt;br /&gt;
&lt;br /&gt;
'''Neural Crest responsibilities '''&lt;br /&gt;
&lt;br /&gt;
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.&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;22659543&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
[[File:Developing_tongue_histology_001.jpg|Left|thumb|200px|HIstological stain of a developing rat tongue]]&lt;br /&gt;
&lt;br /&gt;
'''Augmentation of Endoderm'''&lt;br /&gt;
&lt;br /&gt;
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 &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;22581563&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
&lt;br /&gt;
'''Changes in Taste Cells over time'''&lt;br /&gt;
&lt;br /&gt;
Research by &lt;br /&gt;
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.  &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;22643728&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
'''Shh key component of taste bud proginators'''&lt;br /&gt;
&lt;br /&gt;
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.&lt;br /&gt;
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 &amp;quot;Axiocam CCD camera and Axioplan fluorescence microscope with Axiovision software&amp;quot; a study by Harlow, Yang, Williams, Barlow (2011)&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;PMC2674259&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
'''WNT family exhibit various roles'''&lt;br /&gt;
&lt;br /&gt;
 [[File:Abnormal of tongue.jpg|thumb|200px|Image shows an example of tongue abnormalities, this is called &amp;quot;double tongue&amp;quot; each side has independent movement!]]&lt;br /&gt;
&lt;br /&gt;
The WNT gene family has a function of signaling work antagonistically through receptor tyrosine kinase (RTK) signaling. However, the deletion of Sprouty Homolog 2 (Spry2) led to the increase of chimaeric virus particles (CVPs) and a significant decrease in number of fungiform papillae. In contrast, the absence of Fibroblast growth factor 10 (Fgf10) in conjunction with 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. 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. &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;PMC2768563&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
&lt;br /&gt;
[http://www.surgicalneurologyint.com/article.asp?issn=2152-7806;year=2012;volume=3;issue=1;spage=23;epage=23;aulast=Manjila]&lt;br /&gt;
&lt;br /&gt;
==Glossary==&lt;br /&gt;
&lt;br /&gt;
* '''Circumvallate papillae''' - &lt;br /&gt;
&lt;br /&gt;
* '''Ectoderm'''- outer germ layer of embryo&lt;br /&gt;
&lt;br /&gt;
* '''Endoderm''' - inner germ layer of embryo&lt;br /&gt;
&lt;br /&gt;
* '''Epithelium''' - basic animal tissue that is composed of tightly packed cells, usually covering the outer portion of organs&lt;br /&gt;
&lt;br /&gt;
* '''Exocystosis''' - movement of contents out of cell&lt;br /&gt;
&lt;br /&gt;
* '''Filiform papillae''' - &lt;br /&gt;
&lt;br /&gt;
* '''Foliate papillae''' - &lt;br /&gt;
&lt;br /&gt;
* '''Fungiform papillae''' - &lt;br /&gt;
&lt;br /&gt;
* '''Ganglia''' - the accumulation of a nerve cell body&lt;br /&gt;
&lt;br /&gt;
* '''Growth factor''' - a substance that stimulates the growth of cells&lt;br /&gt;
&lt;br /&gt;
* '''Gustatory''' - anything that relates to the taste sense&lt;br /&gt;
&lt;br /&gt;
* '''Hydrolysis''' - breakdown of a chemical when it reacts with water&lt;br /&gt;
&lt;br /&gt;
* '''Mesoderm''' - middle germ layer of embryo&lt;br /&gt;
&lt;br /&gt;
* '''Mesenchyme''' - multipotential cells&lt;br /&gt;
&lt;br /&gt;
* '''Neural crest''' - a part of the ectoderm found on both sides of the neural tube&lt;br /&gt;
&lt;br /&gt;
* '''Neuron''' - most simplistic unit of the nervous system&lt;br /&gt;
&lt;br /&gt;
* '''Neurotransmitter''' - chemicals which allow the passing of signals from neuron to neuron via connecting part (synapse) &lt;br /&gt;
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* '''Papillae''' - small rough surface projection&lt;br /&gt;
&lt;br /&gt;
* '''Six genes''' - a family of genes&lt;br /&gt;
&lt;br /&gt;
* '''Sonic hedgehog (Shh)''' - signalling protein involved in normal development&lt;br /&gt;
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* '''Sulcus terminalis''' - describes a physical transition point separating the anterior 2/3 of the tongue from the posterior 1/3&lt;br /&gt;
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* '''Tamoxifen''' - hormonal altering drug&lt;br /&gt;
&lt;br /&gt;
* '''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).&lt;br /&gt;
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* '''Type II taste cells''' - Receptor cells acting as primary detectors of sweet, bitter or umami taste.&lt;br /&gt;
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* '''Type III taste cells''' - Presynaptic cells that respond to sweet, salty, sour, bitter and umami compounds.&lt;br /&gt;
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== References ==&lt;br /&gt;
&amp;lt;references/&amp;gt;&lt;br /&gt;
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==External Links==&lt;br /&gt;
{{External Links}}&lt;br /&gt;
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http://embryology.med.unsw.edu.au/embryology/index.php?title=2012_Group_Project_4&lt;br /&gt;
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http://www.webmd.com/oral-health/picture-of-the-tongue&lt;br /&gt;
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http://www.tutorvista.com/content/biology/biology-iv/nervous-coordination/tongue-structure.php#parts-of-tongue&lt;br /&gt;
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http://www.cf.ac.uk/biosi/staffinfo/jacob/teaching/sensory/taste.html&lt;br /&gt;
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--[[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.&lt;br /&gt;
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{{2012Projects}}&lt;/div&gt;</summary>
		<author><name>Z3330795</name></author>
	</entry>
	<entry>
		<id>https://embryology.med.unsw.edu.au/embryology/index.php?title=2012_Group_Project_3&amp;diff=105108</id>
		<title>2012 Group Project 3</title>
		<link rel="alternate" type="text/html" href="https://embryology.med.unsw.edu.au/embryology/index.php?title=2012_Group_Project_3&amp;diff=105108"/>
		<updated>2012-10-02T21:43:18Z</updated>

		<summary type="html">&lt;p&gt;Z3330795: /* Current Research */&lt;/p&gt;
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&lt;div&gt;=Taste Development=&lt;br /&gt;
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You are out to dinner and your meal arrives in front of you, the aromas and the presentation of your food strikes you immediately. Half way through, the waiter returns and asks “How does your meal taste?”  The answer is not as simple as one might think. Why does the meal taste pleasant? How do we experience different tastes? In the following page, we aim to discern how exactly one would answer these questions by looking at the embryological development of the taste system from week to week. &lt;br /&gt;
&lt;br /&gt;
Taste is a complex sensory system and its precise workings are to this day not fully understood. What makes it so complicated is the interaction between the structure of tongue and taste buds and how this contributes to the representation of taste qualities (salty, bitter, sweet, sour and umami) in the brain. We will also look at some current research on animal models being undertaken to evaluate the role of specific genes in the development of sensory structures. By looking at the taste system’s genetic basis, we now have a greater understanding of the abnormalities that may occur during development and a direction to pursue in future research to attempt to fill in the gaps of scientific knowledge.&lt;br /&gt;
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==Adult Tongue and Taste Buds – Structure and Function==&lt;br /&gt;
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'''Structure'''&lt;br /&gt;
&lt;br /&gt;
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.  &lt;br /&gt;
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''''The image below is a simplistic diagram of the surface of the tongue showing the locations of the different papillae and other important features'''&lt;br /&gt;
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{|&lt;br /&gt;
| [[Image:Drawing of Tongue.png|centre|500px]]&lt;br /&gt;
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'''Papillae'''&lt;br /&gt;
[[File:Papillae.jpg|Left|thumb|200px|Close up of Human Tongue Papillae]]&lt;br /&gt;
&lt;br /&gt;
There are 4 types of papillae on the tongue.&lt;br /&gt;
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. &lt;br /&gt;
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[[File:Fungiformpapillae.jpg|Left|thumb|200px|Fungiform Papillae]]&lt;br /&gt;
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[[File:Circumvallatepapillae.jpg |Left|thumb|200px|Circumvallate Papillae]]&lt;br /&gt;
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[[File:Filiformpapillae.jpg|Left|thumb|200px|Foliate Papillae]]&lt;br /&gt;
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'''Function'''&lt;br /&gt;
&lt;br /&gt;
The Tongue has muscular and sensory functions, muscular functions include swallowing and speech where as sensory function involves taste. This section will focus on the sensory functions of the tongue.&lt;br /&gt;
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.&lt;br /&gt;
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'''The image below is a simplistic hand-drawn cross section of a taste bud unit (not to scale)'''&lt;br /&gt;
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[[File:Taste_bud_1.jpg|x400px|alt=Cross section of a taste bud unit|centre|Cross section of a taste bud unit]]&lt;br /&gt;
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'''Link Between Taste and Smell'''&lt;br /&gt;
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The pathways of smell and taste are very similar. Pathways both involve the conversion of a dissolved chemical stimulus into a nerve impulse for interpretation by the brain.	&lt;br /&gt;
Taste does not necessarily equal flavour, flavour involves an interaction of taste, smell, texture and temperature, where taste is only a portion of this interaction. when the brain interprets a taste, contribution from other senses has a significant role in identification. In conclusion Taste and Smell in combination with other senses help develop a sensory interpretation called flavour.&lt;br /&gt;
&lt;br /&gt;
[[File:Taste_pathway.jpg|right|thumb|200px|Simplistic Pathway of Taste]]&lt;br /&gt;
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&lt;br /&gt;
[[File:Human smelling.jpg|500px|centre]]&lt;br /&gt;
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==History of Discoveries==&lt;br /&gt;
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{| cellpadding=5 style=&amp;quot;border:1px solid #BBB&amp;quot;&lt;br /&gt;
|- bgcolor=&amp;quot;#faecc8&amp;quot;&lt;br /&gt;
|''' Date'''|| '''Significant Discovery'''&lt;br /&gt;
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|- bgcolor=&amp;quot;#faf6ed&amp;quot;&lt;br /&gt;
|'''350BC'''&lt;br /&gt;
|| Aristotle writes about the basic tastes, sweet and bitter. He also notes that it can be modified by salty and acidic. &amp;lt;ref name=&amp;quot;PMID22717400&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;22717400&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#faecc8&amp;quot;&lt;br /&gt;
|'''1901'''&lt;br /&gt;
|| D. Hanig publishes a paper describing taste sensitivity in different regions of the tongue. &lt;br /&gt;
''Interesting fact:'' The modern concept of a 'tongue map' is a misinterpretation of this study. &amp;lt;ref name=&amp;quot;PMID22717400&amp;quot;/&amp;gt;&lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#faf6ed&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''1908'''&lt;br /&gt;
|Kikunae Ikeda, a professor of the Tokyo Imperial University, discovered and identified the fifth basic taste: umami (savouriness), made palatable by glutamate.  &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;12438213&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
[http://chemse.oxfordjournals.org/content/27/9/847.long New Seasonings]&lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#faecc8&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''1931-32'''&lt;br /&gt;
| A chemist named Arthur Fox and his college noted that they had different sensitivities to the bitter tasting Phenylthiocarbamide (PTC).&amp;lt;ref&amp;gt;Blakeslee AF, Fox AL. Our different taste worlds. J Hered. 1932;23:97–107.&amp;lt;/ref&amp;gt; Geneticists later confirm these findings, and discover that non-tasting is a recessive genetic trait. &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;17782493&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/pubmed/17782493 Inherited taste deficiency] &lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#faf6ed&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''1965'''&lt;br /&gt;
|Farbman's study of the developing taste but in rat fungiform papilla was significant in increasing our understanding of taste bud development. &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;14300090&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
[http://www.sciencedirect.com/science/article/pii/0012160665900400 Electron microscope study of the developing taste bud in rat fungiform papilla.]&lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#faecc8&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''1992'''&lt;br /&gt;
|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. &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;1608467 &amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
[http://www.nature.com/nature/journal/v357/n6379/abs/357563a0.html Gustducin is a taste-cell-specific G protein closely related to the transducins]&lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#faf6ed&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''1995'''&lt;br /&gt;
|Barlow et al. experimented with Axolotl salamanders and concluded that taste buds from this species arise exclusively from epithelial tissue, &amp;quot;oropharyngeal [[#Glossary |'''epithelium''']]&amp;quot;. &amp;lt;ref name=&amp;quot;PMID17826760&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;17826760&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/pubmed/17826760 Embryonic origin of gustatory cranial sensory neurons] &lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#faecc8&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''1996'''&lt;br /&gt;
| 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 &amp;quot;at least dual function of embryonic/fetal taste buds&amp;quot;, including non-gustatory, paracrine functions prior to the 14th week and gustatory after the 14th week. &amp;lt;ref name=&amp;quot;PMID8955790&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;8955790&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/pubmed/8955790 Embryonic and early fetal development of human taste buds: a transmission electron microscopical study]&lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#faf6ed&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''2000'''&lt;br /&gt;
|Chandrashekar, J. et al. discover the first taste sonsors, the T2R bitter taste receptors. &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;10761935&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
[http://www.sciencedirect.com/science/article/pii/S0092867400807060 T2Rs Function as Bitter Taste Receptors]&lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#faecc8&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''2001'''&lt;br /&gt;
|Nelson, G. et al. discover the sweet receptor: a combination of T1R2 and T1R3. &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;11509186&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/pubmed/11509186?dopt=Abstract&amp;amp;holding=npg Mammalian sweet taste receptors.]&lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#faf6ed&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''2002'''&lt;br /&gt;
|Nelson G. et al. discover the amino acid (umami) taste receptor: a combination of T1R1 and T1R3 identified.  &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;11894099&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/pubmed/11894099?dopt=Abstract&amp;amp;holding=npg An amino-acid taste receptor]&lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#faecc8&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''2005'''&lt;br /&gt;
|Dyer, J. et al. discover sweet taste receptors in the GI tract. &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;17855558&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1986582/ Sweet taste signaling in the gut]&lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#faf6ed&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''2006'''&lt;br /&gt;
|Huang, A. L et al. discover cells for sour taste, identified by PKD2L1 (a polycystic kidney disease-like ion channel). &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;16929298&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1571047/ The Cells and Logic for Mammalian Sour Taste detection]&lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#faecc8&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''2007'''&lt;br /&gt;
|Harlow DE, Barlow LA of the University of Colorado Denver Health Sciences Center provide evidence of the &amp;quot;embryonic origin of gustatory cranial sensory neurons&amp;quot;. &amp;lt;ref name=&amp;quot;PMID17826760&amp;quot;/&amp;gt;&lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/pubmed/17826760 Embryonic origin of gustatory cranial sensory neurons.]&lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#faf6ed&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''2009'''&lt;br /&gt;
|A study by Hevezi P et al, presents &amp;quot;the first comprehensive characterization of gene expression in primate taste buds&amp;quot;, as opposed to previous studies which focused on rodents. &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;19636377&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/pubmed/19636377 Genome-wide analysis of gene expression in primate taste buds reveals links to diverse processes]&lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#faecc8&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''2010'''&lt;br /&gt;
|Chandrashekar, J. et al. identify epithelial sodium channel (ENaC) as the sodium-salt taste receptor. &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;20107438&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/pubmed/20107438?dopt=Abstract&amp;amp;holding=npg The cells and peripheral representation of sodium taste in mice]&lt;br /&gt;
|}&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
== Human Weekly Development - Two Prominent Studies ==&lt;br /&gt;
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. &lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
The findings of these two studies are summarized in the table below. The figures provided relate to the images on their respective research papers.&lt;br /&gt;
&lt;br /&gt;
# [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] &lt;br /&gt;
# [http://chemse.oxfordjournals.org/content/22/6/601.long Scanning electron microscopical studies of developing gustatory papillae in humans, 1997]  &lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
===Timeline of Developmental Processes of Human Taste Buds===&lt;br /&gt;
{| cellpadding=5 style=&amp;quot;border:1px solid #BBB&amp;quot;&lt;br /&gt;
|- bgcolor=&amp;quot;#89CFF0&amp;quot;&lt;br /&gt;
|'''Postovulatory Week'''||'''Description'''&lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#BCD4E6&amp;quot;&lt;br /&gt;
|'''Week 6''' ||&lt;br /&gt;
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. &amp;lt;ref name=&amp;quot;PMID9455607&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;9455607&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#89CFF0&amp;quot;&lt;br /&gt;
