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	<subtitle>User contributions</subtitle>
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		<id>https://embryology.med.unsw.edu.au/embryology/index.php?title=User:Z5020466&amp;diff=256963</id>
		<title>User:Z5020466</title>
		<link rel="alternate" type="text/html" href="https://embryology.med.unsw.edu.au/embryology/index.php?title=User:Z5020466&amp;diff=256963"/>
		<updated>2016-11-10T05:53:55Z</updated>

		<summary type="html">&lt;p&gt;Z5020466: /* Lab 9: Peer Assessment */&lt;/p&gt;
&lt;hr /&gt;
&lt;div&gt;{{ANAT2341Student2016}}&lt;br /&gt;
&lt;br /&gt;
==Lab Attendance==&lt;br /&gt;
[[USER:Z5020466|Z5020466]] ([[User talk:Z5020466|talk]]) 14:34, 5 August 2016 (AEST)&lt;br /&gt;
&lt;br /&gt;
[[User:Z5020466|Z5020466]] ([[User talk:Z5020466|talk]]) 14:42, 12 August 2016 (AEST)&lt;br /&gt;
&lt;br /&gt;
[[User:Z5020466|Z5020466]] ([[User talk:Z5020466|talk]]) 13:46, 26 August 2016 (AEST)&lt;br /&gt;
&lt;br /&gt;
[[User:Z5020466|Z5020466]] ([[User talk:Z5020466|talk]]) 14:18, 2 September 2016 (AEST)&lt;br /&gt;
&lt;br /&gt;
[[User:Z5020466|Z5020466]] ([[User talk:Z5020466|talk]]) 13:23, 16 September 2016 (AEST)&lt;br /&gt;
&lt;br /&gt;
[[User:Z5020466|Z5020466]] ([[User talk:Z5020466|talk]]) 13:53, 7 October 2016 (AEDT)&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
===Belbin Team Roles===&lt;br /&gt;
If I’m completely honest, I think my role in group work is generally the “Co-ordinator”. I’m not too sure about my ability to step back from the ‘nitty gritty’ details and see the bigger picture. But rather I generally like to take on leadership roles and assign people tasks. That way I can do things how I like to and place people in roles that I think they would be suited to. But not only that I think to be a good leader you have to be a good worker. So I try to lead by example and not really depend on others too much so that if something has messed up, I have no one to blame but myself. This part about Co-ordinators made me chuckle. “Sometimes perceived to be manipulative and will tend to delegate all work” which is unfortunately a little true. But at the same time I’ve been open to working an equal amount as others previously as well.&lt;br /&gt;
&lt;br /&gt;
===Lecture 1: Fertilisation===&lt;br /&gt;
In my previous years in attending university I’ve completed many courses which have gone through the fertilization process such as: Evolutionary Biological Sciences, Physiology, Histology and Pathology. From having done these courses already, there were parts which were familiar to me and that I have understood before in the past. However, I still was amazed by the new refreshing things I have not yet encounter which I did during this lecture. Such as polar bodies and their role in fertilization in disposing of extra DNA. It also clarified a point which I was previously confused about on whether or not polar bodies were gametes or not. Cementing all this information and weaving it in with new learnt information has really been a beneficial experience for me, in that I’m building up on topics I thoroughly enjoy.&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
===External Link===&lt;br /&gt;
[http://www.smh.com.au/ SMH]&lt;br /&gt;
&lt;br /&gt;
===Internal Link===&lt;br /&gt;
[[ANAT2341 Lab 1]]&lt;br /&gt;
&lt;br /&gt;
[[ANAT2341 Lab 1|Fertilization Lab]]&lt;br /&gt;
 &lt;br /&gt;
[[Student Page]]&lt;br /&gt;
&lt;br /&gt;
==Referencing==&lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/sites/entrez?db=pubmed&amp;amp;cmd=search&amp;amp;term=fertilization fertilization]&lt;br /&gt;
&lt;br /&gt;
PMID 27486480&lt;br /&gt;
&lt;br /&gt;
==Lab Assessment==&lt;br /&gt;
&lt;br /&gt;
===Assessment 1===&lt;br /&gt;
[[Media:Example.ogg]]&lt;br /&gt;
&amp;lt;pubmed&amp;gt;PMC3528851&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&lt;br /&gt;
The research article called &amp;quot; Tet1 controls meiosis by regulating meiotic gene expression&amp;quot; by Yamaguchi et al. (2012) aims to determine the role of ten-eleven translocation methylcytosine dioxygenase 1 (TET1) which is a member of the TET family of enzymes, in regulating meiotic gene expression and thus meiosis in mice. This study was highly useful since little is known about how the expression of meiotic genes is regulated and how their expression contributes to normal meiosis. &lt;br /&gt;
In the study they performed a whole-genome bisulphite sequencing (WGBS) analysis using an ultra-low input so that they would be able to see how Tet1 is used in the activation of meiotic genes. &lt;br /&gt;
&lt;br /&gt;
Results showed that a decreased functioning of Tet1 caused an increase in the unpaired synaptonemal complex at zygotene-stage oocyte, suggesting a synapsis-formation defect. The meiotic defects seen from Tet1 loss of function included: formation of univalent chromosome, but also homologous recombination and DNA double-strand breaks (DSBs) repair defects. These in turn caused defective meiotic prophase which caused decreased amount of oocytes and in turn reduced litter size and lowering in fertility. The study done was pivotal as it built upon past studies which have already established that DNA methylation levels of certain meiotic genes are lowered with genomic reprogramming.&lt;br /&gt;
&lt;br /&gt;
{| width=95%&lt;br /&gt;
|-bgcolor=&amp;quot;FAF5FF&amp;quot;&lt;br /&gt;
| [mailto:m.hill@unsw.edu.au Mark Hill] 18 August 2016 - You have added the citation correctly and written a good brief summary of the article findings. &lt;br /&gt;
TET1 is part of the family of methylcytosine dioxygenases that involved in cytosine demethylation and gene activation, interesting that it has a meiotic-specific role.&lt;br /&gt;
&lt;br /&gt;
| width=100px| Assessment 5/5&lt;br /&gt;
|}&lt;br /&gt;
&lt;br /&gt;
==Lab 9: Peer Assessment==&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
GROUP 1&lt;br /&gt;
Through reading through and analysing group 1’s project it is starkly clear they have managed to relay some excellent information and present it in quite an easily digestible manner. That said though, there are some things which they could improve upon as well. I shall be dissecting what they have done well and what they could improve upon. The information they have regarding signalling pathways of the Wnt receptor in embryonic development is complex and intricate so they have done well by creating subheadings to more easily navigate the vastness of information displayed. This relates directly to criteria 2 in the “Group Assessment Criteria”. However, as seen in the criteria there are also other techniques such as diagrams, tables, graphs which could be employed to further add upon the excellence of this project. Moving onto criteria 3 we can see that there has been some referencing and citing, however it was hard to find and not clearly written. The part that was well referenced was under the “Non-Canonical Pathway – Caroline”. It’s starkly clear to me that these group members have truly gone beyond the formal teaching activities, as described in criteria 5, and have done some significant research exploring the abnormalities associated with the Wnt pathway be describing the interruptions in the pathway and its relation to cancer. &lt;br /&gt;
&lt;br /&gt;
GROUP 2&lt;br /&gt;
Moving the the 2nd group I can see that their topic is mainly about the Notch receptor. They seem to elucidate upon different aspects of the receptor, like it’s role in embryonic development and molecular pathways. The aspect done especially well in this group is the vastness and breadth of their information. They explore numerous aspects of the Notch receptor, including the abnormalities that can arise in development. By showing such a vastness and clarity in their research they successfully achieve criteria 1. Furthermore, Group 2 has a phenomenal amount of tables, diagrams and figures describing canonical Notch signalling and the history of the discoveries for these receptors. This qualifies criteria 2 very well as they have included all these as well as headings and sub headings in a succinct manner. Moving onto referencing, this group has done a fantastic job in that aspect as they have a separate section for references, which is clear and easy to understand, fulfilling criteria 3. Overall, I have been able to learn from this group’s project and thus I believe that they fulfil an aspect of criteria 4, in that they have an element of teaching for peers. Improvements I might suggest would be having an even larger array of different learning outlets or media types. Examples could include maybe having a video included in your group project. In terms of improvements to specific information, maybe quickly glance over the different types of receptors and the different pathways they have. &lt;br /&gt;
&lt;br /&gt;
GROUP 3&lt;br /&gt;
&lt;br /&gt;
Overall from analysing through Group 3’s project I can starkly see that they have made a good attempt at addressing the marking criteria. The flow and clarity of the information in this project shows some serious thought and is showing a promising coverage of criteria 1. Not only this, but the group has excellently covered criteria 2 by having a plethora of headings, subheadings, tables and diagrams. Not only this but they have included a quiz which really shows an extra level of understanding and effort. One improvement that I might suggest is that they could extend the table by researching more developments in the field of FGF Signaling. Furthermore, this group has covered criteria 3 quite well as well but having a thorough amount of references and in text citations. Also, I have been able to learn a great amount of information from this project which means they have successfully achieved criteria 4. Overall, this project has done very well in presenting their project. &lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
GROUP 4&lt;br /&gt;
From reading through Group 4’s project I can see they are clearly and succinctly describing the topic at hand, which is related to the hedgehog pathway. They explore things such as the mechanism of signalling during embryonic development as well as neural and organ development. From reading their research I can see they have carefully written it according it to criteria 1. Unfortunately, their use of headings and sub-headings, diagrams, tables, graphs is not as good as it could be. They have used an imagine of the Hedgehog signaling pathway, which is a good start, but to improve and further fulfil this criterion I would suggest having more media. The referencing has been done quite well as it has its own section and is easy to find, but also there are quite regular in text citations, fulfilling criteria 3. &lt;br /&gt;
&lt;br /&gt;
GROUP 5&lt;br /&gt;
&lt;br /&gt;
From reading through Group 5’s project I can see that they having clearly and effectively talked about topics relating to Tbx genes. Their subheadings include animal models, history, function in embryonic development, as well as abnormalities. This provides evidence to me that they have obviously considered and addressed both criteria’s 6 and 1. Group 5 has done a fantastic job with criteria 2, in that they provide many visual representations of information with different forms. For examples they provide a table of the main T-box genes, but then also have many visual diagrams relating to the Tbx development. Even though criteria 2 is very well done, it could be improved by having a timeline of the history of the T-box family. Also, I have seen in some other groups that they have included multiple choice questions to test the audience on their knowledge, I think this is a good idea since it makes the learning experience more interactive.&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
{{Stem Cell Presentations 2016}}&lt;/div&gt;</summary>
		<author><name>Z5020466</name></author>
	</entry>
	<entry>
		<id>https://embryology.med.unsw.edu.au/embryology/index.php?title=User:Z5020466&amp;diff=256961</id>
		<title>User:Z5020466</title>
		<link rel="alternate" type="text/html" href="https://embryology.med.unsw.edu.au/embryology/index.php?title=User:Z5020466&amp;diff=256961"/>
		<updated>2016-11-10T05:53:42Z</updated>

		<summary type="html">&lt;p&gt;Z5020466: /* Assessment 1 */&lt;/p&gt;
&lt;hr /&gt;
&lt;div&gt;{{ANAT2341Student2016}}&lt;br /&gt;
&lt;br /&gt;
==Lab Attendance==&lt;br /&gt;
[[USER:Z5020466|Z5020466]] ([[User talk:Z5020466|talk]]) 14:34, 5 August 2016 (AEST)&lt;br /&gt;
&lt;br /&gt;
[[User:Z5020466|Z5020466]] ([[User talk:Z5020466|talk]]) 14:42, 12 August 2016 (AEST)&lt;br /&gt;
&lt;br /&gt;
[[User:Z5020466|Z5020466]] ([[User talk:Z5020466|talk]]) 13:46, 26 August 2016 (AEST)&lt;br /&gt;
&lt;br /&gt;
[[User:Z5020466|Z5020466]] ([[User talk:Z5020466|talk]]) 14:18, 2 September 2016 (AEST)&lt;br /&gt;
&lt;br /&gt;
[[User:Z5020466|Z5020466]] ([[User talk:Z5020466|talk]]) 13:23, 16 September 2016 (AEST)&lt;br /&gt;
&lt;br /&gt;
[[User:Z5020466|Z5020466]] ([[User talk:Z5020466|talk]]) 13:53, 7 October 2016 (AEDT)&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
===Belbin Team Roles===&lt;br /&gt;
If I’m completely honest, I think my role in group work is generally the “Co-ordinator”. I’m not too sure about my ability to step back from the ‘nitty gritty’ details and see the bigger picture. But rather I generally like to take on leadership roles and assign people tasks. That way I can do things how I like to and place people in roles that I think they would be suited to. But not only that I think to be a good leader you have to be a good worker. So I try to lead by example and not really depend on others too much so that if something has messed up, I have no one to blame but myself. This part about Co-ordinators made me chuckle. “Sometimes perceived to be manipulative and will tend to delegate all work” which is unfortunately a little true. But at the same time I’ve been open to working an equal amount as others previously as well.&lt;br /&gt;
&lt;br /&gt;
===Lecture 1: Fertilisation===&lt;br /&gt;
In my previous years in attending university I’ve completed many courses which have gone through the fertilization process such as: Evolutionary Biological Sciences, Physiology, Histology and Pathology. From having done these courses already, there were parts which were familiar to me and that I have understood before in the past. However, I still was amazed by the new refreshing things I have not yet encounter which I did during this lecture. Such as polar bodies and their role in fertilization in disposing of extra DNA. It also clarified a point which I was previously confused about on whether or not polar bodies were gametes or not. Cementing all this information and weaving it in with new learnt information has really been a beneficial experience for me, in that I’m building up on topics I thoroughly enjoy.&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
===External Link===&lt;br /&gt;
[http://www.smh.com.au/ SMH]&lt;br /&gt;
&lt;br /&gt;
===Internal Link===&lt;br /&gt;
[[ANAT2341 Lab 1]]&lt;br /&gt;
&lt;br /&gt;
[[ANAT2341 Lab 1|Fertilization Lab]]&lt;br /&gt;
 &lt;br /&gt;
[[Student Page]]&lt;br /&gt;
&lt;br /&gt;
==Referencing==&lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/sites/entrez?db=pubmed&amp;amp;cmd=search&amp;amp;term=fertilization fertilization]&lt;br /&gt;
&lt;br /&gt;
PMID 27486480&lt;br /&gt;
&lt;br /&gt;
==Lab Assessment==&lt;br /&gt;
&lt;br /&gt;
===Assessment 1===&lt;br /&gt;
[[Media:Example.ogg]]&lt;br /&gt;
&amp;lt;pubmed&amp;gt;PMC3528851&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&lt;br /&gt;
The research article called &amp;quot; Tet1 controls meiosis by regulating meiotic gene expression&amp;quot; by Yamaguchi et al. (2012) aims to determine the role of ten-eleven translocation methylcytosine dioxygenase 1 (TET1) which is a member of the TET family of enzymes, in regulating meiotic gene expression and thus meiosis in mice. This study was highly useful since little is known about how the expression of meiotic genes is regulated and how their expression contributes to normal meiosis. &lt;br /&gt;
In the study they performed a whole-genome bisulphite sequencing (WGBS) analysis using an ultra-low input so that they would be able to see how Tet1 is used in the activation of meiotic genes. &lt;br /&gt;
&lt;br /&gt;
Results showed that a decreased functioning of Tet1 caused an increase in the unpaired synaptonemal complex at zygotene-stage oocyte, suggesting a synapsis-formation defect. The meiotic defects seen from Tet1 loss of function included: formation of univalent chromosome, but also homologous recombination and DNA double-strand breaks (DSBs) repair defects. These in turn caused defective meiotic prophase which caused decreased amount of oocytes and in turn reduced litter size and lowering in fertility. The study done was pivotal as it built upon past studies which have already established that DNA methylation levels of certain meiotic genes are lowered with genomic reprogramming.&lt;br /&gt;
&lt;br /&gt;
{| width=95%&lt;br /&gt;
|-bgcolor=&amp;quot;FAF5FF&amp;quot;&lt;br /&gt;
| [mailto:m.hill@unsw.edu.au Mark Hill] 18 August 2016 - You have added the citation correctly and written a good brief summary of the article findings. &lt;br /&gt;
TET1 is part of the family of methylcytosine dioxygenases that involved in cytosine demethylation and gene activation, interesting that it has a meiotic-specific role.&lt;br /&gt;
&lt;br /&gt;
| width=100px| Assessment 5/5&lt;br /&gt;
|}&lt;br /&gt;
&lt;br /&gt;
==Lab 9: Peer Assessment==&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
GROUP 1&lt;br /&gt;
Through reading through and analysing group 1’s project it is starkly clear they have managed to relay some excellent information and present it in quite an easily digestible manner. That said though, there are some things which they could improve upon as well. I shall be dissecting what they have done well and what they could improve upon. The information they have regarding signalling pathways of the Wnt receptor in embryonic development is complex and intricate so they have done well by creating subheadings to more easily navigate the vastness of information displayed. This relates directly to criteria 2 in the “Group Assessment Criteria”. However, as seen in the criteria there are also other techniques such as diagrams, tables, graphs which could be employed to further add upon the excellence of this project. Moving onto criteria 3 we can see that there has been some referencing and citing, however it was hard to find and not clearly written. The part that was well referenced was under the “Non-Canonical Pathway – Caroline”. It’s starkly clear to me that these group members have truly gone beyond the formal teaching activities, as described in criteria 5, and have done some significant research exploring the abnormalities associated with the Wnt pathway be describing the interruptions in the pathway and its relation to cancer. &lt;br /&gt;
&lt;br /&gt;
GROUP 2&lt;br /&gt;
Moving the the 2nd group I can see that their topic is mainly about the Notch receptor. They seem to elucidate upon different aspects of the receptor, like it’s role in embryonic development and molecular pathways. The aspect done especially well in this group is the vastness and breadth of their information. They explore numerous aspects of the Notch receptor, including the abnormalities that can arise in development. By showing such a vastness and clarity in their research they successfully achieve criteria 1. Furthermore, Group 2 has a phenomenal amount of tables, diagrams and figures describing canonical Notch signalling and the history of the discoveries for these receptors. This qualifies criteria 2 very well as they have included all these as well as headings and sub headings in a succinct manner. Moving onto referencing, this group has done a fantastic job in that aspect as they have a separate section for references, which is clear and easy to understand, fulfilling criteria 3. Overall, I have been able to learn from this group’s project and thus I believe that they fulfil an aspect of criteria 4, in that they have an element of teaching for peers. Improvements I might suggest would be having an even larger array of different learning outlets or media types. Examples could include maybe having a video included in your group project. In terms of improvements to specific information, maybe quickly glance over the different types of receptors and the different pathways they have. &lt;br /&gt;
&lt;br /&gt;
GROUP 3&lt;br /&gt;
&lt;br /&gt;
Overall from analysing through Group 3’s project I can starkly see that they have made a good attempt at addressing the marking criteria. The flow and clarity of the information in this project shows some serious thought and is showing a promising coverage of criteria 1. Not only this, but the group has excellently covered criteria 2 by having a plethora of headings, subheadings, tables and diagrams. Not only this but they have included a quiz which really shows an extra level of understanding and effort. One improvement that I might suggest is that they could extend the table by researching more developments in the field of FGF Signaling. Furthermore, this group has covered criteria 3 quite well as well but having a thorough amount of references and in text citations. Also, I have been able to learn a great amount of information from this project which means they have successfully achieved criteria 4. Overall, this project has done very well in presenting their project. &lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
GROUP 4&lt;br /&gt;
From reading through Group 4’s project I can see they are clearly and succinctly describing the topic at hand, which is related to the hedgehog pathway. They explore things such as the mechanism of signalling during embryonic development as well as neural and organ development. From reading their research I can see they have carefully written it according it to criteria 1. Unfortunately, their use of headings and sub-headings, diagrams, tables, graphs is not as good as it could be. They have used an imagine of the Hedgehog signaling pathway, which is a good start, but to improve and further fulfil this criterion I would suggest having more media. The referencing has been done quite well as it has its own section and is easy to find, but also there are quite regular in text citations, fulfilling criteria 3. &lt;br /&gt;
&lt;br /&gt;
GROUP 5&lt;br /&gt;
&lt;br /&gt;
From reading through Group 5’s project I can see that they having clearly and effectively talked about topics relating to Tbx genes. Their subheadings include animal models, history, function in embryonic development, as well as abnormalities. This provides evidence to me that they have obviously considered and addressed both criteria’s 6 and 1. Group 5 has done a fantastic job with criteria 2, in that they provide many visual representations of information with different forms. For examples they provide a table of the main T-box genes, but then also have many visual diagrams relating to the Tbx development. Even though criteria 2 is very well done, it could be improved by having a timeline of the history of the T-box family. Also, I have seen in some other groups that they have included multiple choice questions to test the audience on their knowledge, I think this is a good idea since it makes the learning experience more interactive.&lt;/div&gt;</summary>
		<author><name>Z5020466</name></author>
	</entry>
	<entry>
		<id>https://embryology.med.unsw.edu.au/embryology/index.php?title=User:Z5020466&amp;diff=256959</id>
		<title>User:Z5020466</title>
		<link rel="alternate" type="text/html" href="https://embryology.med.unsw.edu.au/embryology/index.php?title=User:Z5020466&amp;diff=256959"/>
		<updated>2016-11-10T05:53:07Z</updated>

		<summary type="html">&lt;p&gt;Z5020466: /* Assessment 1 */&lt;/p&gt;
&lt;hr /&gt;
&lt;div&gt;{{ANAT2341Student2016}}&lt;br /&gt;
&lt;br /&gt;
==Lab Attendance==&lt;br /&gt;
[[USER:Z5020466|Z5020466]] ([[User talk:Z5020466|talk]]) 14:34, 5 August 2016 (AEST)&lt;br /&gt;
&lt;br /&gt;
[[User:Z5020466|Z5020466]] ([[User talk:Z5020466|talk]]) 14:42, 12 August 2016 (AEST)&lt;br /&gt;
&lt;br /&gt;
[[User:Z5020466|Z5020466]] ([[User talk:Z5020466|talk]]) 13:46, 26 August 2016 (AEST)&lt;br /&gt;
&lt;br /&gt;
[[User:Z5020466|Z5020466]] ([[User talk:Z5020466|talk]]) 14:18, 2 September 2016 (AEST)&lt;br /&gt;
&lt;br /&gt;
[[User:Z5020466|Z5020466]] ([[User talk:Z5020466|talk]]) 13:23, 16 September 2016 (AEST)&lt;br /&gt;
&lt;br /&gt;
[[User:Z5020466|Z5020466]] ([[User talk:Z5020466|talk]]) 13:53, 7 October 2016 (AEDT)&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
===Belbin Team Roles===&lt;br /&gt;
If I’m completely honest, I think my role in group work is generally the “Co-ordinator”. I’m not too sure about my ability to step back from the ‘nitty gritty’ details and see the bigger picture. But rather I generally like to take on leadership roles and assign people tasks. That way I can do things how I like to and place people in roles that I think they would be suited to. But not only that I think to be a good leader you have to be a good worker. So I try to lead by example and not really depend on others too much so that if something has messed up, I have no one to blame but myself. This part about Co-ordinators made me chuckle. “Sometimes perceived to be manipulative and will tend to delegate all work” which is unfortunately a little true. But at the same time I’ve been open to working an equal amount as others previously as well.&lt;br /&gt;
&lt;br /&gt;
===Lecture 1: Fertilisation===&lt;br /&gt;
In my previous years in attending university I’ve completed many courses which have gone through the fertilization process such as: Evolutionary Biological Sciences, Physiology, Histology and Pathology. From having done these courses already, there were parts which were familiar to me and that I have understood before in the past. However, I still was amazed by the new refreshing things I have not yet encounter which I did during this lecture. Such as polar bodies and their role in fertilization in disposing of extra DNA. It also clarified a point which I was previously confused about on whether or not polar bodies were gametes or not. Cementing all this information and weaving it in with new learnt information has really been a beneficial experience for me, in that I’m building up on topics I thoroughly enjoy.&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
===External Link===&lt;br /&gt;
[http://www.smh.com.au/ SMH]&lt;br /&gt;
&lt;br /&gt;
===Internal Link===&lt;br /&gt;
[[ANAT2341 Lab 1]]&lt;br /&gt;
&lt;br /&gt;
[[ANAT2341 Lab 1|Fertilization Lab]]&lt;br /&gt;
 &lt;br /&gt;
[[Student Page]]&lt;br /&gt;
&lt;br /&gt;
==Referencing==&lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/sites/entrez?db=pubmed&amp;amp;cmd=search&amp;amp;term=fertilization fertilization]&lt;br /&gt;
&lt;br /&gt;
PMID 27486480&lt;br /&gt;
&lt;br /&gt;
==Lab Assessment==&lt;br /&gt;
&lt;br /&gt;
===Assessment 1===&lt;br /&gt;
[[Media:Example.ogg]]&lt;br /&gt;
&amp;lt;pubmed&amp;gt;PMC3528851&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&lt;br /&gt;
The research article called &amp;quot; Tet1 controls meiosis by regulating meiotic gene expression&amp;quot; by Yamaguchi et al. (2012) aims to determine the role of ten-eleven translocation methylcytosine dioxygenase 1 (TET1) which is a member of the TET family of enzymes, in regulating meiotic gene expression and thus meiosis in mice. This study was highly useful since little is known about how the expression of meiotic genes is regulated and how their expression contributes to normal meiosis. &lt;br /&gt;
In the study they performed a whole-genome bisulphite sequencing (WGBS) analysis using an ultra-low input so that they would be able to see how Tet1 is used in the activation of meiotic genes. &lt;br /&gt;
&lt;br /&gt;
Results showed that a decreased functioning of Tet1 caused an increase in the unpaired synaptonemal complex at zygotene-stage oocyte, suggesting a synapsis-formation defect. The meiotic defects seen from Tet1 loss of function included: formation of univalent chromosome, but also homologous recombination and DNA double-strand breaks (DSBs) repair defects. These in turn caused defective meiotic prophase which caused decreased amount of oocytes and in turn reduced litter size and lowering in fertility. The study done was pivotal as it built upon past studies which have already established that DNA methylation levels of certain meiotic genes are lowered with genomic reprogramming.&lt;br /&gt;
&lt;br /&gt;
{| width=95%&lt;br /&gt;
|-bgcolor=&amp;quot;FAF5FF&amp;quot;&lt;br /&gt;
| [mailto:m.hill@unsw.edu.au Mark Hill] 18 August 2016 - You have added the citation correctly and written a good brief summary of the article findings. &lt;br /&gt;
TET1 is part of the family of methylcytosine dioxygenases that involved in cytosine demethylation and gene activation, interesting that it has a meiotic-specific role.&lt;br /&gt;
&lt;br /&gt;
| width=100px| Assessment 5/5&lt;br /&gt;
|}&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
{{Stem Cell Presentations 2016}}&lt;br /&gt;
&lt;br /&gt;
==Lab 9: Peer Assessment==&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
GROUP 1&lt;br /&gt;
Through reading through and analysing group 1’s project it is starkly clear they have managed to relay some excellent information and present it in quite an easily digestible manner. That said though, there are some things which they could improve upon as well. I shall be dissecting what they have done well and what they could improve upon. The information they have regarding signalling pathways of the Wnt receptor in embryonic development is complex and intricate so they have done well by creating subheadings to more easily navigate the vastness of information displayed. This relates directly to criteria 2 in the “Group Assessment Criteria”. However, as seen in the criteria there are also other techniques such as diagrams, tables, graphs which could be employed to further add upon the excellence of this project. Moving onto criteria 3 we can see that there has been some referencing and citing, however it was hard to find and not clearly written. The part that was well referenced was under the “Non-Canonical Pathway – Caroline”. It’s starkly clear to me that these group members have truly gone beyond the formal teaching activities, as described in criteria 5, and have done some significant research exploring the abnormalities associated with the Wnt pathway be describing the interruptions in the pathway and its relation to cancer. &lt;br /&gt;
&lt;br /&gt;
GROUP 2&lt;br /&gt;
Moving the the 2nd group I can see that their topic is mainly about the Notch receptor. They seem to elucidate upon different aspects of the receptor, like it’s role in embryonic development and molecular pathways. The aspect done especially well in this group is the vastness and breadth of their information. They explore numerous aspects of the Notch receptor, including the abnormalities that can arise in development. By showing such a vastness and clarity in their research they successfully achieve criteria 1. Furthermore, Group 2 has a phenomenal amount of tables, diagrams and figures describing canonical Notch signalling and the history of the discoveries for these receptors. This qualifies criteria 2 very well as they have included all these as well as headings and sub headings in a succinct manner. Moving onto referencing, this group has done a fantastic job in that aspect as they have a separate section for references, which is clear and easy to understand, fulfilling criteria 3. Overall, I have been able to learn from this group’s project and thus I believe that they fulfil an aspect of criteria 4, in that they have an element of teaching for peers. Improvements I might suggest would be having an even larger array of different learning outlets or media types. Examples could include maybe having a video included in your group project. In terms of improvements to specific information, maybe quickly glance over the different types of receptors and the different pathways they have. &lt;br /&gt;
&lt;br /&gt;
GROUP 3&lt;br /&gt;
&lt;br /&gt;
Overall from analysing through Group 3’s project I can starkly see that they have made a good attempt at addressing the marking criteria. The flow and clarity of the information in this project shows some serious thought and is showing a promising coverage of criteria 1. Not only this, but the group has excellently covered criteria 2 by having a plethora of headings, subheadings, tables and diagrams. Not only this but they have included a quiz which really shows an extra level of understanding and effort. One improvement that I might suggest is that they could extend the table by researching more developments in the field of FGF Signaling. Furthermore, this group has covered criteria 3 quite well as well but having a thorough amount of references and in text citations. Also, I have been able to learn a great amount of information from this project which means they have successfully achieved criteria 4. Overall, this project has done very well in presenting their project. &lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
GROUP 4&lt;br /&gt;
From reading through Group 4’s project I can see they are clearly and succinctly describing the topic at hand, which is related to the hedgehog pathway. They explore things such as the mechanism of signalling during embryonic development as well as neural and organ development. From reading their research I can see they have carefully written it according it to criteria 1. Unfortunately, their use of headings and sub-headings, diagrams, tables, graphs is not as good as it could be. They have used an imagine of the Hedgehog signaling pathway, which is a good start, but to improve and further fulfil this criterion I would suggest having more media. The referencing has been done quite well as it has its own section and is easy to find, but also there are quite regular in text citations, fulfilling criteria 3. &lt;br /&gt;
&lt;br /&gt;
GROUP 5&lt;br /&gt;
&lt;br /&gt;
From reading through Group 5’s project I can see that they having clearly and effectively talked about topics relating to Tbx genes. Their subheadings include animal models, history, function in embryonic development, as well as abnormalities. This provides evidence to me that they have obviously considered and addressed both criteria’s 6 and 1. Group 5 has done a fantastic job with criteria 2, in that they provide many visual representations of information with different forms. For examples they provide a table of the main T-box genes, but then also have many visual diagrams relating to the Tbx development. Even though criteria 2 is very well done, it could be improved by having a timeline of the history of the T-box family. Also, I have seen in some other groups that they have included multiple choice questions to test the audience on their knowledge, I think this is a good idea since it makes the learning experience more interactive.&lt;/div&gt;</summary>
		<author><name>Z5020466</name></author>
	</entry>
	<entry>
		<id>https://embryology.med.unsw.edu.au/embryology/index.php?title=User:Z5020466&amp;diff=256957</id>
		<title>User:Z5020466</title>
		<link rel="alternate" type="text/html" href="https://embryology.med.unsw.edu.au/embryology/index.php?title=User:Z5020466&amp;diff=256957"/>
		<updated>2016-11-10T05:52:50Z</updated>

		<summary type="html">&lt;p&gt;Z5020466: /* Lab 9: Peer Assessment */&lt;/p&gt;
&lt;hr /&gt;
&lt;div&gt;{{ANAT2341Student2016}}&lt;br /&gt;
&lt;br /&gt;
==Lab Attendance==&lt;br /&gt;
[[USER:Z5020466|Z5020466]] ([[User talk:Z5020466|talk]]) 14:34, 5 August 2016 (AEST)&lt;br /&gt;
&lt;br /&gt;
[[User:Z5020466|Z5020466]] ([[User talk:Z5020466|talk]]) 14:42, 12 August 2016 (AEST)&lt;br /&gt;
&lt;br /&gt;
[[User:Z5020466|Z5020466]] ([[User talk:Z5020466|talk]]) 13:46, 26 August 2016 (AEST)&lt;br /&gt;
&lt;br /&gt;
[[User:Z5020466|Z5020466]] ([[User talk:Z5020466|talk]]) 14:18, 2 September 2016 (AEST)&lt;br /&gt;
&lt;br /&gt;
[[User:Z5020466|Z5020466]] ([[User talk:Z5020466|talk]]) 13:23, 16 September 2016 (AEST)&lt;br /&gt;
&lt;br /&gt;
[[User:Z5020466|Z5020466]] ([[User talk:Z5020466|talk]]) 13:53, 7 October 2016 (AEDT)&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
===Belbin Team Roles===&lt;br /&gt;
If I’m completely honest, I think my role in group work is generally the “Co-ordinator”. I’m not too sure about my ability to step back from the ‘nitty gritty’ details and see the bigger picture. But rather I generally like to take on leadership roles and assign people tasks. That way I can do things how I like to and place people in roles that I think they would be suited to. But not only that I think to be a good leader you have to be a good worker. So I try to lead by example and not really depend on others too much so that if something has messed up, I have no one to blame but myself. This part about Co-ordinators made me chuckle. “Sometimes perceived to be manipulative and will tend to delegate all work” which is unfortunately a little true. But at the same time I’ve been open to working an equal amount as others previously as well.&lt;br /&gt;
&lt;br /&gt;
===Lecture 1: Fertilisation===&lt;br /&gt;
In my previous years in attending university I’ve completed many courses which have gone through the fertilization process such as: Evolutionary Biological Sciences, Physiology, Histology and Pathology. From having done these courses already, there were parts which were familiar to me and that I have understood before in the past. However, I still was amazed by the new refreshing things I have not yet encounter which I did during this lecture. Such as polar bodies and their role in fertilization in disposing of extra DNA. It also clarified a point which I was previously confused about on whether or not polar bodies were gametes or not. Cementing all this information and weaving it in with new learnt information has really been a beneficial experience for me, in that I’m building up on topics I thoroughly enjoy.&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
===External Link===&lt;br /&gt;
[http://www.smh.com.au/ SMH]&lt;br /&gt;
&lt;br /&gt;
===Internal Link===&lt;br /&gt;
[[ANAT2341 Lab 1]]&lt;br /&gt;
&lt;br /&gt;
[[ANAT2341 Lab 1|Fertilization Lab]]&lt;br /&gt;
 &lt;br /&gt;
[[Student Page]]&lt;br /&gt;
&lt;br /&gt;
==Referencing==&lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/sites/entrez?db=pubmed&amp;amp;cmd=search&amp;amp;term=fertilization fertilization]&lt;br /&gt;
&lt;br /&gt;
PMID 27486480&lt;br /&gt;
&lt;br /&gt;
==Lab Assessment==&lt;br /&gt;
&lt;br /&gt;
===Assessment 1===&lt;br /&gt;
[[Media:Example.ogg]]&lt;br /&gt;
&amp;lt;pubmed&amp;gt;PMC3528851&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&lt;br /&gt;
The research article called &amp;quot; Tet1 controls meiosis by regulating meiotic gene expression&amp;quot; by Yamaguchi et al. (2012) aims to determine the role of ten-eleven translocation methylcytosine dioxygenase 1 (TET1) which is a member of the TET family of enzymes, in regulating meiotic gene expression and thus meiosis in mice. This study was highly useful since little is known about how the expression of meiotic genes is regulated and how their expression contributes to normal meiosis. &lt;br /&gt;
In the study they performed a whole-genome bisulphite sequencing (WGBS) analysis using an ultra-low input so that they would be able to see how Tet1 is used in the activation of meiotic genes. &lt;br /&gt;
&lt;br /&gt;
Results showed that a decreased functioning of Tet1 caused an increase in the unpaired synaptonemal complex at zygotene-stage oocyte, suggesting a synapsis-formation defect. The meiotic defects seen from Tet1 loss of function included: formation of univalent chromosome, but also homologous recombination and DNA double-strand breaks (DSBs) repair defects. These in turn caused defective meiotic prophase which caused decreased amount of oocytes and in turn reduced litter size and lowering in fertility. The study done was pivotal as it built upon past studies which have already established that DNA methylation levels of certain meiotic genes are lowered with genomic reprogramming.&lt;br /&gt;
&lt;br /&gt;
==Lab 9: Peer Assessment==&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
GROUP 1&lt;br /&gt;
Through reading through and analysing group 1’s project it is starkly clear they have managed to relay some excellent information and present it in quite an easily digestible manner. That said though, there are some things which they could improve upon as well. I shall be dissecting what they have done well and what they could improve upon. The information they have regarding signalling pathways of the Wnt receptor in embryonic development is complex and intricate so they have done well by creating subheadings to more easily navigate the vastness of information displayed. This relates directly to criteria 2 in the “Group Assessment Criteria”. However, as seen in the criteria there are also other techniques such as diagrams, tables, graphs which could be employed to further add upon the excellence of this project. Moving onto criteria 3 we can see that there has been some referencing and citing, however it was hard to find and not clearly written. The part that was well referenced was under the “Non-Canonical Pathway – Caroline”. It’s starkly clear to me that these group members have truly gone beyond the formal teaching activities, as described in criteria 5, and have done some significant research exploring the abnormalities associated with the Wnt pathway be describing the interruptions in the pathway and its relation to cancer. &lt;br /&gt;
&lt;br /&gt;
GROUP 2&lt;br /&gt;
Moving the the 2nd group I can see that their topic is mainly about the Notch receptor. They seem to elucidate upon different aspects of the receptor, like it’s role in embryonic development and molecular pathways. The aspect done especially well in this group is the vastness and breadth of their information. They explore numerous aspects of the Notch receptor, including the abnormalities that can arise in development. By showing such a vastness and clarity in their research they successfully achieve criteria 1. Furthermore, Group 2 has a phenomenal amount of tables, diagrams and figures describing canonical Notch signalling and the history of the discoveries for these receptors. This qualifies criteria 2 very well as they have included all these as well as headings and sub headings in a succinct manner. Moving onto referencing, this group has done a fantastic job in that aspect as they have a separate section for references, which is clear and easy to understand, fulfilling criteria 3. Overall, I have been able to learn from this group’s project and thus I believe that they fulfil an aspect of criteria 4, in that they have an element of teaching for peers. Improvements I might suggest would be having an even larger array of different learning outlets or media types. Examples could include maybe having a video included in your group project. In terms of improvements to specific information, maybe quickly glance over the different types of receptors and the different pathways they have. &lt;br /&gt;
&lt;br /&gt;
GROUP 3&lt;br /&gt;
&lt;br /&gt;
Overall from analysing through Group 3’s project I can starkly see that they have made a good attempt at addressing the marking criteria. The flow and clarity of the information in this project shows some serious thought and is showing a promising coverage of criteria 1. Not only this, but the group has excellently covered criteria 2 by having a plethora of headings, subheadings, tables and diagrams. Not only this but they have included a quiz which really shows an extra level of understanding and effort. One improvement that I might suggest is that they could extend the table by researching more developments in the field of FGF Signaling. Furthermore, this group has covered criteria 3 quite well as well but having a thorough amount of references and in text citations. Also, I have been able to learn a great amount of information from this project which means they have successfully achieved criteria 4. Overall, this project has done very well in presenting their project. &lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
GROUP 4&lt;br /&gt;
From reading through Group 4’s project I can see they are clearly and succinctly describing the topic at hand, which is related to the hedgehog pathway. They explore things such as the mechanism of signalling during embryonic development as well as neural and organ development. From reading their research I can see they have carefully written it according it to criteria 1. Unfortunately, their use of headings and sub-headings, diagrams, tables, graphs is not as good as it could be. They have used an imagine of the Hedgehog signaling pathway, which is a good start, but to improve and further fulfil this criterion I would suggest having more media. The referencing has been done quite well as it has its own section and is easy to find, but also there are quite regular in text citations, fulfilling criteria 3. &lt;br /&gt;
&lt;br /&gt;
GROUP 5&lt;br /&gt;
&lt;br /&gt;
From reading through Group 5’s project I can see that they having clearly and effectively talked about topics relating to Tbx genes. Their subheadings include animal models, history, function in embryonic development, as well as abnormalities. This provides evidence to me that they have obviously considered and addressed both criteria’s 6 and 1. Group 5 has done a fantastic job with criteria 2, in that they provide many visual representations of information with different forms. For examples they provide a table of the main T-box genes, but then also have many visual diagrams relating to the Tbx development. Even though criteria 2 is very well done, it could be improved by having a timeline of the history of the T-box family. Also, I have seen in some other groups that they have included multiple choice questions to test the audience on their knowledge, I think this is a good idea since it makes the learning experience more interactive.&lt;/div&gt;</summary>
		<author><name>Z5020466</name></author>
	</entry>
	<entry>
		<id>https://embryology.med.unsw.edu.au/embryology/index.php?title=User:Z5020466&amp;diff=256955</id>
		<title>User:Z5020466</title>
		<link rel="alternate" type="text/html" href="https://embryology.med.unsw.edu.au/embryology/index.php?title=User:Z5020466&amp;diff=256955"/>
		<updated>2016-11-10T05:49:20Z</updated>

		<summary type="html">&lt;p&gt;Z5020466: /* Lab Assessment */&lt;/p&gt;
&lt;hr /&gt;
&lt;div&gt;{{ANAT2341Student2016}}&lt;br /&gt;
&lt;br /&gt;
==Lab Attendance==&lt;br /&gt;
[[USER:Z5020466|Z5020466]] ([[User talk:Z5020466|talk]]) 14:34, 5 August 2016 (AEST)&lt;br /&gt;
&lt;br /&gt;
[[User:Z5020466|Z5020466]] ([[User talk:Z5020466|talk]]) 14:42, 12 August 2016 (AEST)&lt;br /&gt;
&lt;br /&gt;
[[User:Z5020466|Z5020466]] ([[User talk:Z5020466|talk]]) 13:46, 26 August 2016 (AEST)&lt;br /&gt;
&lt;br /&gt;
[[User:Z5020466|Z5020466]] ([[User talk:Z5020466|talk]]) 14:18, 2 September 2016 (AEST)&lt;br /&gt;
&lt;br /&gt;
[[User:Z5020466|Z5020466]] ([[User talk:Z5020466|talk]]) 13:23, 16 September 2016 (AEST)&lt;br /&gt;
&lt;br /&gt;
[[User:Z5020466|Z5020466]] ([[User talk:Z5020466|talk]]) 13:53, 7 October 2016 (AEDT)&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
===Belbin Team Roles===&lt;br /&gt;
If I’m completely honest, I think my role in group work is generally the “Co-ordinator”. I’m not too sure about my ability to step back from the ‘nitty gritty’ details and see the bigger picture. But rather I generally like to take on leadership roles and assign people tasks. That way I can do things how I like to and place people in roles that I think they would be suited to. But not only that I think to be a good leader you have to be a good worker. So I try to lead by example and not really depend on others too much so that if something has messed up, I have no one to blame but myself. This part about Co-ordinators made me chuckle. “Sometimes perceived to be manipulative and will tend to delegate all work” which is unfortunately a little true. But at the same time I’ve been open to working an equal amount as others previously as well.&lt;br /&gt;
&lt;br /&gt;
===Lecture 1: Fertilisation===&lt;br /&gt;
In my previous years in attending university I’ve completed many courses which have gone through the fertilization process such as: Evolutionary Biological Sciences, Physiology, Histology and Pathology. From having done these courses already, there were parts which were familiar to me and that I have understood before in the past. However, I still was amazed by the new refreshing things I have not yet encounter which I did during this lecture. Such as polar bodies and their role in fertilization in disposing of extra DNA. It also clarified a point which I was previously confused about on whether or not polar bodies were gametes or not. Cementing all this information and weaving it in with new learnt information has really been a beneficial experience for me, in that I’m building up on topics I thoroughly enjoy.&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
===External Link===&lt;br /&gt;
[http://www.smh.com.au/ SMH]&lt;br /&gt;
&lt;br /&gt;
===Internal Link===&lt;br /&gt;
[[ANAT2341 Lab 1]]&lt;br /&gt;
&lt;br /&gt;
[[ANAT2341 Lab 1|Fertilization Lab]]&lt;br /&gt;
 &lt;br /&gt;
[[Student Page]]&lt;br /&gt;
&lt;br /&gt;
==Referencing==&lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/sites/entrez?db=pubmed&amp;amp;cmd=search&amp;amp;term=fertilization fertilization]&lt;br /&gt;
&lt;br /&gt;
PMID 27486480&lt;br /&gt;
&lt;br /&gt;
==Lab Assessment==&lt;br /&gt;
&lt;br /&gt;
===Assessment 1===&lt;br /&gt;
[[Media:Example.ogg]]&lt;br /&gt;
&amp;lt;pubmed&amp;gt;PMC3528851&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&lt;br /&gt;
The research article called &amp;quot; Tet1 controls meiosis by regulating meiotic gene expression&amp;quot; by Yamaguchi et al. (2012) aims to determine the role of ten-eleven translocation methylcytosine dioxygenase 1 (TET1) which is a member of the TET family of enzymes, in regulating meiotic gene expression and thus meiosis in mice. This study was highly useful since little is known about how the expression of meiotic genes is regulated and how their expression contributes to normal meiosis. &lt;br /&gt;
In the study they performed a whole-genome bisulphite sequencing (WGBS) analysis using an ultra-low input so that they would be able to see how Tet1 is used in the activation of meiotic genes. &lt;br /&gt;
&lt;br /&gt;
Results showed that a decreased functioning of Tet1 caused an increase in the unpaired synaptonemal complex at zygotene-stage oocyte, suggesting a synapsis-formation defect. The meiotic defects seen from Tet1 loss of function included: formation of univalent chromosome, but also homologous recombination and DNA double-strand breaks (DSBs) repair defects. These in turn caused defective meiotic prophase which caused decreased amount of oocytes and in turn reduced litter size and lowering in fertility. The study done was pivotal as it built upon past studies which have already established that DNA methylation levels of certain meiotic genes are lowered with genomic reprogramming.&lt;br /&gt;
&lt;br /&gt;
==Lab 9: Peer Assessment==&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
GROUP 1&lt;br /&gt;
Through reading through and analysing group 1’s project it is starkly clear they have managed to relay some excellent information and present it in quite an easily digestible manner. That said though, there are some things which they could improve upon as well. I shall be dissecting what they have done well and what they could improve upon. The information they have regarding signalling pathways of the Wnt receptor in embryonic development is complex and intricate so they have done well by creating subheadings to more easily navigate the vastness of information displayed. This relates directly to criteria 2 in the “Group Assessment Criteria”. However, as seen in the criteria there are also other techniques such as diagrams, tables, graphs which could be employed to further add upon the excellence of this project. Moving onto criteria 3 we can see that there has been some referencing and citing, however it was hard to find and not clearly written. The part that was well referenced was under the “Non-Canonical Pathway – Caroline”. It’s starkly clear to me that these group members have truly gone beyond the formal teaching activities, as described in criteria 5, and have done some significant research exploring the abnormalities associated with the Wnt pathway be describing the interruptions in the pathway and its relation to cancer. &lt;br /&gt;
&lt;br /&gt;
GROUP 2&lt;br /&gt;
Moving the the 2nd group I can see that their topic is mainly about the Notch receptor. They seem to elucidate upon different aspects of the receptor, like it’s role in embryonic development and molecular pathways. The aspect done especially well in this group is the vastness and breadth of their information. They explore numerous aspects of the Notch receptor, including the abnormalities that can arise in development. By showing such a vastness and clarity in their research they successfully achieve criteria 1. Furthermore, Group 2 has a phenomenal amount of tables, diagrams and figures describing canonical Notch signalling and the history of the discoveries for these receptors. This qualifies criteria 2 very well as they have included all these as well as headings and sub headings in a succinct manner. Moving onto referencing, this group has done a fantastic job in that aspect as they have a separate section for references, which is clear and easy to understand, fulfilling criteria 3. Overall, I have been able to learn from this group’s project and thus I believe that they fulfil an aspect of criteria 4, in that they have an element of teaching for peers. Improvements I might suggest would be having an even larger array of different learning outlets or media types. Examples could include maybe having a video included in your group project. In terms of improvements to specific information, maybe quickly glance over the different types of receptors and the different pathways they have. &lt;br /&gt;
&lt;br /&gt;
GROUP 3&lt;br /&gt;
&lt;br /&gt;
Overall from analysing through Group 3’s project I can starkly see that they have made a good attempt at addressing the marking criteria. The flow and clarity of the information in this project shows some serious thought and is showing a promising coverage of criteria 1. Not only this, but the group has excellently covered criteria 2 by having a plethora of headings, subheadings, tables and diagrams. Not only this but they have included a quiz which really shows an extra level of understanding and effort. One improvement that I might suggest is that they could extend the table by researching more developments in the field of FGF Signaling. Furthermore, this group has covered criteria 3 quite well as well but having a thorough amount of references and in text citations. Also, I have been able to learn a great amount of information from this project which means they have successfully achieved criteria 4. Overall, this project has done very well in presenting their project. &lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
GROUP 4&lt;br /&gt;
From reading through Group 4’s project I can see they are clearly and succinctly describing the topic at hand, which is related to the hedgehog pathway. They explore things such as the mechanism of signalling during embryonic development as well as neural and organ development. From reading their research I can see they have carefully written it according it to criteria 1. Unfortunately, their use of headings and sub-headings, diagrams, tables, graphs is not as good as it could be. They have used an imagine of the Hedgehog signaling pathway, which is a good start, but to improve and further fulfil this criterion I would suggest having more media. The referencing has been done quite well as it has its own section and is easy to find, but also there are quite regular in text citations, fulfilling criteria 3. &lt;br /&gt;
&lt;br /&gt;
GROUP 5&lt;br /&gt;
&lt;br /&gt;
From reading through Group 5’s project I can see that they having clearly and effectively talked about topics relating to Tbx genes. Their subheadings include animal models, history, function in embryonic development, as well as abnormalities. This provides evidence to me that they have obviously considered and addressed both criteria’s 6 and 1. Group 5 has done a fantastic job with criteria 2, in that they provide many visual representations of information with different forms. For examples they provide a table of the main T-box genes, but then also have many visual diagrams relating to the Tbx development. Even though criteria 2 is very well done, it could be improved by having a timeline of the history of the T-box family. Also, I have seen in some other groups that they have included multiple choice questions to test the audience on their knowledge, I think this is a good idea since it makes the learning experience more interactive.&lt;br /&gt;
&lt;br /&gt;
{| width=95%&lt;br /&gt;
|-bgcolor=&amp;quot;FAF5FF&amp;quot;&lt;br /&gt;
| [mailto:m.hill@unsw.edu.au Mark Hill] 18 August 2016 - You have added the citation correctly and written a good brief summary of the article findings. &lt;br /&gt;
TET1 is part of the family of methylcytosine dioxygenases that involved in cytosine demethylation and gene activation, interesting that it has a meiotic-specific role.&lt;br /&gt;
&lt;br /&gt;
| width=100px| Assessment 5/5&lt;br /&gt;
|}&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
{{Stem Cell Presentations 2016}}&lt;/div&gt;</summary>
		<author><name>Z5020466</name></author>
	</entry>
	<entry>
		<id>https://embryology.med.unsw.edu.au/embryology/index.php?title=User:Z5020466&amp;diff=256953</id>
		<title>User:Z5020466</title>
		<link rel="alternate" type="text/html" href="https://embryology.med.unsw.edu.au/embryology/index.php?title=User:Z5020466&amp;diff=256953"/>
		<updated>2016-11-10T05:48:00Z</updated>