| '''Weeks 6 to 7'''|| &lt;br /&gt;
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. &amp;lt;ref name=PMID8955790/&amp;gt;&lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#BCD4E6&amp;quot;&lt;br /&gt;
| '''Week 7 '''||&lt;br /&gt;
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.  &amp;lt;ref name=PMID9455607/&amp;gt; &lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#89CFF0&amp;quot;&lt;br /&gt;
| ''' Week 8  ''' ||&lt;br /&gt;
* The taste bud primordium are still differentiated, elongated epithelial cells, resting on a slightly developed core of young dermal papilla.&lt;br /&gt;
* 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. &lt;br /&gt;
* Ciliated cells also appear around the 8th week, however the significance of these cells which are scattered randomly across the lingual surface remains unclear. &amp;lt;ref name=PMID8955790/&amp;gt; &lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#BCD4E6&amp;quot;&lt;br /&gt;
|'''  Week 9''' ||&lt;br /&gt;
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). &amp;lt;ref name=PMID9455607/&amp;gt;&lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#89CFF0&amp;quot;&lt;br /&gt;
|'''  Weeks 10-11''' ||&lt;br /&gt;
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). &amp;lt;ref name=PMID8955790/&amp;gt; &lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#BCD4E6&amp;quot;&lt;br /&gt;
|''' Week 12 ''' ||&lt;br /&gt;
Taste bud cells are more clearly differentiated into epithelial cell types II and III. &amp;lt;ref name=PMID8955790/&amp;gt; &lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#89CFF0&amp;quot;&lt;br /&gt;
|''' Weeks 12-13  ''' ||&lt;br /&gt;
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). &amp;lt;ref name=PMID8955790/&amp;gt; &lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#BCD4E6&amp;quot;&lt;br /&gt;
|''' Weeks 14 -15 ''' ||&lt;br /&gt;
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. &amp;lt;ref name=PMID8955790/&amp;gt; &lt;br /&gt;
|}&lt;br /&gt;
&lt;br /&gt;
==Abnormalities==&lt;br /&gt;
&lt;br /&gt;
It should be mentioned that gustatory abnormalities have not been widely researched. Most research conducted in this field has been conducted through animal testing on mice and this is the basis of information provided below. &lt;br /&gt;
&lt;br /&gt;
===Knocking out P2X Receptors===&lt;br /&gt;
&lt;br /&gt;
[[File:Image of taste being evoked by visualising ATP release.jpeg|Left|thumb|200px|Evoking taste - ATP release in tongue]]&lt;br /&gt;
&lt;br /&gt;
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. &lt;br /&gt;
&lt;br /&gt;
It should be noted that the taste buds in DKO are functional, but are not stimulated by the administration of tastants. &lt;br /&gt;
&lt;br /&gt;
The transmission of release of ATP is secretion through gap junction hemichannels (pannexin 1 gap junction).&lt;br /&gt;
&lt;br /&gt;
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.&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;21940456&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
===FGF signalling and genes===&lt;br /&gt;
&lt;br /&gt;
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.&lt;br /&gt;
&lt;br /&gt;
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 (&amp;quot;Fgf10&amp;quot;) 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 &amp;quot;Fgf10&amp;quot; to limit the size of the CVP progenitor placode. Exclusive expression of ''Fgf10'' in the [[#Glossary |'''mesenchyme''']] is necessary for the formation of CVP. &lt;br /&gt;
&lt;br /&gt;
'''This image shows the CVP stained with H&amp;amp;E and scanned by Scanning Electron Microscope (SEM)'''&lt;br /&gt;
[[File:CVP of WT(top) and DKO(bottom) mice with H&amp;amp;E and SEM.png]]&lt;br /&gt;
&lt;br /&gt;
'''This image shows the location of the CVP and the increased number in DKO mice by SEM'''&lt;br /&gt;
[[File:Mouse circumvallate papilla 01.jpg|300px]]&lt;br /&gt;
&lt;br /&gt;
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).&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
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).&lt;br /&gt;
&lt;br /&gt;
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''&amp;amp; ''Spry 1&amp;amp;2''work antagonistically through receptor tyrosine kinase (RTK)signalling.&lt;br /&gt;
&lt;br /&gt;
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.&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;21655085&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
==Gustatory System==&lt;br /&gt;
&lt;br /&gt;
[[Image:Taste qualities.gif|thumb|The five basic tastes]]&lt;br /&gt;
&lt;br /&gt;
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.&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
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.&amp;lt;ref name=PMID20696704&amp;gt;&amp;lt;pubmed&amp;gt;20696704&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
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 &amp;lt;ref name=PMID20696704/&amp;gt; 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.&lt;br /&gt;
&lt;br /&gt;
===Cell Biology===&lt;br /&gt;
&lt;br /&gt;
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.&lt;br /&gt;
&lt;br /&gt;
====Type II receptors====&lt;br /&gt;
&lt;br /&gt;
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:&lt;br /&gt;
&lt;br /&gt;
# Stimulates gustatory nerve afferents which project to gustatory nuclei  in the spinal cord&lt;br /&gt;
# Excites Type III presynaptic nerve fibers to release serotonin. &lt;br /&gt;
# Has a positive feedback effect on type II receptor cells, increasing the level of ATP production.&lt;br /&gt;
&lt;br /&gt;
        &lt;br /&gt;
&lt;br /&gt;
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.&lt;br /&gt;
&lt;br /&gt;
==Taste Map==&lt;br /&gt;
[[Image:Taste map.png|thumb|left|250px|Obsolete idea of the tongue map]]&lt;br /&gt;
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.&lt;br /&gt;
&lt;br /&gt;
===Neural Pathways===&lt;br /&gt;
&lt;br /&gt;
'''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''. &lt;br /&gt;
&lt;br /&gt;
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:  &lt;br /&gt;
&lt;br /&gt;
* ''Facial nerve n''. -  carries taste information from the anterior 2/3 of the tongue.&lt;br /&gt;
* ''Hypoglossal n.'' - carries taste information from the posterior 1/3 of the tongue.&lt;br /&gt;
* ''Vagus n''. - carries taste information from the palate&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
'''Second order neurons''' - From the NTS second order neurons carry taste information to the Ventral posteromedial (VPM) nucleus in the thalamus.&amp;lt;ref name=PMID21885776/&amp;gt;&lt;br /&gt;
&lt;br /&gt;
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.  &lt;br /&gt;
&lt;br /&gt;
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.&lt;br /&gt;
&lt;br /&gt;
===Cortical Areas===&lt;br /&gt;
&lt;br /&gt;
[[Image:Primary gustatory cortex.png|thumb|Primary gustatory cortex]]&lt;br /&gt;
&lt;br /&gt;
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)&amp;lt;ref name=PMID22245354&amp;gt;&amp;lt;pubmed&amp;gt;22245354&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;, with the secondary taste cortex in the caudolateral orbitofrontal cortex.&amp;lt;ref name=PMID21305668&amp;gt;&amp;lt;pubmed&amp;gt;21305668&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;  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.&amp;lt;ref name=PMID21885776&amp;gt;&amp;lt;pubmed&amp;gt;21885776&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; These findings lend weight to the idea that there is only one receptor for each taste quality.&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
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).&amp;lt;ref name=PMID21885776/&amp;gt; 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&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
==Current Research==&lt;br /&gt;
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. &lt;br /&gt;
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.&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
[[File:Mousetounge histologicalstain.jpg|Left|thumb|200px|Image shows histological stains of a mice tongue showing dysplasia]]&lt;br /&gt;
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&lt;br /&gt;
'''Synergistic relationships of Six Genes '''&lt;br /&gt;
&lt;br /&gt;
In an animal study using mice by Suzuki Y, Ikeda K, Kawakami K.(2011)  Firstly nominating &amp;quot;[[#Glossary |'''Six Genes''']]&amp;quot; as a major component in [[#Glossary |'''gustatory ''']] development, stating that deficiencies in certain Six genes (specifically Six1 &amp;amp; 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 &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;21978088&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
[[File:Highpowered_microscope.jpg|Left|thumb|200px|Image of a high powered microscope]]&lt;br /&gt;
&lt;br /&gt;
'''Neural Crest responsibilities '''&lt;br /&gt;
&lt;br /&gt;
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.&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;22659543&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
[[File:Developing_tongue_histology_001.jpg|Left|thumb|200px|HIstological stain of a developing rat tongue]]&lt;br /&gt;
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'''Augmentation of Endoderm'''&lt;br /&gt;
&lt;br /&gt;
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 &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;22581563&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
&lt;br /&gt;
'''Changes in Taste Cells over time'''&lt;br /&gt;
&lt;br /&gt;
Research by &lt;br /&gt;
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.  &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;22643728&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
'''Shh key component of taste bud proginators'''&lt;br /&gt;
&lt;br /&gt;
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.&lt;br /&gt;
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 &amp;quot;Axiocam CCD camera and Axioplan fluorescence microscope with Axiovision software&amp;quot; a study by Harlow, Yang, Williams, Barlow (2011)&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;PMC2674259&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
'''WNT family exhibit various roles''' [[File:Abnormal of tongue.jpg|thumb|200px|Image shows an example of tongue abnormalities, this is called &amp;quot;double tongue&amp;quot; each side has independent movement!]]&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
The WNT gene family has a function of signal2''work antagonistically through receptor tyrosine kinase (RTK)signalling.&lt;br /&gt;
&lt;br /&gt;
However, the deletion of Sprouty Homolog 2 (Spry2) led to the increase of chimaeric virus particles (CVPs) it should be noted that they found that a significant decrease in number of fungiform papillae. In contrast, the absence of Fibroblast growth factor 10 (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.ly 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. &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;PMC2768563&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
&lt;br /&gt;
[http://www.surgicalneurologyint.com/article.asp?issn=2152-7806;year=2012;volume=3;issue=1;spage=23;epage=23;aulast=Manjila]&lt;br /&gt;
&lt;br /&gt;
==Glossary==&lt;br /&gt;
&lt;br /&gt;
* '''Circumvallate papillae''' - &lt;br /&gt;
&lt;br /&gt;
* '''Ectoderm'''- outer germ layer of embryo&lt;br /&gt;
&lt;br /&gt;
* '''Endoderm''' - inner germ layer of embryo&lt;br /&gt;
&lt;br /&gt;
* '''Epithelium''' - basic animal tissue that is composed of tightly packed cells, usually covering the outer portion of organs&lt;br /&gt;
&lt;br /&gt;
* '''Exocystosis''' - movement of contents out of cell&lt;br /&gt;
&lt;br /&gt;
* '''Filiform papillae''' - &lt;br /&gt;
&lt;br /&gt;
* '''Foliate papillae''' - &lt;br /&gt;
&lt;br /&gt;
* '''Fungiform papillae''' - &lt;br /&gt;
&lt;br /&gt;
* '''Ganglia''' - the accumulation of a nerve cell body&lt;br /&gt;
&lt;br /&gt;
* '''Growth factor''' - a substance that stimulates the growth of cells&lt;br /&gt;
&lt;br /&gt;
* '''Gustatory''' - anything that relates to the taste sense&lt;br /&gt;
&lt;br /&gt;
* '''Hydrolysis''' - breakdown of a chemical when it reacts with water&lt;br /&gt;
&lt;br /&gt;
* '''Mesoderm''' - middle germ layer of embryo&lt;br /&gt;
&lt;br /&gt;
* '''Mesenchyme''' - multipotential cells&lt;br /&gt;
&lt;br /&gt;
* '''Neural crest''' - a part of the ectoderm found on both sides of the neural tube&lt;br /&gt;
&lt;br /&gt;
* '''Neuron''' - most simplistic unit of the nervous system&lt;br /&gt;
&lt;br /&gt;
* '''Neurotransmitter''' - chemicals which allow the passing of signals from neuron to neuron via connecting part (synapse) &lt;br /&gt;
&lt;br /&gt;
* '''Papillae''' - small rough surface projection&lt;br /&gt;
&lt;br /&gt;
* '''Six genes''' - a family of genes&lt;br /&gt;
&lt;br /&gt;
* '''Sonic hedgehog (Shh)''' - signalling protein involved in normal development&lt;br /&gt;
&lt;br /&gt;
* '''Sulcus terminalis''' - describes a physical transition point separating the anterior 2/3 of the tongue from the posterior 1/3&lt;br /&gt;
&lt;br /&gt;
* '''Tamoxifen''' - hormonal altering drug&lt;br /&gt;
&lt;br /&gt;
* '''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).&lt;br /&gt;
&lt;br /&gt;
* '''Type II taste cells''' - Receptor cells acting as primary detectors of sweet, bitter or umami taste.&lt;br /&gt;
&lt;br /&gt;
* '''Type III taste cells''' - Presynaptic cells that respond to sweet, salty, sour, bitter and umami compounds.&lt;br /&gt;
&lt;br /&gt;
== References ==&lt;br /&gt;
&amp;lt;references/&amp;gt;&lt;br /&gt;
&lt;br /&gt;
==External Links==&lt;br /&gt;
{{External Links}}&lt;br /&gt;
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http://embryology.med.unsw.edu.au/embryology/index.php?title=2012_Group_Project_4&lt;br /&gt;
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http://www.webmd.com/oral-health/picture-of-the-tongue&lt;br /&gt;
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http://www.tutorvista.com/content/biology/biology-iv/nervous-coordination/tongue-structure.php#parts-of-tongue&lt;br /&gt;
&lt;br /&gt;
http://www.cf.ac.uk/biosi/staffinfo/jacob/teaching/sensory/taste.html&lt;br /&gt;
&lt;br /&gt;
--[[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.&lt;br /&gt;
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----&lt;br /&gt;
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{{2012Projects}}&lt;/div&gt;</summary>
		<author><name>Z3330795</name></author>
	</entry>
	<entry>
		<id>https://embryology.med.unsw.edu.au/embryology/index.php?title=2012_Group_Project_3&amp;diff=104778</id>
		<title>2012 Group Project 3</title>
		<link rel="alternate" type="text/html" href="https://embryology.med.unsw.edu.au/embryology/index.php?title=2012_Group_Project_3&amp;diff=104778"/>
		<updated>2012-10-02T07:26:09Z</updated>

		<summary type="html">&lt;p&gt;Z3330795: /* Adult Tongue and Taste Buds – Structure and Function */&lt;/p&gt;
&lt;hr /&gt;
&lt;div&gt;=Taste Development=&lt;br /&gt;
&lt;br /&gt;
You are out to dinner and your meal arrives in front of you, the aromas and the presentation of your food strikes you immediately. Half way through, the waiter returns and asks “How does your meal taste?”  The answer is not as simple as one might think. Why does the meal taste pleasant? How do we experience different tastes? In the following page, we aim to discern how exactly one would answer these questions by looking at the embryological development of the taste system from week to week. &lt;br /&gt;
&lt;br /&gt;
Taste is a complex sensory system and its precise workings are to this day not fully understood. What makes it so complicated is the interaction between the structure of tongue and taste buds and how this contributes to the representation of taste qualities (salty, bitter, sweet, sour and umami) in the brain. We will also look at some current research on animal models being undertaken to evaluate the role of specific genes in the development of sensory structures. By looking at the taste system’s genetic basis, we now have a greater understanding of the abnormalities that may occur during development and a direction to pursue in future research to attempt to fill in the gaps of scientific knowledge.&lt;br /&gt;
&lt;br /&gt;
==Adult Tongue and Taste Buds – Structure and Function==&lt;br /&gt;
&lt;br /&gt;
'''Structure'''&lt;br /&gt;
&lt;br /&gt;
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.  &lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
''''The image below is a simplistic diagram of the surface of the tongue showing the locations of the different papillae and other important features'''&lt;br /&gt;
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{|&lt;br /&gt;
| [[Image:Drawing of Tongue.png|centre|500px]]&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
'''Papillae'''&lt;br /&gt;
[[File:Papillae.jpg|Left|thumb|200px|Close up of Human Tongue Papillae]]&lt;br /&gt;
&lt;br /&gt;
There are 4 types of papillae on the tongue.&lt;br /&gt;
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. &lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
[[File:Fungiformpapillae.jpg|Left|thumb|200px|Fungiform Papillae]]&lt;br /&gt;
&lt;br /&gt;
[[File:Circumvallatepapillae.jpg |Left|thumb|200px|Circumvallate Papillae]]&lt;br /&gt;
&lt;br /&gt;
[[File:Filiformpapillae.jpg|Left|thumb|200px|Foliate Papillae]]&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
'''Function'''&lt;br /&gt;
&lt;br /&gt;
The Tongue has muscular and sensory functions, muscular functions include swallowing and speech where as sensory function involves taste. This section will focus on the sensory functions of the tongue.&lt;br /&gt;
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.&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
'''The image below is a simplistic hand-drawn cross section of a taste bud unit (not to scale)'''&lt;br /&gt;
&lt;br /&gt;
[[File:Taste_bud_1.jpg|x400px|alt=Cross section of a taste bud unit|centre|Cross section of a taste bud unit]]&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
'''Link Between Taste and Smell'''&lt;br /&gt;
&lt;br /&gt;
The pathways of smell and taste are very similar. Pathways both involve the conversion of a dissolved chemical stimulus into a nerve impulse for interpretation by the brain.	&lt;br /&gt;
Taste does not necessarily equal flavour, flavour involves an interaction of taste, smell, texture and temperature, where taste is only a portion of this interaction. when the brain interprets a taste, contribution from other senses has a significant role in identification. In conclusion Taste and Smell in combination with other senses help develop a sensory interpretation called flavour.&lt;br /&gt;
&lt;br /&gt;
[[File:Taste_pathway.jpg|right|thumb|200px|Simplistic Pathway of Taste]]&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
[[File:Human smelling.jpg|500px|centre]]&lt;br /&gt;
&lt;br /&gt;
==History of Discoveries==&lt;br /&gt;
&lt;br /&gt;
{| cellpadding=5 style=&amp;quot;border:1px solid #BBB&amp;quot;&lt;br /&gt;
|- bgcolor=&amp;quot;#faecc8&amp;quot;&lt;br /&gt;
|''' Date'''|| '''Significant Discovery'''&lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#faf6ed&amp;quot;&lt;br /&gt;
|'''350BC'''&lt;br /&gt;
|| Aristotle writes about the basic tastes, sweet and bitter. He also notes that it can be modified by salty and acidic. &amp;lt;ref name=&amp;quot;PMID22717400&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;22717400&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#faecc8&amp;quot;&lt;br /&gt;
|'''1901'''&lt;br /&gt;
|| D. Hanig publishes a paper describing taste sensitivity in different regions of the tongue. &lt;br /&gt;
''Interesting fact:'' The modern concept of a 'tongue map' is a misinterpretation of this study. &amp;lt;ref name=&amp;quot;PMID22717400&amp;quot;/&amp;gt;&lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#faf6ed&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''1908'''&lt;br /&gt;
|Kikunae Ikeda, a professor of the Tokyo Imperial University, discovered and identified the fifth basic taste: umami (savouriness), made palatable by glutamate.  &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;12438213&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
[http://chemse.oxfordjournals.org/content/27/9/847.long New Seasonings]&lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#faecc8&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''1931-32'''&lt;br /&gt;
| A chemist named Arthur Fox and his college noted that they had different sensitivities to the bitter tasting Phenylthiocarbamide (PTC).&amp;lt;ref&amp;gt;Blakeslee AF, Fox AL. Our different taste worlds. J Hered. 1932;23:97–107.&amp;lt;/ref&amp;gt; Geneticists later confirm these findings, and discover that non-tasting is a recessive genetic trait. &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;17782493&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/pubmed/17782493 Inherited taste deficiency] &lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#faf6ed&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''1965'''&lt;br /&gt;
|Farbman's study of the developing taste but in rat fungiform papilla was significant in increasing our understanding of taste bud development. &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;14300090&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
[http://www.sciencedirect.com/science/article/pii/0012160665900400 Electron microscope study of the developing taste bud in rat fungiform papilla.]&lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#faecc8&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''1992'''&lt;br /&gt;
|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. &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;1608467 &amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
[http://www.nature.com/nature/journal/v357/n6379/abs/357563a0.html Gustducin is a taste-cell-specific G protein closely related to the transducins]&lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#faf6ed&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''1995'''&lt;br /&gt;
|Barlow et al. experimented with Axolotl salamanders and concluded that taste buds from this species arise exclusively from epithelial tissue, &amp;quot;oropharyngeal [[#Glossary |'''epithelium''']]&amp;quot;. &amp;lt;ref name=&amp;quot;PMID17826760&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;17826760&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/pubmed/17826760 Embryonic origin of gustatory cranial sensory neurons] &lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#faecc8&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''1996'''&lt;br /&gt;
| 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 &amp;quot;at least dual function of embryonic/fetal taste buds&amp;quot;, including non-gustatory, paracrine functions prior to the 14th week and gustatory after the 14th week. &amp;lt;ref name=&amp;quot;PMID8955790&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;8955790&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/pubmed/8955790 Embryonic and early fetal development of human taste buds: a transmission electron microscopical study]&lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#faf6ed&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''2000'''&lt;br /&gt;
|Chandrashekar, J. et al. discover the first taste sonsors, the T2R bitter taste receptors. &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;10761935&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
[http://www.sciencedirect.com/science/article/pii/S0092867400807060 T2Rs Function as Bitter Taste Receptors]&lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#faecc8&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''2001'''&lt;br /&gt;
|Nelson, G. et al. discover the sweet receptor: a combination of T1R2 and T1R3. &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;11509186&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/pubmed/11509186?dopt=Abstract&amp;amp;holding=npg Mammalian sweet taste receptors.]&lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#faf6ed&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''2002'''&lt;br /&gt;
|Nelson G. et al. discover the amino acid (umami) taste receptor: a combination of T1R1 and T1R3 identified.  &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;11894099&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/pubmed/11894099?dopt=Abstract&amp;amp;holding=npg An amino-acid taste receptor]&lt;br /&gt;
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|- bgcolor=&amp;quot;#faecc8&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''2005'''&lt;br /&gt;
|Dyer, J. et al. discover sweet taste receptors in the GI tract. &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;17855558&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1986582/ Sweet taste signaling in the gut]&lt;br /&gt;
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|- bgcolor=&amp;quot;#faf6ed&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''2006'''&lt;br /&gt;
|Huang, A. L et al. discover cells for sour taste, identified by PKD2L1 (a polycystic kidney disease-like ion channel). &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;16929298&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1571047/ The Cells and Logic for Mammalian Sour Taste detection]&lt;br /&gt;
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|- bgcolor=&amp;quot;#faecc8&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''2007'''&lt;br /&gt;
|Harlow DE, Barlow LA of the University of Colorado Denver Health Sciences Center provide evidence of the &amp;quot;embryonic origin of gustatory cranial sensory neurons&amp;quot;. &amp;lt;ref name=&amp;quot;PMID17826760&amp;quot;/&amp;gt;&lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/pubmed/17826760 Embryonic origin of gustatory cranial sensory neurons.]&lt;br /&gt;
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|- bgcolor=&amp;quot;#faf6ed&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''2009'''&lt;br /&gt;
|A study by Hevezi P et al, presents &amp;quot;the first comprehensive characterization of gene expression in primate taste buds&amp;quot;, as opposed to previous studies which focused on rodents. &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;19636377&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/pubmed/19636377 Genome-wide analysis of gene expression in primate taste buds reveals links to diverse processes]&lt;br /&gt;
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|- bgcolor=&amp;quot;#faecc8&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''2010'''&lt;br /&gt;
|Chandrashekar, J. et al. identify epithelial sodium channel (ENaC) as the sodium-salt taste receptor. &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;20107438&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/pubmed/20107438?dopt=Abstract&amp;amp;holding=npg The cells and peripheral representation of sodium taste in mice]&lt;br /&gt;
|}&lt;br /&gt;
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== Human Weekly Development - Two Prominent Studies ==&lt;br /&gt;
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. &lt;br /&gt;
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The findings of these two studies are summarized in the table below. The figures provided relate to the images on their respective research papers.&lt;br /&gt;
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# [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] &lt;br /&gt;
# [http://chemse.oxfordjournals.org/content/22/6/601.long Scanning electron microscopical studies of developing gustatory papillae in humans, 1997]  &lt;br /&gt;
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===Timeline of Developmental Processes of Human Taste Buds===&lt;br /&gt;
{| cellpadding=5 style=&amp;quot;border:1px solid #BBB&amp;quot;&lt;br /&gt;
|- bgcolor=&amp;quot;#89CFF0&amp;quot;&lt;br /&gt;
|'''Postovulatory Week'''||'''Description'''&lt;br /&gt;
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|- bgcolor=&amp;quot;#BCD4E6&amp;quot;&lt;br /&gt;
|'''Week 6''' ||&lt;br /&gt;
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. &amp;lt;ref name=&amp;quot;PMID9455607&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;9455607&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#89CFF0&amp;quot;&lt;br /&gt;
| '''Weeks 6 to 7'''|| &lt;br /&gt;
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. &amp;lt;ref name=PMID8955790/&amp;gt;&lt;br /&gt;
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|- bgcolor=&amp;quot;#BCD4E6&amp;quot;&lt;br /&gt;
| '''Week 7 '''||&lt;br /&gt;
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.  &amp;lt;ref name=PMID9455607/&amp;gt; &lt;br /&gt;
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|- bgcolor=&amp;quot;#89CFF0&amp;quot;&lt;br /&gt;
| ''' Week 8  ''' ||&lt;br /&gt;
* The taste bud primordium are still differentiated, elongated epithelial cells, resting on a slightly developed core of young dermal papilla.&lt;br /&gt;
* 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. &lt;br /&gt;
* Ciliated cells also appear around the 8th week, however the significance of these cells which are scattered randomly across the lingual surface remains unclear. &amp;lt;ref name=PMID8955790/&amp;gt; &lt;br /&gt;
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|- bgcolor=&amp;quot;#BCD4E6&amp;quot;&lt;br /&gt;
|'''  Week 9''' ||&lt;br /&gt;
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). &amp;lt;ref name=PMID9455607/&amp;gt;&lt;br /&gt;
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|- bgcolor=&amp;quot;#89CFF0&amp;quot;&lt;br /&gt;
|'''  Weeks 10-11''' ||&lt;br /&gt;
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). &amp;lt;ref name=PMID8955790/&amp;gt; &lt;br /&gt;
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|- bgcolor=&amp;quot;#BCD4E6&amp;quot;&lt;br /&gt;
|''' Week 12 ''' ||&lt;br /&gt;
Taste bud cells are more clearly differentiated into epithelial cell types II and III. &amp;lt;ref name=PMID8955790/&amp;gt; &lt;br /&gt;
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|- bgcolor=&amp;quot;#89CFF0&amp;quot;&lt;br /&gt;
|''' Weeks 12-13  ''' ||&lt;br /&gt;
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). &amp;lt;ref name=PMID8955790/&amp;gt; &lt;br /&gt;
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|- bgcolor=&amp;quot;#BCD4E6&amp;quot;&lt;br /&gt;
|''' Weeks 14 -15 ''' ||&lt;br /&gt;
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. &amp;lt;ref name=PMID8955790/&amp;gt; &lt;br /&gt;
|}&lt;br /&gt;
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==Abnormalities==&lt;br /&gt;
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It should be mentioned that gustatory abnormalities have not been widely researched. Most research conducted in this field has been conducted through animal testing on mice and this is the basis of information provided below. &lt;br /&gt;
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===Knocking out P2X Receptors===&lt;br /&gt;
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[[File:Image of taste being evoked by visualising ATP release.jpeg|Left|thumb|200px|Evoking taste - ATP release in tongue]]&lt;br /&gt;
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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. &lt;br /&gt;
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It should be noted that the taste buds in DKO are functional, but are not stimulated by the administration of tastants. &lt;br /&gt;
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The transmission of release of ATP is secretion through gap junction hemichannels (pannexin 1 gap junction).&lt;br /&gt;
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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.&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;21940456&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
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===FGF signalling and genes===&lt;br /&gt;
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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.&lt;br /&gt;
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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 (&amp;quot;Fgf10&amp;quot;) 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 &amp;quot;Fgf10&amp;quot; to limit the size of the CVP progenitor placode. Exclusive expression of ''Fgf10'' in the [[#Glossary |'''mesenchyme''']] is necessary for the formation of CVP. &lt;br /&gt;
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'''This image shows the CVP stained with H&amp;amp;E and scanned by Scanning Electron Microscope (SEM)'''&lt;br /&gt;
[[File:CVP of WT(top) and DKO(bottom) mice with H&amp;amp;E and SEM.png]]&lt;br /&gt;
&lt;br /&gt;
'''This image shows the location of the CVP and the increased number in DKO mice by SEM'''&lt;br /&gt;
[[File:Mouse circumvallate papilla 01.jpg|300px]]&lt;br /&gt;
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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).&lt;br /&gt;
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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).&lt;br /&gt;
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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''&amp;amp; ''Spry 1&amp;amp;2''work antagonistically through receptor tyrosine kinase (RTK)signalling.&lt;br /&gt;
&lt;br /&gt;
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.&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;21655085&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
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==Gustatory System==&lt;br /&gt;
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[[Image:Taste qualities.gif|thumb|The five basic tastes]]&lt;br /&gt;
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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.&lt;br /&gt;
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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.&amp;lt;ref name=PMID20696704&amp;gt;&amp;lt;pubmed&amp;gt;20696704&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
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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 &amp;lt;ref name=PMID20696704/&amp;gt; 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.&lt;br /&gt;
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===Cell Biology===&lt;br /&gt;
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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.&lt;br /&gt;
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====Type II receptors====&lt;br /&gt;
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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:&lt;br /&gt;
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# Stimulates gustatory nerve afferents which project to gustatory nuclei  in the spinal cord&lt;br /&gt;
# Excites Type III presynaptic nerve fibers to release serotonin. &lt;br /&gt;
# Has a positive feedback effect on type II receptor cells, increasing the level of ATP production.&lt;br /&gt;
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        &lt;br /&gt;
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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.&lt;br /&gt;
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==Taste Map==&lt;br /&gt;
[[Image:Taste map.png|thumb|left|250px|Obsolete idea of the tongue map]]&lt;br /&gt;
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.&lt;br /&gt;
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===Neural Pathways===&lt;br /&gt;
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'''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''. &lt;br /&gt;
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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:  &lt;br /&gt;
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* ''Facial nerve n''. -  carries taste information from the anterior 2/3 of the tongue.&lt;br /&gt;
* ''Hypoglossal n.'' - carries taste information from the posterior 1/3 of the tongue.&lt;br /&gt;
* ''Vagus n''. - carries taste information from the palate&lt;br /&gt;
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'''Second order neurons''' - From the NTS second order neurons carry taste information to the Ventral posteromedial (VPM) nucleus in the thalamus.&amp;lt;ref name=PMID21885776/&amp;gt;&lt;br /&gt;
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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.  &lt;br /&gt;
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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.&lt;br /&gt;
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===Cortical Areas===&lt;br /&gt;
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[[Image:Primary gustatory cortex.png|thumb|Primary gustatory cortex]]&lt;br /&gt;
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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)&amp;lt;ref name=PMID22245354&amp;gt;&amp;lt;pubmed&amp;gt;22245354&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;, with the secondary taste cortex in the caudolateral orbitofrontal cortex.&amp;lt;ref name=PMID21305668&amp;gt;&amp;lt;pubmed&amp;gt;21305668&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;  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.&amp;lt;ref name=PMID21885776&amp;gt;&amp;lt;pubmed&amp;gt;21885776&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; These findings lend weight to the idea that there is only one receptor for each taste quality.&lt;br /&gt;
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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).&amp;lt;ref name=PMID21885776/&amp;gt; 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&lt;br /&gt;
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==Current Research==&lt;br /&gt;
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. &lt;br /&gt;
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.&lt;br /&gt;
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[[File:Mousetounge histologicalstain.jpg|Left|thumb|200px|Image shows histological stains of a mice tongue showing dysplasia]]&lt;br /&gt;
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'''Synergistic relationships of Six Genes '''&lt;br /&gt;
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In an animal study using mice by Suzuki Y, Ikeda K, Kawakami K.(2011)  Firstly nominating &amp;quot;[[#Glossary |'''Six Genes''']]&amp;quot; as a major component in [[#Glossary |'''gustatory ''']] development, stating that deficiencies in certain Six genes (specifically Six1 &amp;amp; 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 &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;21978088&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
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[[File:Highpowered_microscope.jpg|Left|thumb|200px|Image of a high powered microscope]]&lt;br /&gt;
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'''Neural Crest responsibilities '''&lt;br /&gt;
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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.&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;22659543&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
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[[File:Developing_tongue_histology_001.jpg|Left|thumb|200px|HIstological stain of a developing rat tongue]]&lt;br /&gt;
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'''Augmentation of Endoderm'''&lt;br /&gt;