		<summary type="html">&lt;p&gt;Z5020466: /* Assessment 1 */&lt;/p&gt;
&lt;hr /&gt;
&lt;div&gt;{{ANAT2341Student2016}}&lt;br /&gt;
&lt;br /&gt;
==Lab Attendance==&lt;br /&gt;
[[USER:Z5020466|Z5020466]] ([[User talk:Z5020466|talk]]) 14:34, 5 August 2016 (AEST)&lt;br /&gt;
&lt;br /&gt;
[[User:Z5020466|Z5020466]] ([[User talk:Z5020466|talk]]) 14:42, 12 August 2016 (AEST)&lt;br /&gt;
&lt;br /&gt;
[[User:Z5020466|Z5020466]] ([[User talk:Z5020466|talk]]) 13:46, 26 August 2016 (AEST)&lt;br /&gt;
&lt;br /&gt;
[[User:Z5020466|Z5020466]] ([[User talk:Z5020466|talk]]) 14:18, 2 September 2016 (AEST)&lt;br /&gt;
&lt;br /&gt;
[[User:Z5020466|Z5020466]] ([[User talk:Z5020466|talk]]) 13:23, 16 September 2016 (AEST)&lt;br /&gt;
&lt;br /&gt;
[[User:Z5020466|Z5020466]] ([[User talk:Z5020466|talk]]) 13:53, 7 October 2016 (AEDT)&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
===Belbin Team Roles===&lt;br /&gt;
If I’m completely honest, I think my role in group work is generally the “Co-ordinator”. I’m not too sure about my ability to step back from the ‘nitty gritty’ details and see the bigger picture. But rather I generally like to take on leadership roles and assign people tasks. That way I can do things how I like to and place people in roles that I think they would be suited to. But not only that I think to be a good leader you have to be a good worker. So I try to lead by example and not really depend on others too much so that if something has messed up, I have no one to blame but myself. This part about Co-ordinators made me chuckle. “Sometimes perceived to be manipulative and will tend to delegate all work” which is unfortunately a little true. But at the same time I’ve been open to working an equal amount as others previously as well.&lt;br /&gt;
&lt;br /&gt;
===Lecture 1: Fertilisation===&lt;br /&gt;
In my previous years in attending university I’ve completed many courses which have gone through the fertilization process such as: Evolutionary Biological Sciences, Physiology, Histology and Pathology. From having done these courses already, there were parts which were familiar to me and that I have understood before in the past. However, I still was amazed by the new refreshing things I have not yet encounter which I did during this lecture. Such as polar bodies and their role in fertilization in disposing of extra DNA. It also clarified a point which I was previously confused about on whether or not polar bodies were gametes or not. Cementing all this information and weaving it in with new learnt information has really been a beneficial experience for me, in that I’m building up on topics I thoroughly enjoy.&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
===External Link===&lt;br /&gt;
[http://www.smh.com.au/ SMH]&lt;br /&gt;
&lt;br /&gt;
===Internal Link===&lt;br /&gt;
[[ANAT2341 Lab 1]]&lt;br /&gt;
&lt;br /&gt;
[[ANAT2341 Lab 1|Fertilization Lab]]&lt;br /&gt;
 &lt;br /&gt;
[[Student Page]]&lt;br /&gt;
&lt;br /&gt;
==Referencing==&lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/sites/entrez?db=pubmed&amp;amp;cmd=search&amp;amp;term=fertilization fertilization]&lt;br /&gt;
&lt;br /&gt;
PMID 27486480&lt;br /&gt;
&lt;br /&gt;
==Lab Assessment==&lt;br /&gt;
&lt;br /&gt;
[[Media:Example.ogg]]===Assessment 1===&lt;br /&gt;
&amp;lt;pubmed&amp;gt;PMC3528851&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&lt;br /&gt;
The research article called &amp;quot; Tet1 controls meiosis by regulating meiotic gene expression&amp;quot; by Yamaguchi et al. (2012) aims to determine the role of ten-eleven translocation methylcytosine dioxygenase 1 (TET1) which is a member of the TET family of enzymes, in regulating meiotic gene expression and thus meiosis in mice. This study was highly useful since little is known about how the expression of meiotic genes is regulated and how their expression contributes to normal meiosis. &lt;br /&gt;
In the study they performed a whole-genome bisulphite sequencing (WGBS) analysis using an ultra-low input so that they would be able to see how Tet1 is used in the activation of meiotic genes. &lt;br /&gt;
&lt;br /&gt;
Results showed that a decreased functioning of Tet1 caused an increase in the unpaired synaptonemal complex at zygotene-stage oocyte, suggesting a synapsis-formation defect. The meiotic defects seen from Tet1 loss of function included: formation of univalent chromosome, but also homologous recombination and DNA double-strand breaks (DSBs) repair defects. These in turn caused defective meiotic prophase which caused decreased amount of oocytes and in turn reduced litter size and lowering in fertility. The study done was pivotal as it built upon past studies which have already established that DNA methylation levels of certain meiotic genes are lowered with genomic reprogramming.&lt;br /&gt;
&lt;br /&gt;
==Lab 9: Peer Assessment==&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
GROUP 1&lt;br /&gt;
Through reading through and analysing group 1’s project it is starkly clear they have managed to relay some excellent information and present it in quite an easily digestible manner. That said though, there are some things which they could improve upon as well. I shall be dissecting what they have done well and what they could improve upon. The information they have regarding signalling pathways of the Wnt receptor in embryonic development is complex and intricate so they have done well by creating subheadings to more easily navigate the vastness of information displayed. This relates directly to criteria 2 in the “Group Assessment Criteria”. However, as seen in the criteria there are also other techniques such as diagrams, tables, graphs which could be employed to further add upon the excellence of this project. Moving onto criteria 3 we can see that there has been some referencing and citing, however it was hard to find and not clearly written. The part that was well referenced was under the “Non-Canonical Pathway – Caroline”. It’s starkly clear to me that these group members have truly gone beyond the formal teaching activities, as described in criteria 5, and have done some significant research exploring the abnormalities associated with the Wnt pathway be describing the interruptions in the pathway and its relation to cancer. &lt;br /&gt;
&lt;br /&gt;
GROUP 2&lt;br /&gt;
Moving the the 2nd group I can see that their topic is mainly about the Notch receptor. They seem to elucidate upon different aspects of the receptor, like it’s role in embryonic development and molecular pathways. The aspect done especially well in this group is the vastness and breadth of their information. They explore numerous aspects of the Notch receptor, including the abnormalities that can arise in development. By showing such a vastness and clarity in their research they successfully achieve criteria 1. Furthermore, Group 2 has a phenomenal amount of tables, diagrams and figures describing canonical Notch signalling and the history of the discoveries for these receptors. This qualifies criteria 2 very well as they have included all these as well as headings and sub headings in a succinct manner. Moving onto referencing, this group has done a fantastic job in that aspect as they have a separate section for references, which is clear and easy to understand, fulfilling criteria 3. Overall, I have been able to learn from this group’s project and thus I believe that they fulfil an aspect of criteria 4, in that they have an element of teaching for peers. Improvements I might suggest would be having an even larger array of different learning outlets or media types. Examples could include maybe having a video included in your group project. In terms of improvements to specific information, maybe quickly glance over the different types of receptors and the different pathways they have. &lt;br /&gt;
&lt;br /&gt;
GROUP 3&lt;br /&gt;
&lt;br /&gt;
Overall from analysing through Group 3’s project I can starkly see that they have made a good attempt at addressing the marking criteria. The flow and clarity of the information in this project shows some serious thought and is showing a promising coverage of criteria 1. Not only this, but the group has excellently covered criteria 2 by having a plethora of headings, subheadings, tables and diagrams. Not only this but they have included a quiz which really shows an extra level of understanding and effort. One improvement that I might suggest is that they could extend the table by researching more developments in the field of FGF Signaling. Furthermore, this group has covered criteria 3 quite well as well but having a thorough amount of references and in text citations. Also, I have been able to learn a great amount of information from this project which means they have successfully achieved criteria 4. Overall, this project has done very well in presenting their project. &lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
GROUP 4&lt;br /&gt;
From reading through Group 4’s project I can see they are clearly and succinctly describing the topic at hand, which is related to the hedgehog pathway. They explore things such as the mechanism of signalling during embryonic development as well as neural and organ development. From reading their research I can see they have carefully written it according it to criteria 1. Unfortunately, their use of headings and sub-headings, diagrams, tables, graphs is not as good as it could be. They have used an imagine of the Hedgehog signaling pathway, which is a good start, but to improve and further fulfil this criterion I would suggest having more media. The referencing has been done quite well as it has its own section and is easy to find, but also there are quite regular in text citations, fulfilling criteria 3. &lt;br /&gt;
&lt;br /&gt;
GROUP 5&lt;br /&gt;
&lt;br /&gt;
From reading through Group 5’s project I can see that they having clearly and effectively talked about topics relating to Tbx genes. Their subheadings include animal models, history, function in embryonic development, as well as abnormalities. This provides evidence to me that they have obviously considered and addressed both criteria’s 6 and 1. Group 5 has done a fantastic job with criteria 2, in that they provide many visual representations of information with different forms. For examples they provide a table of the main T-box genes, but then also have many visual diagrams relating to the Tbx development. Even though criteria 2 is very well done, it could be improved by having a timeline of the history of the T-box family. Also, I have seen in some other groups that they have included multiple choice questions to test the audience on their knowledge, I think this is a good idea since it makes the learning experience more interactive.&lt;br /&gt;
&lt;br /&gt;
{| width=95%&lt;br /&gt;
|-bgcolor=&amp;quot;FAF5FF&amp;quot;&lt;br /&gt;
| [mailto:m.hill@unsw.edu.au Mark Hill] 18 August 2016 - You have added the citation correctly and written a good brief summary of the article findings. &lt;br /&gt;
TET1 is part of the family of methylcytosine dioxygenases that involved in cytosine demethylation and gene activation, interesting that it has a meiotic-specific role.&lt;br /&gt;
&lt;br /&gt;
| width=100px| Assessment 5/5&lt;br /&gt;
|}&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
{{Stem Cell Presentations 2016}}&lt;/div&gt;</summary>
		<author><name>Z5020466</name></author>
	</entry>
	<entry>
		<id>https://embryology.med.unsw.edu.au/embryology/index.php?title=User:Z5020466&amp;diff=256951</id>
		<title>User:Z5020466</title>
		<link rel="alternate" type="text/html" href="https://embryology.med.unsw.edu.au/embryology/index.php?title=User:Z5020466&amp;diff=256951"/>
		<updated>2016-11-10T05:47:31Z</updated>

		<summary type="html">&lt;p&gt;Z5020466: /* Lab Assessment */&lt;/p&gt;
&lt;hr /&gt;
&lt;div&gt;{{ANAT2341Student2016}}&lt;br /&gt;
&lt;br /&gt;
==Lab Attendance==&lt;br /&gt;
[[USER:Z5020466|Z5020466]] ([[User talk:Z5020466|talk]]) 14:34, 5 August 2016 (AEST)&lt;br /&gt;
&lt;br /&gt;
[[User:Z5020466|Z5020466]] ([[User talk:Z5020466|talk]]) 14:42, 12 August 2016 (AEST)&lt;br /&gt;
&lt;br /&gt;
[[User:Z5020466|Z5020466]] ([[User talk:Z5020466|talk]]) 13:46, 26 August 2016 (AEST)&lt;br /&gt;
&lt;br /&gt;
[[User:Z5020466|Z5020466]] ([[User talk:Z5020466|talk]]) 14:18, 2 September 2016 (AEST)&lt;br /&gt;
&lt;br /&gt;
[[User:Z5020466|Z5020466]] ([[User talk:Z5020466|talk]]) 13:23, 16 September 2016 (AEST)&lt;br /&gt;
&lt;br /&gt;
[[User:Z5020466|Z5020466]] ([[User talk:Z5020466|talk]]) 13:53, 7 October 2016 (AEDT)&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
===Belbin Team Roles===&lt;br /&gt;
If I’m completely honest, I think my role in group work is generally the “Co-ordinator”. I’m not too sure about my ability to step back from the ‘nitty gritty’ details and see the bigger picture. But rather I generally like to take on leadership roles and assign people tasks. That way I can do things how I like to and place people in roles that I think they would be suited to. But not only that I think to be a good leader you have to be a good worker. So I try to lead by example and not really depend on others too much so that if something has messed up, I have no one to blame but myself. This part about Co-ordinators made me chuckle. “Sometimes perceived to be manipulative and will tend to delegate all work” which is unfortunately a little true. But at the same time I’ve been open to working an equal amount as others previously as well.&lt;br /&gt;
&lt;br /&gt;
===Lecture 1: Fertilisation===&lt;br /&gt;
In my previous years in attending university I’ve completed many courses which have gone through the fertilization process such as: Evolutionary Biological Sciences, Physiology, Histology and Pathology. From having done these courses already, there were parts which were familiar to me and that I have understood before in the past. However, I still was amazed by the new refreshing things I have not yet encounter which I did during this lecture. Such as polar bodies and their role in fertilization in disposing of extra DNA. It also clarified a point which I was previously confused about on whether or not polar bodies were gametes or not. Cementing all this information and weaving it in with new learnt information has really been a beneficial experience for me, in that I’m building up on topics I thoroughly enjoy.&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
===External Link===&lt;br /&gt;
[http://www.smh.com.au/ SMH]&lt;br /&gt;
&lt;br /&gt;
===Internal Link===&lt;br /&gt;
[[ANAT2341 Lab 1]]&lt;br /&gt;
&lt;br /&gt;
[[ANAT2341 Lab 1|Fertilization Lab]]&lt;br /&gt;
 &lt;br /&gt;
[[Student Page]]&lt;br /&gt;
&lt;br /&gt;
==Referencing==&lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/sites/entrez?db=pubmed&amp;amp;cmd=search&amp;amp;term=fertilization fertilization]&lt;br /&gt;
&lt;br /&gt;
PMID 27486480&lt;br /&gt;
&lt;br /&gt;
==Lab Assessment==&lt;br /&gt;
&lt;br /&gt;
==Assessment 1==&lt;br /&gt;
&amp;lt;pubmed&amp;gt;PMC3528851&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&lt;br /&gt;
The research article called &amp;quot; Tet1 controls meiosis by regulating meiotic gene expression&amp;quot; by Yamaguchi et al. (2012) aims to determine the role of ten-eleven translocation methylcytosine dioxygenase 1 (TET1) which is a member of the TET family of enzymes, in regulating meiotic gene expression and thus meiosis in mice. This study was highly useful since little is known about how the expression of meiotic genes is regulated and how their expression contributes to normal meiosis. &lt;br /&gt;
In the study they performed a whole-genome bisulphite sequencing (WGBS) analysis using an ultra-low input so that they would be able to see how Tet1 is used in the activation of meiotic genes. &lt;br /&gt;
&lt;br /&gt;
Results showed that a decreased functioning of Tet1 caused an increase in the unpaired synaptonemal complex at zygotene-stage oocyte, suggesting a synapsis-formation defect. The meiotic defects seen from Tet1 loss of function included: formation of univalent chromosome, but also homologous recombination and DNA double-strand breaks (DSBs) repair defects. These in turn caused defective meiotic prophase which caused decreased amount of oocytes and in turn reduced litter size and lowering in fertility. The study done was pivotal as it built upon past studies which have already established that DNA methylation levels of certain meiotic genes are lowered with genomic reprogramming.&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
==Lab 9: Peer Assessment==&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
GROUP 1&lt;br /&gt;
Through reading through and analysing group 1’s project it is starkly clear they have managed to relay some excellent information and present it in quite an easily digestible manner. That said though, there are some things which they could improve upon as well. I shall be dissecting what they have done well and what they could improve upon. The information they have regarding signalling pathways of the Wnt receptor in embryonic development is complex and intricate so they have done well by creating subheadings to more easily navigate the vastness of information displayed. This relates directly to criteria 2 in the “Group Assessment Criteria”. However, as seen in the criteria there are also other techniques such as diagrams, tables, graphs which could be employed to further add upon the excellence of this project. Moving onto criteria 3 we can see that there has been some referencing and citing, however it was hard to find and not clearly written. The part that was well referenced was under the “Non-Canonical Pathway – Caroline”. It’s starkly clear to me that these group members have truly gone beyond the formal teaching activities, as described in criteria 5, and have done some significant research exploring the abnormalities associated with the Wnt pathway be describing the interruptions in the pathway and its relation to cancer. &lt;br /&gt;
&lt;br /&gt;
GROUP 2&lt;br /&gt;
Moving the the 2nd group I can see that their topic is mainly about the Notch receptor. They seem to elucidate upon different aspects of the receptor, like it’s role in embryonic development and molecular pathways. The aspect done especially well in this group is the vastness and breadth of their information. They explore numerous aspects of the Notch receptor, including the abnormalities that can arise in development. By showing such a vastness and clarity in their research they successfully achieve criteria 1. Furthermore, Group 2 has a phenomenal amount of tables, diagrams and figures describing canonical Notch signalling and the history of the discoveries for these receptors. This qualifies criteria 2 very well as they have included all these as well as headings and sub headings in a succinct manner. Moving onto referencing, this group has done a fantastic job in that aspect as they have a separate section for references, which is clear and easy to understand, fulfilling criteria 3. Overall, I have been able to learn from this group’s project and thus I believe that they fulfil an aspect of criteria 4, in that they have an element of teaching for peers. Improvements I might suggest would be having an even larger array of different learning outlets or media types. Examples could include maybe having a video included in your group project. In terms of improvements to specific information, maybe quickly glance over the different types of receptors and the different pathways they have. &lt;br /&gt;
&lt;br /&gt;
GROUP 3&lt;br /&gt;
&lt;br /&gt;
Overall from analysing through Group 3’s project I can starkly see that they have made a good attempt at addressing the marking criteria. The flow and clarity of the information in this project shows some serious thought and is showing a promising coverage of criteria 1. Not only this, but the group has excellently covered criteria 2 by having a plethora of headings, subheadings, tables and diagrams. Not only this but they have included a quiz which really shows an extra level of understanding and effort. One improvement that I might suggest is that they could extend the table by researching more developments in the field of FGF Signaling. Furthermore, this group has covered criteria 3 quite well as well but having a thorough amount of references and in text citations. Also, I have been able to learn a great amount of information from this project which means they have successfully achieved criteria 4. Overall, this project has done very well in presenting their project. &lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
GROUP 4&lt;br /&gt;
From reading through Group 4’s project I can see they are clearly and succinctly describing the topic at hand, which is related to the hedgehog pathway. They explore things such as the mechanism of signalling during embryonic development as well as neural and organ development. From reading their research I can see they have carefully written it according it to criteria 1. Unfortunately, their use of headings and sub-headings, diagrams, tables, graphs is not as good as it could be. They have used an imagine of the Hedgehog signaling pathway, which is a good start, but to improve and further fulfil this criterion I would suggest having more media. The referencing has been done quite well as it has its own section and is easy to find, but also there are quite regular in text citations, fulfilling criteria 3. &lt;br /&gt;
&lt;br /&gt;
GROUP 5&lt;br /&gt;
&lt;br /&gt;
From reading through Group 5’s project I can see that they having clearly and effectively talked about topics relating to Tbx genes. Their subheadings include animal models, history, function in embryonic development, as well as abnormalities. This provides evidence to me that they have obviously considered and addressed both criteria’s 6 and 1. Group 5 has done a fantastic job with criteria 2, in that they provide many visual representations of information with different forms. For examples they provide a table of the main T-box genes, but then also have many visual diagrams relating to the Tbx development. Even though criteria 2 is very well done, it could be improved by having a timeline of the history of the T-box family. Also, I have seen in some other groups that they have included multiple choice questions to test the audience on their knowledge, I think this is a good idea since it makes the learning experience more interactive.&lt;br /&gt;
&lt;br /&gt;
{| width=95%&lt;br /&gt;
|-bgcolor=&amp;quot;FAF5FF&amp;quot;&lt;br /&gt;
| [mailto:m.hill@unsw.edu.au Mark Hill] 18 August 2016 - You have added the citation correctly and written a good brief summary of the article findings. &lt;br /&gt;
TET1 is part of the family of methylcytosine dioxygenases that involved in cytosine demethylation and gene activation, interesting that it has a meiotic-specific role.&lt;br /&gt;
&lt;br /&gt;
| width=100px| Assessment 5/5&lt;br /&gt;
|}&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
{{Stem Cell Presentations 2016}}&lt;/div&gt;</summary>
		<author><name>Z5020466</name></author>
	</entry>
	<entry>
		<id>https://embryology.med.unsw.edu.au/embryology/index.php?title=User:Z5020466&amp;diff=256949</id>
		<title>User:Z5020466</title>
		<link rel="alternate" type="text/html" href="https://embryology.med.unsw.edu.au/embryology/index.php?title=User:Z5020466&amp;diff=256949"/>
		<updated>2016-11-10T05:46:35Z</updated>

		<summary type="html">&lt;p&gt;Z5020466: /* Lab Attendance */&lt;/p&gt;
&lt;hr /&gt;
&lt;div&gt;{{ANAT2341Student2016}}&lt;br /&gt;
&lt;br /&gt;
==Lab Attendance==&lt;br /&gt;
[[USER:Z5020466|Z5020466]] ([[User talk:Z5020466|talk]]) 14:34, 5 August 2016 (AEST)&lt;br /&gt;
&lt;br /&gt;
[[User:Z5020466|Z5020466]] ([[User talk:Z5020466|talk]]) 14:42, 12 August 2016 (AEST)&lt;br /&gt;
&lt;br /&gt;
[[User:Z5020466|Z5020466]] ([[User talk:Z5020466|talk]]) 13:46, 26 August 2016 (AEST)&lt;br /&gt;
&lt;br /&gt;
[[User:Z5020466|Z5020466]] ([[User talk:Z5020466|talk]]) 14:18, 2 September 2016 (AEST)&lt;br /&gt;
&lt;br /&gt;
[[User:Z5020466|Z5020466]] ([[User talk:Z5020466|talk]]) 13:23, 16 September 2016 (AEST)&lt;br /&gt;
&lt;br /&gt;
[[User:Z5020466|Z5020466]] ([[User talk:Z5020466|talk]]) 13:53, 7 October 2016 (AEDT)&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
===Belbin Team Roles===&lt;br /&gt;
If I’m completely honest, I think my role in group work is generally the “Co-ordinator”. I’m not too sure about my ability to step back from the ‘nitty gritty’ details and see the bigger picture. But rather I generally like to take on leadership roles and assign people tasks. That way I can do things how I like to and place people in roles that I think they would be suited to. But not only that I think to be a good leader you have to be a good worker. So I try to lead by example and not really depend on others too much so that if something has messed up, I have no one to blame but myself. This part about Co-ordinators made me chuckle. “Sometimes perceived to be manipulative and will tend to delegate all work” which is unfortunately a little true. But at the same time I’ve been open to working an equal amount as others previously as well.&lt;br /&gt;
&lt;br /&gt;
===Lecture 1: Fertilisation===&lt;br /&gt;
In my previous years in attending university I’ve completed many courses which have gone through the fertilization process such as: Evolutionary Biological Sciences, Physiology, Histology and Pathology. From having done these courses already, there were parts which were familiar to me and that I have understood before in the past. However, I still was amazed by the new refreshing things I have not yet encounter which I did during this lecture. Such as polar bodies and their role in fertilization in disposing of extra DNA. It also clarified a point which I was previously confused about on whether or not polar bodies were gametes or not. Cementing all this information and weaving it in with new learnt information has really been a beneficial experience for me, in that I’m building up on topics I thoroughly enjoy.&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
===External Link===&lt;br /&gt;
[http://www.smh.com.au/ SMH]&lt;br /&gt;
&lt;br /&gt;
===Internal Link===&lt;br /&gt;
[[ANAT2341 Lab 1]]&lt;br /&gt;
&lt;br /&gt;
[[ANAT2341 Lab 1|Fertilization Lab]]&lt;br /&gt;
 &lt;br /&gt;
[[Student Page]]&lt;br /&gt;
&lt;br /&gt;
==Referencing==&lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/sites/entrez?db=pubmed&amp;amp;cmd=search&amp;amp;term=fertilization fertilization]&lt;br /&gt;
&lt;br /&gt;
PMID 27486480&lt;br /&gt;
&lt;br /&gt;
===Lab Assessment===&lt;br /&gt;
==Assessment 1==&lt;br /&gt;
&amp;lt;pubmed&amp;gt;PMC3528851&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&lt;br /&gt;
The research article called &amp;quot; Tet1 controls meiosis by regulating meiotic gene expression&amp;quot; by Yamaguchi et al. (2012) aims to determine the role of ten-eleven translocation methylcytosine dioxygenase 1 (TET1) which is a member of the TET family of enzymes, in regulating meiotic gene expression and thus meiosis in mice. This study was highly useful since little is known about how the expression of meiotic genes is regulated and how their expression contributes to normal meiosis. &lt;br /&gt;
In the study they performed a whole-genome bisulphite sequencing (WGBS) analysis using an ultra-low input so that they would be able to see how Tet1 is used in the activation of meiotic genes. &lt;br /&gt;
&lt;br /&gt;
Results showed that a decreased functioning of Tet1 caused an increase in the unpaired synaptonemal complex at zygotene-stage oocyte, suggesting a synapsis-formation defect. The meiotic defects seen from Tet1 loss of function included: formation of univalent chromosome, but also homologous recombination and DNA double-strand breaks (DSBs) repair defects. These in turn caused defective meiotic prophase which caused decreased amount of oocytes and in turn reduced litter size and lowering in fertility. The study done was pivotal as it built upon past studies which have already established that DNA methylation levels of certain meiotic genes are lowered with genomic reprogramming.&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
==Lab 9: Peer Assessment==&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
GROUP 1&lt;br /&gt;
Through reading through and analysing group 1’s project it is starkly clear they have managed to relay some excellent information and present it in quite an easily digestible manner. That said though, there are some things which they could improve upon as well. I shall be dissecting what they have done well and what they could improve upon. The information they have regarding signalling pathways of the Wnt receptor in embryonic development is complex and intricate so they have done well by creating subheadings to more easily navigate the vastness of information displayed. This relates directly to criteria 2 in the “Group Assessment Criteria”. However, as seen in the criteria there are also other techniques such as diagrams, tables, graphs which could be employed to further add upon the excellence of this project. Moving onto criteria 3 we can see that there has been some referencing and citing, however it was hard to find and not clearly written. The part that was well referenced was under the “Non-Canonical Pathway – Caroline”. It’s starkly clear to me that these group members have truly gone beyond the formal teaching activities, as described in criteria 5, and have done some significant research exploring the abnormalities associated with the Wnt pathway be describing the interruptions in the pathway and its relation to cancer. &lt;br /&gt;
&lt;br /&gt;
GROUP 2&lt;br /&gt;
Moving the the 2nd group I can see that their topic is mainly about the Notch receptor. They seem to elucidate upon different aspects of the receptor, like it’s role in embryonic development and molecular pathways. The aspect done especially well in this group is the vastness and breadth of their information. They explore numerous aspects of the Notch receptor, including the abnormalities that can arise in development. By showing such a vastness and clarity in their research they successfully achieve criteria 1. Furthermore, Group 2 has a phenomenal amount of tables, diagrams and figures describing canonical Notch signalling and the history of the discoveries for these receptors. This qualifies criteria 2 very well as they have included all these as well as headings and sub headings in a succinct manner. Moving onto referencing, this group has done a fantastic job in that aspect as they have a separate section for references, which is clear and easy to understand, fulfilling criteria 3. Overall, I have been able to learn from this group’s project and thus I believe that they fulfil an aspect of criteria 4, in that they have an element of teaching for peers. Improvements I might suggest would be having an even larger array of different learning outlets or media types. Examples could include maybe having a video included in your group project. In terms of improvements to specific information, maybe quickly glance over the different types of receptors and the different pathways they have. &lt;br /&gt;
&lt;br /&gt;
GROUP 3&lt;br /&gt;
&lt;br /&gt;
Overall from analysing through Group 3’s project I can starkly see that they have made a good attempt at addressing the marking criteria. The flow and clarity of the information in this project shows some serious thought and is showing a promising coverage of criteria 1. Not only this, but the group has excellently covered criteria 2 by having a plethora of headings, subheadings, tables and diagrams. Not only this but they have included a quiz which really shows an extra level of understanding and effort. One improvement that I might suggest is that they could extend the table by researching more developments in the field of FGF Signaling. Furthermore, this group has covered criteria 3 quite well as well but having a thorough amount of references and in text citations. Also, I have been able to learn a great amount of information from this project which means they have successfully achieved criteria 4. Overall, this project has done very well in presenting their project. &lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
GROUP 4&lt;br /&gt;
From reading through Group 4’s project I can see they are clearly and succinctly describing the topic at hand, which is related to the hedgehog pathway. They explore things such as the mechanism of signalling during embryonic development as well as neural and organ development. From reading their research I can see they have carefully written it according it to criteria 1. Unfortunately, their use of headings and sub-headings, diagrams, tables, graphs is not as good as it could be. They have used an imagine of the Hedgehog signaling pathway, which is a good start, but to improve and further fulfil this criterion I would suggest having more media. The referencing has been done quite well as it has its own section and is easy to find, but also there are quite regular in text citations, fulfilling criteria 3. &lt;br /&gt;
&lt;br /&gt;
GROUP 5&lt;br /&gt;
&lt;br /&gt;
From reading through Group 5’s project I can see that they having clearly and effectively talked about topics relating to Tbx genes. Their subheadings include animal models, history, function in embryonic development, as well as abnormalities. This provides evidence to me that they have obviously considered and addressed both criteria’s 6 and 1. Group 5 has done a fantastic job with criteria 2, in that they provide many visual representations of information with different forms. For examples they provide a table of the main T-box genes, but then also have many visual diagrams relating to the Tbx development. Even though criteria 2 is very well done, it could be improved by having a timeline of the history of the T-box family. Also, I have seen in some other groups that they have included multiple choice questions to test the audience on their knowledge, I think this is a good idea since it makes the learning experience more interactive.&lt;br /&gt;
&lt;br /&gt;
{| width=95%&lt;br /&gt;
|-bgcolor=&amp;quot;FAF5FF&amp;quot;&lt;br /&gt;
| [mailto:m.hill@unsw.edu.au Mark Hill] 18 August 2016 - You have added the citation correctly and written a good brief summary of the article findings. &lt;br /&gt;
TET1 is part of the family of methylcytosine dioxygenases that involved in cytosine demethylation and gene activation, interesting that it has a meiotic-specific role.&lt;br /&gt;
&lt;br /&gt;
| width=100px| Assessment 5/5&lt;br /&gt;
|}&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
{{Stem Cell Presentations 2016}}&lt;/div&gt;</summary>
		<author><name>Z5020466</name></author>
	</entry>
	<entry>
		<id>https://embryology.med.unsw.edu.au/embryology/index.php?title=User:Z5020466&amp;diff=256947</id>
		<title>User:Z5020466</title>
		<link rel="alternate" type="text/html" href="https://embryology.med.unsw.edu.au/embryology/index.php?title=User:Z5020466&amp;diff=256947"/>
		<updated>2016-11-10T05:43:41Z</updated>

		<summary type="html">&lt;p&gt;Z5020466: /* Assessment 1 */&lt;/p&gt;
&lt;hr /&gt;
&lt;div&gt;{{ANAT2341Student2016}}&lt;br /&gt;
&lt;br /&gt;
==Lab Attendance==&lt;br /&gt;
[[User:Z5020466|Z5020466]] ([[User talk:Z5020466|talk]]) 14:42, 12 August 2016 (AEST)&lt;br /&gt;
[[User:Z5020466|Z5020466]] ([[User talk:Z5020466|talk]]) 13:46, 26 August 2016 (AEST)&lt;br /&gt;
[[User:Z5020466|Z5020466]] ([[User talk:Z5020466|talk]]) 13:53, 7 October 2016 (AEDT)&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
===Belbin Team Roles===&lt;br /&gt;
If I’m completely honest, I think my role in group work is generally the “Co-ordinator”. I’m not too sure about my ability to step back from the ‘nitty gritty’ details and see the bigger picture. But rather I generally like to take on leadership roles and assign people tasks. That way I can do things how I like to and place people in roles that I think they would be suited to. But not only that I think to be a good leader you have to be a good worker. So I try to lead by example and not really depend on others too much so that if something has messed up, I have no one to blame but myself. This part about Co-ordinators made me chuckle. “Sometimes perceived to be manipulative and will tend to delegate all work” which is unfortunately a little true. But at the same time I’ve been open to working an equal amount as others previously as well.&lt;br /&gt;
&lt;br /&gt;
===Lecture 1: Fertilisation===&lt;br /&gt;
In my previous years in attending university I’ve completed many courses which have gone through the fertilization process such as: Evolutionary Biological Sciences, Physiology, Histology and Pathology. From having done these courses already, there were parts which were familiar to me and that I have understood before in the past. However, I still was amazed by the new refreshing things I have not yet encounter which I did during this lecture. Such as polar bodies and their role in fertilization in disposing of extra DNA. It also clarified a point which I was previously confused about on whether or not polar bodies were gametes or not. Cementing all this information and weaving it in with new learnt information has really been a beneficial experience for me, in that I’m building up on topics I thoroughly enjoy.&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
===External Link===&lt;br /&gt;
[http://www.smh.com.au/ SMH]&lt;br /&gt;
&lt;br /&gt;
===Internal Link===&lt;br /&gt;
[[ANAT2341 Lab 1]]&lt;br /&gt;
&lt;br /&gt;
[[ANAT2341 Lab 1|Fertilization Lab]]&lt;br /&gt;
 &lt;br /&gt;
[[Student Page]]&lt;br /&gt;
&lt;br /&gt;
==Referencing==&lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/sites/entrez?db=pubmed&amp;amp;cmd=search&amp;amp;term=fertilization fertilization]&lt;br /&gt;
&lt;br /&gt;
PMID 27486480&lt;br /&gt;
&lt;br /&gt;
===Lab Assessment===&lt;br /&gt;
==Assessment 1==&lt;br /&gt;
&amp;lt;pubmed&amp;gt;PMC3528851&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&lt;br /&gt;
The research article called &amp;quot; Tet1 controls meiosis by regulating meiotic gene expression&amp;quot; by Yamaguchi et al. (2012) aims to determine the role of ten-eleven translocation methylcytosine dioxygenase 1 (TET1) which is a member of the TET family of enzymes, in regulating meiotic gene expression and thus meiosis in mice. This study was highly useful since little is known about how the expression of meiotic genes is regulated and how their expression contributes to normal meiosis. &lt;br /&gt;
In the study they performed a whole-genome bisulphite sequencing (WGBS) analysis using an ultra-low input so that they would be able to see how Tet1 is used in the activation of meiotic genes. &lt;br /&gt;
&lt;br /&gt;
Results showed that a decreased functioning of Tet1 caused an increase in the unpaired synaptonemal complex at zygotene-stage oocyte, suggesting a synapsis-formation defect. The meiotic defects seen from Tet1 loss of function included: formation of univalent chromosome, but also homologous recombination and DNA double-strand breaks (DSBs) repair defects. These in turn caused defective meiotic prophase which caused decreased amount of oocytes and in turn reduced litter size and lowering in fertility. The study done was pivotal as it built upon past studies which have already established that DNA methylation levels of certain meiotic genes are lowered with genomic reprogramming.&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
==Lab 9: Peer Assessment==&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
GROUP 1&lt;br /&gt;
Through reading through and analysing group 1’s project it is starkly clear they have managed to relay some excellent information and present it in quite an easily digestible manner. That said though, there are some things which they could improve upon as well. I shall be dissecting what they have done well and what they could improve upon. The information they have regarding signalling pathways of the Wnt receptor in embryonic development is complex and intricate so they have done well by creating subheadings to more easily navigate the vastness of information displayed. This relates directly to criteria 2 in the “Group Assessment Criteria”. However, as seen in the criteria there are also other techniques such as diagrams, tables, graphs which could be employed to further add upon the excellence of this project. Moving onto criteria 3 we can see that there has been some referencing and citing, however it was hard to find and not clearly written. The part that was well referenced was under the “Non-Canonical Pathway – Caroline”. It’s starkly clear to me that these group members have truly gone beyond the formal teaching activities, as described in criteria 5, and have done some significant research exploring the abnormalities associated with the Wnt pathway be describing the interruptions in the pathway and its relation to cancer. &lt;br /&gt;
&lt;br /&gt;
GROUP 2&lt;br /&gt;
Moving the the 2nd group I can see that their topic is mainly about the Notch receptor. They seem to elucidate upon different aspects of the receptor, like it’s role in embryonic development and molecular pathways. The aspect done especially well in this group is the vastness and breadth of their information. They explore numerous aspects of the Notch receptor, including the abnormalities that can arise in development. By showing such a vastness and clarity in their research they successfully achieve criteria 1. Furthermore, Group 2 has a phenomenal amount of tables, diagrams and figures describing canonical Notch signalling and the history of the discoveries for these receptors. This qualifies criteria 2 very well as they have included all these as well as headings and sub headings in a succinct manner. Moving onto referencing, this group has done a fantastic job in that aspect as they have a separate section for references, which is clear and easy to understand, fulfilling criteria 3. Overall, I have been able to learn from this group’s project and thus I believe that they fulfil an aspect of criteria 4, in that they have an element of teaching for peers. Improvements I might suggest would be having an even larger array of different learning outlets or media types. Examples could include maybe having a video included in your group project. In terms of improvements to specific information, maybe quickly glance over the different types of receptors and the different pathways they have. &lt;br /&gt;
&lt;br /&gt;
GROUP 3&lt;br /&gt;
&lt;br /&gt;
Overall from analysing through Group 3’s project I can starkly see that they have made a good attempt at addressing the marking criteria. The flow and clarity of the information in this project shows some serious thought and is showing a promising coverage of criteria 1. Not only this, but the group has excellently covered criteria 2 by having a plethora of headings, subheadings, tables and diagrams. Not only this but they have included a quiz which really shows an extra level of understanding and effort. One improvement that I might suggest is that they could extend the table by researching more developments in the field of FGF Signaling. Furthermore, this group has covered criteria 3 quite well as well but having a thorough amount of references and in text citations. Also, I have been able to learn a great amount of information from this project which means they have successfully achieved criteria 4. Overall, this project has done very well in presenting their project. &lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
GROUP 4&lt;br /&gt;
From reading through Group 4’s project I can see they are clearly and succinctly describing the topic at hand, which is related to the hedgehog pathway. They explore things such as the mechanism of signalling during embryonic development as well as neural and organ development. From reading their research I can see they have carefully written it according it to criteria 1. Unfortunately, their use of headings and sub-headings, diagrams, tables, graphs is not as good as it could be. They have used an imagine of the Hedgehog signaling pathway, which is a good start, but to improve and further fulfil this criterion I would suggest having more media. The referencing has been done quite well as it has its own section and is easy to find, but also there are quite regular in text citations, fulfilling criteria 3. &lt;br /&gt;
&lt;br /&gt;
GROUP 5&lt;br /&gt;
&lt;br /&gt;
From reading through Group 5’s project I can see that they having clearly and effectively talked about topics relating to Tbx genes. Their subheadings include animal models, history, function in embryonic development, as well as abnormalities. This provides evidence to me that they have obviously considered and addressed both criteria’s 6 and 1. Group 5 has done a fantastic job with criteria 2, in that they provide many visual representations of information with different forms. For examples they provide a table of the main T-box genes, but then also have many visual diagrams relating to the Tbx development. Even though criteria 2 is very well done, it could be improved by having a timeline of the history of the T-box family. Also, I have seen in some other groups that they have included multiple choice questions to test the audience on their knowledge, I think this is a good idea since it makes the learning experience more interactive.&lt;br /&gt;
&lt;br /&gt;
{| width=95%&lt;br /&gt;
|-bgcolor=&amp;quot;FAF5FF&amp;quot;&lt;br /&gt;
| [mailto:m.hill@unsw.edu.au Mark Hill] 18 August 2016 - You have added the citation correctly and written a good brief summary of the article findings. &lt;br /&gt;
TET1 is part of the family of methylcytosine dioxygenases that involved in cytosine demethylation and gene activation, interesting that it has a meiotic-specific role.&lt;br /&gt;
&lt;br /&gt;
| width=100px| Assessment 5/5&lt;br /&gt;
|}&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
{{Stem Cell Presentations 2016}}&lt;/div&gt;</summary>
		<author><name>Z5020466</name></author>
	</entry>
	<entry>
		<id>https://embryology.med.unsw.edu.au/embryology/index.php?title=User:Z5020466&amp;diff=256945</id>
		<title>User:Z5020466</title>
		<link rel="alternate" type="text/html" href="https://embryology.med.unsw.edu.au/embryology/index.php?title=User:Z5020466&amp;diff=256945"/>
		<updated>2016-11-10T05:42:56Z</updated>

		<summary type="html">&lt;p&gt;Z5020466: /* Lab Assessments */&lt;/p&gt;
&lt;hr /&gt;
&lt;div&gt;{{ANAT2341Student2016}}&lt;br /&gt;
&lt;br /&gt;
==Lab Attendance==&lt;br /&gt;
[[User:Z5020466|Z5020466]] ([[User talk:Z5020466|talk]]) 14:42, 12 August 2016 (AEST)&lt;br /&gt;
[[User:Z5020466|Z5020466]] ([[User talk:Z5020466|talk]]) 13:46, 26 August 2016 (AEST)&lt;br /&gt;
[[User:Z5020466|Z5020466]] ([[User talk:Z5020466|talk]]) 13:53, 7 October 2016 (AEDT)&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
===Belbin Team Roles===&lt;br /&gt;
If I’m completely honest, I think my role in group work is generally the “Co-ordinator”. I’m not too sure about my ability to step back from the ‘nitty gritty’ details and see the bigger picture. But rather I generally like to take on leadership roles and assign people tasks. That way I can do things how I like to and place people in roles that I think they would be suited to. But not only that I think to be a good leader you have to be a good worker. So I try to lead by example and not really depend on others too much so that if something has messed up, I have no one to blame but myself. This part about Co-ordinators made me chuckle. “Sometimes perceived to be manipulative and will tend to delegate all work” which is unfortunately a little true. But at the same time I’ve been open to working an equal amount as others previously as well.&lt;br /&gt;
&lt;br /&gt;
===Lecture 1: Fertilisation===&lt;br /&gt;
In my previous years in attending university I’ve completed many courses which have gone through the fertilization process such as: Evolutionary Biological Sciences, Physiology, Histology and Pathology. From having done these courses already, there were parts which were familiar to me and that I have understood before in the past. However, I still was amazed by the new refreshing things I have not yet encounter which I did during this lecture. Such as polar bodies and their role in fertilization in disposing of extra DNA. It also clarified a point which I was previously confused about on whether or not polar bodies were gametes or not. Cementing all this information and weaving it in with new learnt information has really been a beneficial experience for me, in that I’m building up on topics I thoroughly enjoy.&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
===External Link===&lt;br /&gt;
[http://www.smh.com.au/ SMH]&lt;br /&gt;
&lt;br /&gt;
===Internal Link===&lt;br /&gt;
[[ANAT2341 Lab 1]]&lt;br /&gt;
&lt;br /&gt;
[[ANAT2341 Lab 1|Fertilization Lab]]&lt;br /&gt;
 &lt;br /&gt;
[[Student Page]]&lt;br /&gt;
&lt;br /&gt;
==Referencing==&lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/sites/entrez?db=pubmed&amp;amp;cmd=search&amp;amp;term=fertilization fertilization]&lt;br /&gt;
&lt;br /&gt;
PMID 27486480&lt;br /&gt;
&lt;br /&gt;
==Assessment 1==&lt;br /&gt;
&amp;lt;pubmed&amp;gt;PMC3528851&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&lt;br /&gt;
The research article called &amp;quot; Tet1 controls meiosis by regulating meiotic gene expression&amp;quot; by Yamaguchi et al. (2012) aims to determine the role of ten-eleven translocation methylcytosine dioxygenase 1 (TET1) which is a member of the TET family of enzymes, in regulating meiotic gene expression and thus meiosis in mice. This study was highly useful since little is known about how the expression of meiotic genes is regulated and how their expression contributes to normal meiosis. &lt;br /&gt;
In the study they performed a whole-genome bisulphite sequencing (WGBS) analysis using an ultra-low input so that they would be able to see how Tet1 is used in the activation of meiotic genes. &lt;br /&gt;
&lt;br /&gt;
Results showed that a decreased functioning of Tet1 caused an increase in the unpaired synaptonemal complex at zygotene-stage oocyte, suggesting a synapsis-formation defect. The meiotic defects seen from Tet1 loss of function included: formation of univalent chromosome, but also homologous recombination and DNA double-strand breaks (DSBs) repair defects. These in turn caused defective meiotic prophase which caused decreased amount of oocytes and in turn reduced litter size and lowering in fertility. The study done was pivotal as it built upon past studies which have already established that DNA methylation levels of certain meiotic genes are lowered with genomic reprogramming.&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
{| width=95%&lt;br /&gt;
|-bgcolor=&amp;quot;FAF5FF&amp;quot;&lt;br /&gt;
| [mailto:m.hill@unsw.edu.au Mark Hill] 18 August 2016 - You have added the citation correctly and written a good brief summary of the article findings. &lt;br /&gt;
TET1 is part of the family of methylcytosine dioxygenases that involved in cytosine demethylation and gene activation, interesting that it has a meiotic-specific role.&lt;br /&gt;
&lt;br /&gt;
| width=100px| Assessment 5/5&lt;br /&gt;
|}&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
{{Stem Cell Presentations 2016}}&lt;br /&gt;
&lt;br /&gt;
===Lab 9: Peer Assessment===&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
GROUP 1&lt;br /&gt;
Through reading through and analysing group 1’s project it is starkly clear they have managed to relay some excellent information and present it in quite an easily digestible manner. That said though, there are some things which they could improve upon as well. I shall be dissecting what they have done well and what they could improve upon. The information they have regarding signalling pathways of the Wnt receptor in embryonic development is complex and intricate so they have done well by creating subheadings to more easily navigate the vastness of information displayed. This relates directly to criteria 2 in the “Group Assessment Criteria”. However, as seen in the criteria there are also other techniques such as diagrams, tables, graphs which could be employed to further add upon the excellence of this project. Moving onto criteria 3 we can see that there has been some referencing and citing, however it was hard to find and not clearly written. The part that was well referenced was under the “Non-Canonical Pathway – Caroline”. It’s starkly clear to me that these group members have truly gone beyond the formal teaching activities, as described in criteria 5, and have done some significant research exploring the abnormalities associated with the Wnt pathway be describing the interruptions in the pathway and its relation to cancer. &lt;br /&gt;
&lt;br /&gt;
GROUP 2&lt;br /&gt;
Moving the the 2nd group I can see that their topic is mainly about the Notch receptor. They seem to elucidate upon different aspects of the receptor, like it’s role in embryonic development and molecular pathways. The aspect done especially well in this group is the vastness and breadth of their information. They explore numerous aspects of the Notch receptor, including the abnormalities that can arise in development. By showing such a vastness and clarity in their research they successfully achieve criteria 1. Furthermore, Group 2 has a phenomenal amount of tables, diagrams and figures describing canonical Notch signalling and the history of the discoveries for these receptors. This qualifies criteria 2 very well as they have included all these as well as headings and sub headings in a succinct manner. Moving onto referencing, this group has done a fantastic job in that aspect as they have a separate section for references, which is clear and easy to understand, fulfilling criteria 3. Overall, I have been able to learn from this group’s project and thus I believe that they fulfil an aspect of criteria 4, in that they have an element of teaching for peers. Improvements I might suggest would be having an even larger array of different learning outlets or media types. Examples could include maybe having a video included in your group project. In terms of improvements to specific information, maybe quickly glance over the different types of receptors and the different pathways they have. &lt;br /&gt;
&lt;br /&gt;
GROUP 3&lt;br /&gt;
&lt;br /&gt;
Overall from analysing through Group 3’s project I can starkly see that they have made a good attempt at addressing the marking criteria. The flow and clarity of the information in this project shows some serious thought and is showing a promising coverage of criteria 1. Not only this, but the group has excellently covered criteria 2 by having a plethora of headings, subheadings, tables and diagrams. Not only this but they have included a quiz which really shows an extra level of understanding and effort. One improvement that I might suggest is that they could extend the table by researching more developments in the field of FGF Signaling. Furthermore, this group has covered criteria 3 quite well as well but having a thorough amount of references and in text citations. Also, I have been able to learn a great amount of information from this project which means they have successfully achieved criteria 4. Overall, this project has done very well in presenting their project. &lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
GROUP 4&lt;br /&gt;
From reading through Group 4’s project I can see they are clearly and succinctly describing the topic at hand, which is related to the hedgehog pathway. They explore things such as the mechanism of signalling during embryonic development as well as neural and organ development. From reading their research I can see they have carefully written it according it to criteria 1. Unfortunately, their use of headings and sub-headings, diagrams, tables, graphs is not as good as it could be. They have used an imagine of the Hedgehog signaling pathway, which is a good start, but to improve and further fulfil this criterion I would suggest having more media. The referencing has been done quite well as it has its own section and is easy to find, but also there are quite regular in text citations, fulfilling criteria 3. &lt;br /&gt;
&lt;br /&gt;
GROUP 5&lt;br /&gt;
&lt;br /&gt;
From reading through Group 5’s project I can see that they having clearly and effectively talked about topics relating to Tbx genes. Their subheadings include animal models, history, function in embryonic development, as well as abnormalities. This provides evidence to me that they have obviously considered and addressed both criteria’s 6 and 1. Group 5 has done a fantastic job with criteria 2, in that they provide many visual representations of information with different forms. For examples they provide a table of the main T-box genes, but then also have many visual diagrams relating to the Tbx development. Even though criteria 2 is very well done, it could be improved by having a timeline of the history of the T-box family. Also, I have seen in some other groups that they have included multiple choice questions to test the audience on their knowledge, I think this is a good idea since it makes the learning experience more interactive.&lt;/div&gt;</summary>
		<author><name>Z5020466</name></author>
	</entry>
	<entry>
		<id>https://embryology.med.unsw.edu.au/embryology/index.php?title=User:Z5020466&amp;diff=256943</id>
		<title>User:Z5020466</title>
		<link rel="alternate" type="text/html" href="https://embryology.med.unsw.edu.au/embryology/index.php?title=User:Z5020466&amp;diff=256943"/>
		<updated>2016-11-10T05:42:01Z</updated>

		<summary type="html">&lt;p&gt;Z5020466: /* New SubHeading */&lt;/p&gt;
&lt;hr /&gt;
&lt;div&gt;{{ANAT2341Student2016}}&lt;br /&gt;
&lt;br /&gt;
==Lab Attendance==&lt;br /&gt;
[[User:Z5020466|Z5020466]] ([[User talk:Z5020466|talk]]) 14:42, 12 August 2016 (AEST)&lt;br /&gt;
[[User:Z5020466|Z5020466]] ([[User talk:Z5020466|talk]]) 13:46, 26 August 2016 (AEST)&lt;br /&gt;
[[User:Z5020466|Z5020466]] ([[User talk:Z5020466|talk]]) 13:53, 7 October 2016 (AEDT)&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
===Belbin Team Roles===&lt;br /&gt;
If I’m completely honest, I think my role in group work is generally the “Co-ordinator”. I’m not too sure about my ability to step back from the ‘nitty gritty’ details and see the bigger picture. But rather I generally like to take on leadership roles and assign people tasks. That way I can do things how I like to and place people in roles that I think they would be suited to. But not only that I think to be a good leader you have to be a good worker. So I try to lead by example and not really depend on others too much so that if something has messed up, I have no one to blame but myself. This part about Co-ordinators made me chuckle. “Sometimes perceived to be manipulative and will tend to delegate all work” which is unfortunately a little true. But at the same time I’ve been open to working an equal amount as others previously as well.&lt;br /&gt;
&lt;br /&gt;
===Lecture 1: Fertilisation===&lt;br /&gt;
In my previous years in attending university I’ve completed many courses which have gone through the fertilization process such as: Evolutionary Biological Sciences, Physiology, Histology and Pathology. From having done these courses already, there were parts which were familiar to me and that I have understood before in the past. However, I still was amazed by the new refreshing things I have not yet encounter which I did during this lecture. Such as polar bodies and their role in fertilization in disposing of extra DNA. It also clarified a point which I was previously confused about on whether or not polar bodies were gametes or not. Cementing all this information and weaving it in with new learnt information has really been a beneficial experience for me, in that I’m building up on topics I thoroughly enjoy.&lt;br /&gt;
&lt;br /&gt;
==Lab Assessments==&lt;br /&gt;
===External Link===&lt;br /&gt;
[http://www.smh.com.au/ SMH]&lt;br /&gt;
&lt;br /&gt;
===Internal Link===&lt;br /&gt;
[[ANAT2341 Lab 1]]&lt;br /&gt;
&lt;br /&gt;
[[ANAT2341 Lab 1|Fertilization Lab]]&lt;br /&gt;
 &lt;br /&gt;
[[Student Page]]&lt;br /&gt;
&lt;br /&gt;
==Referencing==&lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/sites/entrez?db=pubmed&amp;amp;cmd=search&amp;amp;term=fertilization fertilization]&lt;br /&gt;
&lt;br /&gt;
PMID 27486480&lt;br /&gt;
&lt;br /&gt;
==Assessment 1==&lt;br /&gt;
&amp;lt;pubmed&amp;gt;PMC3528851&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&lt;br /&gt;
The research article called &amp;quot; Tet1 controls meiosis by regulating meiotic gene expression&amp;quot; by Yamaguchi et al. (2012) aims to determine the role of ten-eleven translocation methylcytosine dioxygenase 1 (TET1) which is a member of the TET family of enzymes, in regulating meiotic gene expression and thus meiosis in mice. This study was highly useful since little is known about how the expression of meiotic genes is regulated and how their expression contributes to normal meiosis. &lt;br /&gt;
In the study they performed a whole-genome bisulphite sequencing (WGBS) analysis using an ultra-low input so that they would be able to see how Tet1 is used in the activation of meiotic genes. &lt;br /&gt;
&lt;br /&gt;
Results showed that a decreased functioning of Tet1 caused an increase in the unpaired synaptonemal complex at zygotene-stage oocyte, suggesting a synapsis-formation defect. The meiotic defects seen from Tet1 loss of function included: formation of univalent chromosome, but also homologous recombination and DNA double-strand breaks (DSBs) repair defects. These in turn caused defective meiotic prophase which caused decreased amount of oocytes and in turn reduced litter size and lowering in fertility. The study done was pivotal as it built upon past studies which have already established that DNA methylation levels of certain meiotic genes are lowered with genomic reprogramming.&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
{| width=95%&lt;br /&gt;
|-bgcolor=&amp;quot;FAF5FF&amp;quot;&lt;br /&gt;
| [mailto:m.hill@unsw.edu.au Mark Hill] 18 August 2016 - You have added the citation correctly and written a good brief summary of the article findings. &lt;br /&gt;
TET1 is part of the family of methylcytosine dioxygenases that involved in cytosine demethylation and gene activation, interesting that it has a meiotic-specific role.&lt;br /&gt;
&lt;br /&gt;
| width=100px| Assessment 5/5&lt;br /&gt;
|}&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
{{Stem Cell Presentations 2016}}&lt;br /&gt;
&lt;br /&gt;
===Lab 9: Peer Assessment===&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
GROUP 1&lt;br /&gt;
Through reading through and analysing group 1’s project it is starkly clear they have managed to relay some excellent information and present it in quite an easily digestible manner. That said though, there are some things which they could improve upon as well. I shall be dissecting what they have done well and what they could improve upon. The information they have regarding signalling pathways of the Wnt receptor in embryonic development is complex and intricate so they have done well by creating subheadings to more easily navigate the vastness of information displayed. This relates directly to criteria 2 in the “Group Assessment Criteria”. However, as seen in the criteria there are also other techniques such as diagrams, tables, graphs which could be employed to further add upon the excellence of this project. Moving onto criteria 3 we can see that there has been some referencing and citing, however it was hard to find and not clearly written. The part that was well referenced was under the “Non-Canonical Pathway – Caroline”. It’s starkly clear to me that these group members have truly gone beyond the formal teaching activities, as described in criteria 5, and have done some significant research exploring the abnormalities associated with the Wnt pathway be describing the interruptions in the pathway and its relation to cancer. &lt;br /&gt;
&lt;br /&gt;
GROUP 2&lt;br /&gt;
Moving the the 2nd group I can see that their topic is mainly about the Notch receptor. They seem to elucidate upon different aspects of the receptor, like it’s role in embryonic development and molecular pathways. The aspect done especially well in this group is the vastness and breadth of their information. They explore numerous aspects of the Notch receptor, including the abnormalities that can arise in development. By showing such a vastness and clarity in their research they successfully achieve criteria 1. Furthermore, Group 2 has a phenomenal amount of tables, diagrams and figures describing canonical Notch signalling and the history of the discoveries for these receptors. This qualifies criteria 2 very well as they have included all these as well as headings and sub headings in a succinct manner. Moving onto referencing, this group has done a fantastic job in that aspect as they have a separate section for references, which is clear and easy to understand, fulfilling criteria 3. Overall, I have been able to learn from this group’s project and thus I believe that they fulfil an aspect of criteria 4, in that they have an element of teaching for peers. Improvements I might suggest would be having an even larger array of different learning outlets or media types. Examples could include maybe having a video included in your group project. In terms of improvements to specific information, maybe quickly glance over the different types of receptors and the different pathways they have. &lt;br /&gt;
&lt;br /&gt;
GROUP 3&lt;br /&gt;
&lt;br /&gt;
Overall from analysing through Group 3’s project I can starkly see that they have made a good attempt at addressing the marking criteria. The flow and clarity of the information in this project shows some serious thought and is showing a promising coverage of criteria 1. Not only this, but the group has excellently covered criteria 2 by having a plethora of headings, subheadings, tables and diagrams. Not only this but they have included a quiz which really shows an extra level of understanding and effort. One improvement that I might suggest is that they could extend the table by researching more developments in the field of FGF Signaling. Furthermore, this group has covered criteria 3 quite well as well but having a thorough amount of references and in text citations. Also, I have been able to learn a great amount of information from this project which means they have successfully achieved criteria 4. Overall, this project has done very well in presenting their project. &lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
GROUP 4&lt;br /&gt;
From reading through Group 4’s project I can see they are clearly and succinctly describing the topic at hand, which is related to the hedgehog pathway. They explore things such as the mechanism of signalling during embryonic development as well as neural and organ development. From reading their research I can see they have carefully written it according it to criteria 1. Unfortunately, their use of headings and sub-headings, diagrams, tables, graphs is not as good as it could be. They have used an imagine of the Hedgehog signaling pathway, which is a good start, but to improve and further fulfil this criterion I would suggest having more media. The referencing has been done quite well as it has its own section and is easy to find, but also there are quite regular in text citations, fulfilling criteria 3. &lt;br /&gt;
&lt;br /&gt;
GROUP 5&lt;br /&gt;
&lt;br /&gt;
From reading through Group 5’s project I can see that they having clearly and effectively talked about topics relating to Tbx genes. Their subheadings include animal models, history, function in embryonic development, as well as abnormalities. This provides evidence to me that they have obviously considered and addressed both criteria’s 6 and 1. Group 5 has done a fantastic job with criteria 2, in that they provide many visual representations of information with different forms. For examples they provide a table of the main T-box genes, but then also have many visual diagrams relating to the Tbx development. Even though criteria 2 is very well done, it could be improved by having a timeline of the history of the T-box family. Also, I have seen in some other groups that they have included multiple choice questions to test the audience on their knowledge, I think this is a good idea since it makes the learning experience more interactive.&lt;/div&gt;</summary>
		<author><name>Z5020466</name></author>
	</entry>
	<entry>
		<id>https://embryology.med.unsw.edu.au/embryology/index.php?title=User:Z5020466&amp;diff=256941</id>
		<title>User:Z5020466</title>
		<link rel="alternate" type="text/html" href="https://embryology.med.unsw.edu.au/embryology/index.php?title=User:Z5020466&amp;diff=256941"/>
		<updated>2016-11-10T05:41:00Z</updated>