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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 &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;22581563&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
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'''Changes in Taste Cells over time'''&lt;br /&gt;
&lt;br /&gt;
Research by &lt;br /&gt;
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.  &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;22643728&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
'''Shh key component of taste bud proginators'''&lt;br /&gt;
&lt;br /&gt;
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.&lt;br /&gt;
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 &amp;quot;Axiocam CCD camera and Axioplan fluorescence microscope with Axiovision software&amp;quot; a study by Harlow, Yang, Williams, Barlow (2011)&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;PMC2674259&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
'''WNT family exhibit various roles''' [[File:Abnormal of tongue.jpg|thumb|200px|Image shows an example of tongue abnormalities, this is called &amp;quot;double tongue&amp;quot; each side has independent movement!]]&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
The WNT gene family has a function of signal2''work antagonistically through receptor tyrosine kinase (RTK)signalling.&lt;br /&gt;
&lt;br /&gt;
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.ly 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. &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;PMC2768563&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
&lt;br /&gt;
[http://www.surgicalneurologyint.com/article.asp?issn=2152-7806;year=2012;volume=3;issue=1;spage=23;epage=23;aulast=Manjila]&lt;br /&gt;
&lt;br /&gt;
==Glossary==&lt;br /&gt;
&lt;br /&gt;
* '''Circumvallate papillae''' - &lt;br /&gt;
&lt;br /&gt;
* '''Ectoderm'''- outer germ layer of embryo&lt;br /&gt;
&lt;br /&gt;
* '''Endoderm''' - inner germ layer of embryo&lt;br /&gt;
&lt;br /&gt;
* '''Epithelium''' - basic animal tissue that is composed of tightly packed cells, usually covering the outer portion of organs&lt;br /&gt;
&lt;br /&gt;
* '''Exocystosis''' - movement of contents out of cell&lt;br /&gt;
&lt;br /&gt;
* '''Filiform papillae''' - &lt;br /&gt;
&lt;br /&gt;
* '''Foliate papillae''' - &lt;br /&gt;
&lt;br /&gt;
* '''Fungiform papillae''' - &lt;br /&gt;
&lt;br /&gt;
* '''Ganglia''' - the accumulation of a nerve cell body&lt;br /&gt;
&lt;br /&gt;
* '''Growth factor''' - a substance that stimulates the growth of cells&lt;br /&gt;
&lt;br /&gt;
* '''Gustatory''' - anything that relates to the taste sense&lt;br /&gt;
&lt;br /&gt;
* '''Hydrolysis''' - breakdown of a chemical when it reacts with water&lt;br /&gt;
&lt;br /&gt;
* '''Mesoderm''' - middle germ layer of embryo&lt;br /&gt;
&lt;br /&gt;
* '''Mesenchyme''' - multipotential cells&lt;br /&gt;
&lt;br /&gt;
* '''Neural crest''' - a part of the ectoderm found on both sides of the neural tube&lt;br /&gt;
&lt;br /&gt;
* '''Neuron''' - most simplistic unit of the nervous system&lt;br /&gt;
&lt;br /&gt;
* '''Neurotransmitter''' - chemicals which allow the passing of signals from neuron to neuron via connecting part (synapse) &lt;br /&gt;
&lt;br /&gt;
* '''Papillae''' - small rough surface projection&lt;br /&gt;
&lt;br /&gt;
* '''Six genes''' - a family of genes&lt;br /&gt;
&lt;br /&gt;
* '''Sonic hedgehog (Shh)''' - signalling protein involved in normal development&lt;br /&gt;
&lt;br /&gt;
* '''Sulcus terminalis''' - describes a physical transition point separating the anterior 2/3 of the tongue from the posterior 1/3&lt;br /&gt;
&lt;br /&gt;
* '''Tamoxifen''' - hormonal altering drug&lt;br /&gt;
&lt;br /&gt;
* '''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).&lt;br /&gt;
&lt;br /&gt;
* '''Type II taste cells''' - Receptor cells acting as primary detectors of sweet, bitter or umami taste.&lt;br /&gt;
&lt;br /&gt;
* '''Type III taste cells''' - Presynaptic cells that respond to sweet, salty, sour, bitter and umami compounds.&lt;br /&gt;
&lt;br /&gt;
== References ==&lt;br /&gt;
&amp;lt;references/&amp;gt;&lt;br /&gt;
&lt;br /&gt;
==External Links==&lt;br /&gt;
{{External Links}}&lt;br /&gt;
&lt;br /&gt;
http://embryology.med.unsw.edu.au/embryology/index.php?title=2012_Group_Project_4&lt;br /&gt;
&lt;br /&gt;
http://www.webmd.com/oral-health/picture-of-the-tongue&lt;br /&gt;
&lt;br /&gt;
http://www.tutorvista.com/content/biology/biology-iv/nervous-coordination/tongue-structure.php#parts-of-tongue&lt;br /&gt;
&lt;br /&gt;
http://www.cf.ac.uk/biosi/staffinfo/jacob/teaching/sensory/taste.html&lt;br /&gt;
&lt;br /&gt;
--[[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.&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
----&lt;br /&gt;
&lt;br /&gt;
{{2012Projects}}&lt;/div&gt;</summary>
		<author><name>Z3330795</name></author>
	</entry>
	<entry>
		<id>https://embryology.med.unsw.edu.au/embryology/index.php?title=2012_Group_Project_3&amp;diff=104764</id>
		<title>2012 Group Project 3</title>
		<link rel="alternate" type="text/html" href="https://embryology.med.unsw.edu.au/embryology/index.php?title=2012_Group_Project_3&amp;diff=104764"/>
		<updated>2012-10-02T05:27:41Z</updated>

		<summary type="html">&lt;p&gt;Z3330795: /* Adult Tongue and Taste Buds – Structure and Function */&lt;/p&gt;
&lt;hr /&gt;
&lt;div&gt;=Taste Development=&lt;br /&gt;
&lt;br /&gt;
You are out to dinner and your meal arrives in front of you, the aromas and the presentation of your food strikes you immediately. Half way through, the waiter returns and asks “How does your meal taste?”  The answer is not as simple as one might think. Why does the meal taste pleasant? How do we experience different tastes? In the following page, we aim to discern how exactly one would answer these questions by looking at the embryological development of the taste system from week to week. &lt;br /&gt;
&lt;br /&gt;
Taste is a complex sensory system and its precise workings are to this day not fully understood. What makes it so complicated is the interaction between the structure of tongue and taste buds and how this contributes to the representation of taste qualities (salty, bitter, sweet, sour and umami) in the brain. We will also look at some current research on animal models being undertaken to evaluate the role of specific genes in the development of sensory structures. By looking at the taste system’s genetic basis, we now have a greater understanding of the abnormalities that may occur during development and a direction to pursue in future research to attempt to fill in the gaps of scientific knowledge.&lt;br /&gt;
&lt;br /&gt;
==Adult Tongue and Taste Buds – Structure and Function==&lt;br /&gt;
&lt;br /&gt;
'''Structure'''&lt;br /&gt;
&lt;br /&gt;
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.  &lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
''''The image below is a simplistic diagram of the surface of the tongue showing the locations of the different papillae and other important features'''&lt;br /&gt;
&lt;br /&gt;
{|&lt;br /&gt;
| [[Image:Drawing of Tongue.png|centre|500px]]&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
'''Papillae'''&lt;br /&gt;
[[File:Papillae.jpg|Left|thumb|200px|Close up of Human Tongue Papillae]]&lt;br /&gt;
&lt;br /&gt;
There are 4 types of papillae on the tongue.&lt;br /&gt;
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. &lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
[[File:Fungiformpapillae.jpg|Left|thumb|200px|Fungiform Papillae]]&lt;br /&gt;
&lt;br /&gt;
[[File:Circumvallatepapillae.jpg |Left|thumb|200px|Circumvallate Papillae]]&lt;br /&gt;
&lt;br /&gt;
[[File:Filiformpapillae.jpg|Left|thumb|200px|Foliate Papillae]]&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
'''Function'''&lt;br /&gt;
&lt;br /&gt;
The Tongue has muscular and sensory functions, muscular functions include swallowing and speech where as sensory function involves taste. This section will focus on the sensory functions of the tongue.&lt;br /&gt;
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.&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
'''The image below is a simplistic hand-drawn cross section of a taste bud unit (not to scale)'''&lt;br /&gt;
&lt;br /&gt;
[[File:Taste_bud_1.jpg|x400px|alt=Cross section of a taste bud unit|centre|Cross section of a taste bud unit]]&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
'''Link Between Taste and Smell'''&lt;br /&gt;
&lt;br /&gt;
The pathways between smell and taste are very similar. Pathways both involve the conversion of a dissolved chemical stimulus into a nerve impulse for interpretation by the brain.	&lt;br /&gt;
Taste does not necessarily equal flavour, flavour involves an interaction of taste, smell, texture and temperature, where taste is only a portion of this interaction. when the brain interprets a taste, contribution from other senses has a significant role in identification. In conclusion Taste and Smell in combination with other senses help develop a sensory interpretation called flavour.&lt;br /&gt;
&lt;br /&gt;
[[File:Taste_pathway.jpg|right|thumb|200px|Simplistic Pathway of Taste]]&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
[[File:Human smelling.jpg|500px|centre]]&lt;br /&gt;
&lt;br /&gt;
==History of Discoveries==&lt;br /&gt;
&lt;br /&gt;
{| cellpadding=5 style=&amp;quot;border:1px solid #BBB&amp;quot;&lt;br /&gt;
|- bgcolor=&amp;quot;#faecc8&amp;quot;&lt;br /&gt;
|''' Date'''|| '''Significant Discovery'''&lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#faf6ed&amp;quot;&lt;br /&gt;
|'''350BC'''&lt;br /&gt;
|| Aristotle writes about the basic tastes, sweet and bitter. He also notes that it can be modified by salty and acidic. &amp;lt;ref name=&amp;quot;PMID22717400&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;22717400&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#faecc8&amp;quot;&lt;br /&gt;
|'''1901'''&lt;br /&gt;
|| D. Hanig publishes a paper describing taste sensitivity in different regions of the tongue. &lt;br /&gt;
''Interesting fact:'' The modern concept of a 'tongue map' is a misinterpretation of this study. &amp;lt;ref name=&amp;quot;PMID22717400&amp;quot;/&amp;gt;&lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#faf6ed&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''1908'''&lt;br /&gt;
|Kikunae Ikeda, a professor of the Tokyo Imperial University, discovered and identified the fifth basic taste: umami (savouriness), made palatable by glutamate.  &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;12438213&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
[http://chemse.oxfordjournals.org/content/27/9/847.long New Seasonings]&lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#faecc8&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''1931-32'''&lt;br /&gt;
| A chemist named Arthur Fox and his college noted that they had different sensitivities to the bitter tasting Phenylthiocarbamide (PTC).&amp;lt;ref&amp;gt;Blakeslee AF, Fox AL. Our different taste worlds. J Hered. 1932;23:97–107.&amp;lt;/ref&amp;gt; Geneticists later confirm these findings, and discover that non-tasting is a recessive genetic trait. &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;17782493&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/pubmed/17782493 Inherited taste deficiency] &lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#faf6ed&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''1965'''&lt;br /&gt;
|Farbman's study of the developing taste but in rat fungiform papilla was significant in increasing our understanding of taste bud development. &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;14300090&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
[http://www.sciencedirect.com/science/article/pii/0012160665900400 Electron microscope study of the developing taste bud in rat fungiform papilla.]&lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#faecc8&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''1992'''&lt;br /&gt;
|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. &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;1608467 &amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
[http://www.nature.com/nature/journal/v357/n6379/abs/357563a0.html Gustducin is a taste-cell-specific G protein closely related to the transducins]&lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#faf6ed&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''1995'''&lt;br /&gt;
|Barlow et al. experimented with Axolotl salamanders and concluded that taste buds from this species arise exclusively from epithelial tissue, &amp;quot;oropharyngeal [[#Glossary |'''epithelium''']]&amp;quot;. &amp;lt;ref name=&amp;quot;PMID17826760&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;17826760&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/pubmed/17826760 Embryonic origin of gustatory cranial sensory neurons] &lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#faecc8&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''1996'''&lt;br /&gt;
| 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 &amp;quot;at least dual function of embryonic/fetal taste buds&amp;quot;, including non-gustatory, paracrine functions prior to the 14th week and gustatory after the 14th week. &amp;lt;ref name=&amp;quot;PMID8955790&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;8955790&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/pubmed/8955790 Embryonic and early fetal development of human taste buds: a transmission electron microscopical study]&lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#faf6ed&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''2000'''&lt;br /&gt;
|Chandrashekar, J. et al. discover the first taste sonsors, the T2R bitter taste receptors. &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;10761935&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
[http://www.sciencedirect.com/science/article/pii/S0092867400807060 T2Rs Function as Bitter Taste Receptors]&lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#faecc8&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''2001'''&lt;br /&gt;
|Nelson, G. et al. discover the sweet receptor: a combination of T1R2 and T1R3. &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;11509186&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/pubmed/11509186?dopt=Abstract&amp;amp;holding=npg Mammalian sweet taste receptors.]&lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#faf6ed&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''2002'''&lt;br /&gt;
|Nelson G. et al. discover the amino acid (umami) taste receptor: a combination of T1R1 and T1R3 identified.  &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;11894099&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/pubmed/11894099?dopt=Abstract&amp;amp;holding=npg An amino-acid taste receptor]&lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#faecc8&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''2005'''&lt;br /&gt;
|Dyer, J. et al. discover sweet taste receptors in the GI tract. &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;17855558&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1986582/ Sweet taste signaling in the gut]&lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#faf6ed&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''2006'''&lt;br /&gt;
|Huang, A. L et al. discover cells for sour taste, identified by PKD2L1 (a polycystic kidney disease-like ion channel). &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;16929298&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1571047/ The Cells and Logic for Mammalian Sour Taste detection]&lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#faecc8&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''2007'''&lt;br /&gt;
|Harlow DE, Barlow LA of the University of Colorado Denver Health Sciences Center provide evidence of the &amp;quot;embryonic origin of gustatory cranial sensory neurons&amp;quot;. &amp;lt;ref name=&amp;quot;PMID17826760&amp;quot;/&amp;gt;&lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/pubmed/17826760 Embryonic origin of gustatory cranial sensory neurons.]&lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#faf6ed&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''2009'''&lt;br /&gt;
|A study by Hevezi P et al, presents &amp;quot;the first comprehensive characterization of gene expression in primate taste buds&amp;quot;, as opposed to previous studies which focused on rodents. &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;19636377&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/pubmed/19636377 Genome-wide analysis of gene expression in primate taste buds reveals links to diverse processes]&lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#faecc8&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''2010'''&lt;br /&gt;
|Chandrashekar, J. et al. identify epithelial sodium channel (ENaC) as the sodium-salt taste receptor. &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;20107438&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/pubmed/20107438?dopt=Abstract&amp;amp;holding=npg The cells and peripheral representation of sodium taste in mice]&lt;br /&gt;
|}&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
== Human Weekly Development - Two Prominent Studies ==&lt;br /&gt;
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. &lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
The findings of these two studies are summarized in the table below. The figures provided relate to the images on their respective research papers.&lt;br /&gt;
&lt;br /&gt;
# [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] &lt;br /&gt;
# [http://chemse.oxfordjournals.org/content/22/6/601.long Scanning electron microscopical studies of developing gustatory papillae in humans, 1997]  &lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
===Timeline of Developmental Processes of Human Taste Buds===&lt;br /&gt;
{| cellpadding=5 style=&amp;quot;border:1px solid #BBB&amp;quot;&lt;br /&gt;
|- bgcolor=&amp;quot;#89CFF0&amp;quot;&lt;br /&gt;
|'''Postovulatory Week'''||'''Description'''&lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#BCD4E6&amp;quot;&lt;br /&gt;
|'''Week 6''' ||&lt;br /&gt;
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. &amp;lt;ref name=&amp;quot;PMID9455607&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;9455607&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#89CFF0&amp;quot;&lt;br /&gt;
| '''Weeks 6 to 7'''|| &lt;br /&gt;
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. &amp;lt;ref name=PMID8955790/&amp;gt;&lt;br /&gt;
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|- bgcolor=&amp;quot;#BCD4E6&amp;quot;&lt;br /&gt;
| '''Week 7 '''||&lt;br /&gt;
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.  &amp;lt;ref name=PMID9455607/&amp;gt; &lt;br /&gt;
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|- bgcolor=&amp;quot;#89CFF0&amp;quot;&lt;br /&gt;
| ''' Week 8  ''' ||&lt;br /&gt;
* The taste bud primordium are still differentiated, elongated epithelial cells, resting on a slightly developed core of young dermal papilla.&lt;br /&gt;
* 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. &lt;br /&gt;
* Ciliated cells also appear around the 8th week, however the significance of these cells which are scattered randomly across the lingual surface remains unclear. &amp;lt;ref name=PMID8955790/&amp;gt; &lt;br /&gt;
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|- bgcolor=&amp;quot;#BCD4E6&amp;quot;&lt;br /&gt;
|'''  Week 9''' ||&lt;br /&gt;
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). &amp;lt;ref name=PMID9455607/&amp;gt;&lt;br /&gt;
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|- bgcolor=&amp;quot;#89CFF0&amp;quot;&lt;br /&gt;
|'''  Weeks 10-11''' ||&lt;br /&gt;
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). &amp;lt;ref name=PMID8955790/&amp;gt; &lt;br /&gt;
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|- bgcolor=&amp;quot;#BCD4E6&amp;quot;&lt;br /&gt;
|''' Week 12 ''' ||&lt;br /&gt;
Taste bud cells are more clearly differentiated into epithelial cell types II and III. &amp;lt;ref name=PMID8955790/&amp;gt; &lt;br /&gt;
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|- bgcolor=&amp;quot;#89CFF0&amp;quot;&lt;br /&gt;
|''' Weeks 12-13  ''' ||&lt;br /&gt;
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). &amp;lt;ref name=PMID8955790/&amp;gt; &lt;br /&gt;
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|- bgcolor=&amp;quot;#BCD4E6&amp;quot;&lt;br /&gt;
|''' Weeks 14 -15 ''' ||&lt;br /&gt;
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. &amp;lt;ref name=PMID8955790/&amp;gt; &lt;br /&gt;
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==Abnormalities==&lt;br /&gt;
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It should be mentioned that gustatory abnormalities have not been widely researched. Most research conducted in this field has been conducted through animal testing on mice and this is the basis of information provided below. &lt;br /&gt;
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===Knocking out P2X Receptors===&lt;br /&gt;
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[[File:Image of taste being evoked by visualising ATP release.jpeg|Left|thumb|200px|Evoking taste - ATP release in tongue]]&lt;br /&gt;
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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. &lt;br /&gt;
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It should be noted that the taste buds in DKO are functional, but are not stimulated by the administration of tastants. &lt;br /&gt;
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The transmission of release of ATP is secretion through gap junction hemichannels (pannexin 1 gap junction).&lt;br /&gt;
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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.&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;21940456&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
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===FGF signalling and genes===&lt;br /&gt;
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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.&lt;br /&gt;
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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 (&amp;quot;Fgf10&amp;quot;) 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 &amp;quot;Fgf10&amp;quot; to limit the size of the CVP progenitor placode. Exclusive expression of ''Fgf10'' in the [[#Glossary |'''mesenchyme''']] is necessary for the formation of CVP. &lt;br /&gt;
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'''This image shows the CVP stained with H&amp;amp;E and scanned by Scanning Electron Microscope (SEM)'''&lt;br /&gt;
[[File:CVP of WT(top) and DKO(bottom) mice with H&amp;amp;E and SEM.png]]&lt;br /&gt;
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'''This image shows the location of the CVP and the increased number in DKO mice by SEM'''&lt;br /&gt;
[[File:Mouse circumvallate papilla 01.jpg|300px]]&lt;br /&gt;
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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).&lt;br /&gt;
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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).&lt;br /&gt;
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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''&amp;amp; ''Spry 1&amp;amp;2''work antagonistically through receptor tyrosine kinase (RTK)signalling.&lt;br /&gt;
&lt;br /&gt;
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.&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;21655085&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
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==Gustatory System==&lt;br /&gt;
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[[Image:Taste qualities.gif|thumb|The five basic tastes]]&lt;br /&gt;
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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.&lt;br /&gt;
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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.&amp;lt;ref name=PMID20696704&amp;gt;&amp;lt;pubmed&amp;gt;20696704&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
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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 &amp;lt;ref name=PMID20696704/&amp;gt; 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.&lt;br /&gt;
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===Cell Biology===&lt;br /&gt;
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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.&lt;br /&gt;
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====Type II receptors====&lt;br /&gt;
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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:&lt;br /&gt;
&lt;br /&gt;
# Stimulates gustatory nerve afferents which project to gustatory nuclei  in the spinal cord&lt;br /&gt;
# Excites Type III presynaptic nerve fibers to release serotonin. &lt;br /&gt;
# Has a positive feedback effect on type II receptor cells, increasing the level of ATP production.&lt;br /&gt;
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        &lt;br /&gt;
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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.&lt;br /&gt;
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==Taste Map==&lt;br /&gt;
[[Image:Taste map.png|thumb|left|250px|Obsolete idea of the tongue map]]&lt;br /&gt;
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.&lt;br /&gt;
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===Neural Pathways===&lt;br /&gt;
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'''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''. &lt;br /&gt;
&lt;br /&gt;
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:  &lt;br /&gt;
&lt;br /&gt;
* ''Facial nerve n''. -  carries taste information from the anterior 2/3 of the tongue.&lt;br /&gt;
* ''Hypoglossal n.'' - carries taste information from the posterior 1/3 of the tongue.&lt;br /&gt;
* ''Vagus n''. - carries taste information from the palate&lt;br /&gt;
&lt;br /&gt;
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'''Second order neurons''' - From the NTS second order neurons carry taste information to the Ventral posteromedial (VPM) nucleus in the thalamus.&amp;lt;ref name=PMID21885776/&amp;gt;&lt;br /&gt;
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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.  &lt;br /&gt;
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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.&lt;br /&gt;
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===Cortical Areas===&lt;br /&gt;
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[[Image:Primary gustatory cortex.png|thumb|Primary gustatory cortex]]&lt;br /&gt;
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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)&amp;lt;ref name=PMID22245354&amp;gt;&amp;lt;pubmed&amp;gt;22245354&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;, with the secondary taste cortex in the caudolateral orbitofrontal cortex.&amp;lt;ref name=PMID21305668&amp;gt;&amp;lt;pubmed&amp;gt;21305668&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;  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.&amp;lt;ref name=PMID21885776&amp;gt;&amp;lt;pubmed&amp;gt;21885776&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; These findings lend weight to the idea that there is only one receptor for each taste quality.&lt;br /&gt;
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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).&amp;lt;ref name=PMID21885776/&amp;gt; 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&lt;br /&gt;
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==Current Research==&lt;br /&gt;
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. &lt;br /&gt;
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.&lt;br /&gt;
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[[File:Mousetounge histologicalstain.jpg|Left|thumb|200px|Image shows histological stains of a mice tongue showing dysplasia]]&lt;br /&gt;
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'''Synergistic relationships of Six Genes '''&lt;br /&gt;
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In an animal study using mice by Suzuki Y, Ikeda K, Kawakami K.(2011)  Firstly nominating &amp;quot;[[#Glossary |'''Six Genes''']]&amp;quot; as a major component in [[#Glossary |'''gustatory ''']] development, stating that deficiencies in certain Six genes (specifically Six1 &amp;amp; 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 &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;21978088&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
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[[File:Highpowered_microscope.jpg|Left|thumb|200px|Image of a high powered microscope]]&lt;br /&gt;
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'''Neural Crest responsibilities '''&lt;br /&gt;
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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.&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;22659543&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
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[[File:Developing_tongue_histology_001.jpg|Left|thumb|200px|HIstological stain of a developing rat tongue]]&lt;br /&gt;
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'''Augmentation of Endoderm'''&lt;br /&gt;
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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 &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;22581563&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
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'''Changes in Taste Cells over time'''&lt;br /&gt;
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Research by &lt;br /&gt;
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.  &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;22643728&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
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'''Shh key component of taste bud proginators'''&lt;br /&gt;
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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.&lt;br /&gt;
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 &amp;quot;Axiocam CCD camera and Axioplan fluorescence microscope with Axiovision software&amp;quot; a study by Harlow, Yang, Williams, Barlow (2011)&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;PMC2674259&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
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'''WNT family exhibit various roles''' [[File:Abnormal of tongue.jpg|thumb|200px|Image shows an example of tongue abnormalities, this is called &amp;quot;double tongue&amp;quot; each side has independent movement!]]&lt;br /&gt;
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The WNT gene family has a function of signal2''work antagonistically through receptor tyrosine kinase (RTK)signalling.&lt;br /&gt;
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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.ly 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. &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;PMC2768563&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
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[http://www.surgicalneurologyint.com/article.asp?issn=2152-7806;year=2012;volume=3;issue=1;spage=23;epage=23;aulast=Manjila]&lt;br /&gt;
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==Glossary==&lt;br /&gt;
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* '''Circumvallate papillae''' - &lt;br /&gt;
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* '''Ectoderm'''- outer germ layer of embryo&lt;br /&gt;
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* '''Endoderm''' - inner germ layer of embryo&lt;br /&gt;
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* '''Epithelium''' - basic animal tissue that is composed of tightly packed cells, usually covering the outer portion of organs&lt;br /&gt;
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* '''Exocystosis''' - movement of contents out of cell&lt;br /&gt;
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* '''Filiform papillae''' - &lt;br /&gt;
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* '''Foliate papillae''' - &lt;br /&gt;
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* '''Fungiform papillae''' - &lt;br /&gt;
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* '''Ganglia''' - the accumulation of a nerve cell body&lt;br /&gt;
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* '''Growth factor''' - a substance that stimulates the growth of cells&lt;br /&gt;
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* '''Gustatory''' - anything that relates to the taste sense&lt;br /&gt;
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* '''Hydrolysis''' - breakdown of a chemical when it reacts with water&lt;br /&gt;
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* '''Mesoderm''' - middle germ layer of embryo&lt;br /&gt;
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* '''Mesenchyme''' - multipotential cells&lt;br /&gt;
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* '''Neural crest''' - a part of the ectoderm found on both sides of the neural tube&lt;br /&gt;
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* '''Neuron''' - most simplistic unit of the nervous system&lt;br /&gt;
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* '''Neurotransmitter''' - chemicals which allow the passing of signals from neuron to neuron via connecting part (synapse) &lt;br /&gt;
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* '''Papillae''' - small rough surface projection&lt;br /&gt;
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* '''Six genes''' - a family of genes&lt;br /&gt;
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* '''Sonic hedgehog (Shh)''' - signalling protein involved in normal development&lt;br /&gt;
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* '''Sulcus terminalis''' - describes a physical transition point separating the anterior 2/3 of the tongue from the posterior 1/3&lt;br /&gt;
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* '''Tamoxifen''' - hormonal altering drug&lt;br /&gt;
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* '''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).&lt;br /&gt;
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* '''Type II taste cells''' - Receptor cells acting as primary detectors of sweet, bitter or umami taste.&lt;br /&gt;
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* '''Type III taste cells''' - Presynaptic cells that respond to sweet, salty, sour, bitter and umami compounds.&lt;br /&gt;
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== References ==&lt;br /&gt;
&amp;lt;references/&amp;gt;&lt;br /&gt;
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==External Links==&lt;br /&gt;
{{External Links}}&lt;br /&gt;
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http://embryology.med.unsw.edu.au/embryology/index.php?title=2012_Group_Project_4&lt;br /&gt;
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http://www.webmd.com/oral-health/picture-of-the-tongue&lt;br /&gt;
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http://www.tutorvista.com/content/biology/biology-iv/nervous-coordination/tongue-structure.php#parts-of-tongue&lt;br /&gt;
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http://www.cf.ac.uk/biosi/staffinfo/jacob/teaching/sensory/taste.html&lt;br /&gt;
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--[[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.&lt;br /&gt;
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{{2012Projects}}&lt;/div&gt;</summary>
		<author><name>Z3330795</name></author>
	</entry>
	<entry>
		<id>https://embryology.med.unsw.edu.au/embryology/index.php?title=2012_Group_Project_3&amp;diff=104620</id>
		<title>2012 Group Project 3</title>
		<link rel="alternate" type="text/html" href="https://embryology.med.unsw.edu.au/embryology/index.php?title=2012_Group_Project_3&amp;diff=104620"/>
		<updated>2012-10-02T01:57:47Z</updated>

		<summary type="html">&lt;p&gt;Z3330795: /* External Links */&lt;/p&gt;
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&lt;div&gt;=Taste Development=&lt;br /&gt;
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adult structure and function&lt;br /&gt;
This section describes the anatomy and function of the tongue with a focus on the taste function. There are various visual stimuli to allow better understanding of the complex physiological processes involved.&lt;br /&gt;
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current research&lt;br /&gt;
Current research presented involves the use of animal models and the majority using mice as the specimen. The main focus of current research is to understand the patterns of development and what is contributed by various embryonic components to allow more insight into the complex interactions that compose embryonic taste development.&lt;br /&gt;
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==Adult Tongue and Taste Buds – Structure and Function==&lt;br /&gt;
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'''Structure'''&lt;br /&gt;
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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.  &lt;br /&gt;
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''''The image below is a simplistic diagram of the surface of the tongue showing the locations of the different papillae and other important features'''&lt;br /&gt;
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{|&lt;br /&gt;
| [[Image:Drawing of Tongue.png|centre|500px]]&lt;br /&gt;
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'''Papillae'''&lt;br /&gt;
[[File:Papillae.jpg|Left|thumb|200px|Close up of Human Tongue Papillae]]&lt;br /&gt;
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There are 4 types of papillae on the tongue.&lt;br /&gt;
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. &lt;br /&gt;
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[[File:Fungiformpapillae.jpg|Left|thumb|200px|Fungiform Papillae]]&lt;br /&gt;
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[[File:Circumvallatepapillae.jpg |Left|thumb|200px|Circumvallate Papillae]]&lt;br /&gt;
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[[File:Filiformpapillae.jpg|Left|thumb|200px|Foliate Papillae]]&lt;br /&gt;
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'''Function'''&lt;br /&gt;
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The Tongue has muscular and sensory functions, muscular functions include swallowing and speech where as sensory function involves taste. This section will focus on the sensory functions of the tongue.&lt;br /&gt;
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.&lt;br /&gt;
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'''The image below is a simplistic hand-drawn cross section of a taste bud unit (not to scale)'''&lt;br /&gt;
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[[File:Taste_bud_1.jpg|x400px|alt=Cross section of a taste bud unit|centre|Cross section of a taste bud unit]]&lt;br /&gt;
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'''Link Between Taste and Smell'''&lt;br /&gt;
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The pathways between smell and taste are very similar. Pathways both involve the conversion of a chemical stimulus into a nerve impulse for interpretation by the brain. People often mistake taste for flavour, flavour involves an interaction of taste, smell, texture and temperature.&lt;br /&gt;