		<summary type="html">&lt;p&gt;Z5020466: /* Assessment 1 */&lt;/p&gt;
&lt;hr /&gt;
&lt;div&gt;{{ANAT2341Student2016}}&lt;br /&gt;
&lt;br /&gt;
==Lab Attendance==&lt;br /&gt;
[[User:Z5020466|Z5020466]] ([[User talk:Z5020466|talk]]) 14:42, 12 August 2016 (AEST)&lt;br /&gt;
[[User:Z5020466|Z5020466]] ([[User talk:Z5020466|talk]]) 13:46, 26 August 2016 (AEST)&lt;br /&gt;
[[User:Z5020466|Z5020466]] ([[User talk:Z5020466|talk]]) 13:53, 7 October 2016 (AEDT)&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
===Belbin Team Roles===&lt;br /&gt;
If I’m completely honest, I think my role in group work is generally the “Co-ordinator”. I’m not too sure about my ability to step back from the ‘nitty gritty’ details and see the bigger picture. But rather I generally like to take on leadership roles and assign people tasks. That way I can do things how I like to and place people in roles that I think they would be suited to. But not only that I think to be a good leader you have to be a good worker. So I try to lead by example and not really depend on others too much so that if something has messed up, I have no one to blame but myself. This part about Co-ordinators made me chuckle. “Sometimes perceived to be manipulative and will tend to delegate all work” which is unfortunately a little true. But at the same time I’ve been open to working an equal amount as others previously as well.&lt;br /&gt;
&lt;br /&gt;
===Lecture 1: Fertilisation===&lt;br /&gt;
In my previous years in attending university I’ve completed many courses which have gone through the fertilization process such as: Evolutionary Biological Sciences, Physiology, Histology and Pathology. From having done these courses already, there were parts which were familiar to me and that I have understood before in the past. However, I still was amazed by the new refreshing things I have not yet encounter which I did during this lecture. Such as polar bodies and their role in fertilization in disposing of extra DNA. It also clarified a point which I was previously confused about on whether or not polar bodies were gametes or not. Cementing all this information and weaving it in with new learnt information has really been a beneficial experience for me, in that I’m building up on topics I thoroughly enjoy.&lt;br /&gt;
&lt;br /&gt;
==New SubHeading==&lt;br /&gt;
===External Link===&lt;br /&gt;
[http://www.smh.com.au/ SMH]&lt;br /&gt;
&lt;br /&gt;
===Internal Link===&lt;br /&gt;
[[ANAT2341 Lab 1]]&lt;br /&gt;
&lt;br /&gt;
[[ANAT2341 Lab 1|Fertilization Lab]]&lt;br /&gt;
 &lt;br /&gt;
[[Student Page]]&lt;br /&gt;
&lt;br /&gt;
==Referencing==&lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/sites/entrez?db=pubmed&amp;amp;cmd=search&amp;amp;term=fertilization fertilization]&lt;br /&gt;
&lt;br /&gt;
PMID 27486480&lt;br /&gt;
&lt;br /&gt;
==Assessment 1==&lt;br /&gt;
&amp;lt;pubmed&amp;gt;PMC3528851&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&lt;br /&gt;
The research article called &amp;quot; Tet1 controls meiosis by regulating meiotic gene expression&amp;quot; by Yamaguchi et al. (2012) aims to determine the role of ten-eleven translocation methylcytosine dioxygenase 1 (TET1) which is a member of the TET family of enzymes, in regulating meiotic gene expression and thus meiosis in mice. This study was highly useful since little is known about how the expression of meiotic genes is regulated and how their expression contributes to normal meiosis. &lt;br /&gt;
In the study they performed a whole-genome bisulphite sequencing (WGBS) analysis using an ultra-low input so that they would be able to see how Tet1 is used in the activation of meiotic genes. &lt;br /&gt;
&lt;br /&gt;
Results showed that a decreased functioning of Tet1 caused an increase in the unpaired synaptonemal complex at zygotene-stage oocyte, suggesting a synapsis-formation defect. The meiotic defects seen from Tet1 loss of function included: formation of univalent chromosome, but also homologous recombination and DNA double-strand breaks (DSBs) repair defects. These in turn caused defective meiotic prophase which caused decreased amount of oocytes and in turn reduced litter size and lowering in fertility. The study done was pivotal as it built upon past studies which have already established that DNA methylation levels of certain meiotic genes are lowered with genomic reprogramming.&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
{| width=95%&lt;br /&gt;
|-bgcolor=&amp;quot;FAF5FF&amp;quot;&lt;br /&gt;
| [mailto:m.hill@unsw.edu.au Mark Hill] 18 August 2016 - You have added the citation correctly and written a good brief summary of the article findings. &lt;br /&gt;
TET1 is part of the family of methylcytosine dioxygenases that involved in cytosine demethylation and gene activation, interesting that it has a meiotic-specific role.&lt;br /&gt;
&lt;br /&gt;
| width=100px| Assessment 5/5&lt;br /&gt;
|}&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
{{Stem Cell Presentations 2016}}&lt;br /&gt;
&lt;br /&gt;
===Lab 9: Peer Assessment===&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
GROUP 1&lt;br /&gt;
Through reading through and analysing group 1’s project it is starkly clear they have managed to relay some excellent information and present it in quite an easily digestible manner. That said though, there are some things which they could improve upon as well. I shall be dissecting what they have done well and what they could improve upon. The information they have regarding signalling pathways of the Wnt receptor in embryonic development is complex and intricate so they have done well by creating subheadings to more easily navigate the vastness of information displayed. This relates directly to criteria 2 in the “Group Assessment Criteria”. However, as seen in the criteria there are also other techniques such as diagrams, tables, graphs which could be employed to further add upon the excellence of this project. Moving onto criteria 3 we can see that there has been some referencing and citing, however it was hard to find and not clearly written. The part that was well referenced was under the “Non-Canonical Pathway – Caroline”. It’s starkly clear to me that these group members have truly gone beyond the formal teaching activities, as described in criteria 5, and have done some significant research exploring the abnormalities associated with the Wnt pathway be describing the interruptions in the pathway and its relation to cancer. &lt;br /&gt;
&lt;br /&gt;
GROUP 2&lt;br /&gt;
Moving the the 2nd group I can see that their topic is mainly about the Notch receptor. They seem to elucidate upon different aspects of the receptor, like it’s role in embryonic development and molecular pathways. The aspect done especially well in this group is the vastness and breadth of their information. They explore numerous aspects of the Notch receptor, including the abnormalities that can arise in development. By showing such a vastness and clarity in their research they successfully achieve criteria 1. Furthermore, Group 2 has a phenomenal amount of tables, diagrams and figures describing canonical Notch signalling and the history of the discoveries for these receptors. This qualifies criteria 2 very well as they have included all these as well as headings and sub headings in a succinct manner. Moving onto referencing, this group has done a fantastic job in that aspect as they have a separate section for references, which is clear and easy to understand, fulfilling criteria 3. Overall, I have been able to learn from this group’s project and thus I believe that they fulfil an aspect of criteria 4, in that they have an element of teaching for peers. Improvements I might suggest would be having an even larger array of different learning outlets or media types. Examples could include maybe having a video included in your group project. In terms of improvements to specific information, maybe quickly glance over the different types of receptors and the different pathways they have. &lt;br /&gt;
&lt;br /&gt;
GROUP 3&lt;br /&gt;
&lt;br /&gt;
Overall from analysing through Group 3’s project I can starkly see that they have made a good attempt at addressing the marking criteria. The flow and clarity of the information in this project shows some serious thought and is showing a promising coverage of criteria 1. Not only this, but the group has excellently covered criteria 2 by having a plethora of headings, subheadings, tables and diagrams. Not only this but they have included a quiz which really shows an extra level of understanding and effort. One improvement that I might suggest is that they could extend the table by researching more developments in the field of FGF Signaling. Furthermore, this group has covered criteria 3 quite well as well but having a thorough amount of references and in text citations. Also, I have been able to learn a great amount of information from this project which means they have successfully achieved criteria 4. Overall, this project has done very well in presenting their project. &lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
GROUP 4&lt;br /&gt;
From reading through Group 4’s project I can see they are clearly and succinctly describing the topic at hand, which is related to the hedgehog pathway. They explore things such as the mechanism of signalling during embryonic development as well as neural and organ development. From reading their research I can see they have carefully written it according it to criteria 1. Unfortunately, their use of headings and sub-headings, diagrams, tables, graphs is not as good as it could be. They have used an imagine of the Hedgehog signaling pathway, which is a good start, but to improve and further fulfil this criterion I would suggest having more media. The referencing has been done quite well as it has its own section and is easy to find, but also there are quite regular in text citations, fulfilling criteria 3. &lt;br /&gt;
&lt;br /&gt;
GROUP 5&lt;br /&gt;
&lt;br /&gt;
From reading through Group 5’s project I can see that they having clearly and effectively talked about topics relating to Tbx genes. Their subheadings include animal models, history, function in embryonic development, as well as abnormalities. This provides evidence to me that they have obviously considered and addressed both criteria’s 6 and 1. Group 5 has done a fantastic job with criteria 2, in that they provide many visual representations of information with different forms. For examples they provide a table of the main T-box genes, but then also have many visual diagrams relating to the Tbx development. Even though criteria 2 is very well done, it could be improved by having a timeline of the history of the T-box family. Also, I have seen in some other groups that they have included multiple choice questions to test the audience on their knowledge, I think this is a good idea since it makes the learning experience more interactive.&lt;/div&gt;</summary>
		<author><name>Z5020466</name></author>
	</entry>
	<entry>
		<id>https://embryology.med.unsw.edu.au/embryology/index.php?title=User:Z5020466&amp;diff=256939</id>
		<title>User:Z5020466</title>
		<link rel="alternate" type="text/html" href="https://embryology.med.unsw.edu.au/embryology/index.php?title=User:Z5020466&amp;diff=256939"/>
		<updated>2016-11-10T05:40:37Z</updated>

		<summary type="html">&lt;p&gt;Z5020466: /* =Lab 9: Peer Assessment */&lt;/p&gt;
&lt;hr /&gt;
&lt;div&gt;{{ANAT2341Student2016}}&lt;br /&gt;
&lt;br /&gt;
==Lab Attendance==&lt;br /&gt;
[[User:Z5020466|Z5020466]] ([[User talk:Z5020466|talk]]) 14:42, 12 August 2016 (AEST)&lt;br /&gt;
[[User:Z5020466|Z5020466]] ([[User talk:Z5020466|talk]]) 13:46, 26 August 2016 (AEST)&lt;br /&gt;
[[User:Z5020466|Z5020466]] ([[User talk:Z5020466|talk]]) 13:53, 7 October 2016 (AEDT)&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
===Belbin Team Roles===&lt;br /&gt;
If I’m completely honest, I think my role in group work is generally the “Co-ordinator”. I’m not too sure about my ability to step back from the ‘nitty gritty’ details and see the bigger picture. But rather I generally like to take on leadership roles and assign people tasks. That way I can do things how I like to and place people in roles that I think they would be suited to. But not only that I think to be a good leader you have to be a good worker. So I try to lead by example and not really depend on others too much so that if something has messed up, I have no one to blame but myself. This part about Co-ordinators made me chuckle. “Sometimes perceived to be manipulative and will tend to delegate all work” which is unfortunately a little true. But at the same time I’ve been open to working an equal amount as others previously as well.&lt;br /&gt;
&lt;br /&gt;
===Lecture 1: Fertilisation===&lt;br /&gt;
In my previous years in attending university I’ve completed many courses which have gone through the fertilization process such as: Evolutionary Biological Sciences, Physiology, Histology and Pathology. From having done these courses already, there were parts which were familiar to me and that I have understood before in the past. However, I still was amazed by the new refreshing things I have not yet encounter which I did during this lecture. Such as polar bodies and their role in fertilization in disposing of extra DNA. It also clarified a point which I was previously confused about on whether or not polar bodies were gametes or not. Cementing all this information and weaving it in with new learnt information has really been a beneficial experience for me, in that I’m building up on topics I thoroughly enjoy.&lt;br /&gt;
&lt;br /&gt;
==New SubHeading==&lt;br /&gt;
===External Link===&lt;br /&gt;
[http://www.smh.com.au/ SMH]&lt;br /&gt;
&lt;br /&gt;
===Internal Link===&lt;br /&gt;
[[ANAT2341 Lab 1]]&lt;br /&gt;
&lt;br /&gt;
[[ANAT2341 Lab 1|Fertilization Lab]]&lt;br /&gt;
 &lt;br /&gt;
[[Student Page]]&lt;br /&gt;
&lt;br /&gt;
==Referencing==&lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/sites/entrez?db=pubmed&amp;amp;cmd=search&amp;amp;term=fertilization fertilization]&lt;br /&gt;
&lt;br /&gt;
PMID 27486480&lt;br /&gt;
&lt;br /&gt;
==Assessment 1==&lt;br /&gt;
&amp;lt;pubmed&amp;gt;PMC3528851&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&lt;br /&gt;
The research article called &amp;quot; Tet1 controls meiosis by regulating meiotic gene expression&amp;quot; by Yamaguchi et al. (2012) aims to determine the role of ten-eleven translocation methylcytosine dioxygenase 1 (TET1) which is a member of the TET family of enzymes, in regulating meiotic gene expression and thus meiosis in mice. This study was highly useful since little is known about how the expression of meiotic genes is regulated and how their expression contributes to normal meiosis. &lt;br /&gt;
In the study they performed a whole-genome bisulphite sequencing (WGBS) analysis using an ultra-low input so that they would be able to see how Tet1 is used in the activation of meiotic genes. &lt;br /&gt;
&lt;br /&gt;
Results showed that a decreased functioning of Tet1 caused an increase in the unpaired synaptonemal complex at zygotene-stage oocyte, suggesting a synapsis-formation defect. The meiotic defects seen from Tet1 loss of function included: formation of univalent chromosome, but also homologous recombination and DNA double-strand breaks (DSBs) repair defects. These in turn caused defective meiotic prophase which caused decreased amount of oocytes and in turn reduced litter size and lowering in fertility. The study done was pivotal as it built upon past studies which have already established that DNA methylation levels of certain meiotic genes are lowered with genomic reprogramming.&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
{| width=95%&lt;br /&gt;
|-bgcolor=&amp;quot;FAF5FF&amp;quot;&lt;br /&gt;
| [mailto:m.hill@unsw.edu.au Mark Hill] 18 August 2016 - You have added the citation correctly and written a good brief summary of the article findings. &lt;br /&gt;
TET1 is part of the family of methylcytosine dioxygenases that involved in cytosine demethylation and gene activation, interesting that it has a meiotic-specific role.&lt;br /&gt;
&lt;br /&gt;
| width=100px| Assessment 5/5&lt;br /&gt;
|}&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
{{Stem Cell Presentations 2016}}&lt;/div&gt;</summary>
		<author><name>Z5020466</name></author>
	</entry>
	<entry>
		<id>https://embryology.med.unsw.edu.au/embryology/index.php?title=User:Z5020466&amp;diff=256937</id>
		<title>User:Z5020466</title>
		<link rel="alternate" type="text/html" href="https://embryology.med.unsw.edu.au/embryology/index.php?title=User:Z5020466&amp;diff=256937"/>
		<updated>2016-11-10T05:39:35Z</updated>

		<summary type="html">&lt;p&gt;Z5020466: /* Lab Attendance */&lt;/p&gt;
&lt;hr /&gt;
&lt;div&gt;{{ANAT2341Student2016}}&lt;br /&gt;
&lt;br /&gt;
==Lab Attendance==&lt;br /&gt;
[[User:Z5020466|Z5020466]] ([[User talk:Z5020466|talk]]) 14:42, 12 August 2016 (AEST)&lt;br /&gt;
[[User:Z5020466|Z5020466]] ([[User talk:Z5020466|talk]]) 13:46, 26 August 2016 (AEST)&lt;br /&gt;
[[User:Z5020466|Z5020466]] ([[User talk:Z5020466|talk]]) 13:53, 7 October 2016 (AEDT)&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
===Belbin Team Roles===&lt;br /&gt;
If I’m completely honest, I think my role in group work is generally the “Co-ordinator”. I’m not too sure about my ability to step back from the ‘nitty gritty’ details and see the bigger picture. But rather I generally like to take on leadership roles and assign people tasks. That way I can do things how I like to and place people in roles that I think they would be suited to. But not only that I think to be a good leader you have to be a good worker. So I try to lead by example and not really depend on others too much so that if something has messed up, I have no one to blame but myself. This part about Co-ordinators made me chuckle. “Sometimes perceived to be manipulative and will tend to delegate all work” which is unfortunately a little true. But at the same time I’ve been open to working an equal amount as others previously as well.&lt;br /&gt;
&lt;br /&gt;
===Lecture 1: Fertilisation===&lt;br /&gt;
In my previous years in attending university I’ve completed many courses which have gone through the fertilization process such as: Evolutionary Biological Sciences, Physiology, Histology and Pathology. From having done these courses already, there were parts which were familiar to me and that I have understood before in the past. However, I still was amazed by the new refreshing things I have not yet encounter which I did during this lecture. Such as polar bodies and their role in fertilization in disposing of extra DNA. It also clarified a point which I was previously confused about on whether or not polar bodies were gametes or not. Cementing all this information and weaving it in with new learnt information has really been a beneficial experience for me, in that I’m building up on topics I thoroughly enjoy.&lt;br /&gt;
&lt;br /&gt;
====Lab 9: Peer Assessment===&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
GROUP 1&lt;br /&gt;
Through reading through and analysing group 1’s project it is starkly clear they have managed to relay some excellent information and present it in quite an easily digestible manner. That said though, there are some things which they could improve upon as well. I shall be dissecting what they have done well and what they could improve upon. The information they have regarding signalling pathways of the Wnt receptor in embryonic development is complex and intricate so they have done well by creating subheadings to more easily navigate the vastness of information displayed. This relates directly to criteria 2 in the “Group Assessment Criteria”. However, as seen in the criteria there are also other techniques such as diagrams, tables, graphs which could be employed to further add upon the excellence of this project. Moving onto criteria 3 we can see that there has been some referencing and citing, however it was hard to find and not clearly written. The part that was well referenced was under the “Non-Canonical Pathway – Caroline”. It’s starkly clear to me that these group members have truly gone beyond the formal teaching activities, as described in criteria 5, and have done some significant research exploring the abnormalities associated with the Wnt pathway be describing the interruptions in the pathway and its relation to cancer. &lt;br /&gt;
&lt;br /&gt;
GROUP 2&lt;br /&gt;
Moving the the 2nd group I can see that their topic is mainly about the Notch receptor. They seem to elucidate upon different aspects of the receptor, like it’s role in embryonic development and molecular pathways. The aspect done especially well in this group is the vastness and breadth of their information. They explore numerous aspects of the Notch receptor, including the abnormalities that can arise in development. By showing such a vastness and clarity in their research they successfully achieve criteria 1. Furthermore, Group 2 has a phenomenal amount of tables, diagrams and figures describing canonical Notch signalling and the history of the discoveries for these receptors. This qualifies criteria 2 very well as they have included all these as well as headings and sub headings in a succinct manner. Moving onto referencing, this group has done a fantastic job in that aspect as they have a separate section for references, which is clear and easy to understand, fulfilling criteria 3. Overall, I have been able to learn from this group’s project and thus I believe that they fulfil an aspect of criteria 4, in that they have an element of teaching for peers. Improvements I might suggest would be having an even larger array of different learning outlets or media types. Examples could include maybe having a video included in your group project. In terms of improvements to specific information, maybe quickly glance over the different types of receptors and the different pathways they have. &lt;br /&gt;
&lt;br /&gt;
GROUP 3&lt;br /&gt;
&lt;br /&gt;
Overall from analysing through Group 3’s project I can starkly see that they have made a good attempt at addressing the marking criteria. The flow and clarity of the information in this project shows some serious thought and is showing a promising coverage of criteria 1. Not only this, but the group has excellently covered criteria 2 by having a plethora of headings, subheadings, tables and diagrams. Not only this but they have included a quiz which really shows an extra level of understanding and effort. One improvement that I might suggest is that they could extend the table by researching more developments in the field of FGF Signaling. Furthermore, this group has covered criteria 3 quite well as well but having a thorough amount of references and in text citations. Also, I have been able to learn a great amount of information from this project which means they have successfully achieved criteria 4. Overall, this project has done very well in presenting their project. &lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
GROUP 4&lt;br /&gt;
From reading through Group 4’s project I can see they are clearly and succinctly describing the topic at hand, which is related to the hedgehog pathway. They explore things such as the mechanism of signalling during embryonic development as well as neural and organ development. From reading their research I can see they have carefully written it according it to criteria 1. Unfortunately, their use of headings and sub-headings, diagrams, tables, graphs is not as good as it could be. They have used an imagine of the Hedgehog signaling pathway, which is a good start, but to improve and further fulfil this criterion I would suggest having more media. The referencing has been done quite well as it has its own section and is easy to find, but also there are quite regular in text citations, fulfilling criteria 3. &lt;br /&gt;
&lt;br /&gt;
GROUP 5&lt;br /&gt;
&lt;br /&gt;
From reading through Group 5’s project I can see that they having clearly and effectively talked about topics relating to Tbx genes. Their subheadings include animal models, history, function in embryonic development, as well as abnormalities. This provides evidence to me that they have obviously considered and addressed both criteria’s 6 and 1. Group 5 has done a fantastic job with criteria 2, in that they provide many visual representations of information with different forms. For examples they provide a table of the main T-box genes, but then also have many visual diagrams relating to the Tbx development. Even though criteria 2 is very well done, it could be improved by having a timeline of the history of the T-box family. Also, I have seen in some other groups that they have included multiple choice questions to test the audience on their knowledge, I think this is a good idea since it makes the learning experience more interactive.&lt;br /&gt;
&lt;br /&gt;
==New SubHeading==&lt;br /&gt;
===External Link===&lt;br /&gt;
[http://www.smh.com.au/ SMH]&lt;br /&gt;
&lt;br /&gt;
===Internal Link===&lt;br /&gt;
[[ANAT2341 Lab 1]]&lt;br /&gt;
&lt;br /&gt;
[[ANAT2341 Lab 1|Fertilization Lab]]&lt;br /&gt;
 &lt;br /&gt;
[[Student Page]]&lt;br /&gt;
&lt;br /&gt;
==Referencing==&lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/sites/entrez?db=pubmed&amp;amp;cmd=search&amp;amp;term=fertilization fertilization]&lt;br /&gt;
&lt;br /&gt;
PMID 27486480&lt;br /&gt;
&lt;br /&gt;
==Assessment 1==&lt;br /&gt;
&amp;lt;pubmed&amp;gt;PMC3528851&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&lt;br /&gt;
The research article called &amp;quot; Tet1 controls meiosis by regulating meiotic gene expression&amp;quot; by Yamaguchi et al. (2012) aims to determine the role of ten-eleven translocation methylcytosine dioxygenase 1 (TET1) which is a member of the TET family of enzymes, in regulating meiotic gene expression and thus meiosis in mice. This study was highly useful since little is known about how the expression of meiotic genes is regulated and how their expression contributes to normal meiosis. &lt;br /&gt;
In the study they performed a whole-genome bisulphite sequencing (WGBS) analysis using an ultra-low input so that they would be able to see how Tet1 is used in the activation of meiotic genes. &lt;br /&gt;
&lt;br /&gt;
Results showed that a decreased functioning of Tet1 caused an increase in the unpaired synaptonemal complex at zygotene-stage oocyte, suggesting a synapsis-formation defect. The meiotic defects seen from Tet1 loss of function included: formation of univalent chromosome, but also homologous recombination and DNA double-strand breaks (DSBs) repair defects. These in turn caused defective meiotic prophase which caused decreased amount of oocytes and in turn reduced litter size and lowering in fertility. The study done was pivotal as it built upon past studies which have already established that DNA methylation levels of certain meiotic genes are lowered with genomic reprogramming.&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
{| width=95%&lt;br /&gt;
|-bgcolor=&amp;quot;FAF5FF&amp;quot;&lt;br /&gt;
| [mailto:m.hill@unsw.edu.au Mark Hill] 18 August 2016 - You have added the citation correctly and written a good brief summary of the article findings. &lt;br /&gt;
TET1 is part of the family of methylcytosine dioxygenases that involved in cytosine demethylation and gene activation, interesting that it has a meiotic-specific role.&lt;br /&gt;
&lt;br /&gt;
| width=100px| Assessment 5/5&lt;br /&gt;
|}&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
{{Stem Cell Presentations 2016}}&lt;/div&gt;</summary>
		<author><name>Z5020466</name></author>
	</entry>
	<entry>
		<id>https://embryology.med.unsw.edu.au/embryology/index.php?title=2016_Group_Project_6&amp;diff=255386</id>
		<title>2016 Group Project 6</title>
		<link rel="alternate" type="text/html" href="https://embryology.med.unsw.edu.au/embryology/index.php?title=2016_Group_Project_6&amp;diff=255386"/>
		<updated>2016-10-27T13:30:29Z</updated>

		<summary type="html">&lt;p&gt;Z5020466: /* Loeys–Dietz syndrome */&lt;/p&gt;
&lt;hr /&gt;
&lt;div&gt;{{ANAT2341Project2016header}}&lt;br /&gt;
{{Group Assessment Criteria table}}&lt;br /&gt;
&amp;lt;!-- Do not delete the above template from the Group project page. --&amp;gt;&lt;br /&gt;
&lt;br /&gt;
=Transforming Growth Factor-Beta (TGF-β) Signalling Pathway=&lt;br /&gt;
&lt;br /&gt;
==Introduction==&lt;br /&gt;
&lt;br /&gt;
The transforming growth factor beta (TGF-β) is a multifunctional and pleiotropic cytokine &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;26555259&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;.&lt;br /&gt;
The TGF-β signalling pathway is crucial to the control of different biological and pathological processes, such as cellular proliferation and differentiation, angiogenesis, immune regulation/inflammation, apoptosis and cell survival. &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;17896911&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
TGF-β belongs to the Transforming Growth Factor superfamily - a large group of structually connected cell regulatory proteins. It consists of TGF-β 1, 2 AND 3, Growth Differentiation Factors (GDFs), Activins, Inhibins, Bone Morphogenetic Proteins (BMPs), Glial-derived Neurotrophic Factors (GDNFs) and Mullierian Inhibiting Substance (MIS). &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;24270394&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
Most importantly, TGF-β plays a dominant part in the development of the embryo and adult organism. &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;23926286&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
This wiki aims to present a helpful overview of the TGF-β signalling pathway, but is in no means a complete resource on all information regarding the topic. This site focuses on particular aspects of the pathway, such as its history, process, regulation, significance in embryonic development, animal studies and abnormalities.&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&amp;lt;br&amp;gt;&amp;lt;br&amp;gt;&lt;br /&gt;
&amp;lt;div align=&amp;quot;center&amp;quot;&amp;gt;&amp;lt;html5media width=&amp;quot;560&amp;quot; height=&amp;quot;315&amp;quot;&amp;gt;https://www.youtube.com/watch?v=GuKjUearIUI&amp;lt;/html5media&amp;gt;&amp;lt;/div&amp;gt;&lt;br /&gt;
&amp;lt;br&amp;gt;&lt;br /&gt;
&lt;br /&gt;
==History==&lt;br /&gt;
Since the early stages of the TGF beta-signaling pathway, plenty of in-depth research and studies have been conducted that have no doubt contributed to our knowledge of the pathway today.&lt;br /&gt;
&lt;br /&gt;
SMAD signaling and the three receptors for TGF-beta are two of the many fields of interest regarding the topic. In medicine and specific areas such as cancer, cardiovascular disease and inflammatory bowel disease, there are numerous alternatives for drugs that can either heighten or suppress the activity of TGF-beta.&lt;br /&gt;
&lt;br /&gt;
{| class=&amp;quot;pretty table&amp;quot;&lt;br /&gt;
| '''1988'''&lt;br /&gt;
| The process of maturation of follicle-enclosed oocytes and cumulus-oocyte complexes was sped up by TGF beta. It was discovered that TGF beta and other growth factors are effective in vitro stimulators of oocyte maturation in the rat&lt;br /&gt;
&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;3275534&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
|-&lt;br /&gt;
| '''1989'''&lt;br /&gt;
| It was already known that TGF-beta 1 is a strong autocrine growth inhibitor of lymphocytes. Ellingsworth and colleagues found that TGF-beta 1 binds to all three cell surface-binding proteins (280-200 kD, 95-85 kD, 65 kD).&lt;br /&gt;
It was also found that these binding proteins are required for signal transduction. Overall, they discovered that the regulation of the expression of the TGF-beta 1 receptor is controlled by T cell mitogenic signals.&lt;br /&gt;
&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;2785999&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
|-&lt;br /&gt;
| '''1989'''&lt;br /&gt;
| It was made known that the properties of R mutants classify TGF-beta type I binding protein as the receptor involved in mediating TGF-beta actions on cell adhesion and proliferation&lt;br /&gt;
&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;2536702&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
|-&lt;br /&gt;
| '''1989'''&lt;br /&gt;
| Drosophil was the only member of the TGF-beta family to be identified in invertebrates &lt;br /&gt;
&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;2699859&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
|-&lt;br /&gt;
| '''1990'''&lt;br /&gt;
| It was already known that the rapid increase in number response of mink lung epithelial cells to serum and to epidermal growth factor was inhibited by TGF beta 1. A necessary component of TGF-beta 1 mediated growth inhibition in CCL64 epithelial cells is the coupling of TGF beta 1 receptor binding to G-protein activation&lt;br /&gt;
&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;2156499&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
|-&lt;br /&gt;
| '''2000'''&lt;br /&gt;
| VegT function was found to be involved in sequence with the TGF beta pathway. Therefore, TGF beta signaling may be activated by the maternally expressed VegT to participate in endoderm determination&lt;br /&gt;
&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;10640706&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
|-&lt;br /&gt;
| '''2005'''&lt;br /&gt;
| Within the TGF beta superfamily, it was found that a limited number of type I and type II receptors worked together to produce specificity of action &lt;br /&gt;
&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;15483083&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
|-&lt;br /&gt;
| '''2010'''&lt;br /&gt;
| Deregulation of TGF beta signaling was reported in human psoriasis&lt;br /&gt;
&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;19710682&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
|-&lt;br /&gt;
| '''2015'''&lt;br /&gt;
| It was known that TGF is required in the tumorigenicity and metastasis of bone tumour. A significant event in the activation of the TGF beta signaling pathway is the binding of transcription coactivator Yes-associated protein (YAP) to Smad transcription factors&lt;br /&gt;
&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;27491038&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
|}&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
[[File:Canonical and non-canonical signalling TGF beta pathways.png|thumb|500px|Flowchart showing the Canonical and Non-Canonical pathways of TGF-β signalling pathway.&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;24393789&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;]] &lt;br /&gt;
===Canonical pathway===&lt;br /&gt;
In the canonical pathway, the dormant TGF-β complex is formed when the three TGF-β ligand isoforms - TGF-B1, TGF-B2 and TGF-B3 - bind once it is synthesized as precursors. After secretion and extracellular activation, TGF-β ligands can bind to two types of receptors: the membranous TGF-β type III receptor or the TGF-β type II receptor (TGF-βRII) homodimers with high affinity. &lt;br /&gt;
TGF-βRII binding enables dimerization with TGF-β type I receptor (TGF-βRI) homodimers, as well as activation of the TGF-βRI kinase domain and signal transduction across phosphorylation of the C-terminus of receptor-regulated SMADs, SMAD2 and SMAD3.&lt;br /&gt;
A heterotrimeric complex is formed by the TGF-βR dimer and SMAD4, which moves and assemblies in the nucleus.&lt;br /&gt;
TGF-β dependent signalling can operate or subdue numerous target genes through the communication of SMADs with multiple transcription factors. There are many structures in which SMAD activities are regulated, such as SMAD2/3 nucleocytoplasmic shuttling, binding to anchor proteins, phosphorylation and Smurf (SMAD-ubiquitination-regulatory factor).  &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;24393789 &amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
&lt;br /&gt;
===Non-Canonical pathway===&lt;br /&gt;
In the non-canonical pathway, SMAD-independent pathways such as PI3K/AKT and MAPK pathways like ERK, JNK, and p38 MAPK are activated by TGF-β signalling. In addition, transversal signalling, especially at the SMAD level, allows TGF-β pathway activation to incorporate signals from integrins, Notch and Wnt dependent pathways as well as signals from cellular processes like the cell cycle or apoptosis machineries. Thus, the TGF-β signalling pathway has pleiotropic functions regulating cell growth, differentiation, apoptosis, cell motility, extracellular matrix production, angiogenesis and cellular immune response.&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;24393789 &amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
&lt;br /&gt;
==Process of TGF-β signalling pathway==&lt;br /&gt;
&lt;br /&gt;
TGF-β signalling pathway is required for regulation of a large number of cellular processes such as cell proliferation, invasion and inflammation. It is also activated mitogen activated protein kinase signalling. There are two main routes in TGF-β signalling; the SMAD Dependent pathway and SMAD Independent pathway.&lt;br /&gt;
&lt;br /&gt;
===SMAD Dependent TGF-β signalling pathway===&lt;br /&gt;
&lt;br /&gt;
[[File:TGF-B Signalling - Formation of Receptor Hetero-Tetramers.png|thumb|350px|SMAD Dependent TGF-β signalling pathway: Formation of Receptor Hetero-Tetramers&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;16446785&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;]]&lt;br /&gt;
&lt;br /&gt;
The ligands of the TGF-β superfamily form dimers that bind to heterodimeric receptor complexes composed of two type I and two type II transmembrane receptor subunits with serine/threonine kinase domains.&lt;br /&gt;
Following ligand binding on TGF-β1, the dimerized TGF-β type II receptors phosphorylates and activates the TGF-β type I receptors. In most cell types, this leads to recruitment and phosphorylation of the receptor-regulated SMAD2 and SMAD3, presented by the SMAD anchor for receptor activation. SMAD1 and SMAD5 can be activated by the TGF-β signaling depending on the Type I receptor that is expressed.&lt;br /&gt;
Heterologous complexes are formed by the phosphorylated receptor-regulated SMAD with the common-mediator SMAD, SMAD4, and successively move into the nucleus, where they accumulate and act as transcription factors participating in the regulation of target gene expression. &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;21302608&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
In addition, they recruit extra transcriptional regulators, such as DNA-binding transcription factors, co-activators and co-repressors. These control the expression of several target genes and ultimately initiates a SMAD-dependent signaling cascade that induces or represses transcriptional activity. SMADs are widely expressed in most adult tissue and cell types, indicating that the TGF-β signaling pathway is ubiquitous.&lt;br /&gt;
&lt;br /&gt;
===SMAD independent TGF-β signalling pathway===&lt;br /&gt;
&lt;br /&gt;
Rather than SMAD-mediated transciption TGF-β also has the potential to activate other signalling cascades for example the Erk, JNK and p38 MAPK kinase pathways. In some cases these pathways exhibit activation with slow kinetics which indicates SMAD-dependant mechanics, however there has also been rapid activation cases (5-15mins) suggesting independence from transcription mechanisms. Studies carried out with SMAD4 deficient cells and dominant-negative SMADS provide evidence that the MAPK pathway activation is independent from SMADS, as well as this it has be found that p38 MAPK signalling  was activated in response to mutated TGF- β type 1 receptors, which were defective in SMAD activation&amp;lt;ref name=&amp;quot;PMID14534577&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;14534577&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;.&lt;br /&gt;
&lt;br /&gt;
The precise mechanisms and biological consequences of these SMAD-Independent pathways (Erk, JNK, p38 MAPK) are currently poorly characterized. Ras is implicated in TGF- β induced Erk signalling as there is rapid activation of Ras by TGF- β in epithelial cells. The JNK and p38 MAPK signalling are activated by various MAPK kinase kinases (MAPKKK) TGF- β kinase 1 (TAK 1) receptor is a MAPKKK family member. Further research and identification of various interactions between the small signalling molecules and receptor proteins will provide additional insight into the precise mechanism behind the activation of MAPK pathways by TGF- β ligands &amp;lt;ref name=&amp;quot;PMID14534577&amp;quot;/&amp;gt;.&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
==Regulation of the pathway and factors affecting it==&lt;br /&gt;
&lt;br /&gt;
Signalling mechanisms by TGF-β like factors are regulated in both negative and positive fashions, these are all tightly controlled through a multitude of mechanisms at extracellular, membrane, cytoplasmic and all the way to nuclear levels. Positive regulation is required to amplify signalling from TGF-β like factors, while negative regulation is important for the termination and restriction of signalling usually occurring through the mechanism of a feedback loop. There is also additional regulation of TGF-β like factors via cross-talk with other signal transduction pathways such as MAPK and JAK/STAT pathways.&amp;lt;ref name=&amp;quot;PMID10704361&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;10704361&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
===Positive Regulation===&lt;br /&gt;
The positive regulation of TGF-β specifically the induction of ligands and their signalling components often is triggered by the action TGF-β-like factors themselves. For example NODAL, a secretory protein of the TGF-β superfamily which plays a role in early embryogenesis and acts through activin receptors and SMAD2 is induced by nodal signalling itself. In other types of cells TGF-β receptors as well as transcription factors which serve as targets for TGF-β like factors can be induced by ligand stimulation, as identified in case of transcription factor Runx3 which is induced by TGF-β and forms a complex with SMAD3 to be further activated by TGF-β. The mechanism of SMAD signalling is also positively modulated via the &amp;quot;cross-talk&amp;quot; (and hence the process of SMAD dependant TGF-β signalling) with other signalling pathways, SMADS may be activated by the tyrosine kinase receptor under specific circumstances and further positively regulate TGF-β like factors &amp;lt;ref name=&amp;quot;PMID10704361&amp;quot;/&amp;gt;.&lt;br /&gt;
&lt;br /&gt;
===Negative Regulation===&lt;br /&gt;
&lt;br /&gt;
Signalling is regulated at the cell membrane level as well as within the cytoplasm of the cell, specifically by BAMBI, a pseudo-receptor for serine/threonine kinase receptors (in Xenopus embryos however displays a high degree of sequence similarity to human BAMBI gene). This BAMBI receptor is structurally alike to the type 1 serine/threonine kinase receptor, the only difference being that it lacks an intracellular domain. BAMBI  has shown a similar expression profile to that of BMP-4 a growth factor from the TGF-β super family, and has been found to require BMP signalling for expression. BAMBI when goes on to interact with both type 1 and type 2 serine/threonine receptors and works to abolish their abilities to signal via BMPs, activins and TGF-βs, therefore it is postulated that BAMBI can be inductively expressed by BMPS to self regulate BMP signalling as well as cross-regulate signalling from other members of the TGF-β super family. &amp;lt;ref name=&amp;quot;PMID10704361&amp;quot;/&amp;gt;&lt;br /&gt;
&lt;br /&gt;
==Significance in Embryonic Development==&lt;br /&gt;
&lt;br /&gt;
TGF betas are involved in embryogenesis. During development of the embryo, members of the TGF-beta family are essential for bone and cartilage formation, mesoderm induction and patterning and dorso-ventral patterning.&lt;br /&gt;
&lt;br /&gt;
[[File:TGF in Cardiovascular.jpg|thumb|500px|Expression of TGF-β2 and TGF-β3 in wildtype embryonic hearts.&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;12948523&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;]]&lt;br /&gt;
===Cardiovascular Development===&lt;br /&gt;
&lt;br /&gt;
Genetic engineering and tissue explanation studies have revealed many roles for TGF-β ligands and their signaling molecules in development. In the embryo, TGF-β appear to be involved in epithelial-mesenchymal transformations (EMT) during the formation of endocardial cushions, and in epicardial epithelial-mesenchymal transformations essential for coronary vasculature, ventricular myocardial development and compaction. It must be noted that in the normal function of the cardiovascular system in the adult, TGF-β play significant roles in cardiac hypertrophy, vascular remodeling and regulation of the renal renin-angiotensin system.&lt;br /&gt;
&lt;br /&gt;
TGF-β1 is expressed in the endocardium of the developing mouse. TGF-β(-/-) mice have been found with obvious congenital cardiovascular defects, so it’s important to review its expression in the developing heart. In the blood vessels, TGF-β1 is in the intima whereas TGF-β2 and TGF-β3 are in the media and adventitia. TGF-β2 signals are found as early as embryonic day 7.25 (E7.25) &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;7687212&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; in the cardiogenic plate of the precardiac mesoderm and is later prominent in the myocardium of the aortic sac and outflow track regions. TGF-β2 protein is also found in the entire myocardium of the heart at the time when looping occurs. From E8.5-9.5 when the cushion formation process occurs, there is a particularly strong TGF-β2 expression localised to the myocardium as displayed in A, B, D and E in the figure. After cushion formation and EMT, and before myocardialization of the endocardial cushion begins, there is also strong TGF-β2 expression in the OT myocardium and in the adjacent developing cushion mesenchym. However, as myocardialization occurs, TGF-β2 expression is reduced in the myocardium so that from E12.5 onwards, it is only expressed mainly in the mesenchyme of the cushion and OT septum. As can be seen in 2GH, TGF-β2 expression remains high in the cushion mesenchyme of the OT septum. By E15.5, TGF-β1 s now the most highly expressed isoform in the endocardial cells of the myocardium. It is seen in M, N, O of the figure that the epidcardium TGF-β1 and TGF-β3 expression is higher than that of TGF-β2. Thus, it can be seen that all three TGF-β are expressed in the epicardium, and they are not expressed in an overlapping fashion.&lt;br /&gt;
&lt;br /&gt;
Cross talk between mesoderm and underlying endoderm is needed to form the early tubular heart. This cellular and molecular induction in the primary heart forming regions is important for the specification and differentiation of myocardial and endocardial precursor cells &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;10767078&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;. Other endoderm-derived growth factors such as BMP2, FGF2 as well as TGFBS have been implicated in this process in the avian system &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;11322300&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;. TGFB2 and TGFB receptors are expressed in the precardiac mesoderm along with BMP2 &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;7687212&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;10767078&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;10340759&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;. Members of the TGG family can serve as inductive signals at the heart forming fields for the formation of myocardial and endocardial precursor cells. Members such as Activin, BMP, Nodal, Left and others have been found to be crucial for the establishment of embryonic asymmetry &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;11836504&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;, and this asymmetry is in turn critical for heart development &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;11752633&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;.&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
===Mammary Gland Development===&lt;br /&gt;
Similarly, all three TGF-β isoforms are expressed during all stages in the development of the mammary gland except lactation. Specifically, mouse studies have indicated key roles for TGF-β in organizing the architecture of the mammary gland, regulating stem cell kinetics, inducing apoptosis in the involuting gland and maintaining the epithelium in a functionally undifferentiated state. The TGF-β isoforms are expressed in the ductal epithelium at all stages of development and some reviews have found that there may be some isoform specificity for temporal and spatial expression patterns &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;10887507&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;. For example, TGF-β3 is the only isoform present in the endbup cap cells and myoepithelial cells. Additionally, TGF-β1 is present at high levels in the extracellular matrix that surrounds growth-quiescent ducts. As for its effect, TGF-β have been to have induce multiple responses such as inhibiting the proliferation of mammillary epithelial cells. The nature of the target cell of plays a role as TGF-β also induced apoptosis without the inhibiting the proliferation. This highlights the highly variable actions of TGF-β that are affected by cell type, environmental and cell history to name a few. Interestingly, TGF-β have been implicated as both tumour suppressors and oncogenes in mammary tumorigenesis. For example, the overexpression of TGF-β1 inhibits tumorigenesis whilst interfering with its receptor function enhances tumorigenesis, thus hinting at its tumor suppressor role &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;7753792&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;9407968&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;. On the contrary, TGF-β has exhibited the enhancement of tumorigenesis as the TGF-β ligand expression is increased in late human breast cancer. Thus, TGF-β further proves its pleiotropic behaviour as prevalent to the mammary gland as it potentially suppresses and/or promotes tumorigenesis.&lt;br /&gt;
&lt;br /&gt;
===Maintenance of pluripotency in hESC===&lt;br /&gt;
Many of the members within the TGF-β superfamily are enriched within stem cells suggesting they play an important role in these cells, specifically relation to their pluripotency. The ability for a cell to self renew and differentiate is known as  'stemness', the stemness of human as well as mouse embryonic stem cells can be maintained by growing a combined culture with feed cells for example, bone morphogenic protein 4 (BMP4) induces a helix-loophelix-protein known as Id which is a potent inhibitor of differentiation, since this BMP (a member of the TGF-β  superfamily) is a potent inhibitor of neural differentiation in vertebrate embryos it is thought to maintain the stemness of hESCs and thus maintain their pluripotency.&amp;lt;ref name=&amp;quot;PMID24298330 &amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;24298330 &amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
[[File:Flowchart_for_maintenance_of_pluripotency_in_hESCs.png|thumb|upright=1.5|right|Flowchart for mechanism of maintenance of pluripotency in hESCs]]&lt;br /&gt;
&lt;br /&gt;
The nodal secretory protein from the TGF-β superfamily were found to also contribute to mESC pluripotency, this was evidenced by microarray of Nodal deficient mice which were found to have diminished  levels of Oct3/4 (transcription factors)expression, which are markers of undifferentiated stem cells. More importantly a nuclear localization of SMAD2 was found in hESCs, this is generally induced by TGF-β, activin or nodal signalling. Further microarray analysis identified that activin supposedly maintains the pluripotency of hESCs through inducing the expression of Oct4 as well as Nanog both transcription factors which are heavily involved in the self renewal of undifferentiated embryonic stem cells. Consistent with this finding, the subsequent inhibition of SMAD2 phosphorylation resulted in the decrease of expression of the markers of undifferentiated ESCs (Oct3/4, Nanog), suggesting that these were a product of SMAD2 phosphorylation and because SMAD2 is a product of activin/nodal signalling further suggesting that activin or nodal proteins produced by ESCs function to promote the maintenance of pluripotency in hESCs.&amp;lt;ref name=&amp;quot;PMID24298330 &amp;quot;/&amp;gt;.&lt;br /&gt;
&lt;br /&gt;
===Formation of the palate===&lt;br /&gt;
The formation of the palate is a complex procedure which involves a multitude of events including palatal shelf growth, elevation as well as left and right side fusion, as a result of genetic defects this procedure can sometimes result in formation of a cleft palate, one of the most common genetic birth defects. There have been recent findings which indicate TGF-β signalling plays a prime role in regulating the development of the palate in regards to both the palatal mesenchyme and epithelium. In humans the palate develops from two primordiuims, the primary and secondary palate, these progress to develop into palatal shelves which are positioned vertically against each other along the sides of the tongue. Following jaw growth and descent of the tongue these primordial palates orientate themselves horizontally and begin to fuse, in the case of the hard palate the mesenchyme cells are replaced by intramembranous bone as opposed to the soft palate which remains muscular and does not undergo ossification. Alike to humans mice have a similar embryological process of palate formation with the stage of palatal fusion resulting in the formation of a medial edge epithelium (MEE) seam which eventually degrades via apoptosis, thus the mouse serves as a strong candidate to fulfil the role of a reliable animal model. &amp;lt;ref name=&amp;quot;PMID21395922 &amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;21395922&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
With this model being established, it has been identified that TGF-β1 is strongly expressed in MEE cells just prior to adherence of the opposing palatal shelves, following this adherence the level of TGF-β1 gradually decreased until it ceased to be expressed in the mesenchymal cells, TGF-β. TGF-β2 and TGF-β3 were also expressed in the palatal mesenchymal cells during adherence and TGF-β3 was found to be continually expressed during the fusion process, it is further found that TGF-β3 played a crucial role in the cell degradation of MEE cells in addition to palatal fusion. It was found that when TGF-β3 deficient mice developed they expressed defects in MEE seam degradation and fusion.&amp;lt;ref name=&amp;quot;PMID21395922&amp;quot;/&amp;gt;.&lt;br /&gt;
&lt;br /&gt;
The use of these animal models to explore the role of TGF-β in cleft palate formation is fruitful in terms of identifying contributing factors and subtypes of TGF-β family members however there still remains much to discover of the molecular and cellular mechanisms  associated with palate formation.&lt;br /&gt;
&lt;br /&gt;
==Animal Studies==&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
===Wound healing===&lt;br /&gt;
Animal studies have served as a useful way in providing pivotal information regarding the mechanisms of TGF-β action in wound healing. In fact, much of the current information on the action of TGF-β in wound healing has been acquired from animal studies using incisional and/or excisional wounding models and manipulation of TGF-β signalling by adding the exogenous TGF-β protein or anti-TGF-β neutralizing antibodies, or by genetic alteration in components of the TGF-β signalling pathway. This is due to the fact that animal models provide outstanding experimental methods for explaining molecular mechanisms by which TGF-β regulates wound-healing responses. Ultimately, it has led the development of therapeutic strategies focusing on how the TGF-β pathway can improve wound healing and scarring outcome.&lt;br /&gt;
&lt;br /&gt;
[[File:Destination filename.jpeg|thumb|550px|Excisional wound healing in Smad 3 KO mice.&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;24761336&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;]] &lt;br /&gt;
Wound healing is an intricate physiological process distinguished by the successive overlapping stages of inflammation, proliferation and maturation. It that requires numerous growth factors, one of which includes TGF-β, which has the widest range of effects. TGF-β is a multifunctional growth factor that employs pleiotropic effects on wound healing by regulating cell differentiation, extracellular matrix production and immune modulation. The role of TGF-β signalling in wound healing was explored through examination of the development of tissue-specific expression systems for overexpression or knockout of TGF-b signalling pathway components. This study also classified that molecules might serve as molecular targets for the treatment of pathological skin conditions such as chronic wounds and excessive scarring (fibrosis). &lt;br /&gt;
&lt;br /&gt;
Exogenously added TGF-β has the potential to promote wound healing by stimulating angiogenesis, immune cell infiltration, and ECM production, and that diminishing endogenous TGF-β action reduces scarring without adversely affecting wound-healing quality.&lt;br /&gt;
===Direct modulation of TGF-β levels===&lt;br /&gt;
Injecting TGF-β into normal skin of newborn mice led to resilient initiation of angiogenesis and fibrosis. This consisted of important new collagen synthesis combined into the matrix. As a result of these observations, people were encouraged to further study the administration of TGF-β to incisional wounds in rats. It proved that TGF-β treatment resulted in better dermal healing, as showed by prominent collagen deposition and significantly increased wound strength.&lt;br /&gt;
&lt;br /&gt;
Interpreting wound-healing results obtained from the animals brought about its limitations. For instance, an underlying skin abnormality was found on many of the mouse models with genetic alterations in the TGF-β signalling pathway. Also, the pleiotropic effects of TGF-β on many different cell types throughout stages of wound healing highlighted a challenge in designing particular methods in which the TGF-β signalling pathway can assist wound healing or reduce scarring. &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;24761336&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
==Current Research==&lt;br /&gt;
&lt;br /&gt;
==Abnormalities of the TGF-Beta Pathway==&lt;br /&gt;
Mutations or deletion of the TGF-beta 1 or TGF-beta RII gene have been associated with multiple syndromes. In mice, defects have been found in haematopoiesis, vasculogenesis and endothelial differentiation of extra embryonic tissues, while knockout mice for SMAD2 or SMAD4 genes are more likely to have spontaneous tumour development and excessive inflammatory responses. In humans, various diseases have been linked to the mutation of the TGF-beta RII gene and SMAD4 mutation is genetically responsible for familial juvenile polyposis, an autosomal dominant disease characterized by predisposition to gastrointestinal polyps and cancers.&lt;br /&gt;
&lt;br /&gt;
====Cancer====&lt;br /&gt;
Alterations of this signalling pathway are common in cancer. Accessory proteins such as soluble or membrane-bound regulators or co-receptors can also affect TGF-beta signalling. A normal acting cell has a functional TGF-β signalling pathway, in which TGF- β stops proliferation of cells at G1 stage to either encourage apoptosis or induce differentiation. If the TGF-β signaling pathway becomes mutated these cells can become cancerous as the TGF-β no longer controls the cell. Uncontrolled, these cancer cells proliferate and cause surrounding fibroblasts, immune cells, endothelial and smooth-muscle cells to proliferate as well. From this increased production of TGF-β it causes angiogenesis and immunosuppression, further propogating the cancer. &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;10793168&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;The human body has an regulation against this, which is called effector T-cells which destroy cancer cells via an inflammatory reaction. However, TGF-β converts them into regulatory T-cells, which reduce the inflammatory reaction.&lt;br /&gt;
&lt;br /&gt;
 &lt;br /&gt;
====Marfan syndrome====&lt;br /&gt;
[[File:Embryo marfan.jpg|thumb|250px|Patient with Marfan syndrome. Note aesthenic or marfanoid body habitus, pronounced myopia (thick glasses), previous thoracic surgery (composite aortic root/aortic valve replacement)..&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt; PMC1767196 &amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;]]&lt;br /&gt;
&lt;br /&gt;
It is also suggested that TGF-β signaling has a large part to play in the pathogenesis of Marfan syndrome. This disease causes disproportionate height, abnormally long fingers and toes, displaced crystalline lens of the eye. Not only this but heart complications can also occur, like mitral valve prolapse or aortic enlargement. Marfan syndrome is generally known to be caused by defective creation of elastic fibres, more specifically of the glycoprotein fibrillin I. In a study done it was observed that by adding TGF-β antagonist in mice who were affected by Marfan syndrome phenotype, their symptoms were alleviated.&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;16601194&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; From this, we can see that the mechanism involved in Marfan syndrome most likely has an underlying relation with lowered sequestration of TGF-β by fibrillin.&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;16571647&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
====Heart disease====&lt;br /&gt;
The TGF-B pathway has many effects on cardiomyocytes, mesenchymal and immune cells. Not only this, but it plays a vital role in the pathogenesis of cardiac remodeling and fibrosis. Abnormalities in this pathway can cause an overexpression of TGF-β which has been associated with fibrosis and hypertrophy in mice hearts. We see that endogenous TGF-β is capable of varying matrix metabolism in a pressure-overloaded heart. In a heart which has undergone great stress, such as myocardial infarction, TGF-β is seen to inactivate inflammatory macrophages. This allows for less of an immune response but further done by it encouraging myofibroblast transdifferentiation and matrix synthesis. Thus higher levels of TGF-β is causing more inflammatory damage and further propagating the heart disease. &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;21059352&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
====Loeys–Dietz syndrome====&lt;br /&gt;
Abnormalities of the TGF-β signaling can also cause Loeys–Dietz syndrome via mutations in the TGF-β receptor. Loeys-Deitz syndrome connective tissue disorder, mainly in children where there are aneurisms in the aorta. Not only this, but the aorta can undergo dissection in weakened layers of the aortic wall. Further, the disease is labelled into four different types, since it is an autosomal dominant genetic connective tissue disorder, the groups are categorized by their genetic cause. TGFB1 and TGFB2 cause type I and II. Normally these genes allow for the fruition of the body’s development and growth. However, when defective they create non-functioning proteins.&lt;br /&gt;
&lt;br /&gt;
[[File:LDS .jpg|thumb|250px|MR angiogram of the head, shows arterial ectasia and tortuosity of the intracranial vessels, symptoms of Loeys-Dietz Syndrome&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;24393789&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;]]&lt;br /&gt;
&lt;br /&gt;
====Obesity, Diabetes and Hepatic Steatosis====&lt;br /&gt;
Normally, TGF-β signaling pathway has a major role in maintaining a regulated level of glucose and energy under homeostatic conditions. Not only this, but TGF-B could also have a vital task in diabetic kidney disease.  &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;21723505&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
Abnormalities in TGF-β signaling in obesity is one of the reasons why there is so much inflammatory damage in the human body by obesity. [5]&lt;br /&gt;
This was shown again in a study done where mice affected were given a systemic blockade drug for the TGF-B pathway and it was observed that they were protected from obesity, diabetes and hepatic steatosis. &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;21436399&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
====Multiple Sclerosis====&lt;br /&gt;
In Multiple Sclerosis (MS) a common observation is that patients will generally have lower levels of TGF-β, which is suspected to prevent remylentation of neurons. The reason why this is of significance is because MS results in demylentation of neurons causing severe neurological problems. TGF-β is normally responsible for regulating apoptosis of Th17 cells.&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;22942700&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;Thus when TGF-β levels decrease due to abnormalities, they are not able to be regulating Th17 cells apoptosis.[6] This then causes Th17 cells to secrete TNF-α, finally causing a demylenation of the oliodendroglial (neurons).&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;22189514&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;By having a lower amount of TGF-β we get a higer level of Th17 cells and therefore more TNFα and neuronal damage. Thus we can observe that this pathway is vital in maintaining neuronal health.&lt;br /&gt;
&lt;br /&gt;
==Further Reading==&lt;br /&gt;
&lt;br /&gt;
==Glossary==&lt;br /&gt;
{| class=&amp;quot;pretty table&amp;quot;&lt;br /&gt;
|-&lt;br /&gt;
| '''Apoptosis'''&lt;br /&gt;
| Cell death which occurs as a normal and controlled part of an organism's growth or development&lt;br /&gt;
|-&lt;br /&gt;
| '''Avian system'''&lt;br /&gt;
| Respiratory system that delivers oxygen and removes carbon dioxide&lt;br /&gt;
|-&lt;br /&gt;
| '''CCL-64'''&lt;br /&gt;
|  - mink lung epithelial cell&lt;br /&gt;
|-&lt;br /&gt;
| '''Cytokine'''&lt;br /&gt;
| A broad and loose category of small proteins that are important in cell signalling&lt;br /&gt;
|-&lt;br /&gt;
| '''Cushion Formation'''&lt;br /&gt;
| Cells in development that play a role in the formation of the heart septa&lt;br /&gt;
|-&lt;br /&gt;
| '''Dimer'''&lt;br /&gt;
| An oligomer consisting of two structurally similar monomers joined by bonds that can be either strong or weak, covalent or intermolecular&lt;br /&gt;
|-&lt;br /&gt;
| '''Homodimers'''&lt;br /&gt;
| A protein composed of two polypeptide chains that are identical in the order, number, and kind of their amino acid residues&lt;br /&gt;
|-&lt;br /&gt;
| '''Isoform'''&lt;br /&gt;
| A protein that has the same function as another protein but which is encoded by a different gene and may have small differences in its sequence&lt;br /&gt;
|-&lt;br /&gt;
| '''Ligands'''&lt;br /&gt;
| A molecule that binds to a larger molecule&lt;br /&gt;
|-&lt;br /&gt;
| '''Looping'''&lt;br /&gt;
| A morphogenetic process when the heart shape is formed by looping the embryonic tube&lt;br /&gt;
|-&lt;br /&gt;
| '''Pleiotropic'''&lt;br /&gt;
| To produce more than one type of effect&lt;br /&gt;
|-&lt;br /&gt;
| '''BMP'''&lt;br /&gt;
| Bone Morphogenetic Protein, a protein part of the TGF-β superfamily.&lt;/div&gt;</summary>
		<author><name>Z5020466</name></author>
	</entry>
	<entry>
		<id>https://embryology.med.unsw.edu.au/embryology/index.php?title=File:LDS.jpg&amp;diff=255384</id>
		<title>File:LDS.jpg</title>
		<link rel="alternate" type="text/html" href="https://embryology.med.unsw.edu.au/embryology/index.php?title=File:LDS.jpg&amp;diff=255384"/>
		<updated>2016-10-27T13:28:02Z</updated>

		<summary type="html">&lt;p&gt;Z5020466: MR angiogram of the head, shows arterial ectasia and tortuosity of the intracranial vessels.