When there is food in our mouth there is signalling between these senses giving a whole package interpretation instead of just taste itself, the communication of these senses allows an indvidual a more specific perception of what they are eating.&lt;br /&gt;
[http://serendip.brynmawr.edu/exchange/node/1575]&lt;br /&gt;
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[[File:Taste_pathway.jpg|right|thumb|200px|Simplistic Pathway of Taste]]&lt;br /&gt;
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[[File:Human smelling.jpg|500px|centre]]&lt;br /&gt;
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==History of Discoveries==&lt;br /&gt;
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{| cellpadding=5 style=&amp;quot;border:1px solid #BBB&amp;quot;&lt;br /&gt;
|- bgcolor=&amp;quot;#faecc8&amp;quot;&lt;br /&gt;
|''' Date'''|| '''Significant Discovery'''&lt;br /&gt;
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|- bgcolor=&amp;quot;#faf6ed&amp;quot;&lt;br /&gt;
|'''350BC'''&lt;br /&gt;
|| Aristotle writes about the basic tastes, sweet and bitter. He also notes that it can be modified by salty and acidic. &amp;lt;ref name=&amp;quot;PMID22717400&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;22717400&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
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|- bgcolor=&amp;quot;#faecc8&amp;quot;&lt;br /&gt;
|'''1901'''&lt;br /&gt;
|| D. Hanig publishes a paper describing taste sensitivity in different regions of the tongue. &lt;br /&gt;
''Interesting fact:'' The modern concept of a 'tongue map' is a misinterpretation of this study. &amp;lt;ref name=&amp;quot;PMID22717400&amp;quot;/&amp;gt;&lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#faf6ed&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''1908'''&lt;br /&gt;
|Kikunae Ikeda, a professor of the Tokyo Imperial University, discovered and identified the fifth basic taste: umami (savouriness), made palatable by glutamate.  &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;12438213&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
[http://chemse.oxfordjournals.org/content/27/9/847.long New Seasonings]&lt;br /&gt;
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|- bgcolor=&amp;quot;#faecc8&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''1931-32'''&lt;br /&gt;
| A chemist named Arthur Fox and his college noted that they had different sensitivities to the bitter tasting Phenylthiocarbamide (PTC).&amp;lt;ref&amp;gt;Blakeslee AF, Fox AL. Our different taste worlds. J Hered. 1932;23:97–107.&amp;lt;/ref&amp;gt; Geneticists later confirm these findings, and discover that non-tasting is a recessive genetic trait. &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;17782493&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/pubmed/17782493 Inherited taste deficiency] &lt;br /&gt;
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|- bgcolor=&amp;quot;#faf6ed&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''1965'''&lt;br /&gt;
|Farbman's study of the developing taste but in rat fungiform papilla was significant in increasing our understanding of taste bud development. &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;14300090&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
[http://www.sciencedirect.com/science/article/pii/0012160665900400 Electron microscope study of the developing taste bud in rat fungiform papilla.]&lt;br /&gt;
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|- bgcolor=&amp;quot;#faecc8&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''1992'''&lt;br /&gt;
|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. &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;1608467 &amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
[http://www.nature.com/nature/journal/v357/n6379/abs/357563a0.html Gustducin is a taste-cell-specific G protein closely related to the transducins]&lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#faf6ed&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''1995'''&lt;br /&gt;
|Barlow et al. experimented with Axolotl salamanders and concluded that taste buds from this species arise exclusively from epithelial tissue, &amp;quot;oropharyngeal [[#Glossary |'''epithelium''']]&amp;quot;. &amp;lt;ref name=&amp;quot;PMID17826760&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;17826760&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/pubmed/17826760 Embryonic origin of gustatory cranial sensory neurons] &lt;br /&gt;
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|- bgcolor=&amp;quot;#faecc8&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''1996'''&lt;br /&gt;
| 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 &amp;quot;at least dual function of embryonic/fetal taste buds&amp;quot;, including non-gustatory, paracrine functions prior to the 14th week and gustatory after the 14th week. &amp;lt;ref name=&amp;quot;PMID8955790&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;8955790&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/pubmed/8955790 Embryonic and early fetal development of human taste buds: a transmission electron microscopical study]&lt;br /&gt;
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|- bgcolor=&amp;quot;#faf6ed&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''2000'''&lt;br /&gt;
|Chandrashekar, J. et al. discover the first taste sonsors, the T2R bitter taste receptors. &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;10761935&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
[http://www.sciencedirect.com/science/article/pii/S0092867400807060 T2Rs Function as Bitter Taste Receptors]&lt;br /&gt;
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|- bgcolor=&amp;quot;#faecc8&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''2001'''&lt;br /&gt;
|Nelson, G. et al. discover the sweet receptor: a combination of T1R2 and T1R3. &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;11509186&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/pubmed/11509186?dopt=Abstract&amp;amp;holding=npg Mammalian sweet taste receptors.]&lt;br /&gt;
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|- bgcolor=&amp;quot;#faf6ed&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''2002'''&lt;br /&gt;
|Nelson G. et al. discover the amino acid (umami) taste receptor: a combination of T1R1 and T1R3 identified.  &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;11894099&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/pubmed/11894099?dopt=Abstract&amp;amp;holding=npg An amino-acid taste receptor]&lt;br /&gt;
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|- bgcolor=&amp;quot;#faecc8&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''2005'''&lt;br /&gt;
|Dyer, J. et al. discover sweet taste receptors in the GI tract. &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;17855558&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1986582/ Sweet taste signaling in the gut]&lt;br /&gt;
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|- bgcolor=&amp;quot;#faf6ed&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''2006'''&lt;br /&gt;
|Huang, A. L et al. discover cells for sour taste, identified by PKD2L1 (a polycystic kidney disease-like ion channel). &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;16929298&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1571047/ The Cells and Logic for Mammalian Sour Taste detection]&lt;br /&gt;
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|- bgcolor=&amp;quot;#faecc8&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''2007'''&lt;br /&gt;
|Harlow DE, Barlow LA of the University of Colorado Denver Health Sciences Center provide evidence of the &amp;quot;embryonic origin of gustatory cranial sensory neurons&amp;quot;. &amp;lt;ref name=&amp;quot;PMID17826760&amp;quot;/&amp;gt;&lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/pubmed/17826760 Embryonic origin of gustatory cranial sensory neurons.]&lt;br /&gt;
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|- bgcolor=&amp;quot;#faf6ed&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''2009'''&lt;br /&gt;
|A study by Hevezi P et al, presents &amp;quot;the first comprehensive characterization of gene expression in primate taste buds&amp;quot;, as opposed to previous studies which focused on rodents. &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;19636377&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/pubmed/19636377 Genome-wide analysis of gene expression in primate taste buds reveals links to diverse processes]&lt;br /&gt;
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|- bgcolor=&amp;quot;#faecc8&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''2010'''&lt;br /&gt;
|Chandrashekar, J. et al. identify epithelial sodium channel (ENaC) as the sodium-salt taste receptor. &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;20107438&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/pubmed/20107438?dopt=Abstract&amp;amp;holding=npg The cells and peripheral representation of sodium taste in mice]&lt;br /&gt;
|}&lt;br /&gt;
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== Human Weekly Development - Two Prominent Studies ==&lt;br /&gt;
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. &lt;br /&gt;
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The findings of these two studies are summarized in the table below. The figures provided relate to the images on their respective research papers.&lt;br /&gt;
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# [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] &lt;br /&gt;
# [http://chemse.oxfordjournals.org/content/22/6/601.long Scanning electron microscopical studies of developing gustatory papillae in humans, 1997]  &lt;br /&gt;
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===Timeline of Developmental Processes of Human Taste Buds===&lt;br /&gt;
{| cellpadding=5 style=&amp;quot;border:1px solid #BBB&amp;quot;&lt;br /&gt;
|- bgcolor=&amp;quot;#89CFF0&amp;quot;&lt;br /&gt;
|'''Postovulatory Week'''||'''Description'''&lt;br /&gt;
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|- bgcolor=&amp;quot;#BCD4E6&amp;quot;&lt;br /&gt;
|'''Week 6''' ||&lt;br /&gt;
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. &amp;lt;ref name=&amp;quot;PMID9455607&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;9455607&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
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|- bgcolor=&amp;quot;#89CFF0&amp;quot;&lt;br /&gt;
| '''Weeks 6 to 7'''|| &lt;br /&gt;
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. &amp;lt;ref name=PMID8955790/&amp;gt;&lt;br /&gt;
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|- bgcolor=&amp;quot;#BCD4E6&amp;quot;&lt;br /&gt;
| '''Week 7 '''||&lt;br /&gt;
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.  &amp;lt;ref name=PMID9455607/&amp;gt; &lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#89CFF0&amp;quot;&lt;br /&gt;
| ''' Week 8  ''' ||&lt;br /&gt;
* The taste bud primordium are still differentiated, elongated epithelial cells, resting on a slightly developed core of young dermal papilla.&lt;br /&gt;
* 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. &lt;br /&gt;
* Ciliated cells also appear around the 8th week, however the significance of these cells which are scattered randomly across the lingual surface remains unclear. &amp;lt;ref name=PMID8955790/&amp;gt; &lt;br /&gt;
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|- bgcolor=&amp;quot;#BCD4E6&amp;quot;&lt;br /&gt;
|'''  Week 9''' ||&lt;br /&gt;
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). &amp;lt;ref name=PMID9455607/&amp;gt;&lt;br /&gt;
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|- bgcolor=&amp;quot;#89CFF0&amp;quot;&lt;br /&gt;
|'''  Weeks 10-11''' ||&lt;br /&gt;
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). &amp;lt;ref name=PMID8955790/&amp;gt; &lt;br /&gt;
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|- bgcolor=&amp;quot;#BCD4E6&amp;quot;&lt;br /&gt;
|''' Week 12 ''' ||&lt;br /&gt;
Taste bud cells are more clearly differentiated into epithelial cell types II and III. &amp;lt;ref name=PMID8955790/&amp;gt; &lt;br /&gt;
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|- bgcolor=&amp;quot;#89CFF0&amp;quot;&lt;br /&gt;
|''' Weeks 12-13  ''' ||&lt;br /&gt;
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). &amp;lt;ref name=PMID8955790/&amp;gt; &lt;br /&gt;
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|- bgcolor=&amp;quot;#BCD4E6&amp;quot;&lt;br /&gt;
|''' Weeks 14 -15 ''' ||&lt;br /&gt;
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. &amp;lt;ref name=PMID8955790/&amp;gt; &lt;br /&gt;
|}&lt;br /&gt;
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==Abnormalities==&lt;br /&gt;
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It should be mentioned that gustatory abnormalities have not been widely researched. Most research conducted in this field has been conducted through animal testing on mice and this is the basis of information provided below. &lt;br /&gt;
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===Knocking out P2X Receptors===&lt;br /&gt;
&lt;br /&gt;
[[File:Image of taste being evoked by visualising ATP release.jpeg|Left|thumb|200px|Evoking taste - ATP release in tongue]]&lt;br /&gt;
&lt;br /&gt;
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. &lt;br /&gt;
&lt;br /&gt;
It should be noted that the taste buds in DKO are functional, but are not stimulated by the administration of tastants. &lt;br /&gt;
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The transmission of release of ATP is secretion through gap junction hemichannels (pannexin 1 gap junction).&lt;br /&gt;
&lt;br /&gt;
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.&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;21940456&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
===FGF signalling and genes===&lt;br /&gt;
&lt;br /&gt;
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.&lt;br /&gt;
&lt;br /&gt;
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 (&amp;quot;Fgf10&amp;quot;) 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 &amp;quot;Fgf10&amp;quot; to limit the size of the CVP progenitor placode. Exclusive expression of ''Fgf10'' in the [[#Glossary |'''mesenchyme''']] is necessary for the formation of CVP. &lt;br /&gt;
&lt;br /&gt;
'''This image shows the CVP stained with H&amp;amp;E and scanned by Scanning Electron Microscope (SEM)'''&lt;br /&gt;
[[File:CVP of WT(top) and DKO(bottom) mice with H&amp;amp;E and SEM.png]]&lt;br /&gt;
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'''This image shows the location of the CVP and the increased number in DKO mice by SEM'''&lt;br /&gt;
[[File:Mouse circumvallate papilla 01.jpg|300px]]&lt;br /&gt;
&lt;br /&gt;
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).&lt;br /&gt;
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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).&lt;br /&gt;
&lt;br /&gt;
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''&amp;amp; ''Spry 1&amp;amp;2''work antagonistically through receptor tyrosine kinase (RTK)signalling.&lt;br /&gt;
&lt;br /&gt;
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.&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;21655085&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
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==Gustatory System==&lt;br /&gt;
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[[Image:Taste qualities.gif|thumb|The five basic tastes]]&lt;br /&gt;
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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.&lt;br /&gt;
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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.&amp;lt;ref name=PMID20696704&amp;gt;&amp;lt;pubmed&amp;gt;20696704&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
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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 &amp;lt;ref name=PMID20696704/&amp;gt; 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.&lt;br /&gt;
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===Cell Biology===&lt;br /&gt;
&lt;br /&gt;
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.&lt;br /&gt;
&lt;br /&gt;
====Type II receptors====&lt;br /&gt;
&lt;br /&gt;
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:&lt;br /&gt;
&lt;br /&gt;
# Stimulates gustatory nerve afferents which project to gustatory nuclei  in the spinal cord&lt;br /&gt;
# Excites Type III presynaptic nerve fibers to release serotonin. &lt;br /&gt;
# Has a positive feedback effect on type II receptor cells, increasing the level of ATP production.&lt;br /&gt;
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        &lt;br /&gt;
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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.&lt;br /&gt;
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==Taste Map==&lt;br /&gt;
[[Image:Taste map.png|thumb|left|250px|Obsolete idea of the tongue map]]&lt;br /&gt;
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.&lt;br /&gt;
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===Neural Pathways===&lt;br /&gt;
&lt;br /&gt;
'''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''. &lt;br /&gt;
&lt;br /&gt;
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:  &lt;br /&gt;
&lt;br /&gt;
* ''Facial nerve n''. -  carries taste information from the anterior 2/3 of the tongue.&lt;br /&gt;
* ''Hypoglossal n.'' - carries taste information from the posterior 1/3 of the tongue.&lt;br /&gt;
* ''Vagus n''. - carries taste information from the palate&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
'''Second order neurons''' - From the NTS second order neurons carry taste information to the Ventral posteromedial (VPM) nucleus in the thalamus.&amp;lt;ref name=PMID21885776/&amp;gt;&lt;br /&gt;
&lt;br /&gt;
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.  &lt;br /&gt;
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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.&lt;br /&gt;
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===Cortical Areas===&lt;br /&gt;
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[[Image:Primary gustatory cortex.png|thumb|Primary gustatory cortex]]&lt;br /&gt;
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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)&amp;lt;ref name=PMID22245354&amp;gt;&amp;lt;pubmed&amp;gt;22245354&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;, with the secondary taste cortex in the caudolateral orbitofrontal cortex.&amp;lt;ref name=PMID21305668&amp;gt;&amp;lt;pubmed&amp;gt;21305668&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;  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.&amp;lt;ref name=PMID21885776&amp;gt;&amp;lt;pubmed&amp;gt;21885776&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; These findings lend weight to the idea that there is only one receptor for each taste quality.&lt;br /&gt;
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&lt;br /&gt;
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).&amp;lt;ref name=PMID21885776/&amp;gt; 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&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
==Current Research==&lt;br /&gt;
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. &lt;br /&gt;
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.&lt;br /&gt;
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[[File:Mousetounge histologicalstain.jpg|Left|thumb|200px|Image shows histological stains of a mice tongue showing dysplasia]]&lt;br /&gt;
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'''Synergistic relationships of Six Genes '''&lt;br /&gt;
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In an animal study using mice by Suzuki Y, Ikeda K, Kawakami K.(2011)  Firstly nominating &amp;quot;[[#Glossary |'''Six Genes''']]&amp;quot; as a major component in [[#Glossary |'''gustatory ''']] development, stating that deficiencies in certain Six genes (specifically Six1 &amp;amp; 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 &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;21978088&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
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[[File:Highpowered_microscope.jpg|Left|thumb|200px|Image of a high powered microscope]]&lt;br /&gt;
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'''Neural Crest responsibilities '''&lt;br /&gt;
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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.&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;22659543&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
[[File:Developing_tongue_histology_001.jpg|Left|thumb|200px|HIstological stain of a developing rat tongue]]&lt;br /&gt;
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'''Augmentation of Endoderm'''&lt;br /&gt;
&lt;br /&gt;
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 &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;22581563&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
&lt;br /&gt;
'''Changes in Taste Cells over time'''&lt;br /&gt;
&lt;br /&gt;
Research by &lt;br /&gt;
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.  &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;22643728&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
'''Shh key component of taste bud proginators'''&lt;br /&gt;
&lt;br /&gt;
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.&lt;br /&gt;
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 &amp;quot;Axiocam CCD camera and Axioplan fluorescence microscope with Axiovision software&amp;quot; a study by Harlow, Yang, Williams, Barlow (2011)&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;PMC2674259&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
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&lt;br /&gt;
'''WNT family exhibit various roles''' [[File:Abnormal of tongue.jpg|thumb|200px|Image shows an example of tongue abnormalities, this is called &amp;quot;double tongue&amp;quot; each side has independent movement!]]&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
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. &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;PMC2768563&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
&lt;br /&gt;
[http://www.surgicalneurologyint.com/article.asp?issn=2152-7806;year=2012;volume=3;issue=1;spage=23;epage=23;aulast=Manjila]&lt;br /&gt;
&lt;br /&gt;
==Glossary==&lt;br /&gt;
&lt;br /&gt;
* '''Circumvallate papillae''' - &lt;br /&gt;
&lt;br /&gt;
* '''Ectoderm'''- outer germ layer of embryo&lt;br /&gt;
&lt;br /&gt;
* '''Endoderm''' - inner germ layer of embryo&lt;br /&gt;
&lt;br /&gt;
* '''Epithelium''' - basic animal tissue that is composed of tightly packed cells, usually covering the outer portion of organs&lt;br /&gt;
&lt;br /&gt;
* '''Exocystosis''' - movement of contents out of cell&lt;br /&gt;
&lt;br /&gt;
* '''Filiform papillae''' - &lt;br /&gt;
&lt;br /&gt;
* '''Foliate papillae''' - &lt;br /&gt;
&lt;br /&gt;
* '''Fungiform papillae''' - &lt;br /&gt;
&lt;br /&gt;
* '''Ganglia''' - the accumulation of a nerve cell body&lt;br /&gt;
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* '''Growth factor''' - a substance that stimulates the growth of cells&lt;br /&gt;
&lt;br /&gt;
* '''Gustatory''' - anything that relates to the taste sense&lt;br /&gt;
&lt;br /&gt;
* '''Hydrolysis''' - breakdown of a chemical when it reacts with water&lt;br /&gt;
&lt;br /&gt;
* '''Mesoderm''' - middle germ layer of embryo&lt;br /&gt;
&lt;br /&gt;
* '''Mesenchyme''' - multipotential cells&lt;br /&gt;
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* '''Neural crest''' - a part of the ectoderm found on both sides of the neural tube&lt;br /&gt;
&lt;br /&gt;
* '''Neuron''' - most simplistic unit of the nervous system&lt;br /&gt;
&lt;br /&gt;
* '''Neurotransmitter''' - chemicals which allow the passing of signals from neuron to neuron via connecting part (synapse) &lt;br /&gt;
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* '''Papillae''' - small rough surface projection&lt;br /&gt;
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* '''Six genes''' - a family of genes&lt;br /&gt;
&lt;br /&gt;
* '''Sonic hedgehog (Shh)''' - signalling protein involved in normal development&lt;br /&gt;
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* '''Sulcus terminalis''' - describes a physical transition point separating the anterior 2/3 of the tongue from the posterior 1/3&lt;br /&gt;
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* '''Tamoxifen''' - hormonal altering drug&lt;br /&gt;
&lt;br /&gt;
* '''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).&lt;br /&gt;
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* '''Type II taste cells''' - Receptor cells acting as primary detectors of sweet, bitter or umami taste.&lt;br /&gt;
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* '''Type III taste cells''' - Presynaptic cells that respond to sweet, salty, sour, bitter and umami compounds.&lt;br /&gt;
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== References ==&lt;br /&gt;
&amp;lt;references/&amp;gt;&lt;br /&gt;
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==External Links==&lt;br /&gt;
{{External Links}}&lt;br /&gt;
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http://embryology.med.unsw.edu.au/embryology/index.php?title=2012_Group_Project_4&lt;br /&gt;
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http://www.webmd.com/oral-health/picture-of-the-tongue&lt;br /&gt;
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http://www.tutorvista.com/content/biology/biology-iv/nervous-coordination/tongue-structure.php#parts-of-tongue&lt;br /&gt;
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http://www.cf.ac.uk/biosi/staffinfo/jacob/teaching/sensory/taste.html&lt;br /&gt;
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--[[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.&lt;br /&gt;
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{{2012Projects}}&lt;/div&gt;</summary>
		<author><name>Z3330795</name></author>
	</entry>
	<entry>
		<id>https://embryology.med.unsw.edu.au/embryology/index.php?title=2012_Group_Project_3&amp;diff=104613</id>
		<title>2012 Group Project 3</title>
		<link rel="alternate" type="text/html" href="https://embryology.med.unsw.edu.au/embryology/index.php?title=2012_Group_Project_3&amp;diff=104613"/>
		<updated>2012-10-02T01:54:52Z</updated>

		<summary type="html">&lt;p&gt;Z3330795: /* Adult Tongue and Taste Buds – Structure and Function */&lt;/p&gt;
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&lt;div&gt;=Taste Development=&lt;br /&gt;
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adult structure and function&lt;br /&gt;
This section describes the anatomy and function of the tongue with a focus on the taste function. There are various visual stimuli to allow better understanding of the complex physiological processes involved.&lt;br /&gt;
&lt;br /&gt;
current research&lt;br /&gt;
Current research presented involves the use of animal models and the majority using mice as the specimen. The main focus of current research is to understand the patterns of development and what is contributed by various embryonic components to allow more insight into the complex interactions that compose embryonic taste development.&lt;br /&gt;
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==Adult Tongue and Taste Buds – Structure and Function==&lt;br /&gt;
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'''Structure'''&lt;br /&gt;
&lt;br /&gt;
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.  &lt;br /&gt;
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''''The image below is a simplistic diagram of the surface of the tongue showing the locations of the different papillae and other important features'''&lt;br /&gt;
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{|&lt;br /&gt;
| [[Image:Drawing of Tongue.png|centre|500px]]&lt;br /&gt;
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'''Papillae'''&lt;br /&gt;
[[File:Papillae.jpg|Left|thumb|200px|Close up of Human Tongue Papillae]]&lt;br /&gt;
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There are 4 types of papillae on the tongue.&lt;br /&gt;
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. &lt;br /&gt;
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[[File:Fungiformpapillae.jpg|Left|thumb|200px|Fungiform Papillae]]&lt;br /&gt;
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[[File:Circumvallatepapillae.jpg |Left|thumb|200px|Circumvallate Papillae]]&lt;br /&gt;
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[[File:Filiformpapillae.jpg|Left|thumb|200px|Foliate Papillae]]&lt;br /&gt;
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'''Function'''&lt;br /&gt;
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The Tongue has muscular and sensory functions, muscular functions include swallowing and speech where as sensory function involves taste. This section will focus on the sensory functions of the tongue.&lt;br /&gt;
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.&lt;br /&gt;
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'''The image below is a simplistic hand-drawn cross section of a taste bud unit (not to scale)'''&lt;br /&gt;
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[[File:Taste_bud_1.jpg|x400px|alt=Cross section of a taste bud unit|centre|Cross section of a taste bud unit]]&lt;br /&gt;
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'''Link Between Taste and Smell'''&lt;br /&gt;
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The pathways between smell and taste are very similar. Pathways both involve the conversion of a chemical stimulus into a nerve impulse for interpretation by the brain. People often mistake taste for flavour, flavour involves an interaction of taste, smell, texture and temperature.&lt;br /&gt;
When there is food in our mouth there is signalling between these senses giving a whole package interpretation instead of just taste itself, the communication of these senses allows an indvidual a more specific perception of what they are eating.&lt;br /&gt;
[http://serendip.brynmawr.edu/exchange/node/1575]&lt;br /&gt;
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[[File:Taste_pathway.jpg|right|thumb|200px|Simplistic Pathway of Taste]]&lt;br /&gt;
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[[File:Human smelling.jpg|500px|centre]]&lt;br /&gt;
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==History of Discoveries==&lt;br /&gt;
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{| cellpadding=5 style=&amp;quot;border:1px solid #BBB&amp;quot;&lt;br /&gt;
|- bgcolor=&amp;quot;#faecc8&amp;quot;&lt;br /&gt;
|''' Date'''|| '''Significant Discovery'''&lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#faf6ed&amp;quot;&lt;br /&gt;
|'''350BC'''&lt;br /&gt;
|| Aristotle writes about the basic tastes, sweet and bitter. He also notes that it can be modified by salty and acidic. &amp;lt;ref name=&amp;quot;PMID22717400&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;22717400&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#faecc8&amp;quot;&lt;br /&gt;
|'''1901'''&lt;br /&gt;
|| D. Hanig publishes a paper describing taste sensitivity in different regions of the tongue. &lt;br /&gt;
''Interesting fact:'' The modern concept of a 'tongue map' is a misinterpretation of this study. &amp;lt;ref name=&amp;quot;PMID22717400&amp;quot;/&amp;gt;&lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#faf6ed&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''1908'''&lt;br /&gt;
|Kikunae Ikeda, a professor of the Tokyo Imperial University, discovered and identified the fifth basic taste: umami (savouriness), made palatable by glutamate.  &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;12438213&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
[http://chemse.oxfordjournals.org/content/27/9/847.long New Seasonings]&lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#faecc8&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''1931-32'''&lt;br /&gt;
| A chemist named Arthur Fox and his college noted that they had different sensitivities to the bitter tasting Phenylthiocarbamide (PTC).&amp;lt;ref&amp;gt;Blakeslee AF, Fox AL. Our different taste worlds. J Hered. 1932;23:97–107.&amp;lt;/ref&amp;gt; Geneticists later confirm these findings, and discover that non-tasting is a recessive genetic trait. &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;17782493&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/pubmed/17782493 Inherited taste deficiency] &lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#faf6ed&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''1965'''&lt;br /&gt;
|Farbman's study of the developing taste but in rat fungiform papilla was significant in increasing our understanding of taste bud development. &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;14300090&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
[http://www.sciencedirect.com/science/article/pii/0012160665900400 Electron microscope study of the developing taste bud in rat fungiform papilla.]&lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#faecc8&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''1992'''&lt;br /&gt;
|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. &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;1608467 &amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
[http://www.nature.com/nature/journal/v357/n6379/abs/357563a0.html Gustducin is a taste-cell-specific G protein closely related to the transducins]&lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#faf6ed&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''1995'''&lt;br /&gt;
|Barlow et al. experimented with Axolotl salamanders and concluded that taste buds from this species arise exclusively from epithelial tissue, &amp;quot;oropharyngeal [[#Glossary |'''epithelium''']]&amp;quot;. &amp;lt;ref name=&amp;quot;PMID17826760&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;17826760&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/pubmed/17826760 Embryonic origin of gustatory cranial sensory neurons] &lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#faecc8&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''1996'''&lt;br /&gt;
| 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 &amp;quot;at least dual function of embryonic/fetal taste buds&amp;quot;, including non-gustatory, paracrine functions prior to the 14th week and gustatory after the 14th week. &amp;lt;ref name=&amp;quot;PMID8955790&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;8955790&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/pubmed/8955790 Embryonic and early fetal development of human taste buds: a transmission electron microscopical study]&lt;br /&gt;
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|- bgcolor=&amp;quot;#faf6ed&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''2000'''&lt;br /&gt;
|Chandrashekar, J. et al. discover the first taste sonsors, the T2R bitter taste receptors. &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;10761935&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
[http://www.sciencedirect.com/science/article/pii/S0092867400807060 T2Rs Function as Bitter Taste Receptors]&lt;br /&gt;
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|- bgcolor=&amp;quot;#faecc8&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''2001'''&lt;br /&gt;
|Nelson, G. et al. discover the sweet receptor: a combination of T1R2 and T1R3. &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;11509186&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/pubmed/11509186?dopt=Abstract&amp;amp;holding=npg Mammalian sweet taste receptors.]&lt;br /&gt;
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|- bgcolor=&amp;quot;#faf6ed&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''2002'''&lt;br /&gt;
|Nelson G. et al. discover the amino acid (umami) taste receptor: a combination of T1R1 and T1R3 identified.  &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;11894099&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/pubmed/11894099?dopt=Abstract&amp;amp;holding=npg An amino-acid taste receptor]&lt;br /&gt;
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|- bgcolor=&amp;quot;#faecc8&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''2005'''&lt;br /&gt;
|Dyer, J. et al. discover sweet taste receptors in the GI tract. &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;17855558&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1986582/ Sweet taste signaling in the gut]&lt;br /&gt;
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|- bgcolor=&amp;quot;#faf6ed&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''2006'''&lt;br /&gt;
|Huang, A. L et al. discover cells for sour taste, identified by PKD2L1 (a polycystic kidney disease-like ion channel). &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;16929298&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1571047/ The Cells and Logic for Mammalian Sour Taste detection]&lt;br /&gt;
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|- bgcolor=&amp;quot;#faecc8&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''2007'''&lt;br /&gt;
|Harlow DE, Barlow LA of the University of Colorado Denver Health Sciences Center provide evidence of the &amp;quot;embryonic origin of gustatory cranial sensory neurons&amp;quot;. &amp;lt;ref name=&amp;quot;PMID17826760&amp;quot;/&amp;gt;&lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/pubmed/17826760 Embryonic origin of gustatory cranial sensory neurons.]&lt;br /&gt;
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|- bgcolor=&amp;quot;#faf6ed&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''2009'''&lt;br /&gt;
|A study by Hevezi P et al, presents &amp;quot;the first comprehensive characterization of gene expression in primate taste buds&amp;quot;, as opposed to previous studies which focused on rodents. &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;19636377&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/pubmed/19636377 Genome-wide analysis of gene expression in primate taste buds reveals links to diverse processes]&lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#faecc8&amp;quot;&lt;br /&gt;
|style=white-space:nowrap|'''2010'''&lt;br /&gt;
|Chandrashekar, J. et al. identify epithelial sodium channel (ENaC) as the sodium-salt taste receptor. &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;20107438&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/pubmed/20107438?dopt=Abstract&amp;amp;holding=npg The cells and peripheral representation of sodium taste in mice]&lt;br /&gt;
|}&lt;br /&gt;
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&lt;br /&gt;
== Human Weekly Development - Two Prominent Studies ==&lt;br /&gt;
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. &lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
The findings of these two studies are summarized in the table below. The figures provided relate to the images on their respective research papers.&lt;br /&gt;
&lt;br /&gt;
# [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] &lt;br /&gt;
# [http://chemse.oxfordjournals.org/content/22/6/601.long Scanning electron microscopical studies of developing gustatory papillae in humans, 1997]  &lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
===Timeline of Developmental Processes of Human Taste Buds===&lt;br /&gt;
{| cellpadding=5 style=&amp;quot;border:1px solid #BBB&amp;quot;&lt;br /&gt;
|- bgcolor=&amp;quot;#89CFF0&amp;quot;&lt;br /&gt;
|'''Postovulatory Week'''||'''Description'''&lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#BCD4E6&amp;quot;&lt;br /&gt;