&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt; PMC3278033 &amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;/p&gt;
&lt;hr /&gt;
&lt;div&gt;MR angiogram of the head, shows arterial ectasia and tortuosity of the intracranial vessels.&lt;br /&gt;
&lt;br /&gt;
&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt; PMC3278033 &amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;/div&gt;</summary>
		<author><name>Z5020466</name></author>
	</entry>
	<entry>
		<id>https://embryology.med.unsw.edu.au/embryology/index.php?title=2016_Group_Project_6&amp;diff=255378</id>
		<title>2016 Group Project 6</title>
		<link rel="alternate" type="text/html" href="https://embryology.med.unsw.edu.au/embryology/index.php?title=2016_Group_Project_6&amp;diff=255378"/>
		<updated>2016-10-27T13:22:23Z</updated>

		<summary type="html">&lt;p&gt;Z5020466: /* Marfan syndrome */&lt;/p&gt;
&lt;hr /&gt;
&lt;div&gt;{{ANAT2341Project2016header}}&lt;br /&gt;
{{Group Assessment Criteria table}}&lt;br /&gt;
&amp;lt;!-- Do not delete the above template from the Group project page. --&amp;gt;&lt;br /&gt;
&lt;br /&gt;
=Transforming Growth Factor-Beta (TGF-β) Signalling Pathway=&lt;br /&gt;
&lt;br /&gt;
==Introduction==&lt;br /&gt;
&lt;br /&gt;
The transforming growth factor beta (TGF-β) is a multifunctional and pleiotropic cytokine &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;26555259&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;.&lt;br /&gt;
The TGF-β signalling pathway is crucial to the control of different biological and pathological processes, such as cellular proliferation and differentiation, angiogenesis, immune regulation/inflammation, apoptosis and cell survival. &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;17896911&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
TGF-β belongs to the Transforming Growth Factor superfamily - a large group of structually connected cell regulatory proteins. It consists of TGF-β 1, 2 AND 3, Growth Differentiation Factors (GDFs), Activins, Inhibins, Bone Morphogenetic Proteins (BMPs), Glial-derived Neurotrophic Factors (GDNFs) and Mullierian Inhibiting Substance (MIS). &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;24270394&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
Most importantly, TGF-β plays a dominant part in the development of the embryo and adult organism. &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;23926286&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
This wiki aims to present a helpful overview of the TGF-β signalling pathway, but is in no means a complete resource on all information regarding the topic. This site focuses on particular aspects of the pathway, such as its history, process, regulation, significance in embryonic development, animal studies and abnormalities.&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&amp;lt;br&amp;gt;&amp;lt;br&amp;gt;&lt;br /&gt;
&amp;lt;div align=&amp;quot;center&amp;quot;&amp;gt;&amp;lt;html5media width=&amp;quot;560&amp;quot; height=&amp;quot;315&amp;quot;&amp;gt;https://www.youtube.com/watch?v=GuKjUearIUI&amp;lt;/html5media&amp;gt;&amp;lt;/div&amp;gt;&lt;br /&gt;
&amp;lt;br&amp;gt;&lt;br /&gt;
&lt;br /&gt;
==History==&lt;br /&gt;
Since the early stages of the TGF beta-signaling pathway, plenty of in-depth research and studies have been conducted that have no doubt contributed to our knowledge of the pathway today.&lt;br /&gt;
&lt;br /&gt;
SMAD signaling and the three receptors for TGF-beta are two of the many fields of interest regarding the topic. In medicine and specific areas such as cancer, cardiovascular disease and inflammatory bowel disease, there are numerous alternatives for drugs that can either heighten or suppress the activity of TGF-beta.&lt;br /&gt;
&lt;br /&gt;
{| class=&amp;quot;pretty table&amp;quot;&lt;br /&gt;
| '''1988'''&lt;br /&gt;
| The process of maturation of follicle-enclosed oocytes and cumulus-oocyte complexes was sped up by TGF beta. It was discovered that TGF beta and other growth factors are effective in vitro stimulators of oocyte maturation in the rat&lt;br /&gt;
&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;3275534&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
|-&lt;br /&gt;
| '''1989'''&lt;br /&gt;
| It was already known that TGF-beta 1 is a strong autocrine growth inhibitor of lymphocytes. Ellingsworth and colleagues found that TGF-beta 1 binds to all three cell surface-binding proteins (280-200 kD, 95-85 kD, 65 kD).&lt;br /&gt;
It was also found that these binding proteins are required for signal transduction. Overall, they discovered that the regulation of the expression of the TGF-beta 1 receptor is controlled by T cell mitogenic signals.&lt;br /&gt;
&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;2785999&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
|-&lt;br /&gt;
| '''1989'''&lt;br /&gt;
| It was made known that the properties of R mutants classify TGF-beta type I binding protein as the receptor involved in mediating TGF-beta actions on cell adhesion and proliferation&lt;br /&gt;
&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;2536702&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
|-&lt;br /&gt;
| '''1989'''&lt;br /&gt;
| Drosophil was the only member of the TGF-beta family to be identified in invertebrates &lt;br /&gt;
&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;2699859&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
|-&lt;br /&gt;
| '''1990'''&lt;br /&gt;
| It was already known that the rapid increase in number response of mink lung epithelial cells to serum and to epidermal growth factor was inhibited by TGF beta 1. A necessary component of TGF-beta 1 mediated growth inhibition in CCL64 epithelial cells is the coupling of TGF beta 1 receptor binding to G-protein activation&lt;br /&gt;
&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;2156499&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
|-&lt;br /&gt;
| '''2000'''&lt;br /&gt;
| VegT function was found to be involved in sequence with the TGF beta pathway. Therefore, TGF beta signaling may be activated by the maternally expressed VegT to participate in endoderm determination&lt;br /&gt;
&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;10640706&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
|-&lt;br /&gt;
| '''2005'''&lt;br /&gt;
| Within the TGF beta superfamily, it was found that a limited number of type I and type II receptors worked together to produce specificity of action &lt;br /&gt;
&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;15483083&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
|-&lt;br /&gt;
| '''2010'''&lt;br /&gt;
| Deregulation of TGF beta signaling was reported in human psoriasis&lt;br /&gt;
&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;19710682&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
|-&lt;br /&gt;
| '''2015'''&lt;br /&gt;
| It was known that TGF is required in the tumorigenicity and metastasis of bone tumour. A significant event in the activation of the TGF beta signaling pathway is the binding of transcription coactivator Yes-associated protein (YAP) to Smad transcription factors&lt;br /&gt;
&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;27491038&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
|}&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
[[File:Canonical and non-canonical signalling TGF beta pathways.png|thumb|500px|Flowchart showing the Canonical and Non-Canonical pathways of TGF-β signalling pathway.&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;24393789&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;]] &lt;br /&gt;
===Canonical pathway===&lt;br /&gt;
In the canonical pathway, the dormant TGF-β complex is formed when the three TGF-β ligand isoforms - TGF-B1, TGF-B2 and TGF-B3 - bind once it is synthesized as precursors. After secretion and extracellular activation, TGF-β ligands can bind to two types of receptors: the membranous TGF-β type III receptor or the TGF-β type II receptor (TGF-βRII) homodimers with high affinity. &lt;br /&gt;
TGF-βRII binding enables dimerization with TGF-β type I receptor (TGF-βRI) homodimers, as well as activation of the TGF-βRI kinase domain and signal transduction across phosphorylation of the C-terminus of receptor-regulated SMADs, SMAD2 and SMAD3.&lt;br /&gt;
A heterotrimeric complex is formed by the TGF-βR dimer and SMAD4, which moves and assemblies in the nucleus.&lt;br /&gt;
TGF-β dependent signalling can operate or subdue numerous target genes through the communication of SMADs with multiple transcription factors. There are many structures in which SMAD activities are regulated, such as SMAD2/3 nucleocytoplasmic shuttling, binding to anchor proteins, phosphorylation and Smurf (SMAD-ubiquitination-regulatory factor).  &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;24393789 &amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
&lt;br /&gt;
===Non-Canonical pathway===&lt;br /&gt;
In the non-canonical pathway, SMAD-independent pathways such as PI3K/AKT and MAPK pathways like ERK, JNK, and p38 MAPK are activated by TGF-β signalling. In addition, transversal signalling, especially at the SMAD level, allows TGF-β pathway activation to incorporate signals from integrins, Notch and Wnt dependent pathways as well as signals from cellular processes like the cell cycle or apoptosis machineries. Thus, the TGF-β signalling pathway has pleiotropic functions regulating cell growth, differentiation, apoptosis, cell motility, extracellular matrix production, angiogenesis and cellular immune response.&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;24393789 &amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
&lt;br /&gt;
==Process of TGF-β signalling pathway==&lt;br /&gt;
&lt;br /&gt;
TGF-β signalling pathway is required for regulation of a large number of cellular processes such as cell proliferation, invasion and inflammation. It is also activated mitogen activated protein kinase signalling. There are two main routes in TGF-β signalling; the SMAD Dependent pathway and SMAD Independent pathway.&lt;br /&gt;
&lt;br /&gt;
===SMAD Dependent TGF-β signalling pathway===&lt;br /&gt;
&lt;br /&gt;
[[File:TGF-B Signalling - Formation of Receptor Hetero-Tetramers.png|thumb|350px|SMAD Dependent TGF-β signalling pathway: Formation of Receptor Hetero-Tetramers&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;16446785&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;]]&lt;br /&gt;
&lt;br /&gt;
The ligands of the TGF-β superfamily form dimers that bind to heterodimeric receptor complexes composed of two type I and two type II transmembrane receptor subunits with serine/threonine kinase domains.&lt;br /&gt;
Following ligand binding on TGF-β1, the dimerized TGF-β type II receptors phosphorylates and activates the TGF-β type I receptors. In most cell types, this leads to recruitment and phosphorylation of the receptor-regulated SMAD2 and SMAD3, presented by the SMAD anchor for receptor activation. SMAD1 and SMAD5 can be activated by the TGF-β signaling depending on the Type I receptor that is expressed.&lt;br /&gt;
Heterologous complexes are formed by the phosphorylated receptor-regulated SMAD with the common-mediator SMAD, SMAD4, and successively move into the nucleus, where they accumulate and act as transcription factors participating in the regulation of target gene expression. &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;21302608&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
In addition, they recruit extra transcriptional regulators, such as DNA-binding transcription factors, co-activators and co-repressors. These control the expression of several target genes and ultimately initiates a SMAD-dependent signaling cascade that induces or represses transcriptional activity. SMADs are widely expressed in most adult tissue and cell types, indicating that the TGF-β signaling pathway is ubiquitous.&lt;br /&gt;
&lt;br /&gt;
===SMAD independent TGF-β signalling pathway===&lt;br /&gt;
&lt;br /&gt;
Rather than SMAD-mediated transciption TGF-β also has the potential to activate other signalling cascades for example the Erk, JNK and p38 MAPK kinase pathways. In some cases these pathways exhibit activation with slow kinetics which indicates SMAD-dependant mechanics, however there has also been rapid activation cases (5-15mins) suggesting independence from transcription mechanisms. Studies carried out with SMAD4 deficient cells and dominant-negative SMADS provide evidence that the MAPK pathway activation is independent from SMADS, as well as this it has be found that p38 MAPK signalling  was activated in response to mutated TGF- β type 1 receptors, which were defective in SMAD activation&amp;lt;ref name=&amp;quot;PMID14534577&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;14534577&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;.&lt;br /&gt;
&lt;br /&gt;
The precise mechanisms and biological consequences of these SMAD-Independent pathways (Erk, JNK, p38 MAPK) are currently poorly characterized. Ras is implicated in TGF- β induced Erk signalling as there is rapid activation of Ras by TGF- β in epithelial cells. The JNK and p38 MAPK signalling are activated by various MAPK kinase kinases (MAPKKK) TGF- β kinase 1 (TAK 1) receptor is a MAPKKK family member. Further research and identification of various interactions between the small signalling molecules and receptor proteins will provide additional insight into the precise mechanism behind the activation of MAPK pathways by TGF- β ligands &amp;lt;ref name=&amp;quot;PMID14534577&amp;quot;/&amp;gt;.&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
==Regulation of the pathway and factors affecting it==&lt;br /&gt;
&lt;br /&gt;
Signalling mechanisms by TGF-β like factors are regulated in both negative and positive fashions, these are all tightly controlled through a multitude of mechanisms at extracellular, membrane, cytoplasmic and all the way to nuclear levels. Positive regulation is required to amplify signalling from TGF-β like factors, while negative regulation is important for the termination and restriction of signalling usually occurring through the mechanism of a feedback loop. There is also additional regulation of TGF-β like factors via cross-talk with other signal transduction pathways such as MAPK and JAK/STAT pathways.&amp;lt;ref name=&amp;quot;PMID10704361&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;10704361&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
===Positive Regulation===&lt;br /&gt;
The positive regulation of TGF-β specifically the induction of ligands and their signalling components often is triggered by the action TGF-β-like factors themselves. For example NODAL, a secretory protein of the TGF-β superfamily which plays a role in early embryogenesis and acts through activin receptors and SMAD2 is induced by nodal signalling itself. In other types of cells TGF-β receptors as well as transcription factors which serve as targets for TGF-β like factors can be induced by ligand stimulation, as identified in case of transcription factor Runx3 which is induced by TGF-β and forms a complex with SMAD3 to be further activated by TGF-β. The mechanism of SMAD signalling is also positively modulated via the &amp;quot;cross-talk&amp;quot; (and hence the process of SMAD dependant TGF-β signalling) with other signalling pathways, SMADS may be activated by the tyrosine kinase receptor under specific circumstances and further positively regulate TGF-β like factors &amp;lt;ref name=&amp;quot;PMID10704361&amp;quot;/&amp;gt;.&lt;br /&gt;
&lt;br /&gt;
===Negative Regulation===&lt;br /&gt;
&lt;br /&gt;
Signalling is regulated at the cell membrane level as well as within the cytoplasm of the cell, specifically by BAMBI, a pseudo-receptor for serine/threonine kinase receptors (in Xenopus embryos however displays a high degree of sequence similarity to human BAMBI gene). This BAMBI receptor is structurally alike to the type 1 serine/threonine kinase receptor, the only difference being that it lacks an intracellular domain. BAMBI  has shown a similar expression profile to that of BMP-4 a growth factor from the TGF-β super family, and has been found to require BMP signalling for expression. BAMBI when goes on to interact with both type 1 and type 2 serine/threonine receptors and works to abolish their abilities to signal via BMPs, activins and TGF-βs, therefore it is postulated that BAMBI can be inductively expressed by BMPS to self regulate BMP signalling as well as cross-regulate signalling from other members of the TGF-β super family. &amp;lt;ref name=&amp;quot;PMID10704361&amp;quot;/&amp;gt;&lt;br /&gt;
&lt;br /&gt;
==Significance in Embryonic Development==&lt;br /&gt;
&lt;br /&gt;
TGF betas are involved in embryogenesis. During development of the embryo, members of the TGF-beta family are essential for bone and cartilage formation, mesoderm induction and patterning and dorso-ventral patterning.&lt;br /&gt;
&lt;br /&gt;
[[File:TGF in Cardiovascular.jpg|thumb|500px|Expression of TGF-β2 and TGF-β3 in wildtype embryonic hearts.&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;12948523&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;]]&lt;br /&gt;
===Cardiovascular Development===&lt;br /&gt;
&lt;br /&gt;
Genetic engineering and tissue explanation studies have revealed many roles for TGF-β ligands and their signaling molecules in development. In the embryo, TGF-β appear to be involved in epithelial-mesenchymal transformations (EMT) during the formation of endocardial cushions, and in epicardial epithelial-mesenchymal transformations essential for coronary vasculature, ventricular myocardial development and compaction. It must be noted that in the normal function of the cardiovascular system in the adult, TGF-β play significant roles in cardiac hypertrophy, vascular remodeling and regulation of the renal renin-angiotensin system.&lt;br /&gt;
&lt;br /&gt;
TGF-β1 is expressed in the endocardium of the developing mouse. TGF-β(-/-) mice have been found with obvious congenital cardiovascular defects, so it’s important to review its expression in the developing heart. In the blood vessels, TGF-β1 is in the intima whereas TGF-β2 and TGF-β3 are in the media and adventitia. TGF-β2 signals are found as early as embryonic day 7.25 (E7.25) &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;7687212&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; in the cardiogenic plate of the precardiac mesoderm and is later prominent in the myocardium of the aortic sac and outflow track regions. TGF-β2 protein is also found in the entire myocardium of the heart at the time when looping occurs. From E8.5-9.5 when the cushion formation process occurs, there is a particularly strong TGF-β2 expression localised to the myocardium as displayed in A, B, D and E in the figure. After cushion formation and EMT, and before myocardialization of the endocardial cushion begins, there is also strong TGF-β2 expression in the OT myocardium and in the adjacent developing cushion mesenchym. However, as myocardialization occurs, TGF-β2 expression is reduced in the myocardium so that from E12.5 onwards, it is only expressed mainly in the mesenchyme of the cushion and OT septum. As can be seen in 2GH, TGF-β2 expression remains high in the cushion mesenchyme of the OT septum. By E15.5, TGF-β1 s now the most highly expressed isoform in the endocardial cells of the myocardium. It is seen in M, N, O of the figure that the epidcardium TGF-β1 and TGF-β3 expression is higher than that of TGF-β2. Thus, it can be seen that all three TGF-β are expressed in the epicardium, and they are not expressed in an overlapping fashion.&lt;br /&gt;
&lt;br /&gt;
Cross talk between mesoderm and underlying endoderm is needed to form the early tubular heart. This cellular and molecular induction in the primary heart forming regions is important for the specification and differentiation of myocardial and endocardial precursor cells &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;10767078&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;. Other endoderm-derived growth factors such as BMP2, FGF2 as well as TGFBS have been implicated in this process in the avian system &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;11322300&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;. TGFB2 and TGFB receptors are expressed in the precardiac mesoderm along with BMP2 &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;7687212&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;10767078&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;10340759&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;. Members of the TGG family can serve as inductive signals at the heart forming fields for the formation of myocardial and endocardial precursor cells. Members such as Activin, BMP, Nodal, Left and others have been found to be crucial for the establishment of embryonic asymmetry &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;11836504&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;, and this asymmetry is in turn critical for heart development &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;11752633&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;.&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
===Mammary Gland Development===&lt;br /&gt;
Similarly, all three TGF-β isoforms are expressed during all stages in the development of the mammary gland except lactation. Specifically, mouse studies have indicated key roles for TGF-β in organizing the architecture of the mammary gland, regulating stem cell kinetics, inducing apoptosis in the involuting gland and maintaining the epithelium in a functionally undifferentiated state. The TGF-β isoforms are expressed in the ductal epithelium at all stages of development and some reviews have found that there may be some isoform specificity for temporal and spatial expression patterns &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;10887507&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;. For example, TGF-β3 is the only isoform present in the endbup cap cells and myoepithelial cells. Additionally, TGF-β1 is present at high levels in the extracellular matrix that surrounds growth-quiescent ducts. As for its effect, TGF-β have been to have induce multiple responses such as inhibiting the proliferation of mammillary epithelial cells. The nature of the target cell of plays a role as TGF-β also induced apoptosis without the inhibiting the proliferation. This highlights the highly variable actions of TGF-β that are affected by cell type, environmental and cell history to name a few. Interestingly, TGF-β have been implicated as both tumour suppressors and oncogenes in mammary tumorigenesis. For example, the overexpression of TGF-β1 inhibits tumorigenesis whilst interfering with its receptor function enhances tumorigenesis, thus hinting at its tumor suppressor role &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;7753792&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;9407968&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;. On the contrary, TGF-β has exhibited the enhancement of tumorigenesis as the TGF-β ligand expression is increased in late human breast cancer. Thus, TGF-β further proves its pleiotropic behaviour as prevalent to the mammary gland as it potentially suppresses and/or promotes tumorigenesis.&lt;br /&gt;
&lt;br /&gt;
===Maintenance of pluripotency in hESC===&lt;br /&gt;
Many of the members within the TGF-β superfamily are enriched within stem cells suggesting they play an important role in these cells, specifically relation to their pluripotency. The ability for a cell to self renew and differentiate is known as  'stemness', the stemness of human as well as mouse embryonic stem cells can be maintained by growing a combined culture with feed cells for example, bone morphogenic protein 4 (BMP4) induces a helix-loophelix-protein known as Id which is a potent inhibitor of differentiation, since this BMP (a member of the TGF-β  superfamily) is a potent inhibitor of neural differentiation in vertebrate embryos it is thought to maintain the stemness of hESCs and thus maintain their pluripotency.&amp;lt;ref name=&amp;quot;PMID24298330 &amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;24298330 &amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
[[File:Flowchart_for_maintenance_of_pluripotency_in_hESCs.png|thumb|upright=1.5|right|Flowchart for mechanism of maintenance of pluripotency in hESCs]]&lt;br /&gt;
&lt;br /&gt;
The nodal secretory protein from the TGF-β superfamily were found to also contribute to mESC pluripotency, this was evidenced by microarray of Nodal deficient mice which were found to have diminished  levels of Oct3/4 (transcription factors)expression, which are markers of undifferentiated stem cells. More importantly a nuclear localization of SMAD2 was found in hESCs, this is generally induced by TGF-β, activin or nodal signalling. Further microarray analysis identified that activin supposedly maintains the pluripotency of hESCs through inducing the expression of Oct4 as well as Nanog both transcription factors which are heavily involved in the self renewal of undifferentiated embryonic stem cells. Consistent with this finding, the subsequent inhibition of SMAD2 phosphorylation resulted in the decrease of expression of the markers of undifferentiated ESCs (Oct3/4, Nanog), suggesting that these were a product of SMAD2 phosphorylation and because SMAD2 is a product of activin/nodal signalling further suggesting that activin or nodal proteins produced by ESCs function to promote the maintenance of pluripotency in hESCs.&amp;lt;ref name=&amp;quot;PMID24298330 &amp;quot;/&amp;gt;.&lt;br /&gt;
&lt;br /&gt;
===Formation of the palate===&lt;br /&gt;
The formation of the palate is a complex procedure which involves a multitude of events including palatal shelf growth, elevation as well as left and right side fusion, as a result of genetic defects this procedure can sometimes result in formation of a cleft palate, one of the most common genetic birth defects. There have been recent findings which indicate TGF-β signalling plays a prime role in regulating the development of the palate in regards to both the palatal mesenchyme and epithelium. In humans the palate develops from two primordiuims, the primary and secondary palate, these progress to develop into palatal shelves which are positioned vertically against each other along the sides of the tongue. Following jaw growth and descent of the tongue these primordial palates orientate themselves horizontally and begin to fuse, in the case of the hard palate the mesenchyme cells are replaced by intramembranous bone as opposed to the soft palate which remains muscular and does not undergo ossification. Alike to humans mice have a similar embryological process of palate formation with the stage of palatal fusion resulting in the formation of a medial edge epithelium (MEE) seam which eventually degrades via apoptosis, thus the mouse serves as a strong candidate to fulfil the role of a reliable animal model. &amp;lt;ref name=&amp;quot;PMID21395922 &amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;21395922&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
With this model being established, it has been identified that TGF-β1 is strongly expressed in MEE cells just prior to adherence of the opposing palatal shelves, following this adherence the level of TGF-β1 gradually decreased until it ceased to be expressed in the mesenchymal cells, TGF-β. TGF-β2 and TGF-β3 were also expressed in the palatal mesenchymal cells during adherence and TGF-β3 was found to be continually expressed during the fusion process, it is further found that TGF-β3 played a crucial role in the cell degradation of MEE cells in addition to palatal fusion. It was found that when TGF-β3 deficient mice developed they expressed defects in MEE seam degradation and fusion.&amp;lt;ref name=&amp;quot;PMID21395922&amp;quot;/&amp;gt;.&lt;br /&gt;
&lt;br /&gt;
The use of these animal models to explore the role of TGF-β in cleft palate formation is fruitful in terms of identifying contributing factors and subtypes of TGF-β family members however there still remains much to discover of the molecular and cellular mechanisms  associated with palate formation.&lt;br /&gt;
&lt;br /&gt;
==Animal Studies==&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
===Wound healing===&lt;br /&gt;
Animal studies have served as a useful way in providing pivotal information regarding the mechanisms of TGF-β action in wound healing. In fact, much of the current information on the action of TGF-β in wound healing has been acquired from animal studies using incisional and/or excisional wounding models and manipulation of TGF-β signalling by adding the exogenous TGF-β protein or anti-TGF-β neutralizing antibodies, or by genetic alteration in components of the TGF-β signalling pathway. This is due to the fact that animal models provide outstanding experimental methods for explaining molecular mechanisms by which TGF-β regulates wound-healing responses. Ultimately, it has led the development of therapeutic strategies focusing on how the TGF-β pathway can improve wound healing and scarring outcome.&lt;br /&gt;
&lt;br /&gt;
[[File:Destination filename.jpeg|thumb|550px|Excisional wound healing in Smad 3 KO mice.&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;24761336&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;]] &lt;br /&gt;
Wound healing is an intricate physiological process distinguished by the successive overlapping stages of inflammation, proliferation and maturation. It that requires numerous growth factors, one of which includes TGF-β, which has the widest range of effects. TGF-β is a multifunctional growth factor that employs pleiotropic effects on wound healing by regulating cell differentiation, extracellular matrix production and immune modulation. The role of TGF-β signalling in wound healing was explored through examination of the development of tissue-specific expression systems for overexpression or knockout of TGF-b signalling pathway components. This study also classified that molecules might serve as molecular targets for the treatment of pathological skin conditions such as chronic wounds and excessive scarring (fibrosis). &lt;br /&gt;
&lt;br /&gt;
Exogenously added TGF-β has the potential to promote wound healing by stimulating angiogenesis, immune cell infiltration, and ECM production, and that diminishing endogenous TGF-β action reduces scarring without adversely affecting wound-healing quality.&lt;br /&gt;
===Direct modulation of TGF-β levels===&lt;br /&gt;
Injecting TGF-β into normal skin of newborn mice led to resilient initiation of angiogenesis and fibrosis. This consisted of important new collagen synthesis combined into the matrix. As a result of these observations, people were encouraged to further study the administration of TGF-β to incisional wounds in rats. It proved that TGF-β treatment resulted in better dermal healing, as showed by prominent collagen deposition and significantly increased wound strength.&lt;br /&gt;
&lt;br /&gt;
Interpreting wound-healing results obtained from the animals brought about its limitations. For instance, an underlying skin abnormality was found on many of the mouse models with genetic alterations in the TGF-β signalling pathway. Also, the pleiotropic effects of TGF-β on many different cell types throughout stages of wound healing highlighted a challenge in designing particular methods in which the TGF-β signalling pathway can assist wound healing or reduce scarring. &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;24761336&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
==Current Research==&lt;br /&gt;
&lt;br /&gt;
==Abnormalities of the TGF-Beta Pathway==&lt;br /&gt;
Mutations or deletion of the TGF-beta 1 or TGF-beta RII gene have been associated with multiple syndromes. In mice, defects have been found in haematopoiesis, vasculogenesis and endothelial differentiation of extra embryonic tissues, while knockout mice for SMAD2 or SMAD4 genes are more likely to have spontaneous tumour development and excessive inflammatory responses. In humans, various diseases have been linked to the mutation of the TGF-beta RII gene and SMAD4 mutation is genetically responsible for familial juvenile polyposis, an autosomal dominant disease characterized by predisposition to gastrointestinal polyps and cancers.&lt;br /&gt;
&lt;br /&gt;
====Cancer====&lt;br /&gt;
Alterations of this signalling pathway are common in cancer. Accessory proteins such as soluble or membrane-bound regulators or co-receptors can also affect TGF-beta signalling. A normal acting cell has a functional TGF-β signalling pathway, in which TGF- β stops proliferation of cells at G1 stage to either encourage apoptosis or induce differentiation. If the TGF-β signaling pathway becomes mutated these cells can become cancerous as the TGF-β no longer controls the cell. Uncontrolled, these cancer cells proliferate and cause surrounding fibroblasts, immune cells, endothelial and smooth-muscle cells to proliferate as well. From this increased production of TGF-β it causes angiogenesis and immunosuppression, further propogating the cancer. &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;10793168&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;The human body has an regulation against this, which is called effector T-cells which destroy cancer cells via an inflammatory reaction. However, TGF-β converts them into regulatory T-cells, which reduce the inflammatory reaction.&lt;br /&gt;
&lt;br /&gt;
 &lt;br /&gt;
====Marfan syndrome====&lt;br /&gt;
[[File:Embryo marfan.jpg|thumb|250px|Patient with Marfan syndrome. Note aesthenic or marfanoid body habitus, pronounced myopia (thick glasses), previous thoracic surgery (composite aortic root/aortic valve replacement)..&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt; PMC1767196 &amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;]]&lt;br /&gt;
&lt;br /&gt;
It is also suggested that TGF-β signaling has a large part to play in the pathogenesis of Marfan syndrome. This disease causes disproportionate height, abnormally long fingers and toes, displaced crystalline lens of the eye. Not only this but heart complications can also occur, like mitral valve prolapse or aortic enlargement. Marfan syndrome is generally known to be caused by defective creation of elastic fibres, more specifically of the glycoprotein fibrillin I. In a study done it was observed that by adding TGF-β antagonist in mice who were affected by Marfan syndrome phenotype, their symptoms were alleviated.&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;16601194&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; From this, we can see that the mechanism involved in Marfan syndrome most likely has an underlying relation with lowered sequestration of TGF-β by fibrillin.&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;16571647&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
====Heart disease====&lt;br /&gt;
The TGF-B pathway has many effects on cardiomyocytes, mesenchymal and immune cells. Not only this, but it plays a vital role in the pathogenesis of cardiac remodeling and fibrosis. Abnormalities in this pathway can cause an overexpression of TGF-β which has been associated with fibrosis and hypertrophy in mice hearts. We see that endogenous TGF-β is capable of varying matrix metabolism in a pressure-overloaded heart. In a heart which has undergone great stress, such as myocardial infarction, TGF-β is seen to inactivate inflammatory macrophages. This allows for less of an immune response but further done by it encouraging myofibroblast transdifferentiation and matrix synthesis. Thus higher levels of TGF-β is causing more inflammatory damage and further propagating the heart disease. &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;21059352&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
====Loeys–Dietz syndrome====&lt;br /&gt;
Abnormalities of the TGF-β signaling can also cause Loeys–Dietz syndrome via mutations in the TGF-β receptor. Loeys-Deitz syndrome connective tissue disorder, mainly in children where there are aneurisms in the aorta. Not only this, but the aorta can undergo dissection in weakened layers of the aortic wall. Further, the disease is labelled into four different types, since it is an autosomal dominant genetic connective tissue disorder, the groups are categorized by their genetic cause. TGFB1 and TGFB2 cause type I and II. Normally these genes allow for the fruition of the body’s development and growth. However, when defective they create non-functioning proteins.&lt;br /&gt;
&lt;br /&gt;
====Obesity, Diabetes and Hepatic Steatosis====&lt;br /&gt;
Normally, TGF-β signaling pathway has a major role in maintaining a regulated level of glucose and energy under homeostatic conditions. Not only this, but TGF-B could also have a vital task in diabetic kidney disease.  &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;21723505&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
Abnormalities in TGF-β signaling in obesity is one of the reasons why there is so much inflammatory damage in the human body by obesity. [5]&lt;br /&gt;
This was shown again in a study done where mice affected were given a systemic blockade drug for the TGF-B pathway and it was observed that they were protected from obesity, diabetes and hepatic steatosis. &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;21436399&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
====Multiple Sclerosis====&lt;br /&gt;
In Multiple Sclerosis (MS) a common observation is that patients will generally have lower levels of TGF-β, which is suspected to prevent remylentation of neurons. The reason why this is of significance is because MS results in demylentation of neurons causing severe neurological problems. TGF-β is normally responsible for regulating apoptosis of Th17 cells.&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;22942700&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;Thus when TGF-β levels decrease due to abnormalities, they are not able to be regulating Th17 cells apoptosis.[6] This then causes Th17 cells to secrete TNF-α, finally causing a demylenation of the oliodendroglial (neurons).&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;22189514&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;By having a lower amount of TGF-β we get a higer level of Th17 cells and therefore more TNFα and neuronal damage. Thus we can observe that this pathway is vital in maintaining neuronal health.&lt;br /&gt;
&lt;br /&gt;
==Further Reading==&lt;br /&gt;
&lt;br /&gt;
==Glossary==&lt;br /&gt;
{| class=&amp;quot;pretty table&amp;quot;&lt;br /&gt;
|-&lt;br /&gt;
| '''Apoptosis'''&lt;br /&gt;
| Cell death which occurs as a normal and controlled part of an organism's growth or development&lt;br /&gt;
|-&lt;br /&gt;
| '''Avian system'''&lt;br /&gt;
| Respiratory system that delivers oxygen and removes carbon dioxide&lt;br /&gt;
|-&lt;br /&gt;
| '''CCL-64'''&lt;br /&gt;
|  - mink lung epithelial cell&lt;br /&gt;
|-&lt;br /&gt;
| '''Cytokine'''&lt;br /&gt;
| A broad and loose category of small proteins that are important in cell signalling&lt;br /&gt;
|-&lt;br /&gt;
| '''Cushion Formation'''&lt;br /&gt;
| Cells in development that play a role in the formation of the heart septa&lt;br /&gt;
|-&lt;br /&gt;
| '''Dimer'''&lt;br /&gt;
| An oligomer consisting of two structurally similar monomers joined by bonds that can be either strong or weak, covalent or intermolecular&lt;br /&gt;
|-&lt;br /&gt;
| '''Homodimers'''&lt;br /&gt;
| A protein composed of two polypeptide chains that are identical in the order, number, and kind of their amino acid residues&lt;br /&gt;
|-&lt;br /&gt;
| '''Isoform'''&lt;br /&gt;
| A protein that has the same function as another protein but which is encoded by a different gene and may have small differences in its sequence&lt;br /&gt;
|-&lt;br /&gt;
| '''Ligands'''&lt;br /&gt;
| A molecule that binds to a larger molecule&lt;br /&gt;
|-&lt;br /&gt;
| '''Looping'''&lt;br /&gt;
| A morphogenetic process when the heart shape is formed by looping the embryonic tube&lt;br /&gt;
|-&lt;br /&gt;
| '''Pleiotropic'''&lt;br /&gt;
| To produce more than one type of effect&lt;br /&gt;
|-&lt;br /&gt;
| '''BMP'''&lt;br /&gt;
| Bone Morphogenetic Protein, a protein part of the TGF-β superfamily.&lt;/div&gt;</summary>
		<author><name>Z5020466</name></author>
	</entry>
	<entry>
		<id>https://embryology.med.unsw.edu.au/embryology/index.php?title=File:Patient_with_Marfan_syndrome.jpg&amp;diff=255374</id>
		<title>File:Patient with Marfan syndrome.jpg</title>
		<link rel="alternate" type="text/html" href="https://embryology.med.unsw.edu.au/embryology/index.php?title=File:Patient_with_Marfan_syndrome.jpg&amp;diff=255374"/>
		<updated>2016-10-27T13:19:51Z</updated>

		<summary type="html">&lt;p&gt;Z5020466: &lt;/p&gt;
&lt;hr /&gt;
&lt;div&gt;Patient with Marfan syndrome. Note aesthenic or marfanoid body habitus, pronounced myopia (thick glasses), previous thoracic surgery (composite aortic root/aortic valve replacement).&lt;br /&gt;
&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;PMC1767196&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
===Image Copyright===&lt;br /&gt;
Articles published in these journals are in the public domain and may be used and reproduced without special permission. However, anyone using the material is requested to properly cite and acknowledge the source.&lt;br /&gt;
&lt;br /&gt;
{{Template:Student Image}}&lt;/div&gt;</summary>
		<author><name>Z5020466</name></author>
	</entry>
	<entry>
		<id>https://embryology.med.unsw.edu.au/embryology/index.php?title=2016_Group_Project_6&amp;diff=255366</id>
		<title>2016 Group Project 6</title>
		<link rel="alternate" type="text/html" href="https://embryology.med.unsw.edu.au/embryology/index.php?title=2016_Group_Project_6&amp;diff=255366"/>
		<updated>2016-10-27T13:09:05Z</updated>

		<summary type="html">&lt;p&gt;Z5020466: /* Marfan syndrome */&lt;/p&gt;
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&lt;div&gt;{{ANAT2341Project2016header}}&lt;br /&gt;
{{Group Assessment Criteria table}}&lt;br /&gt;
&amp;lt;!-- Do not delete the above template from the Group project page. --&amp;gt;&lt;br /&gt;
&lt;br /&gt;
=Transforming Growth Factor-Beta (TGF-β) Signalling Pathway=&lt;br /&gt;
&lt;br /&gt;
==Introduction==&lt;br /&gt;
&lt;br /&gt;
The transforming growth factor beta (TGF-β) is a multifunctional and pleiotropic cytokine &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;26555259&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;.&lt;br /&gt;
The TGF-β signalling pathway is crucial to the control of different biological and pathological processes, such as cellular proliferation and differentiation, angiogenesis, immune regulation/inflammation, apoptosis and cell survival. &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;17896911&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
TGF-β belongs to the Transforming Growth Factor superfamily - a large group of structually connected cell regulatory proteins. It consists of TGF-β 1, 2 AND 3, Growth Differentiation Factors (GDFs), Activins, Inhibins, Bone Morphogenetic Proteins (BMPs), Glial-derived Neurotrophic Factors (GDNFs) and Mullierian Inhibiting Substance (MIS). &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;24270394&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
Most importantly, TGF-β plays a dominant part in the development of the embryo and adult organism. &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;23926286&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
This wiki aims to present a helpful overview of the TGF-β signalling pathway, but is in no means a complete resource on all information regarding the topic. We focus on ________________&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&amp;lt;br&amp;gt;&amp;lt;br&amp;gt;&lt;br /&gt;
&amp;lt;div align=&amp;quot;center&amp;quot;&amp;gt;&amp;lt;html5media width=&amp;quot;560&amp;quot; height=&amp;quot;315&amp;quot;&amp;gt;https://www.youtube.com/watch?v=GuKjUearIUI&amp;lt;/html5media&amp;gt;&amp;lt;/div&amp;gt;&lt;br /&gt;
&amp;lt;br&amp;gt;&lt;br /&gt;
&lt;br /&gt;
==History==&lt;br /&gt;
Since the early stages of the TGF beta-signaling pathway, plenty of in-depth research and studies have been conducted that have no doubt contributed to our knowledge of the pathway today.&lt;br /&gt;
&lt;br /&gt;
SMAD signaling and the three receptors for TGF-beta are two of the many fields of interest regarding the topic. In medicine and specific areas such as cancer, cardiovascular disease and inflammatory bowel disease, there are numerous alternatives for drugs that can either heighten or suppress the activity of TGF-beta.&lt;br /&gt;
&lt;br /&gt;
{| class=&amp;quot;pretty table&amp;quot;&lt;br /&gt;
| '''1988'''&lt;br /&gt;
| The process of maturation of follicle-enclosed oocytes and cumulus-oocyte complexes was sped up by TGF beta. It was discovered that TGF beta and other growth factors are effective in vitro stimulators of oocyte maturation in the rat&lt;br /&gt;
&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;3275534&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
|-&lt;br /&gt;
| '''1989'''&lt;br /&gt;
| It was already known that TGF-beta 1 is a strong autocrine growth inhibitor of lymphocytes. Ellingsworth and colleagues found that TGF-beta 1 binds to all three cell surface-binding proteins (280-200 kD, 95-85 kD, 65 kD).&lt;br /&gt;
It was also found that these binding proteins are required for signal transduction. Overall, they discovered that the regulation of the expression of the TGF-beta 1 receptor is controlled by T cell mitogenic signals.&lt;br /&gt;
&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;2785999&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
|-&lt;br /&gt;
| '''1989'''&lt;br /&gt;
| It was made known that the properties of R mutants classify TGF-beta type I binding protein as the receptor involved in mediating TGF-beta actions on cell adhesion and proliferation&lt;br /&gt;
&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;2536702&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
|-&lt;br /&gt;
| '''1989'''&lt;br /&gt;
| Drosophil was the only member of the TGF-beta family to be identified in invertebrates &lt;br /&gt;
&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;2699859&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
|-&lt;br /&gt;
| '''1990'''&lt;br /&gt;
| It was already known that the rapid increase in number response of mink lung epithelial cells to serum and to epidermal growth factor was inhibited by TGF beta 1. A necessary component of TGF-beta 1 mediated growth inhibition in CCL64 epithelial cells is the coupling of TGF beta 1 receptor binding to G-protein activation&lt;br /&gt;
&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;2156499&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
|-&lt;br /&gt;
| '''2000'''&lt;br /&gt;
| VegT function was found to be involved in sequence with the TGF beta pathway. Therefore, TGF beta signaling may be activated by the maternally expressed VegT to participate in endoderm determination&lt;br /&gt;
&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;10640706&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
|-&lt;br /&gt;
| '''2005'''&lt;br /&gt;
| Within the TGF beta superfamily, it was found that a limited number of type I and type II receptors worked together to produce specificity of action &lt;br /&gt;
&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;15483083&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
|-&lt;br /&gt;
| '''2010'''&lt;br /&gt;
| Deregulation of TGF beta signaling was reported in human psoriasis&lt;br /&gt;
&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;19710682&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
|-&lt;br /&gt;
| '''2015'''&lt;br /&gt;
| It was known that TGF is required in the tumorigenicity and metastasis of bone tumour. A significant event in the activation of the TGF beta signaling pathway is the binding of transcription coactivator Yes-associated protein (YAP) to Smad transcription factors&lt;br /&gt;
&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;27491038&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
|}&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
[[File:Canonical and non-canonical signalling TGF beta pathways.png|thumb|500px|Flowchart showing the Canonical and Non-Canonical pathways of TGF-β signalling pathway.&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;24393789&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;]] &lt;br /&gt;
===Canonical pathway===&lt;br /&gt;
In the canonical pathway, the dormant TGF-β complex is formed when the three TGF-β ligand isoforms - TGF-B1, TGF-B2 and TGF-B3 - bind once it is synthesized as precursors. After secretion and extracellular activation, TGF-β ligands can bind to two types of receptors: the membranous TGF-β type III receptor or the TGF-β type II receptor (TGF-βRII) homodimers with high affinity. &lt;br /&gt;
TGF-βRII binding enables dimerization with TGF-β type I receptor (TGF-βRI) homodimers, as well as activation of the TGF-βRI kinase domain and signal transduction across phosphorylation of the C-terminus of receptor-regulated SMADs, SMAD2 and SMAD3.&lt;br /&gt;
A heterotrimeric complex is formed by the TGF-βR dimer and SMAD4, which moves and assemblies in the nucleus.&lt;br /&gt;
TGF-β dependent signalling can operate or subdue numerous target genes through the communication of SMADs with multiple transcription factors. There are many structures in which SMAD activities are regulated, such as SMAD2/3 nucleocytoplasmic shuttling, binding to anchor proteins, phosphorylation and Smurf (SMAD-ubiquitination-regulatory factor).  &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;24393789 &amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
&lt;br /&gt;
===Non-Canonical pathway===&lt;br /&gt;
In the non-canonical pathway, SMAD-independent pathways such as PI3K/AKT and MAPK pathways like ERK, JNK, and p38 MAPK are activated by TGF-β signalling. In addition, transversal signalling, especially at the SMAD level, allows TGF-β pathway activation to incorporate signals from integrins, Notch and Wnt dependent pathways as well as signals from cellular processes like the cell cycle or apoptosis machineries. Thus, the TGF-β signalling pathway has pleiotropic functions regulating cell growth, differentiation, apoptosis, cell motility, extracellular matrix production, angiogenesis and cellular immune response.&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;24393789 &amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
&lt;br /&gt;
==Process of TGF-β signalling pathway==&lt;br /&gt;
&lt;br /&gt;
TGF-β signalling pathway is required for regulation of a large number of cellular processes such as cell proliferation, invasion and inflammation. It is also activated mitogen activated protein kinase signalling. There are two main routes in TGF-β signalling; the SMAD Dependent pathway and SMAD Independent pathway.&lt;br /&gt;
&lt;br /&gt;
===SMAD Dependent TGF-β signalling pathway===&lt;br /&gt;
&lt;br /&gt;
[[File:TGF-B Signalling - Formation of Receptor Hetero-Tetramers.png|thumb|350px|SMAD Dependent TGF-β signalling pathway: Formation of Receptor Hetero-Tetramers&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;16446785&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;]]&lt;br /&gt;
&lt;br /&gt;
The ligands of the TGF-β superfamily form dimers that bind to heterodimeric receptor complexes composed of two type I and two type II transmembrane receptor subunits with serine/threonine kinase domains.&lt;br /&gt;
Following ligand binding on TGF-β1, the dimerized TGF-β type II receptors phosphorylates and activates the TGF-β type I receptors. In most cell types, this leads to recruitment and phosphorylation of the receptor-regulated SMAD2 and SMAD3, presented by the SMAD anchor for receptor activation. SMAD1 and SMAD5 can be activated by the TGF-β signaling depending on the Type I receptor that is expressed.&lt;br /&gt;
Heterologous complexes are formed by the phosphorylated receptor-regulated SMAD with the common-mediator SMAD, SMAD4, and successively move into the nucleus, where they accumulate and act as transcription factors participating in the regulation of target gene expression. &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;21302608&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
In addition, they recruit extra transcriptional regulators, such as DNA-binding transcription factors, co-activators and co-repressors. These control the expression of several target genes and ultimately initiates a SMAD-dependent signaling cascade that induces or represses transcriptional activity. SMADs are widely expressed in most adult tissue and cell types, indicating that the TGF-β signaling pathway is ubiquitous.&lt;br /&gt;
&lt;br /&gt;
===SMAD independent TGF-β signalling pathway===&lt;br /&gt;
&lt;br /&gt;
Rather than SMAD-mediated transciption TGF-β also has the potential to activate other signalling cascades for example the Erk, JNK and p38 MAPK kinase pathways. In some cases these pathways exhibit activation with slow kinetics which indicates SMAD-dependant mechanics, however there has also been rapid activation cases (5-15mins) suggesting independence from transcription mechanisms. Studies carried out with SMAD4 deficient cells and dominant-negative SMADS provide evidence that the MAPK pathway activation is independent from SMADS, as well as this it has be found that p38 MAPK signalling  was activated in response to mutated TGF- β type 1 receptors, which were defective in SMAD activation&amp;lt;ref name=&amp;quot;PMID14534577&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;14534577&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;.&lt;br /&gt;
&lt;br /&gt;
The precise mechanisms and biological consequences of these SMAD-Independent pathways (Erk, JNK, p38 MAPK) are currently poorly characterized. Ras is implicated in TGF- β induced Erk signalling as there is rapid activation of Ras by TGF- β in epithelial cells. The JNK and p38 MAPK signalling are activated by various MAPK kinase kinases (MAPKKK) TGF- β kinase 1 (TAK 1) receptor is a MAPKKK family member. Further research and identification of various interactions between the small signalling molecules and receptor proteins will provide additional insight into the precise mechanism behind the activation of MAPK pathways by TGF- β ligands &amp;lt;ref name=&amp;quot;PMID14534577&amp;quot;/&amp;gt;.&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
==Regulation of the pathway and factors affecting it==&lt;br /&gt;
&lt;br /&gt;
Signalling mechanisms by TGF-β like factors are regulated in both negative and positive fashions, these are all tightly controlled through a multitude of mechanisms at extracellular, membrane, cytoplasmic and all the way to nuclear levels. Positive regulation is required to amplify signalling from TGF-β like factors, while negative regulation is important for the termination and restriction of signalling usually occurring through the mechanism of a feedback loop. There is also additional regulation of TGF-β like factors via cross-talk with other signal transduction pathways such as MAPK and JAK/STAT pathways.&amp;lt;ref name=&amp;quot;PMID10704361&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;10704361&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
===Positive Regulation===&lt;br /&gt;
The positive regulation of TGF-β specifically the induction of ligands and their signalling components often is triggered by the action TGF-β-like factors themselves. For example NODAL, a secretory protein of the TGF-β superfamily which plays a role in early embryogenesis and acts through activin receptors and SMAD2 is induced by nodal signalling itself. In other types of cells TGF-β receptors as well as transcription factors which serve as targets for TGF-β like factors can be induced by ligand stimulation, as identified in case of transcription factor Runx3 which is induced by TGF-β and forms a complex with SMAD3 to be further activated by TGF-β. The mechanism of SMAD signalling is also positively modulated via the &amp;quot;cross-talk&amp;quot; (and hence the process of SMAD dependant TGF-β signalling) with other signalling pathways, SMADS may be activated by the tyrosine kinase receptor under specific circumstances and further positively regulate TGF-β like factors &amp;lt;ref name=&amp;quot;PMID10704361&amp;quot;/&amp;gt;.&lt;br /&gt;
&lt;br /&gt;
===Negative Regulation===&lt;br /&gt;
&lt;br /&gt;
Signalling is regulated at the cell membrane level as well as within the cytoplasm of the cell, specifically by BAMBI, a pseudo-receptor for serine/threonine kinase receptors (in Xenopus embryos however displays a high degree of sequence similarity to human BAMBI gene). This BAMBI receptor is structurally alike to the type 1 serine/threonine kinase receptor, the only difference being that it lacks an intracellular domain. BAMBI  has shown a similar expression profile to that of BMP-4 a growth factor from the TGF-β super family, and has been found to require BMP signalling for expression. BAMBI when goes on to interact with both type 1 and type 2 serine/threonine receptors and works to abolish their abilities to signal via BMPs, activins and TGF-βs, therefore it is postulated that BAMBI can be inductively expressed by BMPS to self regulate BMP signalling as well as cross-regulate signalling from other members of the TGF-β super family. &amp;lt;ref name=&amp;quot;PMID10704361&amp;quot;/&amp;gt;&lt;br /&gt;
&lt;br /&gt;
==Significance in Embryonic Development==&lt;br /&gt;
&lt;br /&gt;
TGF betas are involved in embryogenesis. During development of the embryo, members of the TGF-beta family are essential for bone and cartilage formation, mesoderm induction and patterning and dorso-ventral patterning.&lt;br /&gt;
&lt;br /&gt;
[[File:TGF in Cardiovascular.jpg|thumb|500px|Expression of TGF-β2 and TGF-β3 in wildtype embryonic hearts.&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;12948523&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;]]&lt;br /&gt;
===Cardiovascular Development===&lt;br /&gt;
&lt;br /&gt;
Genetic engineering and tissue explanation studies have revealed many roles for TGF-β ligands and their signaling molecules in development. In the embryo, TGF-β appear to be involved in epithelial-mesenchymal transformations (EMT) during the formation of endocardial cushions, and in epicardial epithelial-mesenchymal transformations essential for coronary vasculature, ventricular myocardial development and compaction. It must be noted that in the normal function of the cardiovascular system in the adult, TGF-β play significant roles in cardiac hypertrophy, vascular remodeling and regulation of the renal renin-angiotensin system.&lt;br /&gt;
&lt;br /&gt;
TGF-β1 is expressed in the endocardium of the developing mouse. TGF-β(-/-) mice have been found with obvious congenital cardiovascular defects, so it’s important to review its expression in the developing heart. In the blood vessels, TGF-β1 is in the intima whereas TGF-β2 and TGF-β3 are in the media and adventitia. TGF-β2 signals are found as early as embryonic day 7.25 (E7.25) &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;7687212&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; in the cardiogenic plate of the precardiac mesoderm and is later prominent in the myocardium of the aortic sac and outflow track regions. TGF-β2 protein is also found in the entire myocardium of the heart at the time when looping occurs. From E8.5-9.5 when the cushion formation process occurs, there is a particularly strong TGF-β2 expression localised to the myocardium as displayed in A, B, D and E in the figure. After cushion formation and EMT, and before myocardialization of the endocardial cushion begins, there is also strong TGF-β2 expression in the OT myocardium and in the adjacent developing cushion mesenchym. However, as myocardialization occurs, TGF-β2 expression is reduced in the myocardium so that from E12.5 onwards, it is only expressed mainly in the mesenchyme of the cushion and OT septum. As can be seen in 2GH, TGF-β2 expression remains high in the cushion mesenchyme of the OT septum. By E15.5, TGF-β1 s now the most highly expressed isoform in the endocardial cells of the myocardium. It is seen in M, N, O of the figure that the epidcardium TGF-β1 and TGF-β3 expression is higher than that of TGF-β2. Thus, it can be seen that all three TGF-β are expressed in the epicardium, and they are not expressed in an overlapping fashion.&lt;br /&gt;
&lt;br /&gt;
Cross talk between mesoderm and underlying endoderm is needed to form the early tubular heart. This cellular and molecular induction in the primary heart forming regions is important for the specification and differentiation of myocardial and endocardial precursor cells &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;10767078&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;. Other endoderm-derived growth factors such as BMP2, FGF2 as well as TGFBS have been implicated in this process in the avian system &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;11322300&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;. TGFB2 and TGFB receptors are expressed in the precardiac mesoderm along with BMP2 &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;7687212&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;10767078&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;10340759&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;. Members of the TGG family can serve as inductive signals at the heart forming fields for the formation of myocardial and endocardial precursor cells. Members such as Activin, BMP, Nodal, Left and others have been found to be crucial for the establishment of embryonic asymmetry &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;11836504&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;, and this asymmetry is in turn critical for heart development &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;11752633&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;.&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
===Mammary Gland Development===&lt;br /&gt;
Similarly, all three TGF-β isoforms are expressed during all stages in the development of the mammary gland except lactation. Specifically, mouse studies have indicated key roles for TGF-β in organizing the architecture of the mammary gland, regulating stem cell kinetics, inducing apoptosis in the involuting gland and maintaining the epithelium in a functionally undifferentiated state. The TGF-β isoforms are expressed in the ductal epithelium at all stages of development and some reviews have found that there may be some isoform specificity for temporal and spatial expression patterns &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;10887507&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;. For example, TGF-β3 is the only isoform present in the endbup cap cells and myoepithelial cells. Additionally, TGF-β1 is present at high levels in the extracellular matrix that surrounds growth-quiescent ducts. As for its effect, TGF-β have been to have induce multiple responses such as inhibiting the proliferation of mammillary epithelial cells. The nature of the target cell of plays a role as TGF-β also induced apoptosis without the inhibiting the proliferation. This highlights the highly variable actions of TGF-β that are affected by cell type, environmental and cell history to name a few. Interestingly, TGF-β have been implicated as both tumour suppressors and oncogenes in mammary tumorigenesis. For example, the overexpression of TGF-β1 inhibits tumorigenesis whilst interfering with its receptor function enhances tumorigenesis, thus hinting at its tumor suppressor role &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;7753792&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;9407968&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;. On the contrary, TGF-β has exhibited the enhancement of tumorigenesis as the TGF-β ligand expression is increased in late human breast cancer. Thus, TGF-β further proves its pleiotropic behaviour as prevalent to the mammary gland as it potentially suppresses and/or promotes tumorigenesis.&lt;br /&gt;
&lt;br /&gt;
===Maintenance of pluripotency in hESC===&lt;br /&gt;
Many of the members within the TGF-β superfamily are enriched within stem cells suggesting they play an important role in these cells, specifically relation to their pluripotency. The ability for a cell to self renew and differentiate is known as  'stemness', the stemness of human as well as mouse embryonic stem cells can be maintained by growing a combined culture with feed cells for example, bone morphogenic protein 4 (BMP4) induces a helix-loophelix-protein known as Id which is a potent inhibitor of differentiation, since this BMP (a member of the TGF-β  superfamily) is a potent inhibitor of neural differentiation in vertebrate embryos it is thought to maintain the stemness of hESCs and thus maintain their pluripotency.&amp;lt;ref name=&amp;quot;PMID24298330 &amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;24298330 &amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
[[File:Flowchart_for_maintenance_of_pluripotency_in_hESCs.png|thumb|upright=1.5|right|Flowchart for mechanism of maintenance of pluripotency in hESCs]]&lt;br /&gt;
&lt;br /&gt;
The nodal secretory protein from the TGF-β superfamily were found to also contribute to mESC pluripotency, this was evidenced by microarray of Nodal deficient mice which were found to have diminished  levels of Oct3/4 (transcription factors)expression, which are markers of undifferentiated stem cells. More importantly a nuclear localization of SMAD2 was found in hESCs, this is generally induced by TGF-β, activin or nodal signalling. Further microarray analysis identified that activin supposedly maintains the pluripotency of hESCs through inducing the expression of Oct4 as well as Nanog both transcription factors which are heavily involved in the self renewal of undifferentiated embryonic stem cells. Consistent with this finding, the subsequent inhibition of SMAD2 phosphorylation resulted in the decrease of expression of the markers of undifferentiated ESCs (Oct3/4, Nanog), suggesting that these were a product of SMAD2 phosphorylation and because SMAD2 is a product of activin/nodal signalling further suggesting that activin or nodal proteins produced by ESCs function to promote the maintenance of pluripotency in hESCs.&amp;lt;ref name=&amp;quot;PMID24298330 &amp;quot;/&amp;gt;.&lt;br /&gt;
&lt;br /&gt;
===Formation of the palate===&lt;br /&gt;
The formation of the palate is a complex procedure which involves a multitude of events including palatal shelf growth, elevation as well as left and right side fusion, as a result of genetic defects this procedure can sometimes result in formation of a cleft palate, one of the most common genetic birth defects. There have been recent findings which indicate TGF-β signalling plays a prime role in regulating the development of the palate in regards to both the palatal mesenchyme and epithelium. In humans the palate develops from two primordiuims, the primary and secondary palate, these progress to develop into palatal shelves which are positioned vertically against each other along the sides of the tongue. Following jaw growth and descent of the tongue these primordial palates orientate themselves horizontally and begin to fuse, in the case of the hard palate the mesenchyme cells are replaced by intramembranous bone as opposed to the soft palate which remains muscular and does not undergo ossification. Alike to humans mice have a similar embryological process of palate formation with the stage of palatal fusion resulting in the formation of a medial edge epithelium (MEE) seam which eventually degrades via apoptosis, thus the mouse serves as a strong candidate to fulfil the role of a reliable animal model. &amp;lt;ref name=&amp;quot;PMID21395922 &amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;21395922&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
With this model being established, it has been identified that TGF-β1 is strongly expressed in MEE cells just prior to adherence of the opposing palatal shelves, following this adherence the level of TGF-β1 gradually decreased until it ceased to be expressed in the mesenchymal cells, TGF-β. TGF-β2 and TGF-β3 were also expressed in the palatal mesenchymal cells during adherence and TGF-β3 was found to be continually expressed during the fusion process, it is further found that TGF-β3 played a crucial role in the cell degradation of MEE cells in addition to palatal fusion. It was found that when TGF-β3 deficient mice developed they expressed defects in MEE seam degradation and fusion.&amp;lt;ref name=&amp;quot;PMID21395922&amp;quot;/&amp;gt;.&lt;br /&gt;
&lt;br /&gt;
The use of these animal models to explore the role of TGF-β in cleft palate formation is fruitful in terms of identifying contributing factors and subtypes of TGF-β family members however there still remains much to discover of the molecular and cellular mechanisms  associated with palate formation.&lt;br /&gt;
&lt;br /&gt;
==Animal Studies==&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
===Wound healing===&lt;br /&gt;
Animal studies have served as a useful way in providing pivotal information regarding the mechanisms of TGF-β action in wound healing. In fact, much of the current information on the action of TGF-β in wound healing has been acquired from animal studies using incisional and/or excisional wounding models and manipulation of TGF-β signalling by adding the exogenous TGF-β protein or anti-TGF-β neutralizing antibodies, or by genetic alteration in components of the TGF-β signalling pathway. This is due to the fact that animal models provide outstanding experimental methods for explaining molecular mechanisms by which TGF-β regulates wound-healing responses. Ultimately, it has led the development of therapeutic strategies focusing on how the TGF-β pathway can improve wound healing and scarring outcome.&lt;br /&gt;
&lt;br /&gt;
[[File:Destination filename.jpeg|thumb|550px|Excisional wound healing in Smad 3 KO mice.&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;24761336&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;]] &lt;br /&gt;
Wound healing is an intricate physiological process distinguished by the successive overlapping stages of inflammation, proliferation and maturation. It that requires numerous growth factors, one of which includes TGF-β, which has the widest range of effects. TGF-β is a multifunctional growth factor that employs pleiotropic effects on wound healing by regulating cell differentiation, extracellular matrix production and immune modulation. The role of TGF-β signalling in wound healing was explored through examination of the development of tissue-specific expression systems for overexpression or knockout of TGF-b signalling pathway components. This study also classified that molecules might serve as molecular targets for the treatment of pathological skin conditions such as chronic wounds and excessive scarring (fibrosis). &lt;br /&gt;
&lt;br /&gt;
Exogenously added TGF-β has the potential to promote wound healing by stimulating angiogenesis, immune cell infiltration, and ECM production, and that diminishing endogenous TGF-β action reduces scarring without adversely affecting wound-healing quality.&lt;br /&gt;
===Direct modulation of TGF-β levels===&lt;br /&gt;
Injecting TGF-β into normal skin of newborn mice led to resilient initiation of angiogenesis and fibrosis. This consisted of important new collagen synthesis combined into the matrix. As a result of these observations, people were encouraged to further study the administration of TGF-β to incisional wounds in rats. It proved that TGF-β treatment resulted in better dermal healing, as showed by prominent collagen deposition and significantly increased wound strength.&lt;br /&gt;
&lt;br /&gt;
Interpreting wound-healing results obtained from the animals brought about its limitations. For instance, an underlying skin abnormality was found on many of the mouse models with genetic alterations in the TGF-β signalling pathway. Also, the pleiotropic effects of TGF-β on many different cell types throughout stages of wound healing highlighted a challenge in designing particular methods in which the TGF-β signalling pathway can assist wound healing or reduce scarring. &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;24761336&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
==Current Research==&lt;br /&gt;
&lt;br /&gt;
==Abnormalities of the TGF-Beta Pathway==&lt;br /&gt;
Mutations or deletion of the TGF-beta 1 or TGF-beta RII gene have been associated with multiple syndromes. In mice, defects have been found in haematopoiesis, vasculogenesis and endothelial differentiation of extra embryonic tissues, while knockout mice for SMAD2 or SMAD4 genes are more likely to have spontaneous tumour development and excessive inflammatory responses. In humans, various diseases have been linked to the mutation of the TGF-beta RII gene and SMAD4 mutation is genetically responsible for familial juvenile polyposis, an autosomal dominant disease characterized by predisposition to gastrointestinal polyps and cancers.&lt;br /&gt;
&lt;br /&gt;
====Cancer====&lt;br /&gt;
Alterations of this signalling pathway are common in cancer. Accessory proteins such as soluble or membrane-bound regulators or co-receptors can also affect TGF-beta signalling. A normal acting cell has a functional TGF-β signalling pathway, in which TGF- β stops proliferation of cells at G1 stage to either encourage apoptosis or induce differentiation. If the TGF-β signaling pathway becomes mutated these cells can become cancerous as the TGF-β no longer controls the cell. Uncontrolled, these cancer cells proliferate and cause surrounding fibroblasts, immune cells, endothelial and smooth-muscle cells to proliferate as well. From this increased production of TGF-β it causes angiogenesis and immunosuppression, further propogating the cancer. &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;10793168&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;The human body has an regulation against this, which is called effector T-cells which destroy cancer cells via an inflammatory reaction. However, TGF-β converts them into regulatory T-cells, which reduce the inflammatory reaction.&lt;br /&gt;
&lt;br /&gt;
 &lt;br /&gt;
====Marfan syndrome====&lt;br /&gt;
It is also suggested that TGF-β signaling has a large part to play in the pathogenesis of Marfan syndrome. This disease causes disproportionate height, abnormally long fingers and toes, displaced crystalline lens of the eye. Not only this but heart complications can also occur, like mitral valve prolapse or aortic enlargement. Marfan syndrome is generally known to be caused by defective creation of elastic fibres, more specifically of the glycoprotein fibrillin I. In a study done it was observed that by adding TGF-β antagonist in mice who were affected by Marfan syndrome phenotype, their symptoms were alleviated.&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;16601194&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; From this, we can see that the mechanism involved in Marfan syndrome most likely has an underlying relation with lowered sequestration of TGF-β by fibrillin.&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;16571647&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
[[File:Embryo marfan.jpg|thumb|250px|Patient with Marfan syndrome. Note aesthenic or marfanoid body habitus, pronounced myopia (thick glasses), previous thoracic surgery (composite aortic root/aortic valve replacement)..&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt; PMC1767196 &amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;]]&lt;br /&gt;
&lt;br /&gt;
====Heart disease====&lt;br /&gt;
The TGF-B pathway has many effects on cardiomyocytes, mesenchymal and immune cells. Not only this, but it plays a vital role in the pathogenesis of cardiac remodeling and fibrosis. Abnormalities in this pathway can cause an overexpression of TGF-β which has been associated with fibrosis and hypertrophy in mice hearts. We see that endogenous TGF-β is capable of varying matrix metabolism in a pressure-overloaded heart. In a heart which has undergone great stress, such as myocardial infarction, TGF-β is seen to inactivate inflammatory macrophages. This allows for less of an immune response but further done by it encouraging myofibroblast transdifferentiation and matrix synthesis. Thus higher levels of TGF-β is causing more inflammatory damage and further propagating the heart disease. &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;21059352&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
====Loeys–Dietz syndrome====&lt;br /&gt;
Abnormalities of the TGF-β signaling can also cause Loeys–Dietz syndrome via mutations in the TGF-β receptor. Loeys-Deitz syndrome connective tissue disorder, mainly in children where there are aneurisms in the aorta. Not only this, but the aorta can undergo dissection in weakened layers of the aortic wall. Further, the disease is labelled into four different types, since it is an autosomal dominant genetic connective tissue disorder, the groups are categorized by their genetic cause. TGFB1 and TGFB2 cause type I and II. Normally these genes allow for the fruition of the body’s development and growth. However, when defective they create non-functioning proteins.&lt;br /&gt;
&lt;br /&gt;
====Obesity, Diabetes and Hepatic Steatosis====&lt;br /&gt;
Normally, TGF-β signaling pathway has a major role in maintaining a regulated level of glucose and energy under homeostatic conditions. Not only this, but TGF-B could also have a vital task in diabetic kidney disease.  &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;21723505&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
Abnormalities in TGF-β signaling in obesity is one of the reasons why there is so much inflammatory damage in the human body by obesity. [5]&lt;br /&gt;
This was shown again in a study done where mice affected were given a systemic blockade drug for the TGF-B pathway and it was observed that they were protected from obesity, diabetes and hepatic steatosis. &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;21436399&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
====Multiple Sclerosis====&lt;br /&gt;
In Multiple Sclerosis (MS) a common observation is that patients will generally have lower levels of TGF-β, which is suspected to prevent remylentation of neurons. The reason why this is of significance is because MS results in demylentation of neurons causing severe neurological problems. TGF-β is normally responsible for regulating apoptosis of Th17 cells.&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;22942700&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;Thus when TGF-β levels decrease due to abnormalities, they are not able to be regulating Th17 cells apoptosis.[6] This then causes Th17 cells to secrete TNF-α, finally causing a demylenation of the oliodendroglial (neurons).&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;22189514&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;By having a lower amount of TGF-β we get a higer level of Th17 cells and therefore more TNFα and neuronal damage. Thus we can observe that this pathway is vital in maintaining neuronal health.&lt;br /&gt;
&lt;br /&gt;
==Further Reading==&lt;br /&gt;
&lt;br /&gt;
==Glossary==&lt;br /&gt;
{| class=&amp;quot;pretty table&amp;quot;&lt;br /&gt;
|-&lt;br /&gt;
| '''Apoptosis'''&lt;br /&gt;
| Cell death which occurs as a normal and controlled part of an organism's growth or development&lt;br /&gt;
|-&lt;br /&gt;
| '''Avian system'''&lt;br /&gt;
| Respiratory system that delivers oxygen and removes carbon dioxide&lt;br /&gt;
|-&lt;br /&gt;
| '''CCL-64'''&lt;br /&gt;
|  - mink lung epithelial cell&lt;br /&gt;
|-&lt;br /&gt;
| '''Cytokine'''&lt;br /&gt;
| A broad and loose category of small proteins that are important in cell signalling&lt;br /&gt;
|-&lt;br /&gt;
| '''Cushion Formation'''&lt;br /&gt;
| Cells in development that play a role in the formation of the heart septa&lt;br /&gt;
|-&lt;br /&gt;
| '''Dimer'''&lt;br /&gt;
| An oligomer consisting of two structurally similar monomers joined by bonds that can be either strong or weak, covalent or intermolecular&lt;br /&gt;
|-&lt;br /&gt;
| '''Homodimers'''&lt;br /&gt;
| A protein composed of two polypeptide chains that are identical in the order, number, and kind of their amino acid residues&lt;br /&gt;
|-&lt;br /&gt;
| '''Isoform'''&lt;br /&gt;
| A protein that has the same function as another protein but which is encoded by a different gene and may have small differences in its sequence&lt;br /&gt;
|-&lt;br /&gt;
| '''Ligands'''&lt;br /&gt;
| A molecule that binds to a larger molecule&lt;br /&gt;
|-&lt;br /&gt;
| '''Looping'''&lt;br /&gt;
| A morphogenetic process when the heart shape is formed by looping the embryonic tube&lt;br /&gt;
|-&lt;br /&gt;
| '''Pleiotropic'''&lt;br /&gt;
| To produce more than one type of effect&lt;br /&gt;
|-&lt;br /&gt;
| '''BMP'''&lt;br /&gt;
| Bone Morphogenetic Protein, a protein part of the TGF-β superfamily.&lt;/div&gt;</summary>
		<author><name>Z5020466</name></author>
	</entry>
	<entry>
		<id>https://embryology.med.unsw.edu.au/embryology/index.php?title=2016_Group_Project_6&amp;diff=255364</id>
		<title>2016 Group Project 6</title>
		<link rel="alternate" type="text/html" href="https://embryology.med.unsw.edu.au/embryology/index.php?title=2016_Group_Project_6&amp;diff=255364"/>
		<updated>2016-10-27T13:08:18Z</updated>

		<summary type="html">&lt;p&gt;Z5020466: /* Marfan syndrome */&lt;/p&gt;
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&lt;div&gt;{{ANAT2341Project2016header}}&lt;br /&gt;
{{Group Assessment Criteria table}}&lt;br /&gt;
&amp;lt;!-- Do not delete the above template from the Group project page. --&amp;gt;&lt;br /&gt;
&lt;br /&gt;
=Transforming Growth Factor-Beta (TGF-β) Signalling Pathway=&lt;br /&gt;
&lt;br /&gt;
==Introduction==&lt;br /&gt;
&lt;br /&gt;
The transforming growth factor beta (TGF-β) is a multifunctional and pleiotropic cytokine &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;26555259&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;.&lt;br /&gt;
The TGF-β signalling pathway is crucial to the control of different biological and pathological processes, such as cellular proliferation and differentiation, angiogenesis, immune regulation/inflammation, apoptosis and cell survival. &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;17896911&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
TGF-β belongs to the Transforming Growth Factor superfamily - a large group of structually connected cell regulatory proteins. It consists of TGF-β 1, 2 AND 3, Growth Differentiation Factors (GDFs), Activins, Inhibins, Bone Morphogenetic Proteins (BMPs), Glial-derived Neurotrophic Factors (GDNFs) and Mullierian Inhibiting Substance (MIS). &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;24270394&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
Most importantly, TGF-β plays a dominant part in the development of the embryo and adult organism. &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;23926286&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
This wiki aims to present a helpful overview of the TGF-β signalling pathway, but is in no means a complete resource on all information regarding the topic. We focus on ________________&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&amp;lt;br&amp;gt;&amp;lt;br&amp;gt;&lt;br /&gt;
&amp;lt;div align=&amp;quot;center&amp;quot;&amp;gt;&amp;lt;html5media width=&amp;quot;560&amp;quot; height=&amp;quot;315&amp;quot;&amp;gt;https://www.youtube.com/watch?v=GuKjUearIUI&amp;lt;/html5media&amp;gt;&amp;lt;/div&amp;gt;&lt;br /&gt;
&amp;lt;br&amp;gt;&lt;br /&gt;
&lt;br /&gt;
==History==&lt;br /&gt;
Since the early stages of the TGF beta-signaling pathway, plenty of in-depth research and studies have been conducted that have no doubt contributed to our knowledge of the pathway today.&lt;br /&gt;
&lt;br /&gt;
SMAD signaling and the three receptors for TGF-beta are two of the many fields of interest regarding the topic. In medicine and specific areas such as cancer, cardiovascular disease and inflammatory bowel disease, there are numerous alternatives for drugs that can either heighten or suppress the activity of TGF-beta.&lt;br /&gt;
&lt;br /&gt;
{| class=&amp;quot;pretty table&amp;quot;&lt;br /&gt;
| '''1988'''&lt;br /&gt;
| The process of maturation of follicle-enclosed oocytes and cumulus-oocyte complexes was sped up by TGF beta. It was discovered that TGF beta and other growth factors are effective in vitro stimulators of oocyte maturation in the rat&lt;br /&gt;
&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;3275534&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
|-&lt;br /&gt;
| '''1989'''&lt;br /&gt;
| It was already known that TGF-beta 1 is a strong autocrine growth inhibitor of lymphocytes. Ellingsworth and colleagues found that TGF-beta 1 binds to all three cell surface-binding proteins (280-200 kD, 95-85 kD, 65 kD).&lt;br /&gt;
It was also found that these binding proteins are required for signal transduction. Overall, they discovered that the regulation of the expression of the TGF-beta 1 receptor is controlled by T cell mitogenic signals.&lt;br /&gt;
&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;2785999&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
|-&lt;br /&gt;
| '''1989'''&lt;br /&gt;
| It was made known that the properties of R mutants classify TGF-beta type I binding protein as the receptor involved in mediating TGF-beta actions on cell adhesion and proliferation&lt;br /&gt;
&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;2536702&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
|-&lt;br /&gt;
| '''1989'''&lt;br /&gt;
| Drosophil was the only member of the TGF-beta family to be identified in invertebrates &lt;br /&gt;
&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;2699859&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
|-&lt;br /&gt;
| '''1990'''&lt;br /&gt;
| It was already known that the rapid increase in number response of mink lung epithelial cells to serum and to epidermal growth factor was inhibited by TGF beta 1. A necessary component of TGF-beta 1 mediated growth inhibition in CCL64 epithelial cells is the coupling of TGF beta 1 receptor binding to G-protein activation&lt;br /&gt;
&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;2156499&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
|-&lt;br /&gt;
| '''2000'''&lt;br /&gt;
| VegT function was found to be involved in sequence with the TGF beta pathway. Therefore, TGF beta signaling may be activated by the maternally expressed VegT to participate in endoderm determination&lt;br /&gt;
&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;10640706&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
|-&lt;br /&gt;
| '''2005'''&lt;br /&gt;
| Within the TGF beta superfamily, it was found that a limited number of type I and type II receptors worked together to produce specificity of action &lt;br /&gt;
&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;15483083&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
|-&lt;br /&gt;
| '''2010'''&lt;br /&gt;
| Deregulation of TGF beta signaling was reported in human psoriasis&lt;br /&gt;
&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;19710682&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
|-&lt;br /&gt;
| '''2015'''&lt;br /&gt;
| It was known that TGF is required in the tumorigenicity and metastasis of bone tumour. A significant event in the activation of the TGF beta signaling pathway is the binding of transcription coactivator Yes-associated protein (YAP) to Smad transcription factors&lt;br /&gt;
&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;27491038&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
|}&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
[[File:Canonical and non-canonical signalling TGF beta pathways.png|thumb|500px|Flowchart showing the Canonical and Non-Canonical pathways of TGF-β signalling pathway.&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;24393789&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;]] &lt;br /&gt;
===Canonical pathway===&lt;br /&gt;
In the canonical pathway, the dormant TGF-β complex is formed when the three TGF-β ligand isoforms - TGF-B1, TGF-B2 and TGF-B3 - bind once it is synthesized as precursors. After secretion and extracellular activation, TGF-β ligands can bind to two types of receptors: the membranous TGF-β type III receptor or the TGF-β type II receptor (TGF-βRII) homodimers with high affinity. &lt;br /&gt;
TGF-βRII binding enables dimerization with TGF-β type I receptor (TGF-βRI) homodimers, as well as activation of the TGF-βRI kinase domain and signal transduction across phosphorylation of the C-terminus of receptor-regulated SMADs, SMAD2 and SMAD3.&lt;br /&gt;
A heterotrimeric complex is formed by the TGF-βR dimer and SMAD4, which moves and assemblies in the nucleus.&lt;br /&gt;
TGF-β dependent signalling can operate or subdue numerous target genes through the communication of SMADs with multiple transcription factors. There are many structures in which SMAD activities are regulated, such as SMAD2/3 nucleocytoplasmic shuttling, binding to anchor proteins, phosphorylation and Smurf (SMAD-ubiquitination-regulatory factor).  &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;24393789 &amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
&lt;br /&gt;
===Non-Canonical pathway===&lt;br /&gt;
In the non-canonical pathway, SMAD-independent pathways such as PI3K/AKT and MAPK pathways like ERK, JNK, and p38 MAPK are activated by TGF-β signalling. In addition, transversal signalling, especially at the SMAD level, allows TGF-β pathway activation to incorporate signals from integrins, Notch and Wnt dependent pathways as well as signals from cellular processes like the cell cycle or apoptosis machineries. Thus, the TGF-β signalling pathway has pleiotropic functions regulating cell growth, differentiation, apoptosis, cell motility, extracellular matrix production, angiogenesis and cellular immune response.&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;24393789 &amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
&lt;br /&gt;
==Process of TGF-β signalling pathway==&lt;br /&gt;
&lt;br /&gt;
TGF-β signalling pathway is required for regulation of a large number of cellular processes such as cell proliferation, invasion and inflammation. It is also activated mitogen activated protein kinase signalling. There are two main routes in TGF-β signalling; the SMAD Dependent pathway and SMAD Independent pathway.&lt;br /&gt;
&lt;br /&gt;
===SMAD Dependent TGF-β signalling pathway===&lt;br /&gt;
&lt;br /&gt;
[[File:TGF-B Signalling - Formation of Receptor Hetero-Tetramers.png|thumb|350px|SMAD Dependent TGF-β signalling pathway: Formation of Receptor Hetero-Tetramers&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;16446785&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;]]&lt;br /&gt;
&lt;br /&gt;
The ligands of the TGF-β superfamily form dimers that bind to heterodimeric receptor complexes composed of two type I and two type II transmembrane receptor subunits with serine/threonine kinase domains.&lt;br /&gt;
Following ligand binding on TGF-β1, the dimerized TGF-β type II receptors phosphorylates and activates the TGF-β type I receptors. In most cell types, this leads to recruitment and phosphorylation of the receptor-regulated SMAD2 and SMAD3, presented by the SMAD anchor for receptor activation. SMAD1 and SMAD5 can be activated by the TGF-β signaling depending on the Type I receptor that is expressed.&lt;br /&gt;
Heterologous complexes are formed by the phosphorylated receptor-regulated SMAD with the common-mediator SMAD, SMAD4, and successively move into the nucleus, where they accumulate and act as transcription factors participating in the regulation of target gene expression. &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;21302608&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
In addition, they recruit extra transcriptional regulators, such as DNA-binding transcription factors, co-activators and co-repressors. These control the expression of several target genes and ultimately initiates a SMAD-dependent signaling cascade that induces or represses transcriptional activity. SMADs are widely expressed in most adult tissue and cell types, indicating that the TGF-β signaling pathway is ubiquitous.&lt;br /&gt;
&lt;br /&gt;
===SMAD independent TGF-β signalling pathway===&lt;br /&gt;
&lt;br /&gt;
Rather than SMAD-mediated transciption TGF-β also has the potential to activate other signalling cascades for example the Erk, JNK and p38 MAPK kinase pathways. In some cases these pathways exhibit activation with slow kinetics which indicates SMAD-dependant mechanics, however there has also been rapid activation cases (5-15mins) suggesting independence from transcription mechanisms. Studies carried out with SMAD4 deficient cells and dominant-negative SMADS provide evidence that the MAPK pathway activation is independent from SMADS, as well as this it has be found that p38 MAPK signalling  was activated in response to mutated TGF- β type 1 receptors, which were defective in SMAD activation&amp;lt;ref name=&amp;quot;PMID14534577&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;14534577&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;.&lt;br /&gt;
&lt;br /&gt;
The precise mechanisms and biological consequences of these SMAD-Independent pathways (Erk, JNK, p38 MAPK) are currently poorly characterized. Ras is implicated in TGF- β induced Erk signalling as there is rapid activation of Ras by TGF- β in epithelial cells. The JNK and p38 MAPK signalling are activated by various MAPK kinase kinases (MAPKKK) TGF- β kinase 1 (TAK 1) receptor is a MAPKKK family member. Further research and identification of various interactions between the small signalling molecules and receptor proteins will provide additional insight into the precise mechanism behind the activation of MAPK pathways by TGF- β ligands &amp;lt;ref name=&amp;quot;PMID14534577&amp;quot;/&amp;gt;.&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
==Regulation of the pathway and factors affecting it==&lt;br /&gt;
&lt;br /&gt;
Signalling mechanisms by TGF-β like factors are regulated in both negative and positive fashions, these are all tightly controlled through a multitude of mechanisms at extracellular, membrane, cytoplasmic and all the way to nuclear levels. Positive regulation is required to amplify signalling from TGF-β like factors, while negative regulation is important for the termination and restriction of signalling usually occurring through the mechanism of a feedback loop. There is also additional regulation of TGF-β like factors via cross-talk with other signal transduction pathways such as MAPK and JAK/STAT pathways.&amp;lt;ref name=&amp;quot;PMID10704361&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;10704361&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
===Positive Regulation===&lt;br /&gt;
The positive regulation of TGF-β specifically the induction of ligands and their signalling components often is triggered by the action TGF-β-like factors themselves. For example NODAL, a secretory protein of the TGF-β superfamily which plays a role in early embryogenesis and acts through activin receptors and SMAD2 is induced by nodal signalling itself. In other types of cells TGF-β receptors as well as transcription factors which serve as targets for TGF-β like factors can be induced by ligand stimulation, as identified in case of transcription factor Runx3 which is induced by TGF-β and forms a complex with SMAD3 to be further activated by TGF-β. The mechanism of SMAD signalling is also positively modulated via the &amp;quot;cross-talk&amp;quot; (and hence the process of SMAD dependant TGF-β signalling) with other signalling pathways, SMADS may be activated by the tyrosine kinase receptor under specific circumstances and further positively regulate TGF-β like factors &amp;lt;ref name=&amp;quot;PMID10704361&amp;quot;/&amp;gt;.&lt;br /&gt;
&lt;br /&gt;
===Negative Regulation===&lt;br /&gt;
&lt;br /&gt;
Signalling is regulated at the cell membrane level as well as within the cytoplasm of the cell, specifically by BAMBI, a pseudo-receptor for serine/threonine kinase receptors (in Xenopus embryos however displays a high degree of sequence similarity to human BAMBI gene). This BAMBI receptor is structurally alike to the type 1 serine/threonine kinase receptor, the only difference being that it lacks an intracellular domain. BAMBI  has shown a similar expression profile to that of BMP-4 a growth factor from the TGF-β super family, and has been found to require BMP signalling for expression. BAMBI when goes on to interact with both type 1 and type 2 serine/threonine receptors and works to abolish their abilities to signal via BMPs, activins and TGF-βs, therefore it is postulated that BAMBI can be inductively expressed by BMPS to self regulate BMP signalling as well as cross-regulate signalling from other members of the TGF-β super family. &amp;lt;ref name=&amp;quot;PMID10704361&amp;quot;/&amp;gt;&lt;br /&gt;
&lt;br /&gt;
==Significance in Embryonic Development==&lt;br /&gt;
&lt;br /&gt;
TGF betas are involved in embryogenesis. During development of the embryo, members of the TGF-beta family are essential for bone and cartilage formation, mesoderm induction and patterning and dorso-ventral patterning.&lt;br /&gt;
&lt;br /&gt;
[[File:TGF in Cardiovascular.jpg|thumb|500px|Expression of TGF-β2 and TGF-β3 in wildtype embryonic hearts.&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;12948523&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;]]&lt;br /&gt;
===Cardiovascular Development===&lt;br /&gt;
&lt;br /&gt;
Genetic engineering and tissue explanation studies have revealed many roles for TGF-β ligands and their signaling molecules in development. In the embryo, TGF-β appear to be involved in epithelial-mesenchymal transformations (EMT) during the formation of endocardial cushions, and in epicardial epithelial-mesenchymal transformations essential for coronary vasculature, ventricular myocardial development and compaction. It must be noted that in the normal function of the cardiovascular system in the adult, TGF-β play significant roles in cardiac hypertrophy, vascular remodeling and regulation of the renal renin-angiotensin system.&lt;br /&gt;
&lt;br /&gt;
TGF-β1 is expressed in the endocardium of the developing mouse. TGF-β(-/-) mice have been found with obvious congenital cardiovascular defects, so it’s important to review its expression in the developing heart. In the blood vessels, TGF-β1 is in the intima whereas TGF-β2 and TGF-β3 are in the media and adventitia. TGF-β2 signals are found as early as embryonic day 7.25 (E7.25) &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;7687212&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; in the cardiogenic plate of the precardiac mesoderm and is later prominent in the myocardium of the aortic sac and outflow track regions. TGF-β2 protein is also found in the entire myocardium of the heart at the time when looping occurs. From E8.5-9.5 when the cushion formation process occurs, there is a particularly strong TGF-β2 expression localised to the myocardium as displayed in A, B, D and E in the figure. After cushion formation and EMT, and before myocardialization of the endocardial cushion begins, there is also strong TGF-β2 expression in the OT myocardium and in the adjacent developing cushion mesenchym. However, as myocardialization occurs, TGF-β2 expression is reduced in the myocardium so that from E12.5 onwards, it is only expressed mainly in the mesenchyme of the cushion and OT septum. As can be seen in 2GH, TGF-β2 expression remains high in the cushion mesenchyme of the OT septum. By E15.5, TGF-β1 s now the most highly expressed isoform in the endocardial cells of the myocardium. It is seen in M, N, O of the figure that the epidcardium TGF-β1 and TGF-β3 expression is higher than that of TGF-β2. Thus, it can be seen that all three TGF-β are expressed in the epicardium, and they are not expressed in an overlapping fashion.&lt;br /&gt;
&lt;br /&gt;
Cross talk between mesoderm and underlying endoderm is needed to form the early tubular heart. This cellular and molecular induction in the primary heart forming regions is important for the specification and differentiation of myocardial and endocardial precursor cells &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;10767078&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;. Other endoderm-derived growth factors such as BMP2, FGF2 as well as TGFBS have been implicated in this process in the avian system &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;11322300&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;. TGFB2 and TGFB receptors are expressed in the precardiac mesoderm along with BMP2 &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;7687212&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;10767078&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;10340759&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;. Members of the TGG family can serve as inductive signals at the heart forming fields for the formation of myocardial and endocardial precursor cells. Members such as Activin, BMP, Nodal, Left and others have been found to be crucial for the establishment of embryonic asymmetry &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;11836504&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;, and this asymmetry is in turn critical for heart development &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;11752633&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;.&lt;br /&gt;
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&lt;br /&gt;
===Mammary Gland Development===&lt;br /&gt;
Similarly, all three TGF-β isoforms are expressed during all stages in the development of the mammary gland except lactation. Specifically, mouse studies have indicated key roles for TGF-β in organizing the architecture of the mammary gland, regulating stem cell kinetics, inducing apoptosis in the involuting gland and maintaining the epithelium in a functionally undifferentiated state. The TGF-β isoforms are expressed in the ductal epithelium at all stages of development and some reviews have found that there may be some isoform specificity for temporal and spatial expression patterns &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;10887507&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;. For example, TGF-β3 is the only isoform present in the endbup cap cells and myoepithelial cells. Additionally, TGF-β1 is present at high levels in the extracellular matrix that surrounds growth-quiescent ducts. As for its effect, TGF-β have been to have induce multiple responses such as inhibiting the proliferation of mammillary epithelial cells. The nature of the target cell of plays a role as TGF-β also induced apoptosis without the inhibiting the proliferation. This highlights the highly variable actions of TGF-β that are affected by cell type, environmental and cell history to name a few. Interestingly, TGF-β have been implicated as both tumour suppressors and oncogenes in mammary tumorigenesis. For example, the overexpression of TGF-β1 inhibits tumorigenesis whilst interfering with its receptor function enhances tumorigenesis, thus hinting at its tumor suppressor role &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;7753792&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;9407968&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;. On the contrary, TGF-β has exhibited the enhancement of tumorigenesis as the TGF-β ligand expression is increased in late human breast cancer. Thus, TGF-β further proves its pleiotropic behaviour as prevalent to the mammary gland as it potentially suppresses and/or promotes tumorigenesis.&lt;br /&gt;
&lt;br /&gt;
===Maintenance of pluripotency in hESC===&lt;br /&gt;
Many of the members within the TGF-β superfamily are enriched within stem cells suggesting they play an important role in these cells, specifically relation to their pluripotency. The ability for a cell to self renew and differentiate is known as  'stemness', the stemness of human as well as mouse embryonic stem cells can be maintained by growing a combined culture with feed cells for example, bone morphogenic protein 4 (BMP4) induces a helix-loophelix-protein known as Id which is a potent inhibitor of differentiation, since this BMP (a member of the TGF-β  superfamily) is a potent inhibitor of neural differentiation in vertebrate embryos it is thought to maintain the stemness of hESCs and thus maintain their pluripotency.&amp;lt;ref name=&amp;quot;PMID24298330 &amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;24298330 &amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
[[File:Flowchart_for_maintenance_of_pluripotency_in_hESCs.png|thumb|upright=1.5|right|Flowchart for mechanism of maintenance of pluripotency in hESCs]]&lt;br /&gt;
&lt;br /&gt;
The nodal secretory protein from the TGF-β superfamily were found to also contribute to mESC pluripotency, this was evidenced by microarray of Nodal deficient mice which were found to have diminished  levels of Oct3/4 (transcription factors)expression, which are markers of undifferentiated stem cells. More importantly a nuclear localization of SMAD2 was found in hESCs, this is generally induced by TGF-β, activin or nodal signalling. Further microarray analysis identified that activin supposedly maintains the pluripotency of hESCs through inducing the expression of Oct4 as well as Nanog both transcription factors which are heavily involved in the self renewal of undifferentiated embryonic stem cells. Consistent with this finding, the subsequent inhibition of SMAD2 phosphorylation resulted in the decrease of expression of the markers of undifferentiated ESCs (Oct3/4, Nanog), suggesting that these were a product of SMAD2 phosphorylation and because SMAD2 is a product of activin/nodal signalling further suggesting that activin or nodal proteins produced by ESCs function to promote the maintenance of pluripotency in hESCs.&amp;lt;ref name=&amp;quot;PMID24298330 &amp;quot;/&amp;gt;.&lt;br /&gt;
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===Formation of the palate===&lt;br /&gt;
The formation of the palate is a complex procedure which involves a multitude of events including palatal shelf growth, elevation as well as left and right side fusion, as a result of genetic defects this procedure can sometimes result in formation of a cleft palate, one of the most common genetic birth defects. There have been recent findings which indicate TGF-β signalling plays a prime role in regulating the development of the palate in regards to both the palatal mesenchyme and epithelium. In humans the palate develops from two primordiuims, the primary and secondary palate, these progress to develop into palatal shelves which are positioned vertically against each other along the sides of the tongue. Following jaw growth and descent of the tongue these primordial palates orientate themselves horizontally and begin to fuse, in the case of the hard palate the mesenchyme cells are replaced by intramembranous bone as opposed to the soft palate which remains muscular and does not undergo ossification. Alike to humans mice have a similar embryological process of palate formation with the stage of palatal fusion resulting in the formation of a medial edge epithelium (MEE) seam which eventually degrades via apoptosis, thus the mouse serves as a strong candidate to fulfil the role of a reliable animal model. &amp;lt;ref name=&amp;quot;PMID21395922 &amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;21395922&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
With this model being established, it has been identified that TGF-β1 is strongly expressed in MEE cells just prior to adherence of the opposing palatal shelves, following this adherence the level of TGF-β1 gradually decreased until it ceased to be expressed in the mesenchymal cells, TGF-β. TGF-β2 and TGF-β3 were also expressed in the palatal mesenchymal cells during adherence and TGF-β3 was found to be continually expressed during the fusion process, it is further found that TGF-β3 played a crucial role in the cell degradation of MEE cells in addition to palatal fusion. It was found that when TGF-β3 deficient mice developed they expressed defects in MEE seam degradation and fusion.&amp;lt;ref name=&amp;quot;PMID21395922&amp;quot;/&amp;gt;.&lt;br /&gt;
&lt;br /&gt;
The use of these animal models to explore the role of TGF-β in cleft palate formation is fruitful in terms of identifying contributing factors and subtypes of TGF-β family members however there still remains much to discover of the molecular and cellular mechanisms  associated with palate formation.&lt;br /&gt;
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==Animal Studies==&lt;br /&gt;
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===Wound healing===&lt;br /&gt;
Animal studies have served as a useful way in providing pivotal information regarding the mechanisms of TGF-β action in wound healing. In fact, much of the current information on the action of TGF-β in wound healing has been acquired from animal studies using incisional and/or excisional wounding models and manipulation of TGF-β signalling by adding the exogenous TGF-β protein or anti-TGF-β neutralizing antibodies, or by genetic alteration in components of the TGF-β signalling pathway. This is due to the fact that animal models provide outstanding experimental methods for explaining molecular mechanisms by which TGF-β regulates wound-healing responses. Ultimately, it has led the development of therapeutic strategies focusing on how the TGF-β pathway can improve wound healing and scarring outcome.&lt;br /&gt;
&lt;br /&gt;
[[File:Destination filename.jpeg|thumb|550px|Excisional wound healing in Smad 3 KO mice.&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;24761336&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;]] &lt;br /&gt;
Wound healing is an intricate physiological process distinguished by the successive overlapping stages of inflammation, proliferation and maturation. It that requires numerous growth factors, one of which includes TGF-β, which has the widest range of effects. TGF-β is a multifunctional growth factor that employs pleiotropic effects on wound healing by regulating cell differentiation, extracellular matrix production and immune modulation. The role of TGF-β signalling in wound healing was explored through examination of the development of tissue-specific expression systems for overexpression or knockout of TGF-b signalling pathway components. This study also classified that molecules might serve as molecular targets for the treatment of pathological skin conditions such as chronic wounds and excessive scarring (fibrosis). &lt;br /&gt;
&lt;br /&gt;
Exogenously added TGF-β has the potential to promote wound healing by stimulating angiogenesis, immune cell infiltration, and ECM production, and that diminishing endogenous TGF-β action reduces scarring without adversely affecting wound-healing quality.&lt;br /&gt;
===Direct modulation of TGF-β levels===&lt;br /&gt;
Injecting TGF-β into normal skin of newborn mice led to resilient initiation of angiogenesis and fibrosis. This consisted of important new collagen synthesis combined into the matrix. As a result of these observations, people were encouraged to further study the administration of TGF-β to incisional wounds in rats. It proved that TGF-β treatment resulted in better dermal healing, as showed by prominent collagen deposition and significantly increased wound strength.&lt;br /&gt;
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Interpreting wound-healing results obtained from the animals brought about its limitations. For instance, an underlying skin abnormality was found on many of the mouse models with genetic alterations in the TGF-β signalling pathway. Also, the pleiotropic effects of TGF-β on many different cell types throughout stages of wound healing highlighted a challenge in designing particular methods in which the TGF-β signalling pathway can assist wound healing or reduce scarring. &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;24761336&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
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==Current Research==&lt;br /&gt;
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==Abnormalities of the TGF-Beta Pathway==&lt;br /&gt;
Mutations or deletion of the TGF-beta 1 or TGF-beta RII gene have been associated with multiple syndromes. In mice, defects have been found in haematopoiesis, vasculogenesis and endothelial differentiation of extra embryonic tissues, while knockout mice for SMAD2 or SMAD4 genes are more likely to have spontaneous tumour development and excessive inflammatory responses. In humans, various diseases have been linked to the mutation of the TGF-beta RII gene and SMAD4 mutation is genetically responsible for familial juvenile polyposis, an autosomal dominant disease characterized by predisposition to gastrointestinal polyps and cancers.&lt;br /&gt;
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====Cancer====&lt;br /&gt;
Alterations of this signalling pathway are common in cancer. Accessory proteins such as soluble or membrane-bound regulators or co-receptors can also affect TGF-beta signalling. A normal acting cell has a functional TGF-β signalling pathway, in which TGF- β stops proliferation of cells at G1 stage to either encourage apoptosis or induce differentiation. If the TGF-β signaling pathway becomes mutated these cells can become cancerous as the TGF-β no longer controls the cell. Uncontrolled, these cancer cells proliferate and cause surrounding fibroblasts, immune cells, endothelial and smooth-muscle cells to proliferate as well. From this increased production of TGF-β it causes angiogenesis and immunosuppression, further propogating the cancer. &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;10793168&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;The human body has an regulation against this, which is called effector T-cells which destroy cancer cells via an inflammatory reaction. However, TGF-β converts them into regulatory T-cells, which reduce the inflammatory reaction.&lt;br /&gt;
&lt;br /&gt;
 &lt;br /&gt;
====Marfan syndrome====&lt;br /&gt;
It is also suggested that TGF-β signaling has a large part to play in the pathogenesis of Marfan syndrome. This disease causes disproportionate height, abnormally long fingers and toes, displaced crystalline lens of the eye. Not only this but heart complications can also occur, like mitral valve prolapse or aortic enlargement. Marfan syndrome is generally known to be caused by defective creation of elastic fibres, more specifically of the glycoprotein fibrillin I. In a study done it was observed that by adding TGF-β antagonist in mice who were affected by Marfan syndrome phenotype, their symptoms were alleviated.&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;16601194&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; From this, we can see that the mechanism involved in Marfan syndrome most likely has an underlying relation with lowered sequestration of TGF-β by fibrillin.&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;16571647&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
[[File:Embryo marfan.jpg|thumb|100px|Patient with Marfan syndrome. Note aesthenic or marfanoid body habitus, pronounced myopia (thick glasses), previous thoracic surgery (composite aortic root/aortic valve replacement)..&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt; PMC1767196 &amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;]]&lt;br /&gt;
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====Heart disease====&lt;br /&gt;
The TGF-B pathway has many effects on cardiomyocytes, mesenchymal and immune cells. Not only this, but it plays a vital role in the pathogenesis of cardiac remodeling and fibrosis. Abnormalities in this pathway can cause an overexpression of TGF-β which has been associated with fibrosis and hypertrophy in mice hearts. We see that endogenous TGF-β is capable of varying matrix metabolism in a pressure-overloaded heart. In a heart which has undergone great stress, such as myocardial infarction, TGF-β is seen to inactivate inflammatory macrophages. This allows for less of an immune response but further done by it encouraging myofibroblast transdifferentiation and matrix synthesis. Thus higher levels of TGF-β is causing more inflammatory damage and further propagating the heart disease. &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;21059352&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
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====Loeys–Dietz syndrome====&lt;br /&gt;
Abnormalities of the TGF-β signaling can also cause Loeys–Dietz syndrome via mutations in the TGF-β receptor. Loeys-Deitz syndrome connective tissue disorder, mainly in children where there are aneurisms in the aorta. Not only this, but the aorta can undergo dissection in weakened layers of the aortic wall. Further, the disease is labelled into four different types, since it is an autosomal dominant genetic connective tissue disorder, the groups are categorized by their genetic cause. TGFB1 and TGFB2 cause type I and II. Normally these genes allow for the fruition of the body’s development and growth. However, when defective they create non-functioning proteins.&lt;br /&gt;
&lt;br /&gt;
====Obesity, Diabetes and Hepatic Steatosis====&lt;br /&gt;
Normally, TGF-β signaling pathway has a major role in maintaining a regulated level of glucose and energy under homeostatic conditions. Not only this, but TGF-B could also have a vital task in diabetic kidney disease.  &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;21723505&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
Abnormalities in TGF-β signaling in obesity is one of the reasons why there is so much inflammatory damage in the human body by obesity. [5]&lt;br /&gt;
This was shown again in a study done where mice affected were given a systemic blockade drug for the TGF-B pathway and it was observed that they were protected from obesity, diabetes and hepatic steatosis. &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;21436399&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
====Multiple Sclerosis====&lt;br /&gt;
In Multiple Sclerosis (MS) a common observation is that patients will generally have lower levels of TGF-β, which is suspected to prevent remylentation of neurons. The reason why this is of significance is because MS results in demylentation of neurons causing severe neurological problems. TGF-β is normally responsible for regulating apoptosis of Th17 cells.&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;22942700&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;Thus when TGF-β levels decrease due to abnormalities, they are not able to be regulating Th17 cells apoptosis.[6] This then causes Th17 cells to secrete TNF-α, finally causing a demylenation of the oliodendroglial (neurons).&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;22189514&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;By having a lower amount of TGF-β we get a higer level of Th17 cells and therefore more TNFα and neuronal damage. Thus we can observe that this pathway is vital in maintaining neuronal health.&lt;br /&gt;
&lt;br /&gt;
==Further Reading==&lt;br /&gt;
&lt;br /&gt;
==Glossary==&lt;br /&gt;
{| class=&amp;quot;pretty table&amp;quot;&lt;br /&gt;
|-&lt;br /&gt;
| '''Apoptosis'''&lt;br /&gt;
| Cell death which occurs as a normal and controlled part of an organism's growth or development&lt;br /&gt;
|-&lt;br /&gt;
| '''Avian system'''&lt;br /&gt;
| Respiratory system that delivers oxygen and removes carbon dioxide&lt;br /&gt;
|-&lt;br /&gt;
| '''CCL-64'''&lt;br /&gt;
|  - mink lung epithelial cell&lt;br /&gt;
|-&lt;br /&gt;
| '''Cytokine'''&lt;br /&gt;
| A broad and loose category of small proteins that are important in cell signalling&lt;br /&gt;
|-&lt;br /&gt;
| '''Cushion Formation'''&lt;br /&gt;
| Cells in development that play a role in the formation of the heart septa&lt;br /&gt;
|-&lt;br /&gt;
| '''Dimer'''&lt;br /&gt;
| An oligomer consisting of two structurally similar monomers joined by bonds that can be either strong or weak, covalent or intermolecular&lt;br /&gt;
|-&lt;br /&gt;
| '''Homodimers'''&lt;br /&gt;
| A protein composed of two polypeptide chains that are identical in the order, number, and kind of their amino acid residues&lt;br /&gt;
|-&lt;br /&gt;
| '''Isoform'''&lt;br /&gt;
| A protein that has the same function as another protein but which is encoded by a different gene and may have small differences in its sequence&lt;br /&gt;
|-&lt;br /&gt;
| '''Ligands'''&lt;br /&gt;
| A molecule that binds to a larger molecule&lt;br /&gt;
|-&lt;br /&gt;
| '''Looping'''&lt;br /&gt;
| A morphogenetic process when the heart shape is formed by looping the embryonic tube&lt;br /&gt;
|-&lt;br /&gt;
| '''Pleiotropic'''&lt;br /&gt;
| To produce more than one type of effect&lt;br /&gt;
|-&lt;br /&gt;
| '''BMP'''&lt;br /&gt;
| Bone Morphogenetic Protein, a protein part of the TGF-β superfamily.&lt;/div&gt;</summary>
		<author><name>Z5020466</name></author>
	</entry>
	<entry>
		<id>https://embryology.med.unsw.edu.au/embryology/index.php?title=2016_Group_Project_6&amp;diff=255362</id>
		<title>2016 Group Project 6</title>
		<link rel="alternate" type="text/html" href="https://embryology.med.unsw.edu.au/embryology/index.php?title=2016_Group_Project_6&amp;diff=255362"/>
		<updated>2016-10-27T13:06:16Z</updated>