|'''Week 6''' ||&lt;br /&gt;
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. &amp;lt;ref name=&amp;quot;PMID9455607&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;9455607&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#89CFF0&amp;quot;&lt;br /&gt;
| '''Weeks 6 to 7'''|| &lt;br /&gt;
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. &amp;lt;ref name=PMID8955790/&amp;gt;&lt;br /&gt;
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|- bgcolor=&amp;quot;#BCD4E6&amp;quot;&lt;br /&gt;
| '''Week 7 '''||&lt;br /&gt;
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.  &amp;lt;ref name=PMID9455607/&amp;gt; &lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#89CFF0&amp;quot;&lt;br /&gt;
| ''' Week 8  ''' ||&lt;br /&gt;
* The taste bud primordium are still differentiated, elongated epithelial cells, resting on a slightly developed core of young dermal papilla.&lt;br /&gt;
* 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. &lt;br /&gt;
* Ciliated cells also appear around the 8th week, however the significance of these cells which are scattered randomly across the lingual surface remains unclear. &amp;lt;ref name=PMID8955790/&amp;gt; &lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#BCD4E6&amp;quot;&lt;br /&gt;
|'''  Week 9''' ||&lt;br /&gt;
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). &amp;lt;ref name=PMID9455607/&amp;gt;&lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#89CFF0&amp;quot;&lt;br /&gt;
|'''  Weeks 10-11''' ||&lt;br /&gt;
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). &amp;lt;ref name=PMID8955790/&amp;gt; &lt;br /&gt;
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|- bgcolor=&amp;quot;#BCD4E6&amp;quot;&lt;br /&gt;
|''' Week 12 ''' ||&lt;br /&gt;
Taste bud cells are more clearly differentiated into epithelial cell types II and III. &amp;lt;ref name=PMID8955790/&amp;gt; &lt;br /&gt;
&lt;br /&gt;
|- bgcolor=&amp;quot;#89CFF0&amp;quot;&lt;br /&gt;
|''' Weeks 12-13  ''' ||&lt;br /&gt;
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). &amp;lt;ref name=PMID8955790/&amp;gt; &lt;br /&gt;
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|- bgcolor=&amp;quot;#BCD4E6&amp;quot;&lt;br /&gt;
|''' Weeks 14 -15 ''' ||&lt;br /&gt;
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. &amp;lt;ref name=PMID8955790/&amp;gt; &lt;br /&gt;
|}&lt;br /&gt;
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==Abnormalities==&lt;br /&gt;
&lt;br /&gt;
It should be mentioned that gustatory abnormalities have not been widely researched. Most research conducted in this field has been conducted through animal testing on mice and this is the basis of information provided below. &lt;br /&gt;
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===Knocking out P2X Receptors===&lt;br /&gt;
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[[File:Image of taste being evoked by visualising ATP release.jpeg|Left|thumb|200px|Evoking taste - ATP release in tongue]]&lt;br /&gt;
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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. &lt;br /&gt;
&lt;br /&gt;
It should be noted that the taste buds in DKO are functional, but are not stimulated by the administration of tastants. &lt;br /&gt;
&lt;br /&gt;
The transmission of release of ATP is secretion through gap junction hemichannels (pannexin 1 gap junction).&lt;br /&gt;
&lt;br /&gt;
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.&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;21940456&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
===FGF signalling and genes===&lt;br /&gt;
&lt;br /&gt;
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.&lt;br /&gt;
&lt;br /&gt;
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 (&amp;quot;Fgf10&amp;quot;) 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 &amp;quot;Fgf10&amp;quot; to limit the size of the CVP progenitor placode. Exclusive expression of ''Fgf10'' in the [[#Glossary |'''mesenchyme''']] is necessary for the formation of CVP. &lt;br /&gt;
&lt;br /&gt;
'''This image shows the CVP stained with H&amp;amp;E and scanned by Scanning Electron Microscope (SEM)'''&lt;br /&gt;
[[File:CVP of WT(top) and DKO(bottom) mice with H&amp;amp;E and SEM.png]]&lt;br /&gt;
&lt;br /&gt;
'''This image shows the location of the CVP and the increased number in DKO mice by SEM'''&lt;br /&gt;
[[File:Mouse circumvallate papilla 01.jpg|300px]]&lt;br /&gt;
&lt;br /&gt;
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).&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
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).&lt;br /&gt;
&lt;br /&gt;
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''&amp;amp; ''Spry 1&amp;amp;2''work antagonistically through receptor tyrosine kinase (RTK)signalling.&lt;br /&gt;
&lt;br /&gt;
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.&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;21655085&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
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==Gustatory System==&lt;br /&gt;
&lt;br /&gt;
[[Image:Taste qualities.gif|thumb|The five basic tastes]]&lt;br /&gt;
&lt;br /&gt;
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.&lt;br /&gt;
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&lt;br /&gt;
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.&amp;lt;ref name=PMID20696704&amp;gt;&amp;lt;pubmed&amp;gt;20696704&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
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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 &amp;lt;ref name=PMID20696704/&amp;gt; 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.&lt;br /&gt;
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===Cell Biology===&lt;br /&gt;
&lt;br /&gt;
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.&lt;br /&gt;
&lt;br /&gt;
====Type II receptors====&lt;br /&gt;
&lt;br /&gt;
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:&lt;br /&gt;
&lt;br /&gt;
# Stimulates gustatory nerve afferents which project to gustatory nuclei  in the spinal cord&lt;br /&gt;
# Excites Type III presynaptic nerve fibers to release serotonin. &lt;br /&gt;
# Has a positive feedback effect on type II receptor cells, increasing the level of ATP production.&lt;br /&gt;
&lt;br /&gt;
        &lt;br /&gt;
&lt;br /&gt;
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.&lt;br /&gt;
&lt;br /&gt;
==Taste Map==&lt;br /&gt;
[[Image:Taste map.png|thumb|left|250px|Obsolete idea of the tongue map]]&lt;br /&gt;
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.&lt;br /&gt;
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===Neural Pathways===&lt;br /&gt;
&lt;br /&gt;
'''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''. &lt;br /&gt;
&lt;br /&gt;
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:  &lt;br /&gt;
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* ''Facial nerve n''. -  carries taste information from the anterior 2/3 of the tongue.&lt;br /&gt;
* ''Hypoglossal n.'' - carries taste information from the posterior 1/3 of the tongue.&lt;br /&gt;
* ''Vagus n''. - carries taste information from the palate&lt;br /&gt;
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'''Second order neurons''' - From the NTS second order neurons carry taste information to the Ventral posteromedial (VPM) nucleus in the thalamus.&amp;lt;ref name=PMID21885776/&amp;gt;&lt;br /&gt;
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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.  &lt;br /&gt;
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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.&lt;br /&gt;
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===Cortical Areas===&lt;br /&gt;
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[[Image:Primary gustatory cortex.png|thumb|Primary gustatory cortex]]&lt;br /&gt;
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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)&amp;lt;ref name=PMID22245354&amp;gt;&amp;lt;pubmed&amp;gt;22245354&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;, with the secondary taste cortex in the caudolateral orbitofrontal cortex.&amp;lt;ref name=PMID21305668&amp;gt;&amp;lt;pubmed&amp;gt;21305668&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;  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.&amp;lt;ref name=PMID21885776&amp;gt;&amp;lt;pubmed&amp;gt;21885776&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; These findings lend weight to the idea that there is only one receptor for each taste quality.&lt;br /&gt;
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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).&amp;lt;ref name=PMID21885776/&amp;gt; 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&lt;br /&gt;
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==Current Research==&lt;br /&gt;
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. &lt;br /&gt;
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.&lt;br /&gt;
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[[File:Mousetounge histologicalstain.jpg|Left|thumb|200px|Image shows histological stains of a mice tongue showing dysplasia]]&lt;br /&gt;
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'''Synergistic relationships of Six Genes '''&lt;br /&gt;
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In an animal study using mice by Suzuki Y, Ikeda K, Kawakami K.(2011)  Firstly nominating &amp;quot;[[#Glossary |'''Six Genes''']]&amp;quot; as a major component in [[#Glossary |'''gustatory ''']] development, stating that deficiencies in certain Six genes (specifically Six1 &amp;amp; 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 &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;21978088&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
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[[File:Highpowered_microscope.jpg|Left|thumb|200px|Image of a high powered microscope]]&lt;br /&gt;
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'''Neural Crest responsibilities '''&lt;br /&gt;
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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.&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;22659543&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
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[[File:Developing_tongue_histology_001.jpg|Left|thumb|200px|HIstological stain of a developing rat tongue]]&lt;br /&gt;
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'''Augmentation of Endoderm'''&lt;br /&gt;
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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 &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;22581563&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
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'''Changes in Taste Cells over time'''&lt;br /&gt;
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Research by &lt;br /&gt;
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.  &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;22643728&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
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'''Shh key component of taste bud proginators'''&lt;br /&gt;
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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.&lt;br /&gt;
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 &amp;quot;Axiocam CCD camera and Axioplan fluorescence microscope with Axiovision software&amp;quot; a study by Harlow, Yang, Williams, Barlow (2011)&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;PMC2674259&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
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'''WNT family exhibit various roles''' [[File:Abnormal of tongue.jpg|thumb|200px|Image shows an example of tongue abnormalities, this is called &amp;quot;double tongue&amp;quot; each side has independent movement!]]&lt;br /&gt;
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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. &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;PMC2768563&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
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[http://www.surgicalneurologyint.com/article.asp?issn=2152-7806;year=2012;volume=3;issue=1;spage=23;epage=23;aulast=Manjila]&lt;br /&gt;
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==Glossary==&lt;br /&gt;
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* '''Circumvallate papillae''' - &lt;br /&gt;
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* '''Ectoderm'''- outer germ layer of embryo&lt;br /&gt;
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* '''Endoderm''' - inner germ layer of embryo&lt;br /&gt;
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* '''Epithelium''' - basic animal tissue that is composed of tightly packed cells, usually covering the outer portion of organs&lt;br /&gt;
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* '''Exocystosis''' - movement of contents out of cell&lt;br /&gt;
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* '''Filiform papillae''' - &lt;br /&gt;
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* '''Foliate papillae''' - &lt;br /&gt;
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* '''Fungiform papillae''' - &lt;br /&gt;
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* '''Ganglia''' - the accumulation of a nerve cell body&lt;br /&gt;
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* '''Growth factor''' - a substance that stimulates the growth of cells&lt;br /&gt;
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* '''Gustatory''' - anything that relates to the taste sense&lt;br /&gt;
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* '''Hydrolysis''' - breakdown of a chemical when it reacts with water&lt;br /&gt;
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* '''Mesoderm''' - middle germ layer of embryo&lt;br /&gt;
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* '''Mesenchyme''' - multipotential cells&lt;br /&gt;
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* '''Neural crest''' - a part of the ectoderm found on both sides of the neural tube&lt;br /&gt;
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* '''Neuron''' - most simplistic unit of the nervous system&lt;br /&gt;
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* '''Neurotransmitter''' - chemicals which allow the passing of signals from neuron to neuron via connecting part (synapse) &lt;br /&gt;
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* '''Papillae''' - small rough surface projection&lt;br /&gt;
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* '''Six genes''' - a family of genes&lt;br /&gt;
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* '''Sonic hedgehog (Shh)''' - signalling protein involved in normal development&lt;br /&gt;
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* '''Sulcus terminalis''' - describes a physical transition point separating the anterior 2/3 of the tongue from the posterior 1/3&lt;br /&gt;
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* '''Tamoxifen''' - hormonal altering drug&lt;br /&gt;
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* '''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).&lt;br /&gt;
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* '''Type II taste cells''' - Receptor cells acting as primary detectors of sweet, bitter or umami taste.&lt;br /&gt;
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* '''Type III taste cells''' - Presynaptic cells that respond to sweet, salty, sour, bitter and umami compounds.&lt;br /&gt;
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== References ==&lt;br /&gt;
&amp;lt;references/&amp;gt;&lt;br /&gt;
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==External Links==&lt;br /&gt;
{{External Links}}&lt;br /&gt;
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http://www.webmd.com/oral-health/picture-of-the-tongue&lt;br /&gt;
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http://www.tutorvista.com/content/biology/biology-iv/nervous-coordination/tongue-structure.php#parts-of-tongue&lt;br /&gt;
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http://www.cf.ac.uk/biosi/staffinfo/jacob/teaching/sensory/taste.html&lt;br /&gt;
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--[[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.&lt;br /&gt;
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{{2012Projects}}&lt;/div&gt;</summary>
		<author><name>Z3330795</name></author>
	</entry>
	<entry>
		<id>https://embryology.med.unsw.edu.au/embryology/index.php?title=File:Papillae.jpg&amp;diff=104610</id>
		<title>File:Papillae.jpg</title>
		<link rel="alternate" type="text/html" href="https://embryology.med.unsw.edu.au/embryology/index.php?title=File:Papillae.jpg&amp;diff=104610"/>
		<updated>2012-10-02T01:50:23Z</updated>

		<summary type="html">&lt;p&gt;Z3330795: &lt;/p&gt;
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&lt;div&gt;{Student image||2012}&lt;br /&gt;
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 Close up picture of human tongue. showing papillae(little bumps).&lt;br /&gt;
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This picture is for the purpose to appreciate a macroscopic perspective of the papillae. &lt;br /&gt;
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http://shiftingpixel.com/2007/01/25/tongue/&lt;br /&gt;
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&lt;br /&gt;
This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 2.5 License. Attribution requirements for my work&lt;br /&gt;
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to Share — to copy, distribute and transmit the work&lt;br /&gt;
to Remix — to adapt the work&lt;br /&gt;
Under the following conditions:&lt;br /&gt;
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Attribution — You must attribute the work in the manner specified by the author or licensor (but not in any way that suggests that they endorse you or your use of the work).&lt;br /&gt;
Noncommercial — You may not use this work for commercial purposes.&lt;br /&gt;
Share Alike — If you alter, transform, or build upon this work, you may distribute the resulting work only under the same or similar license to this one.&lt;/div&gt;</summary>
		<author><name>Z3330795</name></author>
	</entry>
	<entry>
		<id>https://embryology.med.unsw.edu.au/embryology/index.php?title=File:Taste_pathway.jpg&amp;diff=104608</id>
		<title>File:Taste pathway.jpg</title>
		<link rel="alternate" type="text/html" href="https://embryology.med.unsw.edu.au/embryology/index.php?title=File:Taste_pathway.jpg&amp;diff=104608"/>
		<updated>2012-10-02T01:49:46Z</updated>

		<summary type="html">&lt;p&gt;Z3330795: &lt;/p&gt;
&lt;hr /&gt;
&lt;div&gt;{Student image||2012}&lt;br /&gt;
&lt;br /&gt;
This is an extremely simplistic break down of the pathway of taste, involving the functional steps, more so an overview of the 4 basic steps involved.&lt;br /&gt;
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1. The chemicals (food) are absorbed though the taste pores in the oral cavity.&lt;br /&gt;
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2. the taste cells within the taste buds receive these chemical stimulus and convert into a nerve impulse.&lt;br /&gt;
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3. this nerve impulse travels from the oral cavity cranial nerves towards the brain.&lt;br /&gt;
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4 the brain receives impulse for interpretation of taste.&lt;br /&gt;
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This illustration by Jared Berndt UNSW student who gives permission to anyone to reuse.&lt;/div&gt;</summary>
		<author><name>Z3330795</name></author>
	</entry>
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