		<summary type="html">&lt;p&gt;Z5020466: /* Marfan syndrome */&lt;/p&gt;
&lt;hr /&gt;
&lt;div&gt;{{ANAT2341Project2016header}}&lt;br /&gt;
{{Group Assessment Criteria table}}&lt;br /&gt;
&amp;lt;!-- Do not delete the above template from the Group project page. --&amp;gt;&lt;br /&gt;
&lt;br /&gt;
=Transforming Growth Factor-Beta (TGF-β) Signalling Pathway=&lt;br /&gt;
&lt;br /&gt;
==Introduction==&lt;br /&gt;
&lt;br /&gt;
The transforming growth factor beta (TGF-β) is a multifunctional and pleiotropic cytokine &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;26555259&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;.&lt;br /&gt;
The TGF-β signalling pathway is crucial to the control of different biological and pathological processes, such as cellular proliferation and differentiation, angiogenesis, immune regulation/inflammation, apoptosis and cell survival. &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;17896911&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
TGF-β belongs to the Transforming Growth Factor superfamily - a large group of structually connected cell regulatory proteins. It consists of TGF-β 1, 2 AND 3, Growth Differentiation Factors (GDFs), Activins, Inhibins, Bone Morphogenetic Proteins (BMPs), Glial-derived Neurotrophic Factors (GDNFs) and Mullierian Inhibiting Substance (MIS). &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;24270394&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
Most importantly, TGF-β plays a dominant part in the development of the embryo and adult organism. &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;23926286&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
This wiki aims to present a helpful overview of the TGF-β signalling pathway, but is in no means a complete resource on all information regarding the topic. We focus on ________________&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&amp;lt;br&amp;gt;&amp;lt;br&amp;gt;&lt;br /&gt;
&amp;lt;div align=&amp;quot;center&amp;quot;&amp;gt;&amp;lt;html5media width=&amp;quot;560&amp;quot; height=&amp;quot;315&amp;quot;&amp;gt;https://www.youtube.com/watch?v=GuKjUearIUI&amp;lt;/html5media&amp;gt;&amp;lt;/div&amp;gt;&lt;br /&gt;
&amp;lt;br&amp;gt;&lt;br /&gt;
&lt;br /&gt;
==History==&lt;br /&gt;
Since the early stages of the TGF beta-signaling pathway, plenty of in-depth research and studies have been conducted that have no doubt contributed to our knowledge of the pathway today.&lt;br /&gt;
&lt;br /&gt;
SMAD signaling and the three receptors for TGF-beta are two of the many fields of interest regarding the topic. In medicine and specific areas such as cancer, cardiovascular disease and inflammatory bowel disease, there are numerous alternatives for drugs that can either heighten or suppress the activity of TGF-beta.&lt;br /&gt;
&lt;br /&gt;
{| class=&amp;quot;pretty table&amp;quot;&lt;br /&gt;
| '''1988'''&lt;br /&gt;
| The process of maturation of follicle-enclosed oocytes and cumulus-oocyte complexes was sped up by TGF beta. It was discovered that TGF beta and other growth factors are effective in vitro stimulators of oocyte maturation in the rat&lt;br /&gt;
&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;3275534&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
|-&lt;br /&gt;
| '''1989'''&lt;br /&gt;
| It was already known that TGF-beta 1 is a strong autocrine growth inhibitor of lymphocytes. Ellingsworth and colleagues found that TGF-beta 1 binds to all three cell surface-binding proteins (280-200 kD, 95-85 kD, 65 kD).&lt;br /&gt;
It was also found that these binding proteins are required for signal transduction. Overall, they discovered that the regulation of the expression of the TGF-beta 1 receptor is controlled by T cell mitogenic signals.&lt;br /&gt;
&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;2785999&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
|-&lt;br /&gt;
| '''1989'''&lt;br /&gt;
| It was made known that the properties of R mutants classify TGF-beta type I binding protein as the receptor involved in mediating TGF-beta actions on cell adhesion and proliferation&lt;br /&gt;
&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;2536702&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
|-&lt;br /&gt;
| '''1989'''&lt;br /&gt;
| Drosophil was the only member of the TGF-beta family to be identified in invertebrates &lt;br /&gt;
&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;2699859&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
|-&lt;br /&gt;
| '''1990'''&lt;br /&gt;
| It was already known that the rapid increase in number response of mink lung epithelial cells to serum and to epidermal growth factor was inhibited by TGF beta 1. A necessary component of TGF-beta 1 mediated growth inhibition in CCL64 epithelial cells is the coupling of TGF beta 1 receptor binding to G-protein activation&lt;br /&gt;
&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;2156499&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
|-&lt;br /&gt;
| '''2000'''&lt;br /&gt;
| VegT function was found to be involved in sequence with the TGF beta pathway. Therefore, TGF beta signaling may be activated by the maternally expressed VegT to participate in endoderm determination&lt;br /&gt;
&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;10640706&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
|-&lt;br /&gt;
| '''2005'''&lt;br /&gt;
| Within the TGF beta superfamily, it was found that a limited number of type I and type II receptors worked together to produce specificity of action &lt;br /&gt;
&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;15483083&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
|-&lt;br /&gt;
| '''2010'''&lt;br /&gt;
| Deregulation of TGF beta signaling was reported in human psoriasis&lt;br /&gt;
&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;19710682&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
|-&lt;br /&gt;
| '''2015'''&lt;br /&gt;
| It was known that TGF is required in the tumorigenicity and metastasis of bone tumour. A significant event in the activation of the TGF beta signaling pathway is the binding of transcription coactivator Yes-associated protein (YAP) to Smad transcription factors&lt;br /&gt;
&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;27491038&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
|}&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
[[File:Canonical and non-canonical signalling TGF beta pathways.png|thumb|500px|Flowchart showing the Canonical and Non-Canonical pathways of TGF-β signalling pathway.&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;24393789&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;]] &lt;br /&gt;
===Canonical pathway===&lt;br /&gt;
In the canonical pathway, the dormant TGF-β complex is formed when the three TGF-β ligand isoforms - TGF-B1, TGF-B2 and TGF-B3 - bind once it is synthesized as precursors. After secretion and extracellular activation, TGF-β ligands can bind to two types of receptors: the membranous TGF-β type III receptor or the TGF-β type II receptor (TGF-βRII) homodimers with high affinity. &lt;br /&gt;
TGF-βRII binding enables dimerization with TGF-β type I receptor (TGF-βRI) homodimers, as well as activation of the TGF-βRI kinase domain and signal transduction across phosphorylation of the C-terminus of receptor-regulated SMADs, SMAD2 and SMAD3.&lt;br /&gt;
A heterotrimeric complex is formed by the TGF-βR dimer and SMAD4, which moves and assemblies in the nucleus.&lt;br /&gt;
TGF-β dependent signalling can operate or subdue numerous target genes through the communication of SMADs with multiple transcription factors. There are many structures in which SMAD activities are regulated, such as SMAD2/3 nucleocytoplasmic shuttling, binding to anchor proteins, phosphorylation and Smurf (SMAD-ubiquitination-regulatory factor).  &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;24393789 &amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
&lt;br /&gt;
===Non-Canonical pathway===&lt;br /&gt;
In the non-canonical pathway, SMAD-independent pathways such as PI3K/AKT and MAPK pathways like ERK, JNK, and p38 MAPK are activated by TGF-β signalling. In addition, transversal signalling, especially at the SMAD level, allows TGF-β pathway activation to incorporate signals from integrins, Notch and Wnt dependent pathways as well as signals from cellular processes like the cell cycle or apoptosis machineries. Thus, the TGF-β signalling pathway has pleiotropic functions regulating cell growth, differentiation, apoptosis, cell motility, extracellular matrix production, angiogenesis and cellular immune response.&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;24393789 &amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
&lt;br /&gt;
==Process of TGF-β signalling pathway==&lt;br /&gt;
&lt;br /&gt;
TGF-β signalling pathway is required for regulation of a large number of cellular processes such as cell proliferation, invasion and inflammation. It is also activated mitogen activated protein kinase signalling. There are two main routes in TGF-β signalling; the SMAD Dependent pathway and SMAD Independent pathway.&lt;br /&gt;
&lt;br /&gt;
===SMAD Dependent TGF-β signalling pathway===&lt;br /&gt;
&lt;br /&gt;
[[File:TGF-B Signalling - Formation of Receptor Hetero-Tetramers.png|thumb|350px|SMAD Dependent TGF-β signalling pathway: Formation of Receptor Hetero-Tetramers&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;16446785&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;]]&lt;br /&gt;
&lt;br /&gt;
The ligands of the TGF-β superfamily form dimers that bind to heterodimeric receptor complexes composed of two type I and two type II transmembrane receptor subunits with serine/threonine kinase domains.&lt;br /&gt;
Following ligand binding on TGF-β1, the dimerized TGF-β type II receptors phosphorylates and activates the TGF-β type I receptors. In most cell types, this leads to recruitment and phosphorylation of the receptor-regulated SMAD2 and SMAD3, presented by the SMAD anchor for receptor activation. SMAD1 and SMAD5 can be activated by the TGF-β signaling depending on the Type I receptor that is expressed.&lt;br /&gt;
Heterologous complexes are formed by the phosphorylated receptor-regulated SMAD with the common-mediator SMAD, SMAD4, and successively move into the nucleus, where they accumulate and act as transcription factors participating in the regulation of target gene expression. &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;21302608&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
In addition, they recruit extra transcriptional regulators, such as DNA-binding transcription factors, co-activators and co-repressors. These control the expression of several target genes and ultimately initiates a SMAD-dependent signaling cascade that induces or represses transcriptional activity. SMADs are widely expressed in most adult tissue and cell types, indicating that the TGF-β signaling pathway is ubiquitous.&lt;br /&gt;
&lt;br /&gt;
===SMAD independent TGF-β signalling pathway===&lt;br /&gt;
&lt;br /&gt;
Rather than SMAD-mediated transciption TGF-β also has the potential to activate other signalling cascades for example the Erk, JNK and p38 MAPK kinase pathways. In some cases these pathways exhibit activation with slow kinetics which indicates SMAD-dependant mechanics, however there has also been rapid activation cases (5-15mins) suggesting independence from transcription mechanisms. Studies carried out with SMAD4 deficient cells and dominant-negative SMADS provide evidence that the MAPK pathway activation is independent from SMADS, as well as this it has be found that p38 MAPK signalling  was activated in response to mutated TGF- β type 1 receptors, which were defective in SMAD activation&amp;lt;ref name=&amp;quot;PMID14534577&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;14534577&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;.&lt;br /&gt;
&lt;br /&gt;
The precise mechanisms and biological consequences of these SMAD-Independent pathways (Erk, JNK, p38 MAPK) are currently poorly characterized. Ras is implicated in TGF- β induced Erk signalling as there is rapid activation of Ras by TGF- β in epithelial cells. The JNK and p38 MAPK signalling are activated by various MAPK kinase kinases (MAPKKK) TGF- β kinase 1 (TAK 1) receptor is a MAPKKK family member. Further research and identification of various interactions between the small signalling molecules and receptor proteins will provide additional insight into the precise mechanism behind the activation of MAPK pathways by TGF- β ligands &amp;lt;ref name=&amp;quot;PMID14534577&amp;quot;/&amp;gt;.&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
==Regulation of the pathway and factors affecting it==&lt;br /&gt;
&lt;br /&gt;
Signalling mechanisms by TGF-β like factors are regulated in both negative and positive fashions, these are all tightly controlled through a multitude of mechanisms at extracellular, membrane, cytoplasmic and all the way to nuclear levels. Positive regulation is required to amplify signalling from TGF-β like factors, while negative regulation is important for the termination and restriction of signalling usually occurring through the mechanism of a feedback loop. There is also additional regulation of TGF-β like factors via cross-talk with other signal transduction pathways such as MAPK and JAK/STAT pathways.&amp;lt;ref name=&amp;quot;PMID10704361&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;10704361&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
===Positive Regulation===&lt;br /&gt;
The positive regulation of TGF-β specifically the induction of ligands and their signalling components often is triggered by the action TGF-β-like factors themselves. For example NODAL, a secretory protein of the TGF-β superfamily which plays a role in early embryogenesis and acts through activin receptors and SMAD2 is induced by nodal signalling itself. In other types of cells TGF-β receptors as well as transcription factors which serve as targets for TGF-β like factors can be induced by ligand stimulation, as identified in case of transcription factor Runx3 which is induced by TGF-β and forms a complex with SMAD3 to be further activated by TGF-β. The mechanism of SMAD signalling is also positively modulated via the &amp;quot;cross-talk&amp;quot; (and hence the process of SMAD dependant TGF-β signalling) with other signalling pathways, SMADS may be activated by the tyrosine kinase receptor under specific circumstances and further positively regulate TGF-β like factors &amp;lt;ref name=&amp;quot;PMID10704361&amp;quot;/&amp;gt;.&lt;br /&gt;
&lt;br /&gt;
===Negative Regulation===&lt;br /&gt;
&lt;br /&gt;
Signalling is regulated at the cell membrane level as well as within the cytoplasm of the cell, specifically by BAMBI, a pseudo-receptor for serine/threonine kinase receptors (in Xenopus embryos however displays a high degree of sequence similarity to human BAMBI gene). This BAMBI receptor is structurally alike to the type 1 serine/threonine kinase receptor, the only difference being that it lacks an intracellular domain. BAMBI  has shown a similar expression profile to that of BMP-4 a growth factor from the TGF-β super family, and has been found to require BMP signalling for expression. BAMBI when goes on to interact with both type 1 and type 2 serine/threonine receptors and works to abolish their abilities to signal via BMPs, activins and TGF-βs, therefore it is postulated that BAMBI can be inductively expressed by BMPS to self regulate BMP signalling as well as cross-regulate signalling from other members of the TGF-β super family. &amp;lt;ref name=&amp;quot;PMID10704361&amp;quot;/&amp;gt;&lt;br /&gt;
&lt;br /&gt;
==Significance in Embryonic Development==&lt;br /&gt;
&lt;br /&gt;
TGF betas are involved in embryogenesis. During development of the embryo, members of the TGF-beta family are essential for bone and cartilage formation, mesoderm induction and patterning and dorso-ventral patterning.&lt;br /&gt;
&lt;br /&gt;
[[File:TGF in Cardiovascular.jpg|thumb|500px|Expression of TGF-β2 and TGF-β3 in wildtype embryonic hearts.&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;12948523&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;]]&lt;br /&gt;
===Cardiovascular Development===&lt;br /&gt;
&lt;br /&gt;
Genetic engineering and tissue explanation studies have revealed many roles for TGF-β ligands and their signaling molecules in development. In the embryo, TGF-β appear to be involved in epithelial-mesenchymal transformations (EMT) during the formation of endocardial cushions, and in epicardial epithelial-mesenchymal transformations essential for coronary vasculature, ventricular myocardial development and compaction. It must be noted that in the normal function of the cardiovascular system in the adult, TGF-β play significant roles in cardiac hypertrophy, vascular remodeling and regulation of the renal renin-angiotensin system.&lt;br /&gt;
&lt;br /&gt;
TGF-β1 is expressed in the endocardium of the developing mouse. TGF-β(-/-) mice have been found with obvious congenital cardiovascular defects, so it’s important to review its expression in the developing heart. In the blood vessels, TGF-β1 is in the intima whereas TGF-β2 and TGF-β3 are in the media and adventitia. TGF-β2 signals are found as early as embryonic day 7.25 (E7.25) &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;7687212&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; in the cardiogenic plate of the precardiac mesoderm and is later prominent in the myocardium of the aortic sac and outflow track regions. TGF-β2 protein is also found in the entire myocardium of the heart at the time when looping occurs. From E8.5-9.5 when the cushion formation process occurs, there is a particularly strong TGF-β2 expression localised to the myocardium as displayed in A, B, D and E in the figure. After cushion formation and EMT, and before myocardialization of the endocardial cushion begins, there is also strong TGF-β2 expression in the OT myocardium and in the adjacent developing cushion mesenchym. However, as myocardialization occurs, TGF-β2 expression is reduced in the myocardium so that from E12.5 onwards, it is only expressed mainly in the mesenchyme of the cushion and OT septum. As can be seen in 2GH, TGF-β2 expression remains high in the cushion mesenchyme of the OT septum. By E15.5, TGF-β1 s now the most highly expressed isoform in the endocardial cells of the myocardium. It is seen in M, N, O of the figure that the epidcardium TGF-β1 and TGF-β3 expression is higher than that of TGF-β2. Thus, it can be seen that all three TGF-β are expressed in the epicardium, and they are not expressed in an overlapping fashion.&lt;br /&gt;
&lt;br /&gt;
Cross talk between mesoderm and underlying endoderm is needed to form the early tubular heart. This cellular and molecular induction in the primary heart forming regions is important for the specification and differentiation of myocardial and endocardial precursor cells &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;10767078&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;. Other endoderm-derived growth factors such as BMP2, FGF2 as well as TGFBS have been implicated in this process in the avian system &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;11322300&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;. TGFB2 and TGFB receptors are expressed in the precardiac mesoderm along with BMP2 &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;7687212&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;10767078&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;10340759&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;. Members of the TGG family can serve as inductive signals at the heart forming fields for the formation of myocardial and endocardial precursor cells. Members such as Activin, BMP, Nodal, Left and others have been found to be crucial for the establishment of embryonic asymmetry &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;11836504&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;, and this asymmetry is in turn critical for heart development &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;11752633&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;.&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
===Mammary Gland Development===&lt;br /&gt;
Similarly, all three TGF-β isoforms are expressed during all stages in the development of the mammary gland except lactation. Specifically, mouse studies have indicated key roles for TGF-β in organizing the architecture of the mammary gland, regulating stem cell kinetics, inducing apoptosis in the involuting gland and maintaining the epithelium in a functionally undifferentiated state. The TGF-β isoforms are expressed in the ductal epithelium at all stages of development and some reviews have found that there may be some isoform specificity for temporal and spatial expression patterns &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;10887507&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;. For example, TGF-β3 is the only isoform present in the endbup cap cells and myoepithelial cells. Additionally, TGF-β1 is present at high levels in the extracellular matrix that surrounds growth-quiescent ducts. As for its effect, TGF-β have been to have induce multiple responses such as inhibiting the proliferation of mammillary epithelial cells. The nature of the target cell of plays a role as TGF-β also induced apoptosis without the inhibiting the proliferation. This highlights the highly variable actions of TGF-β that are affected by cell type, environmental and cell history to name a few. Interestingly, TGF-β have been implicated as both tumour suppressors and oncogenes in mammary tumorigenesis. For example, the overexpression of TGF-β1 inhibits tumorigenesis whilst interfering with its receptor function enhances tumorigenesis, thus hinting at its tumor suppressor role &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;7753792&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;9407968&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;. On the contrary, TGF-β has exhibited the enhancement of tumorigenesis as the TGF-β ligand expression is increased in late human breast cancer. Thus, TGF-β further proves its pleiotropic behaviour as prevalent to the mammary gland as it potentially suppresses and/or promotes tumorigenesis.&lt;br /&gt;
&lt;br /&gt;
===Maintenance of pluripotency in hESC===&lt;br /&gt;
Many of the members within the TGF-β superfamily are enriched within stem cells suggesting they play an important role in these cells, specifically relation to their pluripotency. The ability for a cell to self renew and differentiate is known as  'stemness', the stemness of human as well as mouse embryonic stem cells can be maintained by growing a combined culture with feed cells for example, bone morphogenic protein 4 (BMP4) induces a helix-loophelix-protein known as Id which is a potent inhibitor of differentiation, since this BMP (a member of the TGF-β  superfamily) is a potent inhibitor of neural differentiation in vertebrate embryos it is thought to maintain the stemness of hESCs and thus maintain their pluripotency.&amp;lt;ref name=&amp;quot;PMID24298330 &amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;24298330 &amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
[[File:Flowchart_for_maintenance_of_pluripotency_in_hESCs.png|thumb|upright=1.5|right|Flowchart for mechanism of maintenance of pluripotency in hESCs]]&lt;br /&gt;
&lt;br /&gt;
The nodal secretory protein from the TGF-β superfamily were found to also contribute to mESC pluripotency, this was evidenced by microarray of Nodal deficient mice which were found to have diminished  levels of Oct3/4 (transcription factors)expression, which are markers of undifferentiated stem cells. More importantly a nuclear localization of SMAD2 was found in hESCs, this is generally induced by TGF-β, activin or nodal signalling. Further microarray analysis identified that activin supposedly maintains the pluripotency of hESCs through inducing the expression of Oct4 as well as Nanog both transcription factors which are heavily involved in the self renewal of undifferentiated embryonic stem cells. Consistent with this finding, the subsequent inhibition of SMAD2 phosphorylation resulted in the decrease of expression of the markers of undifferentiated ESCs (Oct3/4, Nanog), suggesting that these were a product of SMAD2 phosphorylation and because SMAD2 is a product of activin/nodal signalling further suggesting that activin or nodal proteins produced by ESCs function to promote the maintenance of pluripotency in hESCs.&amp;lt;ref name=&amp;quot;PMID24298330 &amp;quot;/&amp;gt;.&lt;br /&gt;
&lt;br /&gt;
===Formation of the palate===&lt;br /&gt;
The formation of the palate is a complex procedure which involves a multitude of events including palatal shelf growth, elevation as well as left and right side fusion, as a result of genetic defects this procedure can sometimes result in formation of a cleft palate, one of the most common genetic birth defects. There have been recent findings which indicate TGF-β signalling plays a prime role in regulating the development of the palate in regards to both the palatal mesenchyme and epithelium. In humans the palate develops from two primordiuims, the primary and secondary palate, these progress to develop into palatal shelves which are positioned vertically against each other along the sides of the tongue. Following jaw growth and descent of the tongue these primordial palates orientate themselves horizontally and begin to fuse, in the case of the hard palate the mesenchyme cells are replaced by intramembranous bone as opposed to the soft palate which remains muscular and does not undergo ossification. Alike to humans mice have a similar embryological process of palate formation with the stage of palatal fusion resulting in the formation of a medial edge epithelium (MEE) seam which eventually degrades via apoptosis, thus the mouse serves as a strong candidate to fulfil the role of a reliable animal model. &amp;lt;ref name=&amp;quot;PMID21395922 &amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;21395922&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
With this model being established, it has been identified that TGF-β1 is strongly expressed in MEE cells just prior to adherence of the opposing palatal shelves, following this adherence the level of TGF-β1 gradually decreased until it ceased to be expressed in the mesenchymal cells, TGF-β. TGF-β2 and TGF-β3 were also expressed in the palatal mesenchymal cells during adherence and TGF-β3 was found to be continually expressed during the fusion process, it is further found that TGF-β3 played a crucial role in the cell degradation of MEE cells in addition to palatal fusion. It was found that when TGF-β3 deficient mice developed they expressed defects in MEE seam degradation and fusion.&amp;lt;ref name=&amp;quot;PMID21395922&amp;quot;/&amp;gt;.&lt;br /&gt;
&lt;br /&gt;
The use of these animal models to explore the role of TGF-β in cleft palate formation is fruitful in terms of identifying contributing factors and subtypes of TGF-β family members however there still remains much to discover of the molecular and cellular mechanisms  associated with palate formation.&lt;br /&gt;
&lt;br /&gt;
==Animal Studies==&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
===Wound healing===&lt;br /&gt;
Animal studies have served as a useful way in providing pivotal information regarding the mechanisms of TGF-β action in wound healing. In fact, much of the current information on the action of TGF-β in wound healing has been acquired from animal studies using incisional and/or excisional wounding models and manipulation of TGF-β signalling by adding the exogenous TGF-β protein or anti-TGF-β neutralizing antibodies, or by genetic alteration in components of the TGF-β signalling pathway. This is due to the fact that animal models provide outstanding experimental methods for explaining molecular mechanisms by which TGF-β regulates wound-healing responses. Ultimately, it has led the development of therapeutic strategies focusing on how the TGF-β pathway can improve wound healing and scarring outcome.&lt;br /&gt;
&lt;br /&gt;
[[File:Destination filename.jpeg|thumb|550px|Excisional wound healing in Smad 3 KO mice.&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;24761336&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;]] &lt;br /&gt;
Wound healing is an intricate physiological process distinguished by the successive overlapping stages of inflammation, proliferation and maturation. It that requires numerous growth factors, one of which includes TGF-β, which has the widest range of effects. TGF-β is a multifunctional growth factor that employs pleiotropic effects on wound healing by regulating cell differentiation, extracellular matrix production and immune modulation. The role of TGF-β signalling in wound healing was explored through examination of the development of tissue-specific expression systems for overexpression or knockout of TGF-b signalling pathway components. This study also classified that molecules might serve as molecular targets for the treatment of pathological skin conditions such as chronic wounds and excessive scarring (fibrosis). &lt;br /&gt;
&lt;br /&gt;
Exogenously added TGF-β has the potential to promote wound healing by stimulating angiogenesis, immune cell infiltration, and ECM production, and that diminishing endogenous TGF-β action reduces scarring without adversely affecting wound-healing quality.&lt;br /&gt;
===Direct modulation of TGF-β levels===&lt;br /&gt;
Injecting TGF-β into normal skin of newborn mice led to resilient initiation of angiogenesis and fibrosis. This consisted of important new collagen synthesis combined into the matrix. As a result of these observations, people were encouraged to further study the administration of TGF-β to incisional wounds in rats. It proved that TGF-β treatment resulted in better dermal healing, as showed by prominent collagen deposition and significantly increased wound strength.&lt;br /&gt;
&lt;br /&gt;
Interpreting wound-healing results obtained from the animals brought about its limitations. For instance, an underlying skin abnormality was found on many of the mouse models with genetic alterations in the TGF-β signalling pathway. Also, the pleiotropic effects of TGF-β on many different cell types throughout stages of wound healing highlighted a challenge in designing particular methods in which the TGF-β signalling pathway can assist wound healing or reduce scarring. &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;24761336&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
==Current Research==&lt;br /&gt;
&lt;br /&gt;
==Abnormalities of the TGF-Beta Pathway==&lt;br /&gt;
Mutations or deletion of the TGF-beta 1 or TGF-beta RII gene have been associated with multiple syndromes. In mice, defects have been found in haematopoiesis, vasculogenesis and endothelial differentiation of extra embryonic tissues, while knockout mice for SMAD2 or SMAD4 genes are more likely to have spontaneous tumour development and excessive inflammatory responses. In humans, various diseases have been linked to the mutation of the TGF-beta RII gene and SMAD4 mutation is genetically responsible for familial juvenile polyposis, an autosomal dominant disease characterized by predisposition to gastrointestinal polyps and cancers.&lt;br /&gt;
&lt;br /&gt;
====Cancer====&lt;br /&gt;
Alterations of this signalling pathway are common in cancer. Accessory proteins such as soluble or membrane-bound regulators or co-receptors can also affect TGF-beta signalling. A normal acting cell has a functional TGF-β signalling pathway, in which TGF- β stops proliferation of cells at G1 stage to either encourage apoptosis or induce differentiation. If the TGF-β signaling pathway becomes mutated these cells can become cancerous as the TGF-β no longer controls the cell. Uncontrolled, these cancer cells proliferate and cause surrounding fibroblasts, immune cells, endothelial and smooth-muscle cells to proliferate as well. From this increased production of TGF-β it causes angiogenesis and immunosuppression, further propogating the cancer. &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;10793168&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;The human body has an regulation against this, which is called effector T-cells which destroy cancer cells via an inflammatory reaction. However, TGF-β converts them into regulatory T-cells, which reduce the inflammatory reaction.&lt;br /&gt;
&lt;br /&gt;
 &lt;br /&gt;
====Marfan syndrome====&lt;br /&gt;
It is also suggested that TGF-β signaling has a large part to play in the pathogenesis of Marfan syndrome. This disease causes disproportionate height, abnormally long fingers and toes, displaced crystalline lens of the eye. Not only this but heart complications can also occur, like mitral valve prolapse or aortic enlargement. Marfan syndrome is generally known to be caused by defective creation of elastic fibres, more specifically of the glycoprotein fibrillin I. In a study done it was observed that by adding TGF-β antagonist in mice who were affected by Marfan syndrome phenotype, their symptoms were alleviated.&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;16601194&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; From this, we can see that the mechanism involved in Marfan syndrome most likely has an underlying relation with lowered sequestration of TGF-β by fibrillin.&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;16571647&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
[[File:Embryo marfan.jpg|thumb|500px|Flowchart showing the Canonical and Non-Canonical pathways of TGF-β signalling pathway.&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt; PMC1767196 &amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;]]&lt;br /&gt;
&lt;br /&gt;
====Heart disease====&lt;br /&gt;
The TGF-B pathway has many effects on cardiomyocytes, mesenchymal and immune cells. Not only this, but it plays a vital role in the pathogenesis of cardiac remodeling and fibrosis. Abnormalities in this pathway can cause an overexpression of TGF-β which has been associated with fibrosis and hypertrophy in mice hearts. We see that endogenous TGF-β is capable of varying matrix metabolism in a pressure-overloaded heart. In a heart which has undergone great stress, such as myocardial infarction, TGF-β is seen to inactivate inflammatory macrophages. This allows for less of an immune response but further done by it encouraging myofibroblast transdifferentiation and matrix synthesis. Thus higher levels of TGF-β is causing more inflammatory damage and further propagating the heart disease. &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;21059352&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
====Loeys–Dietz syndrome====&lt;br /&gt;
Abnormalities of the TGF-β signaling can also cause Loeys–Dietz syndrome via mutations in the TGF-β receptor. Loeys-Deitz syndrome connective tissue disorder, mainly in children where there are aneurisms in the aorta. Not only this, but the aorta can undergo dissection in weakened layers of the aortic wall. Further, the disease is labelled into four different types, since it is an autosomal dominant genetic connective tissue disorder, the groups are categorized by their genetic cause. TGFB1 and TGFB2 cause type I and II. Normally these genes allow for the fruition of the body’s development and growth. However, when defective they create non-functioning proteins.&lt;br /&gt;
&lt;br /&gt;
====Obesity, Diabetes and Hepatic Steatosis====&lt;br /&gt;
Normally, TGF-β signaling pathway has a major role in maintaining a regulated level of glucose and energy under homeostatic conditions. Not only this, but TGF-B could also have a vital task in diabetic kidney disease.  &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;21723505&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
Abnormalities in TGF-β signaling in obesity is one of the reasons why there is so much inflammatory damage in the human body by obesity. [5]&lt;br /&gt;
This was shown again in a study done where mice affected were given a systemic blockade drug for the TGF-B pathway and it was observed that they were protected from obesity, diabetes and hepatic steatosis. &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;21436399&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
====Multiple Sclerosis====&lt;br /&gt;
In Multiple Sclerosis (MS) a common observation is that patients will generally have lower levels of TGF-β, which is suspected to prevent remylentation of neurons. The reason why this is of significance is because MS results in demylentation of neurons causing severe neurological problems. TGF-β is normally responsible for regulating apoptosis of Th17 cells.&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;22942700&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;Thus when TGF-β levels decrease due to abnormalities, they are not able to be regulating Th17 cells apoptosis.[6] This then causes Th17 cells to secrete TNF-α, finally causing a demylenation of the oliodendroglial (neurons).&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;22189514&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;By having a lower amount of TGF-β we get a higer level of Th17 cells and therefore more TNFα and neuronal damage. Thus we can observe that this pathway is vital in maintaining neuronal health.&lt;br /&gt;
&lt;br /&gt;
==Further Reading==&lt;br /&gt;
&lt;br /&gt;
==Glossary==&lt;br /&gt;
{| class=&amp;quot;pretty table&amp;quot;&lt;br /&gt;
|-&lt;br /&gt;
| '''Apoptosis'''&lt;br /&gt;
| Cell death which occurs as a normal and controlled part of an organism's growth or development&lt;br /&gt;
|-&lt;br /&gt;
| '''Avian system'''&lt;br /&gt;
| Respiratory system that delivers oxygen and removes carbon dioxide&lt;br /&gt;
|-&lt;br /&gt;
| '''CCL-64'''&lt;br /&gt;
|  - mink lung epithelial cell&lt;br /&gt;
|-&lt;br /&gt;
| '''Cytokine'''&lt;br /&gt;
| A broad and loose category of small proteins that are important in cell signalling&lt;br /&gt;
|-&lt;br /&gt;
| '''Cushion Formation'''&lt;br /&gt;
| Cells in development that play a role in the formation of the heart septa&lt;br /&gt;
|-&lt;br /&gt;
| '''Dimer'''&lt;br /&gt;
| An oligomer consisting of two structurally similar monomers joined by bonds that can be either strong or weak, covalent or intermolecular&lt;br /&gt;
|-&lt;br /&gt;
| '''Homodimers'''&lt;br /&gt;
| A protein composed of two polypeptide chains that are identical in the order, number, and kind of their amino acid residues&lt;br /&gt;
|-&lt;br /&gt;
| '''Isoform'''&lt;br /&gt;
| A protein that has the same function as another protein but which is encoded by a different gene and may have small differences in its sequence&lt;br /&gt;
|-&lt;br /&gt;
| '''Ligands'''&lt;br /&gt;
| A molecule that binds to a larger molecule&lt;br /&gt;
|-&lt;br /&gt;
| '''Looping'''&lt;br /&gt;
| A morphogenetic process when the heart shape is formed by looping the embryonic tube&lt;br /&gt;
|-&lt;br /&gt;
| '''Pleiotropic'''&lt;br /&gt;
| To produce more than one type of effect&lt;br /&gt;
|-&lt;br /&gt;
| '''BMP'''&lt;br /&gt;
| Bone Morphogenetic Protein, a protein part of the TGF-β superfamily.&lt;/div&gt;</summary>
		<author><name>Z5020466</name></author>
	</entry>
	<entry>
		<id>https://embryology.med.unsw.edu.au/embryology/index.php?title=2016_Group_Project_6&amp;diff=255354</id>
		<title>2016 Group Project 6</title>
		<link rel="alternate" type="text/html" href="https://embryology.med.unsw.edu.au/embryology/index.php?title=2016_Group_Project_6&amp;diff=255354"/>
		<updated>2016-10-27T13:03:33Z</updated>

		<summary type="html">&lt;p&gt;Z5020466: /* Marfan syndrome */&lt;/p&gt;
&lt;hr /&gt;
&lt;div&gt;{{ANAT2341Project2016header}}&lt;br /&gt;
{{Group Assessment Criteria table}}&lt;br /&gt;
&amp;lt;!-- Do not delete the above template from the Group project page. --&amp;gt;&lt;br /&gt;
&lt;br /&gt;
=Transforming Growth Factor-Beta (TGF-β) Signalling Pathway=&lt;br /&gt;
&lt;br /&gt;
==Introduction==&lt;br /&gt;
&lt;br /&gt;
The transforming growth factor beta (TGF-β) is a multifunctional and pleiotropic cytokine &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;26555259&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;.&lt;br /&gt;
The TGF-β signalling pathway is crucial to the control of different biological and pathological processes, such as cellular proliferation and differentiation, angiogenesis, immune regulation/inflammation, apoptosis and cell survival. &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;17896911&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
TGF-β belongs to the Transforming Growth Factor superfamily - a large group of structually connected cell regulatory proteins. It consists of TGF-β 1, 2 AND 3, Growth Differentiation Factors (GDFs), Activins, Inhibins, Bone Morphogenetic Proteins (BMPs), Glial-derived Neurotrophic Factors (GDNFs) and Mullierian Inhibiting Substance (MIS). &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;24270394&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
Most importantly, TGF-β plays a dominant part in the development of the embryo and adult organism. &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;23926286&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
This wiki aims to present a helpful overview of the TGF-β signalling pathway, but is in no means a complete resource on all information regarding the topic. We focus on ________________&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&amp;lt;br&amp;gt;&amp;lt;br&amp;gt;&lt;br /&gt;
&amp;lt;div align=&amp;quot;center&amp;quot;&amp;gt;&amp;lt;html5media width=&amp;quot;560&amp;quot; height=&amp;quot;315&amp;quot;&amp;gt;https://www.youtube.com/watch?v=GuKjUearIUI&amp;lt;/html5media&amp;gt;&amp;lt;/div&amp;gt;&lt;br /&gt;
&amp;lt;br&amp;gt;&lt;br /&gt;
&lt;br /&gt;
==History==&lt;br /&gt;
Since the early stages of the TGF beta-signaling pathway, plenty of in-depth research and studies have been conducted that have no doubt contributed to our knowledge of the pathway today.&lt;br /&gt;
&lt;br /&gt;
SMAD signaling and the three receptors for TGF-beta are two of the many fields of interest regarding the topic. In medicine and specific areas such as cancer, cardiovascular disease and inflammatory bowel disease, there are numerous alternatives for drugs that can either heighten or suppress the activity of TGF-beta.&lt;br /&gt;
&lt;br /&gt;
{| class=&amp;quot;pretty table&amp;quot;&lt;br /&gt;
| '''1988'''&lt;br /&gt;
| The process of maturation of follicle-enclosed oocytes and cumulus-oocyte complexes was sped up by TGF beta. It was discovered that TGF beta and other growth factors are effective in vitro stimulators of oocyte maturation in the rat&lt;br /&gt;
&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;3275534&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
|-&lt;br /&gt;
| '''1989'''&lt;br /&gt;
| It was already known that TGF-beta 1 is a strong autocrine growth inhibitor of lymphocytes. Ellingsworth and colleagues found that TGF-beta 1 binds to all three cell surface-binding proteins (280-200 kD, 95-85 kD, 65 kD).&lt;br /&gt;
It was also found that these binding proteins are required for signal transduction. Overall, they discovered that the regulation of the expression of the TGF-beta 1 receptor is controlled by T cell mitogenic signals.&lt;br /&gt;
&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;2785999&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
|-&lt;br /&gt;
| '''1989'''&lt;br /&gt;
| It was made known that the properties of R mutants classify TGF-beta type I binding protein as the receptor involved in mediating TGF-beta actions on cell adhesion and proliferation&lt;br /&gt;
&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;2536702&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
|-&lt;br /&gt;
| '''1989'''&lt;br /&gt;
| Drosophil was the only member of the TGF-beta family to be identified in invertebrates &lt;br /&gt;
&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;2699859&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
|-&lt;br /&gt;
| '''1990'''&lt;br /&gt;
| It was already known that the rapid increase in number response of mink lung epithelial cells to serum and to epidermal growth factor was inhibited by TGF beta 1. A necessary component of TGF-beta 1 mediated growth inhibition in CCL64 epithelial cells is the coupling of TGF beta 1 receptor binding to G-protein activation&lt;br /&gt;
&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;2156499&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
|-&lt;br /&gt;
| '''2000'''&lt;br /&gt;
| VegT function was found to be involved in sequence with the TGF beta pathway. Therefore, TGF beta signaling may be activated by the maternally expressed VegT to participate in endoderm determination&lt;br /&gt;
&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;10640706&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
|-&lt;br /&gt;
| '''2005'''&lt;br /&gt;
| Within the TGF beta superfamily, it was found that a limited number of type I and type II receptors worked together to produce specificity of action &lt;br /&gt;
&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;15483083&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
|-&lt;br /&gt;
| '''2010'''&lt;br /&gt;
| Deregulation of TGF beta signaling was reported in human psoriasis&lt;br /&gt;
&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;19710682&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
|-&lt;br /&gt;
| '''2015'''&lt;br /&gt;
| It was known that TGF is required in the tumorigenicity and metastasis of bone tumour. A significant event in the activation of the TGF beta signaling pathway is the binding of transcription coactivator Yes-associated protein (YAP) to Smad transcription factors&lt;br /&gt;
&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;27491038&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
|}&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
[[File:Canonical and non-canonical signalling TGF beta pathways.png|thumb|500px|Flowchart showing the Canonical and Non-Canonical pathways of TGF-β signalling pathway.&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;24393789&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;]] &lt;br /&gt;
===Canonical pathway===&lt;br /&gt;
In the canonical pathway, the dormant TGF-β complex is formed when the three TGF-β ligand isoforms - TGF-B1, TGF-B2 and TGF-B3 - bind once it is synthesized as precursors. After secretion and extracellular activation, TGF-β ligands can bind to two types of receptors: the membranous TGF-β type III receptor or the TGF-β type II receptor (TGF-βRII) homodimers with high affinity. &lt;br /&gt;
TGF-βRII binding enables dimerization with TGF-β type I receptor (TGF-βRI) homodimers, as well as activation of the TGF-βRI kinase domain and signal transduction across phosphorylation of the C-terminus of receptor-regulated SMADs, SMAD2 and SMAD3.&lt;br /&gt;
A heterotrimeric complex is formed by the TGF-βR dimer and SMAD4, which moves and assemblies in the nucleus.&lt;br /&gt;
TGF-β dependent signalling can operate or subdue numerous target genes through the communication of SMADs with multiple transcription factors. There are many structures in which SMAD activities are regulated, such as SMAD2/3 nucleocytoplasmic shuttling, binding to anchor proteins, phosphorylation and Smurf (SMAD-ubiquitination-regulatory factor).  &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;24393789 &amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
&lt;br /&gt;
===Non-Canonical pathway===&lt;br /&gt;
In the non-canonical pathway, SMAD-independent pathways such as PI3K/AKT and MAPK pathways like ERK, JNK, and p38 MAPK are activated by TGF-β signalling. In addition, transversal signalling, especially at the SMAD level, allows TGF-β pathway activation to incorporate signals from integrins, Notch and Wnt dependent pathways as well as signals from cellular processes like the cell cycle or apoptosis machineries. Thus, the TGF-β signalling pathway has pleiotropic functions regulating cell growth, differentiation, apoptosis, cell motility, extracellular matrix production, angiogenesis and cellular immune response.&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;24393789 &amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
&lt;br /&gt;
==Process of TGF-β signalling pathway==&lt;br /&gt;
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TGF-β signalling pathway is required for regulation of a large number of cellular processes such as cell proliferation, invasion and inflammation. It is also activated mitogen activated protein kinase signalling. There are two main routes in TGF-β signalling; the SMAD Dependent pathway and SMAD Independent pathway.&lt;br /&gt;
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===SMAD Dependent TGF-β signalling pathway===&lt;br /&gt;
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[[File:TGF-B Signalling - Formation of Receptor Hetero-Tetramers.png|thumb|350px|SMAD Dependent TGF-β signalling pathway: Formation of Receptor Hetero-Tetramers&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;16446785&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;]]&lt;br /&gt;
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The ligands of the TGF-β superfamily form dimers that bind to heterodimeric receptor complexes composed of two type I and two type II transmembrane receptor subunits with serine/threonine kinase domains.&lt;br /&gt;
Following ligand binding on TGF-β1, the dimerized TGF-β type II receptors phosphorylates and activates the TGF-β type I receptors. In most cell types, this leads to recruitment and phosphorylation of the receptor-regulated SMAD2 and SMAD3, presented by the SMAD anchor for receptor activation. SMAD1 and SMAD5 can be activated by the TGF-β signaling depending on the Type I receptor that is expressed.&lt;br /&gt;
Heterologous complexes are formed by the phosphorylated receptor-regulated SMAD with the common-mediator SMAD, SMAD4, and successively move into the nucleus, where they accumulate and act as transcription factors participating in the regulation of target gene expression. &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;21302608&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
In addition, they recruit extra transcriptional regulators, such as DNA-binding transcription factors, co-activators and co-repressors. These control the expression of several target genes and ultimately initiates a SMAD-dependent signaling cascade that induces or represses transcriptional activity. SMADs are widely expressed in most adult tissue and cell types, indicating that the TGF-β signaling pathway is ubiquitous.&lt;br /&gt;
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===SMAD independent TGF-β signalling pathway===&lt;br /&gt;
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Rather than SMAD-mediated transciption TGF-β also has the potential to activate other signalling cascades for example the Erk, JNK and p38 MAPK kinase pathways. In some cases these pathways exhibit activation with slow kinetics which indicates SMAD-dependant mechanics, however there has also been rapid activation cases (5-15mins) suggesting independence from transcription mechanisms. Studies carried out with SMAD4 deficient cells and dominant-negative SMADS provide evidence that the MAPK pathway activation is independent from SMADS, as well as this it has be found that p38 MAPK signalling  was activated in response to mutated TGF- β type 1 receptors, which were defective in SMAD activation&amp;lt;ref name=&amp;quot;PMID14534577&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;14534577&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;.&lt;br /&gt;
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The precise mechanisms and biological consequences of these SMAD-Independent pathways (Erk, JNK, p38 MAPK) are currently poorly characterized. Ras is implicated in TGF- β induced Erk signalling as there is rapid activation of Ras by TGF- β in epithelial cells. The JNK and p38 MAPK signalling are activated by various MAPK kinase kinases (MAPKKK) TGF- β kinase 1 (TAK 1) receptor is a MAPKKK family member. Further research and identification of various interactions between the small signalling molecules and receptor proteins will provide additional insight into the precise mechanism behind the activation of MAPK pathways by TGF- β ligands &amp;lt;ref name=&amp;quot;PMID14534577&amp;quot;/&amp;gt;.&lt;br /&gt;
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==Regulation of the pathway and factors affecting it==&lt;br /&gt;
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Signalling mechanisms by TGF-β like factors are regulated in both negative and positive fashions, these are all tightly controlled through a multitude of mechanisms at extracellular, membrane, cytoplasmic and all the way to nuclear levels. Positive regulation is required to amplify signalling from TGF-β like factors, while negative regulation is important for the termination and restriction of signalling usually occurring through the mechanism of a feedback loop. There is also additional regulation of TGF-β like factors via cross-talk with other signal transduction pathways such as MAPK and JAK/STAT pathways.&amp;lt;ref name=&amp;quot;PMID10704361&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;10704361&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
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===Positive Regulation===&lt;br /&gt;
The positive regulation of TGF-β specifically the induction of ligands and their signalling components often is triggered by the action TGF-β-like factors themselves. For example NODAL, a secretory protein of the TGF-β superfamily which plays a role in early embryogenesis and acts through activin receptors and SMAD2 is induced by nodal signalling itself. In other types of cells TGF-β receptors as well as transcription factors which serve as targets for TGF-β like factors can be induced by ligand stimulation, as identified in case of transcription factor Runx3 which is induced by TGF-β and forms a complex with SMAD3 to be further activated by TGF-β. The mechanism of SMAD signalling is also positively modulated via the &amp;quot;cross-talk&amp;quot; (and hence the process of SMAD dependant TGF-β signalling) with other signalling pathways, SMADS may be activated by the tyrosine kinase receptor under specific circumstances and further positively regulate TGF-β like factors &amp;lt;ref name=&amp;quot;PMID10704361&amp;quot;/&amp;gt;.&lt;br /&gt;
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===Negative Regulation===&lt;br /&gt;
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Signalling is regulated at the cell membrane level as well as within the cytoplasm of the cell, specifically by BAMBI, a pseudo-receptor for serine/threonine kinase receptors (in Xenopus embryos however displays a high degree of sequence similarity to human BAMBI gene). This BAMBI receptor is structurally alike to the type 1 serine/threonine kinase receptor, the only difference being that it lacks an intracellular domain. BAMBI  has shown a similar expression profile to that of BMP-4 a growth factor from the TGF-β super family, and has been found to require BMP signalling for expression. BAMBI when goes on to interact with both type 1 and type 2 serine/threonine receptors and works to abolish their abilities to signal via BMPs, activins and TGF-βs, therefore it is postulated that BAMBI can be inductively expressed by BMPS to self regulate BMP signalling as well as cross-regulate signalling from other members of the TGF-β super family. &amp;lt;ref name=&amp;quot;PMID10704361&amp;quot;/&amp;gt;&lt;br /&gt;
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==Significance in Embryonic Development==&lt;br /&gt;
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TGF betas are involved in embryogenesis. During development of the embryo, members of the TGF-beta family are essential for bone and cartilage formation, mesoderm induction and patterning and dorso-ventral patterning.&lt;br /&gt;
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[[File:TGF in Cardiovascular.jpg|thumb|500px|Expression of TGF-β2 and TGF-β3 in wildtype embryonic hearts.&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;12948523&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;]]&lt;br /&gt;
===Cardiovascular Development===&lt;br /&gt;
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Genetic engineering and tissue explanation studies have revealed many roles for TGF-β ligands and their signaling molecules in development. In the embryo, TGF-β appear to be involved in epithelial-mesenchymal transformations (EMT) during the formation of endocardial cushions, and in epicardial epithelial-mesenchymal transformations essential for coronary vasculature, ventricular myocardial development and compaction. It must be noted that in the normal function of the cardiovascular system in the adult, TGF-β play significant roles in cardiac hypertrophy, vascular remodeling and regulation of the renal renin-angiotensin system.&lt;br /&gt;
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TGF-β1 is expressed in the endocardium of the developing mouse. TGF-β(-/-) mice have been found with obvious congenital cardiovascular defects, so it’s important to review its expression in the developing heart. In the blood vessels, TGF-β1 is in the intima whereas TGF-β2 and TGF-β3 are in the media and adventitia. TGF-β2 signals are found as early as embryonic day 7.25 (E7.25) &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;7687212&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; in the cardiogenic plate of the precardiac mesoderm and is later prominent in the myocardium of the aortic sac and outflow track regions. TGF-β2 protein is also found in the entire myocardium of the heart at the time when looping occurs. From E8.5-9.5 when the cushion formation process occurs, there is a particularly strong TGF-β2 expression localised to the myocardium as displayed in A, B, D and E in the figure. After cushion formation and EMT, and before myocardialization of the endocardial cushion begins, there is also strong TGF-β2 expression in the OT myocardium and in the adjacent developing cushion mesenchym. However, as myocardialization occurs, TGF-β2 expression is reduced in the myocardium so that from E12.5 onwards, it is only expressed mainly in the mesenchyme of the cushion and OT septum. As can be seen in 2GH, TGF-β2 expression remains high in the cushion mesenchyme of the OT septum. By E15.5, TGF-β1 s now the most highly expressed isoform in the endocardial cells of the myocardium. It is seen in M, N, O of the figure that the epidcardium TGF-β1 and TGF-β3 expression is higher than that of TGF-β2. Thus, it can be seen that all three TGF-β are expressed in the epicardium, and they are not expressed in an overlapping fashion.&lt;br /&gt;
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Cross talk between mesoderm and underlying endoderm is needed to form the early tubular heart. This cellular and molecular induction in the primary heart forming regions is important for the specification and differentiation of myocardial and endocardial precursor cells &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;10767078&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;. Other endoderm-derived growth factors such as BMP2, FGF2 as well as TGFBS have been implicated in this process in the avian system &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;11322300&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;. TGFB2 and TGFB receptors are expressed in the precardiac mesoderm along with BMP2 &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;7687212&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;10767078&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;10340759&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;. Members of the TGG family can serve as inductive signals at the heart forming fields for the formation of myocardial and endocardial precursor cells. Members such as Activin, BMP, Nodal, Left and others have been found to be crucial for the establishment of embryonic asymmetry &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;11836504&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;, and this asymmetry is in turn critical for heart development &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;11752633&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;.&lt;br /&gt;
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===Mammary Gland Development===&lt;br /&gt;
Similarly, all three TGF-β isoforms are expressed during all stages in the development of the mammary gland except lactation. Specifically, mouse studies have indicated key roles for TGF-β in organizing the architecture of the mammary gland, regulating stem cell kinetics, inducing apoptosis in the involuting gland and maintaining the epithelium in a functionally undifferentiated state. The TGF-β isoforms are expressed in the ductal epithelium at all stages of development and some reviews have found that there may be some isoform specificity for temporal and spatial expression patterns &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;10887507&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;. For example, TGF-β3 is the only isoform present in the endbup cap cells and myoepithelial cells. Additionally, TGF-β1 is present at high levels in the extracellular matrix that surrounds growth-quiescent ducts. As for its effect, TGF-β have been to have induce multiple responses such as inhibiting the proliferation of mammillary epithelial cells. The nature of the target cell of plays a role as TGF-β also induced apoptosis without the inhibiting the proliferation. This highlights the highly variable actions of TGF-β that are affected by cell type, environmental and cell history to name a few. Interestingly, TGF-β have been implicated as both tumour suppressors and oncogenes in mammary tumorigenesis. For example, the overexpression of TGF-β1 inhibits tumorigenesis whilst interfering with its receptor function enhances tumorigenesis, thus hinting at its tumor suppressor role &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;7753792&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;9407968&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;. On the contrary, TGF-β has exhibited the enhancement of tumorigenesis as the TGF-β ligand expression is increased in late human breast cancer. Thus, TGF-β further proves its pleiotropic behaviour as prevalent to the mammary gland as it potentially suppresses and/or promotes tumorigenesis.&lt;br /&gt;
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===Maintenance of pluripotency in hESC===&lt;br /&gt;
Many of the members within the TGF-β superfamily are enriched within stem cells suggesting they play an important role in these cells, specifically relation to their pluripotency. The ability for a cell to self renew and differentiate is known as  'stemness', the stemness of human as well as mouse embryonic stem cells can be maintained by growing a combined culture with feed cells for example, bone morphogenic protein 4 (BMP4) induces a helix-loophelix-protein known as Id which is a potent inhibitor of differentiation, since this BMP (a member of the TGF-β  superfamily) is a potent inhibitor of neural differentiation in vertebrate embryos it is thought to maintain the stemness of hESCs and thus maintain their pluripotency.&amp;lt;ref name=&amp;quot;PMID24298330 &amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;24298330 &amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
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[[File:Flowchart_for_maintenance_of_pluripotency_in_hESCs.png|Flowchart for mechanism of maintenance of pluripotency in hESCs|thumb|upright=1.5|right|]]&lt;br /&gt;
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The nodal secretory protein from the TGF-β superfamily were found to also contribute to mESC pluripotency, this was evidenced by microarray of Nodal deficient mice which were found to have diminished  levels of Oct3/4 (transcription factors)expression, which are markers of undifferentiated stem cells. More importantly a nuclear localization of SMAD2 was found in hESCs, this is generally induced by TGF-β, activin or nodal signalling. Further microarray analysis identified that activin supposedly maintains the pluripotency of hESCs through inducing the expression of Oct4 as well as Nanog both transcription factors which are heavily involved in the self renewal of undifferentiated embryonic stem cells. Consistent with this finding, the subsequent inhibition of SMAD2 phosphorylation resulted in the decrease of expression of the markers of undifferentiated ESCs (Oct3/4, Nanog), suggesting that these were a product of SMAD2 phosphorylation and because SMAD2 is a product of activin/nodal signalling further suggesting that activin or nodal proteins produced by ESCs function to promote the maintenance of pluripotency in hESCs.&amp;lt;ref name=&amp;quot;PMID24298330 &amp;quot;/&amp;gt;.&lt;br /&gt;
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===Formation of the palate===&lt;br /&gt;
The formation of the palate is a complex procedure which involves a multitude of events including palatal shelf growth, elevation as well as left and right side fusion, as a result of genetic defects this procedure can sometimes result in formation of a cleft palate, one of the most common genetic birth defects. There have been recent findings which indicate TGF-β signalling plays a prime role in regulating the development of the palate in regards to both the palatal mesenchyme and epithelium. In humans the palate develops from two primordiuims, the primary and secondary palate, these progress to develop into palatal shelves which are positioned vertically against each other along the sides of the tongue. Following jaw growth and descent of the tongue these primordial palates orientate themselves horizontally and begin to fuse, in the case of the hard palate the mesenchyme cells are replaced by intramembranous bone as opposed to the soft palate which remains muscular and does not undergo ossification. Alike to humans mice have a similar embryological process of palate formation with the stage of palatal fusion resulting in the formation of a medial edge epithelium (MEE) seam which eventually degrades via apoptosis, thus the mouse serves as a strong candidate to fulfil the role of a reliable animal model. &amp;lt;ref name=&amp;quot;PMID21395922 &amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;21395922&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
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With this model being established, it has been identified that TGF-β1 is strongly expressed in MEE cells just prior to adherence of the opposing palatal shelves, following this adherence the level of TGF-β1 gradually decreased until it ceased to be expressed in the mesenchymal cells, TGF-β. TGF-β2 and TGF-β3 were also expressed in the palatal mesenchymal cells during adherence and TGF-β3 was found to be continually expressed during the fusion process, it is further found that TGF-β3 played a crucial role in the cell degradation of MEE cells in addition to palatal fusion. It was found that when TGF-β3 deficient mice developed they expressed defects in MEE seam degradation and fusion.&amp;lt;ref name=&amp;quot;PMID21395922&amp;quot;/&amp;gt;.&lt;br /&gt;
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The use of these animal models to explore the role of TGF-β in cleft palate formation is fruitful in terms of identifying contributing factors and subtypes of TGF-β family members however there still remains much to discover of the molecular and cellular mechanisms  associated with palate formation.&lt;br /&gt;
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==Animal Studies==&lt;br /&gt;
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===Wound healing===&lt;br /&gt;
Animal studies have served as a useful way in providing pivotal information regarding the mechanisms of TGF-β action in wound healing. In fact, much of the current information on the action of TGF-β in wound healing has been acquired from animal studies using incisional and/or excisional wounding models and manipulation of TGF-β signalling by adding the exogenous TGF-β protein or anti-TGF-β neutralizing antibodies, or by genetic alteration in components of the TGF-β signalling pathway. This is due to the fact that animal models provide outstanding experimental methods for explaining molecular mechanisms by which TGF-β regulates wound-healing responses. Ultimately, it has led the development of therapeutic strategies focusing on how the TGF-β pathway can improve wound healing and scarring outcome.&lt;br /&gt;
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[[File:Destination filename.jpeg|thumb|550px|Excisional wound healing in Smad 3 KO mice.&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;24761336&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;]] &lt;br /&gt;
Wound healing is an intricate physiological process distinguished by the successive overlapping stages of inflammation, proliferation and maturation. It that requires numerous growth factors, one of which includes TGF-β, which has the widest range of effects. TGF-β is a multifunctional growth factor that employs pleiotropic effects on wound healing by regulating cell differentiation, extracellular matrix production and immune modulation. The role of TGF-β signalling in wound healing was explored through examination of the development of tissue-specific expression systems for overexpression or knockout of TGF-b signalling pathway components. This study also classified that molecules might serve as molecular targets for the treatment of pathological skin conditions such as chronic wounds and excessive scarring (fibrosis). &lt;br /&gt;
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Exogenously added TGF-β has the potential to promote wound healing by stimulating angiogenesis, immune cell infiltration, and ECM production, and that diminishing endogenous TGF-β action reduces scarring without adversely affecting wound-healing quality.&lt;br /&gt;
====Direct modulation of TGF-β levels====&lt;br /&gt;
Injecting TGF-β into normal skin of newborn mice led to resilient initiation of angiogenesis and fibrosis. This consisted of important new collagen synthesis combined into the matrix. As a result of these observations, people were encouraged to further study the administration of TGF-β to incisional wounds in rats. It proved that TGF-β treatment resulted in better dermal healing, as showed by prominent collagen deposition and significantly increased wound strength.&lt;br /&gt;
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Interpreting wound-healing results obtained from the animals brought about its limitations. For instance, an underlying skin abnormality was found on many of the mouse models with genetic alterations in the TGF-β signalling pathway. Also, the pleiotropic effects of TGF-β on many different cell types throughout stages of wound healing highlighted a challenge in designing particular methods in which the TGF-β signalling pathway can assist wound healing or reduce scarring. &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;24761336&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
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==Current Research==&lt;br /&gt;
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==Abnormalities of the TGF-Beta Pathway==&lt;br /&gt;
Mutations or deletion of the TGF-beta 1 or TGF-beta RII gene have been associated with multiple syndromes. In mice, defects have been found in haematopoiesis, vasculogenesis and endothelial differentiation of extra embryonic tissues, while knockout mice for SMAD2 or SMAD4 genes are more likely to have spontaneous tumour development and excessive inflammatory responses. In humans, various diseases have been linked to the mutation of the TGF-beta RII gene and SMAD4 mutation is genetically responsible for familial juvenile polyposis, an autosomal dominant disease characterized by predisposition to gastrointestinal polyps and cancers.&lt;br /&gt;
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====Cancer====&lt;br /&gt;
Alterations of this signalling pathway are common in cancer. Accessory proteins such as soluble or membrane-bound regulators or co-receptors can also affect TGF-beta signalling. A normal acting cell has a functional TGF-β signalling pathway, in which TGF- β stops proliferation of cells at G1 stage to either encourage apoptosis or induce differentiation. If the TGF-β signaling pathway becomes mutated these cells can become cancerous as the TGF-β no longer controls the cell. Uncontrolled, these cancer cells proliferate and cause surrounding fibroblasts, immune cells, endothelial and smooth-muscle cells to proliferate as well. From this increased production of TGF-β it causes angiogenesis and immunosuppression, further propogating the cancer. &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;10793168&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;The human body has an regulation against this, which is called effector T-cells which destroy cancer cells via an inflammatory reaction. However, TGF-β converts them into regulatory T-cells, which reduce the inflammatory reaction.&lt;br /&gt;
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====Marfan syndrome====&lt;br /&gt;
It is also suggested that TGF-β signaling has a large part to play in the pathogenesis of Marfan syndrome. This disease causes disproportionate height, abnormally long fingers and toes, displaced crystalline lens of the eye. Not only this but heart complications can also occur, like mitral valve prolapse or aortic enlargement. Marfan syndrome is generally known to be caused by defective creation of elastic fibres, more specifically of the glycoprotein fibrillin I. In a study done it was observed that by adding TGF-β antagonist in mice who were affected by Marfan syndrome phenotype, their symptoms were alleviated.&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;16601194&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; From this, we can see that the mechanism involved in Marfan syndrome most likely has an underlying relation with lowered sequestration of TGF-β by fibrillin.&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;16571647&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
 File:Embryo marfan.jpg&lt;br /&gt;
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====Heart disease====&lt;br /&gt;
The TGF-B pathway has many effects on cardiomyocytes, mesenchymal and immune cells. Not only this, but it plays a vital role in the pathogenesis of cardiac remodeling and fibrosis. Abnormalities in this pathway can cause an overexpression of TGF-β which has been associated with fibrosis and hypertrophy in mice hearts. We see that endogenous TGF-β is capable of varying matrix metabolism in a pressure-overloaded heart. In a heart which has undergone great stress, such as myocardial infarction, TGF-β is seen to inactivate inflammatory macrophages. This allows for less of an immune response but further done by it encouraging myofibroblast transdifferentiation and matrix synthesis. Thus higher levels of TGF-β is causing more inflammatory damage and further propagating the heart disease. &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;21059352&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
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====Loeys–Dietz syndrome====&lt;br /&gt;
Abnormalities of the TGF-β signaling can also cause Loeys–Dietz syndrome via mutations in the TGF-β receptor. Loeys-Deitz syndrome connective tissue disorder, mainly in children where there are aneurisms in the aorta. Not only this, but the aorta can undergo dissection in weakened layers of the aortic wall. Further, the disease is labelled into four different types, since it is an autosomal dominant genetic connective tissue disorder, the groups are categorized by their genetic cause. TGFB1 and TGFB2 cause type I and II. Normally these genes allow for the fruition of the body’s development and growth. However, when defective they create non-functioning proteins.&lt;br /&gt;
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====Obesity, Diabetes and Hepatic Steatosis====&lt;br /&gt;
Normally, TGF-β signaling pathway has a major role in maintaining a regulated level of glucose and energy under homeostatic conditions. Not only this, but TGF-B could also have a vital task in diabetic kidney disease.  &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;21723505&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
Abnormalities in TGF-β signaling in obesity is one of the reasons why there is so much inflammatory damage in the human body by obesity. [5]&lt;br /&gt;
This was shown again in a study done where mice affected were given a systemic blockade drug for the TGF-B pathway and it was observed that they were protected from obesity, diabetes and hepatic steatosis. &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;21436399&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
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====Multiple Sclerosis====&lt;br /&gt;
In Multiple Sclerosis (MS) a common observation is that patients will generally have lower levels of TGF-β, which is suspected to prevent remylentation of neurons. The reason why this is of significance is because MS results in demylentation of neurons causing severe neurological problems. TGF-β is normally responsible for regulating apoptosis of Th17 cells.&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;22942700&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;Thus when TGF-β levels decrease due to abnormalities, they are not able to be regulating Th17 cells apoptosis.[6] This then causes Th17 cells to secrete TNF-α, finally causing a demylenation of the oliodendroglial (neurons).&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;22189514&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;By having a lower amount of TGF-β we get a higer level of Th17 cells and therefore more TNFα and neuronal damage. Thus we can observe that this pathway is vital in maintaining neuronal health.&lt;br /&gt;
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==Further Reading==&lt;br /&gt;
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==Glossary==&lt;br /&gt;
{| class=&amp;quot;pretty table&amp;quot;&lt;br /&gt;
|-&lt;br /&gt;
| '''Apoptosis'''&lt;br /&gt;
| Cell death which occurs as a normal and controlled part of an organism's growth or development&lt;br /&gt;
|-&lt;br /&gt;
| '''Avian system'''&lt;br /&gt;
| Respiratory system that delivers oxygen and removes carbon dioxide&lt;br /&gt;
|-&lt;br /&gt;
| '''CCL-64'''&lt;br /&gt;
|  - mink lung epithelial cell&lt;br /&gt;
|-&lt;br /&gt;
| '''Cytokine'''&lt;br /&gt;
| A broad and loose category of small proteins that are important in cell signalling&lt;br /&gt;
|-&lt;br /&gt;
| '''Cushion Formation'''&lt;br /&gt;
| Cells in development that play a role in the formation of the heart septa&lt;br /&gt;
|-&lt;br /&gt;
| '''Dimer'''&lt;br /&gt;
| An oligomer consisting of two structurally similar monomers joined by bonds that can be either strong or weak, covalent or intermolecular&lt;br /&gt;
|-&lt;br /&gt;
| '''Homodimers'''&lt;br /&gt;
| A protein composed of two polypeptide chains that are identical in the order, number, and kind of their amino acid residues&lt;br /&gt;
|-&lt;br /&gt;
| '''Isoform'''&lt;br /&gt;
| A protein that has the same function as another protein but which is encoded by a different gene and may have small differences in its sequence&lt;br /&gt;
|-&lt;br /&gt;
| '''Ligands'''&lt;br /&gt;
| A molecule that binds to a larger molecule&lt;br /&gt;
|-&lt;br /&gt;
| '''Looping'''&lt;br /&gt;
| A morphogenetic process when the heart shape is formed by looping the embryonic tube&lt;br /&gt;
|-&lt;br /&gt;
| '''Pleiotropic'''&lt;br /&gt;
| To produce more than one type of effect&lt;br /&gt;
|-&lt;br /&gt;
| '''BMP'''&lt;br /&gt;
| Bone Morphogenetic Protein, a protein part of the TGF-β superfamily.&lt;/div&gt;</summary>
		<author><name>Z5020466</name></author>
	</entry>
	<entry>
		<id>https://embryology.med.unsw.edu.au/embryology/index.php?title=File:Patient_with_Marfan_syndrome.jpg&amp;diff=255352</id>
		<title>File:Patient with Marfan syndrome.jpg</title>
		<link rel="alternate" type="text/html" href="https://embryology.med.unsw.edu.au/embryology/index.php?title=File:Patient_with_Marfan_syndrome.jpg&amp;diff=255352"/>
		<updated>2016-10-27T13:01:41Z</updated>

		<summary type="html">&lt;p&gt;Z5020466: Z5020466 uploaded a new version of File:Patient with Marfan syndrome.jpg&lt;/p&gt;
&lt;hr /&gt;
&lt;div&gt;Patient with Marfan syndrome. Note aesthenic or marfanoid body habitus, pronounced myopia (thick glasses), previous thoracic surgery (composite aortic root/aortic valve replacement).&lt;br /&gt;
&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;PMC1767196&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;/div&gt;</summary>
		<author><name>Z5020466</name></author>
	</entry>
	<entry>
		<id>https://embryology.med.unsw.edu.au/embryology/index.php?title=File:Patient_with_Marfan_syndrome.jpg&amp;diff=255350</id>
		<title>File:Patient with Marfan syndrome.jpg</title>
		<link rel="alternate" type="text/html" href="https://embryology.med.unsw.edu.au/embryology/index.php?title=File:Patient_with_Marfan_syndrome.jpg&amp;diff=255350"/>
		<updated>2016-10-27T12:59:59Z</updated>

		<summary type="html">&lt;p&gt;Z5020466: Patient with Marfan syndrome. Note aesthenic or marfanoid body habitus, pronounced myopia (thick glasses), previous thoracic surgery (composite aortic root/aortic valve replacement).
&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;PMC1767196&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;/p&gt;
&lt;hr /&gt;
&lt;div&gt;Patient with Marfan syndrome. Note aesthenic or marfanoid body habitus, pronounced myopia (thick glasses), previous thoracic surgery (composite aortic root/aortic valve replacement).&lt;br /&gt;
&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;PMC1767196&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;/div&gt;</summary>
		<author><name>Z5020466</name></author>
	</entry>
	<entry>
		<id>https://embryology.med.unsw.edu.au/embryology/index.php?title=File:Embryo_marfan.jpg&amp;diff=255346</id>
		<title>File:Embryo marfan.jpg</title>
		<link rel="alternate" type="text/html" href="https://embryology.med.unsw.edu.au/embryology/index.php?title=File:Embryo_marfan.jpg&amp;diff=255346"/>
		<updated>2016-10-27T12:56:21Z</updated>

		<summary type="html">&lt;p&gt;Z5020466: Patient with Marfan syndrome. Note aesthenic or marfanoid body habitus, pronounced myopia (thick glasses), previous thoracic surgery (composite aortic root/aortic valve replacement).
&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;PMC1767196&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;/p&gt;
&lt;hr /&gt;
&lt;div&gt;Patient with Marfan syndrome. Note aesthenic or marfanoid body habitus, pronounced myopia (thick glasses), previous thoracic surgery (composite aortic root/aortic valve replacement).&lt;br /&gt;
&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;PMC1767196&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;/div&gt;</summary>
		<author><name>Z5020466</name></author>
	</entry>
	<entry>
		<id>https://embryology.med.unsw.edu.au/embryology/index.php?title=2016_Group_Project_6&amp;diff=255334</id>
		<title>2016 Group Project 6</title>
		<link rel="alternate" type="text/html" href="https://embryology.med.unsw.edu.au/embryology/index.php?title=2016_Group_Project_6&amp;diff=255334"/>
		<updated>2016-10-27T12:45:51Z</updated>

		<summary type="html">&lt;p&gt;Z5020466: /* Abnormalities of the TGF-Beta Pathway */&lt;/p&gt;
&lt;hr /&gt;
&lt;div&gt;{{ANAT2341Project2016header}}&lt;br /&gt;
{{Group Assessment Criteria table}}&lt;br /&gt;
&amp;lt;!-- Do not delete the above template from the Group project page. --&amp;gt;&lt;br /&gt;
&lt;br /&gt;
=Transforming Growth Factor-Beta (TGF-β) Signalling Pathway=&lt;br /&gt;
&lt;br /&gt;
==Introduction==&lt;br /&gt;
&lt;br /&gt;
The transforming growth factor beta (TGF-β) is a multifunctional and pleiotropic cytokine &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;26555259&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;.&lt;br /&gt;
The TGF-β signalling pathway is crucial to the control of different biological and pathological processes, such as cellular proliferation and differentiation, angiogenesis, immune regulation/inflammation, apoptosis and cell survival. &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;17896911&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
TGF-β belongs to the Transforming Growth Factor superfamily - a large group of structually connected cell regulatory proteins. It consists of TGF-β 1, 2 AND 3, Growth Differentiation Factors (GDFs), Activins, Inhibins, Bone Morphogenetic Proteins (BMPs), Glial-derived Neurotrophic Factors (GDNFs) and Mullierian Inhibiting Substance (MIS). &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;24270394&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
Most importantly, TGF-β plays a dominant part in the development of the embryo and adult organism. &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;23926286&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
This wiki aims to present a helpful overview of the TGF-β signalling pathway, but is in no means a complete resource on all information regarding the topic. We focus on ________________&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&amp;lt;br&amp;gt;&amp;lt;br&amp;gt;&lt;br /&gt;
&amp;lt;div align=&amp;quot;center&amp;quot;&amp;gt;&amp;lt;html5media width=&amp;quot;560&amp;quot; height=&amp;quot;315&amp;quot;&amp;gt;https://www.youtube.com/watch?v=GuKjUearIUI&amp;lt;/html5media&amp;gt;&amp;lt;/div&amp;gt;&lt;br /&gt;
&amp;lt;br&amp;gt;&lt;br /&gt;
&lt;br /&gt;
==History==&lt;br /&gt;
Since the early stages of the TGF beta-signaling pathway, plenty of in-depth research and studies have been conducted that have no doubt contributed to our knowledge of the pathway today.&lt;br /&gt;
&lt;br /&gt;
SMAD signaling and the three receptors for TGF-beta are two of the many fields of interest regarding the topic. In medicine and specific areas such as cancer, cardiovascular disease and inflammatory bowel disease, there are numerous alternatives for drugs that can either heighten or suppress the activity of TGF-beta.&lt;br /&gt;
&lt;br /&gt;
{| class=&amp;quot;pretty table&amp;quot;&lt;br /&gt;
| '''1988'''&lt;br /&gt;
| The process of maturation of follicle-enclosed oocytes and cumulus-oocyte complexes was sped up by TGF beta. It was discovered that TGF beta and other growth factors are effective in vitro stimulators of oocyte maturation in the rat&lt;br /&gt;
&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;3275534&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
|-&lt;br /&gt;
| '''1989'''&lt;br /&gt;
| It was already known that TGF-beta 1 is a strong autocrine growth inhibitor of lymphocytes. Ellingsworth and colleagues found that TGF-beta 1 binds to all three cell surface-binding proteins (280-200 kD, 95-85 kD, 65 kD).&lt;br /&gt;
It was also found that these binding proteins are required for signal transduction. Overall, they discovered that the regulation of the expression of the TGF-beta 1 receptor is controlled by T cell mitogenic signals.&lt;br /&gt;
&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;2785999&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
|-&lt;br /&gt;
| '''1989'''&lt;br /&gt;
| It was made known that the properties of R mutants classify TGF-beta type I binding protein as the receptor involved in mediating TGF-beta actions on cell adhesion and proliferation&lt;br /&gt;
&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;2536702&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
|-&lt;br /&gt;
| '''1989'''&lt;br /&gt;
| Drosophil was the only member of the TGF-beta family to be identified in invertebrates &lt;br /&gt;
&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;2699859&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
|-&lt;br /&gt;
| '''1990'''&lt;br /&gt;
| It was already known that the rapid increase in number response of mink lung epithelial cells to serum and to epidermal growth factor was inhibited by TGF beta 1. A necessary component of TGF-beta 1 mediated growth inhibition in CCL64 epithelial cells is the coupling of TGF beta 1 receptor binding to G-protein activation&lt;br /&gt;
&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;2156499&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
|-&lt;br /&gt;
| '''2000'''&lt;br /&gt;
| VegT function was found to be involved in sequence with the TGF beta pathway. Therefore, TGF beta signaling may be activated by the maternally expressed VegT to participate in endoderm determination&lt;br /&gt;
&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;10640706&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
|-&lt;br /&gt;
| '''2005'''&lt;br /&gt;
| Within the TGF beta superfamily, it was found that a limited number of type I and type II receptors worked together to produce specificity of action &lt;br /&gt;
&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;15483083&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
|-&lt;br /&gt;
| '''2010'''&lt;br /&gt;
| Deregulation of TGF beta signaling was reported in human psoriasis&lt;br /&gt;
&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;19710682&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
|-&lt;br /&gt;
| '''2015'''&lt;br /&gt;
| It was known that TGF is required in the tumorigenicity and metastasis of bone tumour. A significant event in the activation of the TGF beta signaling pathway is the binding of transcription coactivator Yes-associated protein (YAP) to Smad transcription factors&lt;br /&gt;
&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;27491038&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
|}&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
[[File:Canonical and non-canonical signalling TGF beta pathways.png|thumb|500px|Flowchart showing the Canonical and Non-Canonical pathways of TGF-β signalling pathway.&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;24393789&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;]] &lt;br /&gt;
===Canonical pathway===&lt;br /&gt;
In the canonical pathway, the dormant TGF-β complex is formed when the three TGF-β ligand isoforms - TGF-B1, TGF-B2 and TGF-B3 - bind once it is synthesized as precursors. After secretion and extracellular activation, TGF-β ligands can bind to two types of receptors: the membranous TGF-β type III receptor or the TGF-β type II receptor (TGF-βRII) homodimers with high affinity. &lt;br /&gt;
TGF-βRII binding enables dimerization with TGF-β type I receptor (TGF-βRI) homodimers, as well as activation of the TGF-βRI kinase domain and signal transduction across phosphorylation of the C-terminus of receptor-regulated SMADs, SMAD2 and SMAD3.&lt;br /&gt;
A heterotrimeric complex is formed by the TGF-βR dimer and SMAD4, which moves and assemblies in the nucleus.&lt;br /&gt;
TGF-β dependent signalling can operate or subdue numerous target genes through the communication of SMADs with multiple transcription factors. There are many structures in which SMAD activities are regulated, such as SMAD2/3 nucleocytoplasmic shuttling, binding to anchor proteins, phosphorylation and Smurf (SMAD-ubiquitination-regulatory factor).  &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;24393789 &amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
&lt;br /&gt;
===Non-Canonical pathway===&lt;br /&gt;
In the non-canonical pathway, SMAD-independent pathways such as PI3K/AKT and MAPK pathways like ERK, JNK, and p38 MAPK are activated by TGF-β signalling. In addition, transversal signalling, especially at the SMAD level, allows TGF-β pathway activation to incorporate signals from integrins, Notch and Wnt dependent pathways as well as signals from cellular processes like the cell cycle or apoptosis machineries. Thus, the TGF-β signalling pathway has pleiotropic functions regulating cell growth, differentiation, apoptosis, cell motility, extracellular matrix production, angiogenesis and cellular immune response.&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;24393789 &amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
&lt;br /&gt;
==Process of TGF-β signalling pathway==&lt;br /&gt;
&lt;br /&gt;
TGF-β signalling pathway is required for regulation of a large number of cellular processes such as cell proliferation, invasion and inflammation. It is also activated mitogen activated protein kinase signalling. There are two main routes in TGF-β signalling; the SMAD Dependent pathway and SMAD Independent pathway.&lt;br /&gt;
&lt;br /&gt;
===SMAD Dependent TGF-β signalling pathway===&lt;br /&gt;
&lt;br /&gt;
[[File:TGF-B Signalling - Formation of Receptor Hetero-Tetramers.png|thumb|350px|SMAD Dependent TGF-β signalling pathway: Formation of Receptor Hetero-Tetramers&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;16446785&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;]]&lt;br /&gt;
&lt;br /&gt;
The ligands of the TGF-β superfamily form dimers that bind to heterodimeric receptor complexes composed of two type I and two type II transmembrane receptor subunits with serine/threonine kinase domains.&lt;br /&gt;
Following ligand binding on TGF-β1, the dimerized TGF-β type II receptors phosphorylates and activates the TGF-β type I receptors. In most cell types, this leads to recruitment and phosphorylation of the receptor-regulated SMAD2 and SMAD3, presented by the SMAD anchor for receptor activation. SMAD1 and SMAD5 can be activated by the TGF-β signaling depending on the Type I receptor that is expressed.&lt;br /&gt;
Heterologous complexes are formed by the phosphorylated receptor-regulated SMAD with the common-mediator SMAD, SMAD4, and successively move into the nucleus, where they accumulate and act as transcription factors participating in the regulation of target gene expression. &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;21302608&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
In addition, they recruit extra transcriptional regulators, such as DNA-binding transcription factors, co-activators and co-repressors. These control the expression of several target genes and ultimately initiates a SMAD-dependent signaling cascade that induces or represses transcriptional activity. SMADs are widely expressed in most adult tissue and cell types, indicating that the TGF-β signaling pathway is ubiquitous.&lt;br /&gt;
&lt;br /&gt;
===SMAD independent TGF-β signalling pathway===&lt;br /&gt;
&lt;br /&gt;
Rather than SMAD-mediated transciption TGF-β also has the potential to activate other signalling cascades for example the Erk, JNK and p38 MAPK kinase pathways. In some cases these pathways exhibit activation with slow kinetics which indicates SMAD-dependant mechanics, however there has also been rapid activation cases (5-15mins) suggesting independence from transcription mechanisms. Studies carried out with SMAD4 deficient cells and dominant-negative SMADS provide evidence that the MAPK pathway activation is independent from SMADS, as well as this it has be found that p38 MAPK signalling  was activated in response to mutated TGF- β type 1 receptors, which were defective in SMAD activation&amp;lt;ref name=&amp;quot;PMID14534577&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;14534577&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;.&lt;br /&gt;
&lt;br /&gt;
The precise mechanisms and biological consequences of these SMAD-Independent pathways (Erk, JNK, p38 MAPK) are currently poorly characterized. Ras is implicated in TGF- β induced Erk signalling as there is rapid activation of Ras by TGF- β in epithelial cells. The JNK and p38 MAPK signalling are activated by various MAPK kinase kinases (MAPKKK) TGF- β kinase 1 (TAK 1) receptor is a MAPKKK family member. Further research and identification of various interactions between the small signalling molecules and receptor proteins will provide additional insight into the precise mechanism behind the activation of MAPK pathways by TGF- β ligands &amp;lt;ref name=&amp;quot;PMID14534577&amp;quot;/&amp;gt;.&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
==Regulation of the pathway and factors affecting it==&lt;br /&gt;
&lt;br /&gt;
Signalling mechanisms by TGF-β like factors are regulated in both negative and positive fashions, these are all tightly controlled through a multitude of mechanisms at extracellular, membrane, cytoplasmic and all the way to nuclear levels. Positive regulation is required to amplify signalling from TGF-β like factors, while negative regulation is important for the termination and restriction of signalling usually occurring through the mechanism of a feedback loop. There is also additional regulation of TGF-β like factors via cross-talk with other signal transduction pathways such as MAPK and JAK/STAT pathways.&amp;lt;ref name=&amp;quot;PMID10704361&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;10704361&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
===Positive Regulation===&lt;br /&gt;
The positive regulation of TGF-β specifically the induction of ligands and their signalling components often is triggered by the action TGF-β-like factors themselves. For example NODAL, a secretory protein of the TGF-β superfamily which plays a role in early embryogenesis and acts through activin receptors and SMAD2 is induced by nodal signalling itself. In other types of cells TGF-β receptors as well as transcription factors which serve as targets for TGF-β like factors can be induced by ligand stimulation, as identified in case of transcription factor Runx3 which is induced by TGF-β and forms a complex with SMAD3 to be further activated by TGF-β. The mechanism of SMAD signalling is also positively modulated via the &amp;quot;cross-talk&amp;quot; (and hence the process of SMAD dependant TGF-β signalling) with other signalling pathways, SMADS may be activated by the tyrosine kinase receptor under specific circumstances and further positively regulate TGF-β like factors &amp;lt;ref name=&amp;quot;PMID10704361&amp;quot;/&amp;gt;.&lt;br /&gt;
&lt;br /&gt;
===Negative Regulation===&lt;br /&gt;
&lt;br /&gt;
Signalling is regulated at the cell membrane level as well as within the cytoplasm of the cell, specifically by BAMBI, a pseudo-receptor for serine/threonine kinase receptors (in Xenopus embryos however displays a high degree of sequence similarity to human BAMBI gene). This BAMBI receptor is structurally alike to the type 1 serine/threonine kinase receptor, the only difference being that it lacks an intracellular domain. BAMBI  has shown a similar expression profile to that of BMP-4 a growth factor from the TGF-β super family, and has been found to require BMP signalling for expression. BAMBI when goes on to interact with both type 1 and type 2 serine/threonine receptors and works to abolish their abilities to signal via BMPs, activins and TGF-βs, therefore it is postulated that BAMBI can be inductively expressed by BMPS to self regulate BMP signalling as well as cross-regulate signalling from other members of the TGF-β super family. &amp;lt;ref name=&amp;quot;PMID10704361&amp;quot;/&amp;gt;&lt;br /&gt;
&lt;br /&gt;
==Significance in Embryonic Development==&lt;br /&gt;
&lt;br /&gt;
TGF betas are involved in embryogenesis. During development of the embryo, members of the TGF-beta family are essential for bone and cartilage formation, mesoderm induction and patterning and dorso-ventral patterning.&lt;br /&gt;
&lt;br /&gt;
[[File:TGF in Cardiovascular.jpg|thumb|500px|Expression of TGF-β2 and TGF-β3 in wildtype embryonic hearts.&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;12948523&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;]]&lt;br /&gt;
===Cardiovascular Development===&lt;br /&gt;
&lt;br /&gt;
Genetic engineering and tissue explanation studies have revealed many roles for TGF-β ligands and their signaling molecules in development. In the embryo, TGF-β appear to be involved in epithelial-mesenchymal transformations (EMT) during the formation of endocardial cushions, and in epicardial epithelial-mesenchymal transformations essential for coronary vasculature, ventricular myocardial development and compaction. It must be noted that in the normal function of the cardiovascular system in the adult, TGF-β play significant roles in cardiac hypertrophy, vascular remodeling and regulation of the renal renin-angiotensin system.&lt;br /&gt;
&lt;br /&gt;
TGF-β1 is expressed in the endocardium of the developing mouse. TGF-β(-/-) mice have been found with obvious congenital cardiovascular defects, so it’s important to review its expression in the developing heart. In the blood vessels, TGF-β1 is in the intima whereas TGF-β2 and TGF-β3 are in the media and adventitia. TGF-β2 signals are found as early as embryonic day 7.25 (E7.25) &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;7687212&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; in the cardiogenic plate of the precardiac mesoderm and is later prominent in the myocardium of the aortic sac and outflow track regions. TGF-β2 protein is also found in the entire myocardium of the heart at the time when looping occurs. From E8.5-9.5 when the cushion formation process occurs, there is a particularly strong TGF-β2 expression localised to the myocardium as displayed in A, B, D and E in the figure. After cushion formation and EMT, and before myocardialization of the endocardial cushion begins, there is also strong TGF-β2 expression in the OT myocardium and in the adjacent developing cushion mesenchym. However, as myocardialization occurs, TGF-β2 expression is reduced in the myocardium so that from E12.5 onwards, it is only expressed mainly in the mesenchyme of the cushion and OT septum. As can be seen in 2GH, TGF-β2 expression remains high in the cushion mesenchyme of the OT septum. By E15.5, TGF-β1 s now the most highly expressed isoform in the endocardial cells of the myocardium. It is seen in M, N, O of the figure that the epidcardium TGF-β1 and TGF-β3 expression is higher than that of TGF-β2. Thus, it can be seen that all three TGF-β are expressed in the epicardium, and they are not expressed in an overlapping fashion.&lt;br /&gt;
&lt;br /&gt;
Cross talk between mesoderm and underlying endoderm is needed to form the early tubular heart. This cellular and molecular induction in the primary heart forming regions is important for the specification and differentiation of myocardial and endocardial precursor cells &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;10767078&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;. Other endoderm-derived growth factors such as BMP2, FGF2 as well as TGFBS have been implicated in this process in the avian system &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;11322300&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;. TGFB2 and TGFB receptors are expressed in the precardiac mesoderm along with BMP2 &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;7687212&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;10767078&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;10340759&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;. Members of the TGG family can serve as inductive signals at the heart forming fields for the formation of myocardial and endocardial precursor cells. Members such as Activin, BMP, Nodal, Left and others have been found to be crucial for the establishment of embryonic asymmetry &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;11836504&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;, and this asymmetry is in turn critical for heart development &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;11752633&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;.&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
===Mammary Gland Development===&lt;br /&gt;
Similarly, all three TGF-β isoforms are expressed during all stages in the development of the mammary gland except lactation. Specifically, mouse studies have indicated key roles for TGF-β in organizing the architecture of the mammary gland, regulating stem cell kinetics, inducing apoptosis in the involuting gland and maintaining the epithelium in a functionally undifferentiated state. The TGF-β isoforms are expressed in the ductal epithelium at all stages of development and some reviews have found that there may be some isoform specificity for temporal and spatial expression patterns &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;10887507&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;. For example, TGF-β3 is the only isoform present in the endbup cap cells and myoepithelial cells. Additionally, TGF-β1 is present at high levels in the extracellular matrix that surrounds growth-quiescent ducts. As for its effect, TGF-β have been to have induce multiple responses such as inhibiting the proliferation of mammillary epithelial cells. The nature of the target cell of plays a role as TGF-β also induced apoptosis without the inhibiting the proliferation. This highlights the highly variable actions of TGF-β that are affected by cell type, environmental and cell history to name a few. Interestingly, TGF-β have been implicated as both tumour suppressors and oncogenes in mammary tumorigenesis. For example, the overexpression of TGF-β1 inhibits tumorigenesis whilst interfering with its receptor function enhances tumorigenesis, thus hinting at its tumor suppressor role &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;7753792&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;9407968&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;. On the contrary, TGF-β has exhibited the enhancement of tumorigenesis as the TGF-β ligand expression is increased in late human breast cancer. Thus, TGF-β further proves its pleiotropic behaviour as prevalent to the mammary gland as it potentially suppresses and/or promotes tumorigenesis.&lt;br /&gt;
&lt;br /&gt;
===Maintenance of pluripotency in hESC===&lt;br /&gt;
Many of the members within the TGF-β superfamily are enriched within stem cells suggesting they play an important role in these cells, specifically relation to their pluripotency. The ability for a cell to self renew and differentiate is known as  'stemness', the stemness of human as well as mouse embryonic stem cells can be maintained by growing a combined culture with feed cells for example, bone morphogenic protein 4 (BMP4) induces a helix-loophelix-protein known as Id which is a potent inhibitor of differentiation, since this BMP (a member of the TGF-β  superfamily) is a potent inhibitor of neural differentiation in vertebrate embryos it is thought to maintain the stemness of hESCs and thus maintain their pluripotency.&amp;lt;ref name=&amp;quot;PMID24298330 &amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;24298330 &amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
[[File:Flowchart_for_maintenance_of_pluripotency_in_hESCs.png|550px|Flowchart for mechanism of maintenance of pluripotency in hESCs|]]&lt;br /&gt;
&lt;br /&gt;
The nodal secretory protein from the TGF-β superfamily were found to also contribute to mESC pluripotency, this was evidenced by microarray of Nodal deficient mice which were found to have diminished  levels of Oct3/4 (transcription factors)expression, which are markers of undifferentiated stem cells. More importantly a nuclear localization of SMAD2 was found in hESCs, this is generally induced by TGF-β, activin or nodal signalling. Further microarray analysis identified that activin supposedly maintains the pluripotency of hESCs through inducing the expression of Oct4 as well as Nanog both transcription factors which are heavily involved in the self renewal of undifferentiated embryonic stem cells. Consistent with this finding, the subsequent inhibition of SMAD2 phosphorylation resulted in the decrease of expression of the markers of undifferentiated ESCs (Oct3/4, Nanog), suggesting that these were a product of SMAD2 phosphorylation and because SMAD2 is a product of activin/nodal signalling further suggesting that activin or nodal proteins produced by ESCs function to promote the maintenance of pluripotency in hESCs.&amp;lt;ref name=&amp;quot;PMID24298330 &amp;quot;/&amp;gt;.&lt;br /&gt;
&lt;br /&gt;
===Formation of the palate===&lt;br /&gt;
The formation of the palate is a complex procedure which involves a multitude of events including palatal shelf growth, elevation as well as left and right side fusion, as a result of genetic defects this procedure can sometimes result in formation of a cleft palate, one of the most common genetic birth defects. There have been recent findings which indicate TGF-β signalling plays a prime role in regulating the development of the palate in regards to both the palatal mesenchyme and epithelium. In humans the palate develops from two primordiuims, the primary and secondary palate, these progress to develop into palatal shelves which are positioned vertically against each other along the sides of the tongue. Following jaw growth and descent of the tongue these primordial palates orientate themselves horizontally and begin to fuse, in the case of the hard palate the mesenchyme cells are replaced by intramembranous bone as opposed to the soft palate which remains muscular and does not undergo ossification. Alike to humans mice have a similar embryological process of palate formation with the stage of palatal fusion resulting in the formation of a medial edge epithelium (MEE) seam which eventually degrades via apoptosis, thus the mouse serves as a strong candidate to fulfil the role of a reliable animal model. &amp;lt;ref name=&amp;quot;PMID21395922 &amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;21395922&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
With this model being established, it has been identified that TGF-β1 is strongly expressed in MEE cells just prior to adherence of the opposing palatal shelves, following this adherence the level of TGF-β1 gradually decreased until it ceased to be expressed in the mesenchymal cells, TGF-β. TGF-β2 and TGF-β3 were also expressed in the palatal mesenchymal cells during adherence and TGF-β3 was found to be continually expressed during the fusion process, it is further found that TGF-β3 played a crucial role in the cell degradation of MEE cells in addition to palatal fusion. It was found that when TGF-β3 deficient mice developed they expressed defects in MEE seam degradation and fusion.&amp;lt;ref name=&amp;quot;PMID21395922&amp;quot;/&amp;gt;.&lt;br /&gt;
&lt;br /&gt;
The use of these animal models to explore the role of TGF-β in cleft palate formation is fruitful in terms of identifying contributing factors and subtypes of TGF-β family members however there still remains much to discover of the molecular and cellular mechanisms  associated with palate formation.&lt;br /&gt;
&lt;br /&gt;
==Animal Studies==&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
===Wound healing===&lt;br /&gt;
Animal studies have served as a useful way in providing pivotal information regarding the mechanisms of TGF-β action in wound healing. In fact, much of the current information on the action of TGF-β in wound healing has been acquired from animal studies using incisional and/or excisional wounding models and manipulation of TGF-β signalling by adding the exogenous TGF-β protein or anti-TGF-β neutralizing antibodies, or by genetic alteration in components of the TGF-β signalling pathway. This is due to the fact that animal models provide outstanding experimental methods for explaining molecular mechanisms by which TGF-β regulates wound-healing responses. Ultimately, it has led the development of therapeutic strategies focusing on how the TGF-β pathway can improve wound healing and scarring outcome.&lt;br /&gt;
&lt;br /&gt;
[[File:Destination filename.jpeg|thumb|550px|Excisional wound healing in Smad 3 KO mice.&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;24761336&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;]] &lt;br /&gt;
Wound healing is an intricate physiological process distinguished by the successive overlapping stages of inflammation, proliferation and maturation. It that requires numerous growth factors, one of which includes TGF-β, which has the widest range of effects. TGF-β is a multifunctional growth factor that employs pleiotropic effects on wound healing by regulating cell differentiation, extracellular matrix production and immune modulation. The role of TGF-β signalling in wound healing was explored through examination of the development of tissue-specific expression systems for overexpression or knockout of TGF-b signalling pathway components. This study also classified that molecules might serve as molecular targets for the treatment of pathological skin conditions such as chronic wounds and excessive scarring (fibrosis). &lt;br /&gt;
&lt;br /&gt;
Exogenously added TGF-β has the potential to promote wound healing by stimulating angiogenesis, immune cell infiltration, and ECM production, and that diminishing endogenous TGF-β action reduces scarring without adversely affecting wound-healing quality.&lt;br /&gt;
====Direct modulation of TGF-β levels====&lt;br /&gt;
Injecting TGF-β into normal skin of newborn mice led to resilient initiation of angiogenesis and fibrosis. This consisted of important new collagen synthesis combined into the matrix. As a result of these observations, people were encouraged to further study the administration of TGF-β to incisional wounds in rats. It proved that TGF-β treatment resulted in better dermal healing, as showed by prominent collagen deposition and significantly increased wound strength.&lt;br /&gt;
&lt;br /&gt;
Interpreting wound-healing results obtained from the animals brought about its limitations. For instance, an underlying skin abnormality was found on many of the mouse models with genetic alterations in the TGF-β signalling pathway. Also, the pleiotropic effects of TGF-β on many different cell types throughout stages of wound healing highlighted a challenge in designing particular methods in which the TGF-β signalling pathway can assist wound healing or reduce scarring. &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;24761336&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;
==Current Research==&lt;br /&gt;
&lt;br /&gt;
==Abnormalities of the TGF-Beta Pathway==&lt;br /&gt;
Mutations or deletion of the TGF-beta 1 or TGF-beta RII gene have been associated with multiple syndromes. In mice, defects have been found in haematopoiesis, vasculogenesis and endothelial differentiation of extra embryonic tissues, while knockout mice for SMAD2 or SMAD4 genes are more likely to have spontaneous tumour development and excessive inflammatory responses. In humans, various diseases have been linked to the mutation of the TGF-beta RII gene and SMAD4 mutation is genetically responsible for familial juvenile polyposis, an autosomal dominant disease characterized by predisposition to gastrointestinal polyps and cancers.&lt;br /&gt;
&lt;br /&gt;
====Cancer====&lt;br /&gt;
Alterations of this signalling pathway are common in cancer. Accessory proteins such as soluble or membrane-bound regulators or co-receptors can also affect TGF-beta signalling. A normal acting cell has a functional TGF-β signalling pathway, in which TGF- β stops proliferation of cells at G1 stage to either encourage apoptosis or induce differentiation. If the TGF-β signaling pathway becomes mutated these cells can become cancerous as the TGF-β no longer controls the cell. Uncontrolled, these cancer cells proliferate and cause surrounding fibroblasts, immune cells, endothelial and smooth-muscle cells to proliferate as well. From this increased production of TGF-β it causes angiogenesis and immunosuppression, further propogating the cancer. &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;10793168&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;The human body has an regulation against this, which is called effector T-cells which destroy cancer cells via an inflammatory reaction. However, TGF-β converts them into regulatory T-cells, which reduce the inflammatory reaction.&lt;br /&gt;
&lt;br /&gt;
 &lt;br /&gt;
====Marfan syndrome====&lt;br /&gt;
It is also suggested that TGF-β signaling has a large part to play in the pathogenesis of Marfan syndrome. This disease causes disproportionate height, abnormally long fingers and toes, displaced crystalline lens of the eye. Not only this but heart complications can also occur, like mitral valve prolapse or aortic enlargement. Marfan syndrome is generally known to be caused by defective creation of elastic fibres, more specifically of the glycoprotein fibrillin I. In a study done it was observed that by adding TGF-β antagonist in mice who were affected by Marfan syndrome phenotype, their symptoms were alleviated.&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;16601194&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; From this, we can see that the mechanism involved in Marfan syndrome most likely has an underlying relation with lowered sequestration of TGF-β by fibrillin.&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;16571647&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
 &lt;br /&gt;
&lt;br /&gt;
====Heart disease====&lt;br /&gt;
The TGF-B pathway has many effects on cardiomyocytes, mesenchymal and immune cells. Not only this, but it plays a vital role in the pathogenesis of cardiac remodeling and fibrosis. Abnormalities in this pathway can cause an overexpression of TGF-β which has been associated with fibrosis and hypertrophy in mice hearts. We see that endogenous TGF-β is capable of varying matrix metabolism in a pressure-overloaded heart. In a heart which has undergone great stress, such as myocardial infarction, TGF-β is seen to inactivate inflammatory macrophages. This allows for less of an immune response but further done by it encouraging myofibroblast transdifferentiation and matrix synthesis. Thus higher levels of TGF-β is causing more inflammatory damage and further propagating the heart disease. &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;21059352&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
====Loeys–Dietz syndrome====&lt;br /&gt;
Abnormalities of the TGF-β signaling can also cause Loeys–Dietz syndrome via mutations in the TGF-β receptor. Loeys-Deitz syndrome connective tissue disorder, mainly in children where there are aneurisms in the aorta. Not only this, but the aorta can undergo dissection in weakened layers of the aortic wall. Further, the disease is labelled into four different types, since it is an autosomal dominant genetic connective tissue disorder, the groups are categorized by their genetic cause. TGFB1 and TGFB2 cause type I and II. Normally these genes allow for the fruition of the body’s development and growth. However, when defective they create non-functioning proteins.&lt;br /&gt;
&lt;br /&gt;
====Obesity, Diabetes and Hepatic Steatosis====&lt;br /&gt;
Normally, TGF-β signaling pathway has a major role in maintaining a regulated level of glucose and energy under homeostatic conditions. Not only this, but TGF-B could also have a vital task in diabetic kidney disease.  &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;21723505&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
Abnormalities in TGF-β signaling in obesity is one of the reasons why there is so much inflammatory damage in the human body by obesity. [5]&lt;br /&gt;
This was shown again in a study done where mice affected were given a systemic blockade drug for the TGF-B pathway and it was observed that they were protected from obesity, diabetes and hepatic steatosis. &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;21436399&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
====Multiple Sclerosis====&lt;br /&gt;
In Multiple Sclerosis (MS) a common observation is that patients will generally have lower levels of TGF-β, which is suspected to prevent remylentation of neurons. The reason why this is of significance is because MS results in demylentation of neurons causing severe neurological problems. TGF-β is normally responsible for regulating apoptosis of Th17 cells.&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;22942700&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;Thus when TGF-β levels decrease due to abnormalities, they are not able to be regulating Th17 cells apoptosis.[6] This then causes Th17 cells to secrete TNF-α, finally causing a demylenation of the oliodendroglial (neurons).&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;22189514&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;By having a lower amount of TGF-β we get a higer level of Th17 cells and therefore more TNFα and neuronal damage. Thus we can observe that this pathway is vital in maintaining neuronal health.&lt;br /&gt;
&lt;br /&gt;
==Further Reading==&lt;br /&gt;
&lt;br /&gt;
==Glossary==&lt;br /&gt;
{| class=&amp;quot;pretty table&amp;quot;&lt;br /&gt;
|-&lt;br /&gt;
| '''Apoptosis'''&lt;br /&gt;
| Cell death which occurs as a normal and controlled part of an organism's growth or development&lt;br /&gt;
|-&lt;br /&gt;
| '''Avian system'''&lt;br /&gt;
| Respiratory system that delivers oxygen and removes carbon dioxide&lt;br /&gt;
|-&lt;br /&gt;
| '''CCL-64'''&lt;br /&gt;
|  - mink lung epithelial cell&lt;br /&gt;
|-&lt;br /&gt;
| '''Cytokine'''&lt;br /&gt;
| A broad and loose category of small proteins that are important in cell signalling&lt;br /&gt;
|-&lt;br /&gt;
| '''Cushion Formation'''&lt;br /&gt;
| Cells in development that play a role in the formation of the heart septa&lt;br /&gt;
|-&lt;br /&gt;
| '''Dimer'''&lt;br /&gt;
| An oligomer consisting of two structurally similar monomers joined by bonds that can be either strong or weak, covalent or intermolecular&lt;br /&gt;
|-&lt;br /&gt;
| '''Homodimers'''&lt;br /&gt;
| A protein composed of two polypeptide chains that are identical in the order, number, and kind of their amino acid residues&lt;br /&gt;
|-&lt;br /&gt;
| '''Isoform'''&lt;br /&gt;
| A protein that has the same function as another protein but which is encoded by a different gene and may have small differences in its sequence&lt;br /&gt;
|-&lt;br /&gt;
| '''Ligands'''&lt;br /&gt;
| A molecule that binds to a larger molecule&lt;br /&gt;
|-&lt;br /&gt;
| '''Looping'''&lt;br /&gt;
| A morphogenetic process when the heart shape is formed by looping the embryonic tube&lt;br /&gt;
|-&lt;br /&gt;
| '''Pleiotropic'''&lt;br /&gt;
| To produce more than one type of effect&lt;br /&gt;
|-&lt;br /&gt;
| '''BMP'''&lt;br /&gt;
| Bone Morphogenetic Protein, a protein part of the TGF-β superfamily.&lt;/div&gt;</summary>
		<author><name>Z5020466</name></author>
	</entry>
	<entry>
		<id>https://embryology.med.unsw.edu.au/embryology/index.php?title=2016_Group_Project_6&amp;diff=255332</id>
		<title>2016 Group Project 6</title>
		<link rel="alternate" type="text/html" href="https://embryology.med.unsw.edu.au/embryology/index.php?title=2016_Group_Project_6&amp;diff=255332"/>
		<updated>2016-10-27T12:44:44Z</updated>

		<summary type="html">&lt;p&gt;Z5020466: /* Abnormalities of the TGF-Beta Pathway */&lt;/p&gt;
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&amp;lt;!-- Do not delete the above template from the Group project page. --&amp;gt;&lt;br /&gt;
&lt;br /&gt;
=Transforming Growth Factor-Beta (TGF-β) Signalling Pathway=&lt;br /&gt;
&lt;br /&gt;
==Introduction==&lt;br /&gt;
&lt;br /&gt;
The transforming growth factor beta (TGF-β) is a multifunctional and pleiotropic cytokine &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;26555259&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;.&lt;br /&gt;
The TGF-β signalling pathway is crucial to the control of different biological and pathological processes, such as cellular proliferation and differentiation, angiogenesis, immune regulation/inflammation, apoptosis and cell survival. &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;17896911&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
TGF-β belongs to the Transforming Growth Factor superfamily - a large group of structually connected cell regulatory proteins. It consists of TGF-β 1, 2 AND 3, Growth Differentiation Factors (GDFs), Activins, Inhibins, Bone Morphogenetic Proteins (BMPs), Glial-derived Neurotrophic Factors (GDNFs) and Mullierian Inhibiting Substance (MIS). &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;24270394&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
Most importantly, TGF-β plays a dominant part in the development of the embryo and adult organism. &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;23926286&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
This wiki aims to present a helpful overview of the TGF-β signalling pathway, but is in no means a complete resource on all information regarding the topic. We focus on ________________&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&amp;lt;br&amp;gt;&amp;lt;br&amp;gt;&lt;br /&gt;
&amp;lt;div align=&amp;quot;center&amp;quot;&amp;gt;&amp;lt;html5media width=&amp;quot;560&amp;quot; height=&amp;quot;315&amp;quot;&amp;gt;https://www.youtube.com/watch?v=GuKjUearIUI&amp;lt;/html5media&amp;gt;&amp;lt;/div&amp;gt;&lt;br /&gt;
&amp;lt;br&amp;gt;&lt;br /&gt;
&lt;br /&gt;
==History==&lt;br /&gt;
Since the early stages of the TGF beta-signaling pathway, plenty of in-depth research and studies have been conducted that have no doubt contributed to our knowledge of the pathway today.&lt;br /&gt;
&lt;br /&gt;
SMAD signaling and the three receptors for TGF-beta are two of the many fields of interest regarding the topic. In medicine and specific areas such as cancer, cardiovascular disease and inflammatory bowel disease, there are numerous alternatives for drugs that can either heighten or suppress the activity of TGF-beta.&lt;br /&gt;
&lt;br /&gt;
{| class=&amp;quot;pretty table&amp;quot;&lt;br /&gt;
| '''1988'''&lt;br /&gt;
| The process of maturation of follicle-enclosed oocytes and cumulus-oocyte complexes was sped up by TGF beta. It was discovered that TGF beta and other growth factors are effective in vitro stimulators of oocyte maturation in the rat&lt;br /&gt;
&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;3275534&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
|-&lt;br /&gt;
| '''1989'''&lt;br /&gt;
| It was already known that TGF-beta 1 is a strong autocrine growth inhibitor of lymphocytes. Ellingsworth and colleagues found that TGF-beta 1 binds to all three cell surface-binding proteins (280-200 kD, 95-85 kD, 65 kD).&lt;br /&gt;
It was also found that these binding proteins are required for signal transduction. Overall, they discovered that the regulation of the expression of the TGF-beta 1 receptor is controlled by T cell mitogenic signals.&lt;br /&gt;
&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;2785999&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
|-&lt;br /&gt;
| '''1989'''&lt;br /&gt;
| It was made known that the properties of R mutants classify TGF-beta type I binding protein as the receptor involved in mediating TGF-beta actions on cell adhesion and proliferation&lt;br /&gt;
&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;2536702&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
|-&lt;br /&gt;
| '''1989'''&lt;br /&gt;
| Drosophil was the only member of the TGF-beta family to be identified in invertebrates &lt;br /&gt;
&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;2699859&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
|-&lt;br /&gt;
| '''1990'''&lt;br /&gt;
| It was already known that the rapid increase in number response of mink lung epithelial cells to serum and to epidermal growth factor was inhibited by TGF beta 1. A necessary component of TGF-beta 1 mediated growth inhibition in CCL64 epithelial cells is the coupling of TGF beta 1 receptor binding to G-protein activation&lt;br /&gt;
&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;2156499&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
|-&lt;br /&gt;
| '''2000'''&lt;br /&gt;
| VegT function was found to be involved in sequence with the TGF beta pathway. Therefore, TGF beta signaling may be activated by the maternally expressed VegT to participate in endoderm determination&lt;br /&gt;
&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;10640706&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
|-&lt;br /&gt;
| '''2005'''&lt;br /&gt;
| Within the TGF beta superfamily, it was found that a limited number of type I and type II receptors worked together to produce specificity of action &lt;br /&gt;
&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;15483083&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
|-&lt;br /&gt;
| '''2010'''&lt;br /&gt;
| Deregulation of TGF beta signaling was reported in human psoriasis&lt;br /&gt;
&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;19710682&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
|-&lt;br /&gt;
| '''2015'''&lt;br /&gt;
| It was known that TGF is required in the tumorigenicity and metastasis of bone tumour. A significant event in the activation of the TGF beta signaling pathway is the binding of transcription coactivator Yes-associated protein (YAP) to Smad transcription factors&lt;br /&gt;
&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;27491038&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
|}&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
[[File:Canonical and non-canonical signalling TGF beta pathways.png|thumb|500px|Flowchart showing the Canonical and Non-Canonical pathways of TGF-β signalling pathway.&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;24393789&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;]] &lt;br /&gt;
===Canonical pathway===&lt;br /&gt;
In the canonical pathway, the dormant TGF-β complex is formed when the three TGF-β ligand isoforms - TGF-B1, TGF-B2 and TGF-B3 - bind once it is synthesized as precursors. After secretion and extracellular activation, TGF-β ligands can bind to two types of receptors: the membranous TGF-β type III receptor or the TGF-β type II receptor (TGF-βRII) homodimers with high affinity. &lt;br /&gt;
TGF-βRII binding enables dimerization with TGF-β type I receptor (TGF-βRI) homodimers, as well as activation of the TGF-βRI kinase domain and signal transduction across phosphorylation of the C-terminus of receptor-regulated SMADs, SMAD2 and SMAD3.&lt;br /&gt;
A heterotrimeric complex is formed by the TGF-βR dimer and SMAD4, which moves and assemblies in the nucleus.&lt;br /&gt;
TGF-β dependent signalling can operate or subdue numerous target genes through the communication of SMADs with multiple transcription factors. There are many structures in which SMAD activities are regulated, such as SMAD2/3 nucleocytoplasmic shuttling, binding to anchor proteins, phosphorylation and Smurf (SMAD-ubiquitination-regulatory factor).  &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;24393789 &amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
&lt;br /&gt;
===Non-Canonical pathway===&lt;br /&gt;
In the non-canonical pathway, SMAD-independent pathways such as PI3K/AKT and MAPK pathways like ERK, JNK, and p38 MAPK are activated by TGF-β signalling. In addition, transversal signalling, especially at the SMAD level, allows TGF-β pathway activation to incorporate signals from integrins, Notch and Wnt dependent pathways as well as signals from cellular processes like the cell cycle or apoptosis machineries. Thus, the TGF-β signalling pathway has pleiotropic functions regulating cell growth, differentiation, apoptosis, cell motility, extracellular matrix production, angiogenesis and cellular immune response.&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;24393789 &amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
&lt;br /&gt;
==Process of TGF-β signalling pathway==&lt;br /&gt;
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TGF-β signalling pathway is required for regulation of a large number of cellular processes such as cell proliferation, invasion and inflammation. It is also activated mitogen activated protein kinase signalling. There are two main routes in TGF-β signalling; the SMAD Dependent pathway and SMAD Independent pathway.&lt;br /&gt;
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===SMAD Dependent TGF-β signalling pathway===&lt;br /&gt;
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[[File:TGF-B Signalling - Formation of Receptor Hetero-Tetramers.png|thumb|350px|SMAD Dependent TGF-β signalling pathway: Formation of Receptor Hetero-Tetramers&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;16446785&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;]]&lt;br /&gt;
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The ligands of the TGF-β superfamily form dimers that bind to heterodimeric receptor complexes composed of two type I and two type II transmembrane receptor subunits with serine/threonine kinase domains.&lt;br /&gt;
Following ligand binding on TGF-β1, the dimerized TGF-β type II receptors phosphorylates and activates the TGF-β type I receptors. In most cell types, this leads to recruitment and phosphorylation of the receptor-regulated SMAD2 and SMAD3, presented by the SMAD anchor for receptor activation. SMAD1 and SMAD5 can be activated by the TGF-β signaling depending on the Type I receptor that is expressed.&lt;br /&gt;
Heterologous complexes are formed by the phosphorylated receptor-regulated SMAD with the common-mediator SMAD, SMAD4, and successively move into the nucleus, where they accumulate and act as transcription factors participating in the regulation of target gene expression. &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;21302608&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
In addition, they recruit extra transcriptional regulators, such as DNA-binding transcription factors, co-activators and co-repressors. These control the expression of several target genes and ultimately initiates a SMAD-dependent signaling cascade that induces or represses transcriptional activity. SMADs are widely expressed in most adult tissue and cell types, indicating that the TGF-β signaling pathway is ubiquitous.&lt;br /&gt;
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===SMAD independent TGF-β signalling pathway===&lt;br /&gt;
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Rather than SMAD-mediated transciption TGF-β also has the potential to activate other signalling cascades for example the Erk, JNK and p38 MAPK kinase pathways. In some cases these pathways exhibit activation with slow kinetics which indicates SMAD-dependant mechanics, however there has also been rapid activation cases (5-15mins) suggesting independence from transcription mechanisms. Studies carried out with SMAD4 deficient cells and dominant-negative SMADS provide evidence that the MAPK pathway activation is independent from SMADS, as well as this it has be found that p38 MAPK signalling  was activated in response to mutated TGF- β type 1 receptors, which were defective in SMAD activation&amp;lt;ref name=&amp;quot;PMID14534577&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;14534577&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;.&lt;br /&gt;
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The precise mechanisms and biological consequences of these SMAD-Independent pathways (Erk, JNK, p38 MAPK) are currently poorly characterized. Ras is implicated in TGF- β induced Erk signalling as there is rapid activation of Ras by TGF- β in epithelial cells. The JNK and p38 MAPK signalling are activated by various MAPK kinase kinases (MAPKKK) TGF- β kinase 1 (TAK 1) receptor is a MAPKKK family member. Further research and identification of various interactions between the small signalling molecules and receptor proteins will provide additional insight into the precise mechanism behind the activation of MAPK pathways by TGF- β ligands &amp;lt;ref name=&amp;quot;PMID14534577&amp;quot;/&amp;gt;.&lt;br /&gt;
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==Regulation of the pathway and factors affecting it==&lt;br /&gt;
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Signalling mechanisms by TGF-β like factors are regulated in both negative and positive fashions, these are all tightly controlled through a multitude of mechanisms at extracellular, membrane, cytoplasmic and all the way to nuclear levels. Positive regulation is required to amplify signalling from TGF-β like factors, while negative regulation is important for the termination and restriction of signalling usually occurring through the mechanism of a feedback loop. There is also additional regulation of TGF-β like factors via cross-talk with other signal transduction pathways such as MAPK and JAK/STAT pathways.&amp;lt;ref name=&amp;quot;PMID10704361&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;10704361&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
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===Positive Regulation===&lt;br /&gt;
The positive regulation of TGF-β specifically the induction of ligands and their signalling components often is triggered by the action TGF-β-like factors themselves. For example NODAL, a secretory protein of the TGF-β superfamily which plays a role in early embryogenesis and acts through activin receptors and SMAD2 is induced by nodal signalling itself. In other types of cells TGF-β receptors as well as transcription factors which serve as targets for TGF-β like factors can be induced by ligand stimulation, as identified in case of transcription factor Runx3 which is induced by TGF-β and forms a complex with SMAD3 to be further activated by TGF-β. The mechanism of SMAD signalling is also positively modulated via the &amp;quot;cross-talk&amp;quot; (and hence the process of SMAD dependant TGF-β signalling) with other signalling pathways, SMADS may be activated by the tyrosine kinase receptor under specific circumstances and further positively regulate TGF-β like factors &amp;lt;ref name=&amp;quot;PMID10704361&amp;quot;/&amp;gt;.&lt;br /&gt;
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===Negative Regulation===&lt;br /&gt;
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Signalling is regulated at the cell membrane level as well as within the cytoplasm of the cell, specifically by BAMBI, a pseudo-receptor for serine/threonine kinase receptors (in Xenopus embryos however displays a high degree of sequence similarity to human BAMBI gene). This BAMBI receptor is structurally alike to the type 1 serine/threonine kinase receptor, the only difference being that it lacks an intracellular domain. BAMBI  has shown a similar expression profile to that of BMP-4 a growth factor from the TGF-β super family, and has been found to require BMP signalling for expression. BAMBI when goes on to interact with both type 1 and type 2 serine/threonine receptors and works to abolish their abilities to signal via BMPs, activins and TGF-βs, therefore it is postulated that BAMBI can be inductively expressed by BMPS to self regulate BMP signalling as well as cross-regulate signalling from other members of the TGF-β super family. &amp;lt;ref name=&amp;quot;PMID10704361&amp;quot;/&amp;gt;&lt;br /&gt;
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==Significance in Embryonic Development==&lt;br /&gt;
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TGF betas are involved in embryogenesis. During development of the embryo, members of the TGF-beta family are essential for bone and cartilage formation, mesoderm induction and patterning and dorso-ventral patterning.&lt;br /&gt;
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[[File:TGF in Cardiovascular.jpg|thumb|500px|Expression of TGF-β2 and TGF-β3 in wildtype embryonic hearts.&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;12948523&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;]]&lt;br /&gt;
===Cardiovascular Development===&lt;br /&gt;
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Genetic engineering and tissue explanation studies have revealed many roles for TGF-β ligands and their signaling molecules in development. In the embryo, TGF-β appear to be involved in epithelial-mesenchymal transformations (EMT) during the formation of endocardial cushions, and in epicardial epithelial-mesenchymal transformations essential for coronary vasculature, ventricular myocardial development and compaction. It must be noted that in the normal function of the cardiovascular system in the adult, TGF-β play significant roles in cardiac hypertrophy, vascular remodeling and regulation of the renal renin-angiotensin system.&lt;br /&gt;
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TGF-β1 is expressed in the endocardium of the developing mouse. TGF-β(-/-) mice have been found with obvious congenital cardiovascular defects, so it’s important to review its expression in the developing heart. In the blood vessels, TGF-β1 is in the intima whereas TGF-β2 and TGF-β3 are in the media and adventitia. TGF-β2 signals are found as early as embryonic day 7.25 (E7.25) &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;7687212&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; in the cardiogenic plate of the precardiac mesoderm and is later prominent in the myocardium of the aortic sac and outflow track regions. TGF-β2 protein is also found in the entire myocardium of the heart at the time when looping occurs. From E8.5-9.5 when the cushion formation process occurs, there is a particularly strong TGF-β2 expression localised to the myocardium as displayed in A, B, D and E in the figure. After cushion formation and EMT, and before myocardialization of the endocardial cushion begins, there is also strong TGF-β2 expression in the OT myocardium and in the adjacent developing cushion mesenchym. However, as myocardialization occurs, TGF-β2 expression is reduced in the myocardium so that from E12.5 onwards, it is only expressed mainly in the mesenchyme of the cushion and OT septum. As can be seen in 2GH, TGF-β2 expression remains high in the cushion mesenchyme of the OT septum. By E15.5, TGF-β1 s now the most highly expressed isoform in the endocardial cells of the myocardium. It is seen in M, N, O of the figure that the epidcardium TGF-β1 and TGF-β3 expression is higher than that of TGF-β2. Thus, it can be seen that all three TGF-β are expressed in the epicardium, and they are not expressed in an overlapping fashion.&lt;br /&gt;
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Cross talk between mesoderm and underlying endoderm is needed to form the early tubular heart. This cellular and molecular induction in the primary heart forming regions is important for the specification and differentiation of myocardial and endocardial precursor cells &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;10767078&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;. Other endoderm-derived growth factors such as BMP2, FGF2 as well as TGFBS have been implicated in this process in the avian system &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;11322300&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;. TGFB2 and TGFB receptors are expressed in the precardiac mesoderm along with BMP2 &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;7687212&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;10767078&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;10340759&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;. Members of the TGG family can serve as inductive signals at the heart forming fields for the formation of myocardial and endocardial precursor cells. Members such as Activin, BMP, Nodal, Left and others have been found to be crucial for the establishment of embryonic asymmetry &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;11836504&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;, and this asymmetry is in turn critical for heart development &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;11752633&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;.&lt;br /&gt;
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===Mammary Gland Development===&lt;br /&gt;
Similarly, all three TGF-β isoforms are expressed during all stages in the development of the mammary gland except lactation. Specifically, mouse studies have indicated key roles for TGF-β in organizing the architecture of the mammary gland, regulating stem cell kinetics, inducing apoptosis in the involuting gland and maintaining the epithelium in a functionally undifferentiated state. The TGF-β isoforms are expressed in the ductal epithelium at all stages of development and some reviews have found that there may be some isoform specificity for temporal and spatial expression patterns &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;10887507&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;. For example, TGF-β3 is the only isoform present in the endbup cap cells and myoepithelial cells. Additionally, TGF-β1 is present at high levels in the extracellular matrix that surrounds growth-quiescent ducts. As for its effect, TGF-β have been to have induce multiple responses such as inhibiting the proliferation of mammillary epithelial cells. The nature of the target cell of plays a role as TGF-β also induced apoptosis without the inhibiting the proliferation. This highlights the highly variable actions of TGF-β that are affected by cell type, environmental and cell history to name a few. Interestingly, TGF-β have been implicated as both tumour suppressors and oncogenes in mammary tumorigenesis. For example, the overexpression of TGF-β1 inhibits tumorigenesis whilst interfering with its receptor function enhances tumorigenesis, thus hinting at its tumor suppressor role &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;7753792&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;9407968&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;. On the contrary, TGF-β has exhibited the enhancement of tumorigenesis as the TGF-β ligand expression is increased in late human breast cancer. Thus, TGF-β further proves its pleiotropic behaviour as prevalent to the mammary gland as it potentially suppresses and/or promotes tumorigenesis.&lt;br /&gt;
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===Maintenance of pluripotency in hESC===&lt;br /&gt;
Many of the members within the TGF-β superfamily are enriched within stem cells suggesting they play an important role in these cells, specifically relation to their pluripotency. The ability for a cell to self renew and differentiate is known as  'stemness', the stemness of human as well as mouse embryonic stem cells can be maintained by growing a combined culture with feed cells for example, bone morphogenic protein 4 (BMP4) induces a helix-loophelix-protein known as Id which is a potent inhibitor of differentiation, since this BMP (a member of the TGF-β  superfamily) is a potent inhibitor of neural differentiation in vertebrate embryos it is thought to maintain the stemness of hESCs and thus maintain their pluripotency.&amp;lt;ref name=&amp;quot;PMID24298330 &amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;24298330 &amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
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[[File:Flowchart_for_maintenance_of_pluripotency_in_hESCs.png|550px|Flowchart for mechanism of maintenance of pluripotency in hESCs|]]&lt;br /&gt;
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The nodal secretory protein from the TGF-β superfamily were found to also contribute to mESC pluripotency, this was evidenced by microarray of Nodal deficient mice which were found to have diminished  levels of Oct3/4 (transcription factors)expression, which are markers of undifferentiated stem cells. More importantly a nuclear localization of SMAD2 was found in hESCs, this is generally induced by TGF-β, activin or nodal signalling. Further microarray analysis identified that activin supposedly maintains the pluripotency of hESCs through inducing the expression of Oct4 as well as Nanog both transcription factors which are heavily involved in the self renewal of undifferentiated embryonic stem cells. Consistent with this finding, the subsequent inhibition of SMAD2 phosphorylation resulted in the decrease of expression of the markers of undifferentiated ESCs (Oct3/4, Nanog), suggesting that these were a product of SMAD2 phosphorylation and because SMAD2 is a product of activin/nodal signalling further suggesting that activin or nodal proteins produced by ESCs function to promote the maintenance of pluripotency in hESCs.&amp;lt;ref name=&amp;quot;PMID24298330 &amp;quot;/&amp;gt;.&lt;br /&gt;
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===Formation of the palate===&lt;br /&gt;
The formation of the palate is a complex procedure which involves a multitude of events including palatal shelf growth, elevation as well as left and right side fusion, as a result of genetic defects this procedure can sometimes result in formation of a cleft palate, one of the most common genetic birth defects. There have been recent findings which indicate TGF-β signalling plays a prime role in regulating the development of the palate in regards to both the palatal mesenchyme and epithelium. In humans the palate develops from two primordiuims, the primary and secondary palate, these progress to develop into palatal shelves which are positioned vertically against each other along the sides of the tongue. Following jaw growth and descent of the tongue these primordial palates orientate themselves horizontally and begin to fuse, in the case of the hard palate the mesenchyme cells are replaced by intramembranous bone as opposed to the soft palate which remains muscular and does not undergo ossification. Alike to humans mice have a similar embryological process of palate formation with the stage of palatal fusion resulting in the formation of a medial edge epithelium (MEE) seam which eventually degrades via apoptosis, thus the mouse serves as a strong candidate to fulfil the role of a reliable animal model. &amp;lt;ref name=&amp;quot;PMID21395922 &amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;21395922&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
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With this model being established, it has been identified that TGF-β1 is strongly expressed in MEE cells just prior to adherence of the opposing palatal shelves, following this adherence the level of TGF-β1 gradually decreased until it ceased to be expressed in the mesenchymal cells, TGF-β. TGF-β2 and TGF-β3 were also expressed in the palatal mesenchymal cells during adherence and TGF-β3 was found to be continually expressed during the fusion process, it is further found that TGF-β3 played a crucial role in the cell degradation of MEE cells in addition to palatal fusion. It was found that when TGF-β3 deficient mice developed they expressed defects in MEE seam degradation and fusion.&amp;lt;ref name=&amp;quot;PMID21395922&amp;quot;/&amp;gt;.&lt;br /&gt;
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The use of these animal models to explore the role of TGF-β in cleft palate formation is fruitful in terms of identifying contributing factors and subtypes of TGF-β family members however there still remains much to discover of the molecular and cellular mechanisms  associated with palate formation.&lt;br /&gt;
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==Animal Studies==&lt;br /&gt;
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===Wound healing===&lt;br /&gt;
Animal studies have served as a useful way in providing pivotal information regarding the mechanisms of TGF-β action in wound healing. In fact, much of the current information on the action of TGF-β in wound healing has been acquired from animal studies using incisional and/or excisional wounding models and manipulation of TGF-β signalling by adding the exogenous TGF-β protein or anti-TGF-β neutralizing antibodies, or by genetic alteration in components of the TGF-β signalling pathway. This is due to the fact that animal models provide outstanding experimental methods for explaining molecular mechanisms by which TGF-β regulates wound-healing responses. Ultimately, it has led the development of therapeutic strategies focusing on how the TGF-β pathway can improve wound healing and scarring outcome.&lt;br /&gt;
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[[File:Destination filename.jpeg|thumb|550px|Excisional wound healing in Smad 3 KO mice.&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;24761336&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;]] &lt;br /&gt;
Wound healing is an intricate physiological process distinguished by the successive overlapping stages of inflammation, proliferation and maturation. It that requires numerous growth factors, one of which includes TGF-β, which has the widest range of effects. TGF-β is a multifunctional growth factor that employs pleiotropic effects on wound healing by regulating cell differentiation, extracellular matrix production and immune modulation. The role of TGF-β signalling in wound healing was explored through examination of the development of tissue-specific expression systems for overexpression or knockout of TGF-b signalling pathway components. This study also classified that molecules might serve as molecular targets for the treatment of pathological skin conditions such as chronic wounds and excessive scarring (fibrosis). &lt;br /&gt;
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Exogenously added TGF-β has the potential to promote wound healing by stimulating angiogenesis, immune cell infiltration, and ECM production, and that diminishing endogenous TGF-β action reduces scarring without adversely affecting wound-healing quality.&lt;br /&gt;
====Direct modulation of TGF-β levels====&lt;br /&gt;
Injecting TGF-β into normal skin of newborn mice led to resilient initiation of angiogenesis and fibrosis. This consisted of important new collagen synthesis combined into the matrix. As a result of these observations, people were encouraged to further study the administration of TGF-β to incisional wounds in rats. It proved that TGF-β treatment resulted in better dermal healing, as showed by prominent collagen deposition and significantly increased wound strength.&lt;br /&gt;
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Interpreting wound-healing results obtained from the animals brought about its limitations. For instance, an underlying skin abnormality was found on many of the mouse models with genetic alterations in the TGF-β signalling pathway. Also, the pleiotropic effects of TGF-β on many different cell types throughout stages of wound healing highlighted a challenge in designing particular methods in which the TGF-β signalling pathway can assist wound healing or reduce scarring. &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;24761336&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
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==Current Research==&lt;br /&gt;
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==Abnormalities of the TGF-Beta Pathway==&lt;br /&gt;
Mutations or deletion of the TGF-beta 1 or TGF-beta RII gene have been associated with multiple syndromes. In mice, defects have been found in haematopoiesis, vasculogenesis and endothelial differentiation of extra embryonic tissues, while knockout mice for SMAD2 or SMAD4 genes are more likely to have spontaneous tumour development and excessive inflammatory responses. In humans, various diseases have been linked to the mutation of the TGF-beta RII gene and SMAD4 mutation is genetically responsible for familial juvenile polyposis, an autosomal dominant disease characterized by predisposition to gastrointestinal polyps and cancers.&lt;br /&gt;
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====Cancer====&lt;br /&gt;
Alterations of this signalling pathway are common in cancer. Accessory proteins such as soluble or membrane-bound regulators or co-receptors can also affect TGF-beta signalling. A normal acting cell has a functional TGF-β signalling pathway, in which TGF- β stops proliferation of cells at G1 stage to either encourage apoptosis or induce differentiation. If the TGF-β signaling pathway becomes mutated these cells can become cancerous as the TGF-β no longer controls the cell. Uncontrolled, these cancer cells proliferate and cause surrounding fibroblasts, immune cells, endothelial and smooth-muscle cells to proliferate as well. From this increased production of TGF-β it causes angiogenesis and immunosuppression, further propogating the cancer. &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;10793168&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;The human body has an regulation against this, which is called effector T-cells which destroy cancer cells via an inflammatory reaction. However, TGF-β converts them into regulatory T-cells, which reduce the inflammatory reaction.&lt;br /&gt;
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====Marfan syndrome====&lt;br /&gt;
It is also suggested that TGF-β signaling has a large part to play in the pathogenesis of Marfan syndrome. This disease causes disproportionate height, abnormally long fingers and toes, displaced crystalline lens of the eye. Not only this but heart complications can also occur, like mitral valve prolapse or aortic enlargement. Marfan syndrome is generally known to be caused by defective creation of elastic fibres, more specifically of the glycoprotein fibrillin I. In a study done it was observed that by adding TGF-β antagonist in mice who were affected by Marfan syndrome phenotype, their symptoms were alleviated.&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;16601194&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; From this, we can see that the mechanism involved in Marfan syndrome most likely has an underlying relation with lowered sequestration of TGF-β by fibrillin.&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;16571647&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
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====Heart disease====&lt;br /&gt;
https://www.ncbi.nlm.nih.gov/pubmed/21059352 &lt;br /&gt;
The TGF-B pathway has many effects on cardiomyocytes, mesenchymal and immune cells. Not only this, but it plays a vital role in the pathogenesis of cardiac remodeling and fibrosis. Abnormalities in this pathway can cause an overexpression of TGF-β which has been associated with fibrosis and hypertrophy in mice hearts. We see that endogenous TGF-β is capable of varying matrix metabolism in a pressure-overloaded heart. In a heart which has undergone great stress, such as myocardial infarction, TGF-β is seen to inactivate inflammatory macrophages. This allows for less of an immune response but further done by it encouraging myofibroblast transdifferentiation and matrix synthesis. Thus higher levels of TGF-β is causing more inflammatory damage and further propagating the heart disease. &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;21059352&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
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====Loeys–Dietz syndrome====&lt;br /&gt;
Abnormalities of the TGF-β signaling can also cause Loeys–Dietz syndrome via mutations in the TGF-β receptor. Loeys-Deitz syndrome connective tissue disorder, mainly in children where there are aneurisms in the aorta. Not only this, but the aorta can undergo dissection in weakened layers of the aortic wall. Further, the disease is labelled into four different types, since it is an autosomal dominant genetic connective tissue disorder, the groups are categorized by their genetic cause. TGFB1 and TGFB2 cause type I and II. Normally these genes allow for the fruition of the body’s development and growth. However, when defective they create non-functioning proteins.&lt;br /&gt;
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====Obesity, Diabetes and Hepatic Steatosis====&lt;br /&gt;
Normally, TGF-β signaling pathway has a major role in maintaining a regulated level of glucose and energy under homeostatic conditions. Not only this, but TGF-B could also have a vital task in diabetic kidney disease.  &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;21723505&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
Abnormalities in TGF-β signaling in obesity is one of the reasons why there is so much inflammatory damage in the human body by obesity. [5]&lt;br /&gt;
This was shown again in a study done where mice affected were given a systemic blockade drug for the TGF-B pathway and it was observed that they were protected from obesity, diabetes and hepatic steatosis. &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;21436399&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
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====Multiple Sclerosis====&lt;br /&gt;
In Multiple Sclerosis (MS) a common observation is that patients will generally have lower levels of TGF-β, which is suspected to prevent remylentation of neurons. The reason why this is of significance is because MS results in demylentation of neurons causing severe neurological problems. TGF-β is normally responsible for regulating apoptosis of Th17 cells.&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;22942700&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;Thus when TGF-β levels decrease due to abnormalities, they are not able to be regulating Th17 cells apoptosis.[6] This then causes Th17 cells to secrete TNF-α, finally causing a demylenation of the oliodendroglial (neurons).&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;22189514&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;By having a lower amount of TGF-β we get a higer level of Th17 cells and therefore more TNFα and neuronal damage. Thus we can observe that this pathway is vital in maintaining neuronal health.&lt;br /&gt;
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==Further Reading==&lt;br /&gt;
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==Glossary==&lt;br /&gt;
{| class=&amp;quot;pretty table&amp;quot;&lt;br /&gt;
|-&lt;br /&gt;
| '''Apoptosis'''&lt;br /&gt;
| Cell death which occurs as a normal and controlled part of an organism's growth or development&lt;br /&gt;
|-&lt;br /&gt;
| '''Avian system'''&lt;br /&gt;
| Respiratory system that delivers oxygen and removes carbon dioxide&lt;br /&gt;
|-&lt;br /&gt;
| '''CCL-64'''&lt;br /&gt;
|  - mink lung epithelial cell&lt;br /&gt;
|-&lt;br /&gt;
| '''Cytokine'''&lt;br /&gt;
| A broad and loose category of small proteins that are important in cell signalling&lt;br /&gt;
|-&lt;br /&gt;
| '''Cushion Formation'''&lt;br /&gt;
| Cells in development that play a role in the formation of the heart septa&lt;br /&gt;
|-&lt;br /&gt;
| '''Dimer'''&lt;br /&gt;
| An oligomer consisting of two structurally similar monomers joined by bonds that can be either strong or weak, covalent or intermolecular&lt;br /&gt;
|-&lt;br /&gt;
| '''Homodimers'''&lt;br /&gt;
| A protein composed of two polypeptide chains that are identical in the order, number, and kind of their amino acid residues&lt;br /&gt;
|-&lt;br /&gt;
| '''Isoform'''&lt;br /&gt;
| A protein that has the same function as another protein but which is encoded by a different gene and may have small differences in its sequence&lt;br /&gt;
|-&lt;br /&gt;
| '''Ligands'''&lt;br /&gt;
| A molecule that binds to a larger molecule&lt;br /&gt;
|-&lt;br /&gt;
| '''Looping'''&lt;br /&gt;
| A morphogenetic process when the heart shape is formed by looping the embryonic tube&lt;br /&gt;
|-&lt;br /&gt;
| '''Pleiotropic'''&lt;br /&gt;
| To produce more than one type of effect&lt;br /&gt;
|-&lt;br /&gt;
| '''BMP'''&lt;br /&gt;
| Bone Morphogenetic Protein, a protein part of the TGF-β superfamily.&lt;/div&gt;</summary>
		<author><name>Z5020466</name></author>
	</entry>
	<entry>
		<id>https://embryology.med.unsw.edu.au/embryology/index.php?title=2016_Group_Project_6&amp;diff=255328</id>
		<title>2016 Group Project 6</title>
		<link rel="alternate" type="text/html" href="https://embryology.med.unsw.edu.au/embryology/index.php?title=2016_Group_Project_6&amp;diff=255328"/>
		<updated>2016-10-27T12:40:31Z</updated>

		<summary type="html">&lt;p&gt;Z5020466: /* Abnormalities of the TGF-Beta Pathway */&lt;/p&gt;
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=Transforming Growth Factor-Beta (TGF-β) Signalling Pathway=&lt;br /&gt;
&lt;br /&gt;
==Introduction==&lt;br /&gt;
&lt;br /&gt;
The transforming growth factor beta (TGF-β) is a multifunctional and pleiotropic cytokine &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;26555259&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;.&lt;br /&gt;
The TGF-β signalling pathway is crucial to the control of different biological and pathological processes, such as cellular proliferation and differentiation, angiogenesis, immune regulation/inflammation, apoptosis and cell survival. &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;17896911&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
TGF-β belongs to the Transforming Growth Factor superfamily - a large group of structually connected cell regulatory proteins. It consists of TGF-β 1, 2 AND 3, Growth Differentiation Factors (GDFs), Activins, Inhibins, Bone Morphogenetic Proteins (BMPs), Glial-derived Neurotrophic Factors (GDNFs) and Mullierian Inhibiting Substance (MIS). &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;24270394&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
Most importantly, TGF-β plays a dominant part in the development of the embryo and adult organism. &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;23926286&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
This wiki aims to present a helpful overview of the TGF-β signalling pathway, but is in no means a complete resource on all information regarding the topic. We focus on ________________&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&amp;lt;br&amp;gt;&amp;lt;br&amp;gt;&lt;br /&gt;
&amp;lt;div align=&amp;quot;center&amp;quot;&amp;gt;&amp;lt;html5media width=&amp;quot;560&amp;quot; height=&amp;quot;315&amp;quot;&amp;gt;https://www.youtube.com/watch?v=GuKjUearIUI&amp;lt;/html5media&amp;gt;&amp;lt;/div&amp;gt;&lt;br /&gt;
&amp;lt;br&amp;gt;&lt;br /&gt;
&lt;br /&gt;
==History==&lt;br /&gt;
Since the early stages of the TGF beta-signaling pathway, plenty of in-depth research and studies have been conducted that have no doubt contributed to our knowledge of the pathway today.&lt;br /&gt;
&lt;br /&gt;
SMAD signaling and the three receptors for TGF-beta are two of the many fields of interest regarding the topic. In medicine and specific areas such as cancer, cardiovascular disease and inflammatory bowel disease, there are numerous alternatives for drugs that can either heighten or suppress the activity of TGF-beta.&lt;br /&gt;
&lt;br /&gt;
{| class=&amp;quot;pretty table&amp;quot;&lt;br /&gt;
| '''1988'''&lt;br /&gt;
| The process of maturation of follicle-enclosed oocytes and cumulus-oocyte complexes was sped up by TGF beta. It was discovered that TGF beta and other growth factors are effective in vitro stimulators of oocyte maturation in the rat&lt;br /&gt;
&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;3275534&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
|-&lt;br /&gt;
| '''1989'''&lt;br /&gt;
| It was already known that TGF-beta 1 is a strong autocrine growth inhibitor of lymphocytes. Ellingsworth and colleagues found that TGF-beta 1 binds to all three cell surface-binding proteins (280-200 kD, 95-85 kD, 65 kD).&lt;br /&gt;
It was also found that these binding proteins are required for signal transduction. Overall, they discovered that the regulation of the expression of the TGF-beta 1 receptor is controlled by T cell mitogenic signals.&lt;br /&gt;
&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;2785999&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
|-&lt;br /&gt;
| '''1989'''&lt;br /&gt;
| It was made known that the properties of R mutants classify TGF-beta type I binding protein as the receptor involved in mediating TGF-beta actions on cell adhesion and proliferation&lt;br /&gt;
&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;2536702&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
|-&lt;br /&gt;
| '''1989'''&lt;br /&gt;
| Drosophil was the only member of the TGF-beta family to be identified in invertebrates &lt;br /&gt;
&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;2699859&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
|-&lt;br /&gt;
| '''1990'''&lt;br /&gt;
| It was already known that the rapid increase in number response of mink lung epithelial cells to serum and to epidermal growth factor was inhibited by TGF beta 1. A necessary component of TGF-beta 1 mediated growth inhibition in CCL64 epithelial cells is the coupling of TGF beta 1 receptor binding to G-protein activation&lt;br /&gt;
&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;2156499&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
|-&lt;br /&gt;
| '''2000'''&lt;br /&gt;
| VegT function was found to be involved in sequence with the TGF beta pathway. Therefore, TGF beta signaling may be activated by the maternally expressed VegT to participate in endoderm determination&lt;br /&gt;
&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;10640706&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
|-&lt;br /&gt;
| '''2005'''&lt;br /&gt;
| Within the TGF beta superfamily, it was found that a limited number of type I and type II receptors worked together to produce specificity of action &lt;br /&gt;
&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;15483083&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
|-&lt;br /&gt;
| '''2010'''&lt;br /&gt;
| Deregulation of TGF beta signaling was reported in human psoriasis&lt;br /&gt;
&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;19710682&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
|-&lt;br /&gt;
| '''2015'''&lt;br /&gt;
| It was known that TGF is required in the tumorigenicity and metastasis of bone tumour. A significant event in the activation of the TGF beta signaling pathway is the binding of transcription coactivator Yes-associated protein (YAP) to Smad transcription factors&lt;br /&gt;
&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;27491038&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
|}&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
[[File:Canonical and non-canonical signalling TGF beta pathways.png|thumb|500px|Flowchart showing the Canonical and Non-Canonical pathways of TGF-β signalling pathway.&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;24393789&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;]] &lt;br /&gt;
===Canonical pathway===&lt;br /&gt;
In the canonical pathway, the dormant TGF-β complex is formed when the three TGF-β ligand isoforms - TGF-B1, TGF-B2 and TGF-B3 - bind once it is synthesized as precursors. After secretion and extracellular activation, TGF-β ligands can bind to two types of receptors: the membranous TGF-β type III receptor or the TGF-β type II receptor (TGF-βRII) homodimers with high affinity. &lt;br /&gt;
TGF-βRII binding enables dimerization with TGF-β type I receptor (TGF-βRI) homodimers, as well as activation of the TGF-βRI kinase domain and signal transduction across phosphorylation of the C-terminus of receptor-regulated SMADs, SMAD2 and SMAD3.&lt;br /&gt;
A heterotrimeric complex is formed by the TGF-βR dimer and SMAD4, which moves and assemblies in the nucleus.&lt;br /&gt;
TGF-β dependent signalling can operate or subdue numerous target genes through the communication of SMADs with multiple transcription factors. There are many structures in which SMAD activities are regulated, such as SMAD2/3 nucleocytoplasmic shuttling, binding to anchor proteins, phosphorylation and Smurf (SMAD-ubiquitination-regulatory factor).  &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;24393789 &amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
&lt;br /&gt;
===Non-Canonical pathway===&lt;br /&gt;
In the non-canonical pathway, SMAD-independent pathways such as PI3K/AKT and MAPK pathways like ERK, JNK, and p38 MAPK are activated by TGF-β signalling. In addition, transversal signalling, especially at the SMAD level, allows TGF-β pathway activation to incorporate signals from integrins, Notch and Wnt dependent pathways as well as signals from cellular processes like the cell cycle or apoptosis machineries. Thus, the TGF-β signalling pathway has pleiotropic functions regulating cell growth, differentiation, apoptosis, cell motility, extracellular matrix production, angiogenesis and cellular immune response.&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;24393789 &amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
&lt;br /&gt;
==Process of TGF-β signalling pathway==&lt;br /&gt;
&lt;br /&gt;
TGF-β signalling pathway is required for regulation of a large number of cellular processes such as cell proliferation, invasion and inflammation. It is also activated mitogen activated protein kinase signalling. There are two main routes in TGF-β signalling; the SMAD Dependent pathway and SMAD Independent pathway.&lt;br /&gt;
&lt;br /&gt;
===SMAD Dependent TGF-β signalling pathway===&lt;br /&gt;
&lt;br /&gt;
[[File:TGF-B Signalling - Formation of Receptor Hetero-Tetramers.png|thumb|350px|SMAD Dependent TGF-β signalling pathway: Formation of Receptor Hetero-Tetramers&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;16446785&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;]]&lt;br /&gt;
&lt;br /&gt;
The ligands of the TGF-β superfamily form dimers that bind to heterodimeric receptor complexes composed of two type I and two type II transmembrane receptor subunits with serine/threonine kinase domains.&lt;br /&gt;
Following ligand binding on TGF-β1, the dimerized TGF-β type II receptors phosphorylates and activates the TGF-β type I receptors. In most cell types, this leads to recruitment and phosphorylation of the receptor-regulated SMAD2 and SMAD3, presented by the SMAD anchor for receptor activation. SMAD1 and SMAD5 can be activated by the TGF-β signaling depending on the Type I receptor that is expressed.&lt;br /&gt;
Heterologous complexes are formed by the phosphorylated receptor-regulated SMAD with the common-mediator SMAD, SMAD4, and successively move into the nucleus, where they accumulate and act as transcription factors participating in the regulation of target gene expression. &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;21302608&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
In addition, they recruit extra transcriptional regulators, such as DNA-binding transcription factors, co-activators and co-repressors. These control the expression of several target genes and ultimately initiates a SMAD-dependent signaling cascade that induces or represses transcriptional activity. SMADs are widely expressed in most adult tissue and cell types, indicating that the TGF-β signaling pathway is ubiquitous.&lt;br /&gt;
&lt;br /&gt;
===SMAD independent TGF-β signalling pathway===&lt;br /&gt;
&lt;br /&gt;
Rather than SMAD-mediated transciption TGF-β also has the potential to activate other signalling cascades for example the Erk, JNK and p38 MAPK kinase pathways. In some cases these pathways exhibit activation with slow kinetics which indicates SMAD-dependant mechanics, however there has also been rapid activation cases (5-15mins) suggesting independence from transcription mechanisms. Studies carried out with SMAD4 deficient cells and dominant-negative SMADS provide evidence that the MAPK pathway activation is independent from SMADS, as well as this it has be found that p38 MAPK signalling  was activated in response to mutated TGF- β type 1 receptors, which were defective in SMAD activation&amp;lt;ref name=&amp;quot;PMID14534577&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;14534577&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;.&lt;br /&gt;
&lt;br /&gt;
The precise mechanisms and biological consequences of these SMAD-Independent pathways (Erk, JNK, p38 MAPK) are currently poorly characterized. Ras is implicated in TGF- β induced Erk signalling as there is rapid activation of Ras by TGF- β in epithelial cells. The JNK and p38 MAPK signalling are activated by various MAPK kinase kinases (MAPKKK) TGF- β kinase 1 (TAK 1) receptor is a MAPKKK family member. Further research and identification of various interactions between the small signalling molecules and receptor proteins will provide additional insight into the precise mechanism behind the activation of MAPK pathways by TGF- β ligands &amp;lt;ref name=&amp;quot;PMID14534577&amp;quot;/&amp;gt;.&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
==Regulation of the pathway and factors affecting it==&lt;br /&gt;
&lt;br /&gt;
Signalling mechanisms by TGF-β like factors are regulated in both negative and positive fashions, these are all tightly controlled through a multitude of mechanisms at extracellular, membrane, cytoplasmic and all the way to nuclear levels. Positive regulation is required to amplify signalling from TGF-β like factors, while negative regulation is important for the termination and restriction of signalling usually occurring through the mechanism of a feedback loop. There is also additional regulation of TGF-β like factors via cross-talk with other signal transduction pathways such as MAPK and JAK/STAT pathways.&amp;lt;ref name=&amp;quot;PMID10704361&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;10704361&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
===Positive Regulation===&lt;br /&gt;
The positive regulation of TGF-β specifically the induction of ligands and their signalling components often is triggered by the action TGF-β-like factors themselves. For example NODAL, a secretory protein of the TGF-β superfamily which plays a role in early embryogenesis and acts through activin receptors and SMAD2 is induced by nodal signalling itself. In other types of cells TGF-β receptors as well as transcription factors which serve as targets for TGF-β like factors can be induced by ligand stimulation, as identified in case of transcription factor Runx3 which is induced by TGF-β and forms a complex with SMAD3 to be further activated by TGF-β. The mechanism of SMAD signalling is also positively modulated via the &amp;quot;cross-talk&amp;quot; (and hence the process of SMAD dependant TGF-β signalling) with other signalling pathways, SMADS may be activated by the tyrosine kinase receptor under specific circumstances and further positively regulate TGF-β like factors &amp;lt;ref name=&amp;quot;PMID10704361&amp;quot;/&amp;gt;.&lt;br /&gt;
&lt;br /&gt;
===Negative Regulation===&lt;br /&gt;
&lt;br /&gt;
Signalling is regulated at the cell membrane level as well as within the cytoplasm of the cell, specifically by BAMBI, a pseudo-receptor for serine/threonine kinase receptors (in Xenopus embryos however displays a high degree of sequence similarity to human BAMBI gene). This BAMBI receptor is structurally alike to the type 1 serine/threonine kinase receptor, the only difference being that it lacks an intracellular domain. BAMBI  has shown a similar expression profile to that of BMP-4 a growth factor from the TGF-β super family, and has been found to require BMP signalling for expression. BAMBI when goes on to interact with both type 1 and type 2 serine/threonine receptors and works to abolish their abilities to signal via BMPs, activins and TGF-βs, therefore it is postulated that BAMBI can be inductively expressed by BMPS to self regulate BMP signalling as well as cross-regulate signalling from other members of the TGF-β super family. &amp;lt;ref name=&amp;quot;PMID10704361&amp;quot;/&amp;gt;&lt;br /&gt;
&lt;br /&gt;
==Significance in Embryonic Development==&lt;br /&gt;
&lt;br /&gt;
TGF betas are involved in embryogenesis. During development of the embryo, members of the TGF-beta family are essential for bone and cartilage formation, mesoderm induction and patterning and dorso-ventral patterning.&lt;br /&gt;
&lt;br /&gt;
[[File:TGF in Cardiovascular.jpg|thumb|500px|Expression of TGF-β2 and TGF-β3 in wildtype embryonic hearts.&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;12948523&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;]]&lt;br /&gt;
===Cardiovascular Development===&lt;br /&gt;
&lt;br /&gt;
Genetic engineering and tissue explanation studies have revealed many roles for TGF-β ligands and their signaling molecules in development. In the embryo, TGF-β appear to be involved in epithelial-mesenchymal transformations (EMT) during the formation of endocardial cushions, and in epicardial epithelial-mesenchymal transformations essential for coronary vasculature, ventricular myocardial development and compaction. It must be noted that in the normal function of the cardiovascular system in the adult, TGF-β play significant roles in cardiac hypertrophy, vascular remodeling and regulation of the renal renin-angiotensin system.&lt;br /&gt;
&lt;br /&gt;
TGF-β1 is expressed in the endocardium of the developing mouse. TGF-β(-/-) mice have been found with obvious congenital cardiovascular defects, so it’s important to review its expression in the developing heart. In the blood vessels, TGF-β1 is in the intima whereas TGF-β2 and TGF-β3 are in the media and adventitia. TGF-β2 signals are found as early as embryonic day 7.25 (E7.25) &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;7687212&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; in the cardiogenic plate of the precardiac mesoderm and is later prominent in the myocardium of the aortic sac and outflow track regions. TGF-β2 protein is also found in the entire myocardium of the heart at the time when looping occurs. From E8.5-9.5 when the cushion formation process occurs, there is a particularly strong TGF-β2 expression localised to the myocardium as displayed in A, B, D and E in the figure. After cushion formation and EMT, and before myocardialization of the endocardial cushion begins, there is also strong TGF-β2 expression in the OT myocardium and in the adjacent developing cushion mesenchym. However, as myocardialization occurs, TGF-β2 expression is reduced in the myocardium so that from E12.5 onwards, it is only expressed mainly in the mesenchyme of the cushion and OT septum. As can be seen in 2GH, TGF-β2 expression remains high in the cushion mesenchyme of the OT septum. By E15.5, TGF-β1 s now the most highly expressed isoform in the endocardial cells of the myocardium. It is seen in M, N, O of the figure that the epidcardium TGF-β1 and TGF-β3 expression is higher than that of TGF-β2. Thus, it can be seen that all three TGF-β are expressed in the epicardium, and they are not expressed in an overlapping fashion.&lt;br /&gt;
&lt;br /&gt;
Cross talk between mesoderm and underlying endoderm is needed to form the early tubular heart. This cellular and molecular induction in the primary heart forming regions is important for the specification and differentiation of myocardial and endocardial precursor cells &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;10767078&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;. Other endoderm-derived growth factors such as BMP2, FGF2 as well as TGFBS have been implicated in this process in the avian system &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;11322300&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;. TGFB2 and TGFB receptors are expressed in the precardiac mesoderm along with BMP2 &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;7687212&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;10767078&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;10340759&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;. Members of the TGG family can serve as inductive signals at the heart forming fields for the formation of myocardial and endocardial precursor cells. Members such as Activin, BMP, Nodal, Left and others have been found to be crucial for the establishment of embryonic asymmetry &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;11836504&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;, and this asymmetry is in turn critical for heart development &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;11752633&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;.&lt;br /&gt;
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&lt;br /&gt;
===Mammary Gland Development===&lt;br /&gt;
Similarly, all three TGF-β isoforms are expressed during all stages in the development of the mammary gland except lactation. Specifically, mouse studies have indicated key roles for TGF-β in organizing the architecture of the mammary gland, regulating stem cell kinetics, inducing apoptosis in the involuting gland and maintaining the epithelium in a functionally undifferentiated state. The TGF-β isoforms are expressed in the ductal epithelium at all stages of development and some reviews have found that there may be some isoform specificity for temporal and spatial expression patterns &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;10887507&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;. For example, TGF-β3 is the only isoform present in the endbup cap cells and myoepithelial cells. Additionally, TGF-β1 is present at high levels in the extracellular matrix that surrounds growth-quiescent ducts. As for its effect, TGF-β have been to have induce multiple responses such as inhibiting the proliferation of mammillary epithelial cells. The nature of the target cell of plays a role as TGF-β also induced apoptosis without the inhibiting the proliferation. This highlights the highly variable actions of TGF-β that are affected by cell type, environmental and cell history to name a few. Interestingly, TGF-β have been implicated as both tumour suppressors and oncogenes in mammary tumorigenesis. For example, the overexpression of TGF-β1 inhibits tumorigenesis whilst interfering with its receptor function enhances tumorigenesis, thus hinting at its tumor suppressor role &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;7753792&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;9407968&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;. On the contrary, TGF-β has exhibited the enhancement of tumorigenesis as the TGF-β ligand expression is increased in late human breast cancer. Thus, TGF-β further proves its pleiotropic behaviour as prevalent to the mammary gland as it potentially suppresses and/or promotes tumorigenesis.&lt;br /&gt;
&lt;br /&gt;
===Maintenance of pluripotency in hESC===&lt;br /&gt;
Many of the members within the TGF-β superfamily are enriched within stem cells suggesting they play an important role in these cells, specifically relation to their pluripotency. The ability for a cell to self renew and differentiate is known as  'stemness', the stemness of human as well as mouse embryonic stem cells can be maintained by growing a combined culture with feed cells for example, bone morphogenic protein 4 (BMP4) induces a helix-loophelix-protein known as Id which is a potent inhibitor of differentiation, since this BMP (a member of the TGF-β  superfamily) is a potent inhibitor of neural differentiation in vertebrate embryos it is thought to maintain the stemness of hESCs and thus maintain their pluripotency.&amp;lt;ref name=&amp;quot;PMID24298330 &amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;24298330 &amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
[[File:Flowchart_for_maintenance_of_pluripotency_in_hESCs.png|550px|Flowchart for mechanism of maintenance of pluripotency in hESCs|]]&lt;br /&gt;
&lt;br /&gt;
The nodal secretory protein from the TGF-β superfamily were found to also contribute to mESC pluripotency, this was evidenced by microarray of Nodal deficient mice which were found to have diminished  levels of Oct3/4 (transcription factors)expression, which are markers of undifferentiated stem cells. More importantly a nuclear localization of SMAD2 was found in hESCs, this is generally induced by TGF-β, activin or nodal signalling. Further microarray analysis identified that activin supposedly maintains the pluripotency of hESCs through inducing the expression of Oct4 as well as Nanog both transcription factors which are heavily involved in the self renewal of undifferentiated embryonic stem cells. Consistent with this finding, the subsequent inhibition of SMAD2 phosphorylation resulted in the decrease of expression of the markers of undifferentiated ESCs (Oct3/4, Nanog), suggesting that these were a product of SMAD2 phosphorylation and because SMAD2 is a product of activin/nodal signalling further suggesting that activin or nodal proteins produced by ESCs function to promote the maintenance of pluripotency in hESCs.&amp;lt;ref name=&amp;quot;PMID24298330 &amp;quot;/&amp;gt;.&lt;br /&gt;
&lt;br /&gt;
===Formation of the palate===&lt;br /&gt;
The formation of the palate is a complex procedure which involves a multitude of events including palatal shelf growth, elevation as well as left and right side fusion, as a result of genetic defects this procedure can sometimes result in formation of a cleft palate, one of the most common genetic birth defects. There have been recent findings which indicate TGF-β signalling plays a prime role in regulating the development of the palate in regards to both the palatal mesenchyme and epithelium. In humans the palate develops from two primordiuims, the primary and secondary palate, these progress to develop into palatal shelves which are positioned vertically against each other along the sides of the tongue. Following jaw growth and descent of the tongue these primordial palates orientate themselves horizontally and begin to fuse, in the case of the hard palate the mesenchyme cells are replaced by intramembranous bone as opposed to the soft palate which remains muscular and does not undergo ossification. Alike to humans mice have a similar embryological process of palate formation with the stage of palatal fusion resulting in the formation of a medial edge epithelium (MEE) seam which eventually degrades via apoptosis, thus the mouse serves as a strong candidate to fulfil the role of a reliable animal model. &amp;lt;ref name=&amp;quot;PMID21395922 &amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;21395922&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
With this model being established, it has been identified that TGF-β1 is strongly expressed in MEE cells just prior to adherence of the opposing palatal shelves, following this adherence the level of TGF-β1 gradually decreased until it ceased to be expressed in the mesenchymal cells, TGF-β. TGF-β2 and TGF-β3 were also expressed in the palatal mesenchymal cells during adherence and TGF-β3 was found to be continually expressed during the fusion process, it is further found that TGF-β3 played a crucial role in the cell degradation of MEE cells in addition to palatal fusion. It was found that when TGF-β3 deficient mice developed they expressed defects in MEE seam degradation and fusion.&amp;lt;ref name=&amp;quot;PMID21395922&amp;quot;/&amp;gt;.&lt;br /&gt;
&lt;br /&gt;
The use of these animal models to explore the role of TGF-β in cleft palate formation is fruitful in terms of identifying contributing factors and subtypes of TGF-β family members however there still remains much to discover of the molecular and cellular mechanisms  associated with palate formation.&lt;br /&gt;
&lt;br /&gt;
==Animal Studies==&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
===Wound healing===&lt;br /&gt;
Animal studies have served as a useful way in providing pivotal information regarding the mechanisms of TGF-β action in wound healing. In fact, much of the current information on the action of TGF-β in wound healing has been acquired from animal studies using incisional and/or excisional wounding models and manipulation of TGF-β signalling by adding the exogenous TGF-β protein or anti-TGF-β neutralizing antibodies, or by genetic alteration in components of the TGF-β signalling pathway. This is due to the fact that animal models provide outstanding experimental methods for explaining molecular mechanisms by which TGF-β regulates wound-healing responses. Ultimately, it has led the development of therapeutic strategies focusing on how the TGF-β pathway can improve wound healing and scarring outcome.&lt;br /&gt;
&lt;br /&gt;
[[File:Destination filename.jpeg|thumb|550px|Excisional wound healing in Smad 3 KO mice.&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;24761336&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;]] &lt;br /&gt;
Wound healing is an intricate physiological process distinguished by the successive overlapping stages of inflammation, proliferation and maturation. It that requires numerous growth factors, one of which includes TGF-β, which has the widest range of effects. TGF-β is a multifunctional growth factor that employs pleiotropic effects on wound healing by regulating cell differentiation, extracellular matrix production and immune modulation. The role of TGF-β signalling in wound healing was explored through examination of the development of tissue-specific expression systems for overexpression or knockout of TGF-b signalling pathway components. This study also classified that molecules might serve as molecular targets for the treatment of pathological skin conditions such as chronic wounds and excessive scarring (fibrosis). &lt;br /&gt;
&lt;br /&gt;
Exogenously added TGF-β has the potential to promote wound healing by stimulating angiogenesis, immune cell infiltration, and ECM production, and that diminishing endogenous TGF-β action reduces scarring without adversely affecting wound-healing quality.&lt;br /&gt;
====Direct modulation of TGF-β levels====&lt;br /&gt;
Injecting TGF-β into normal skin of newborn mice led to resilient initiation of angiogenesis and fibrosis. This consisted of important new collagen synthesis combined into the matrix. As a result of these observations, people were encouraged to further study the administration of TGF-β to incisional wounds in rats. It proved that TGF-β treatment resulted in better dermal healing, as showed by prominent collagen deposition and significantly increased wound strength.&lt;br /&gt;
&lt;br /&gt;
Interpreting wound-healing results obtained from the animals brought about its limitations. For instance, an underlying skin abnormality was found on many of the mouse models with genetic alterations in the TGF-β signalling pathway. Also, the pleiotropic effects of TGF-β on many different cell types throughout stages of wound healing highlighted a challenge in designing particular methods in which the TGF-β signalling pathway can assist wound healing or reduce scarring. &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;24761336&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;
==Current Research==&lt;br /&gt;
&lt;br /&gt;
==Abnormalities of the TGF-Beta Pathway==&lt;br /&gt;
Mutations or deletion of the TGF-beta 1 or TGF-beta RII gene have been associated with multiple syndromes. In mice, defects have been found in haematopoiesis, vasculogenesis and endothelial differentiation of extra embryonic tissues, while knockout mice for SMAD2 or SMAD4 genes are more likely to have spontaneous tumour development and excessive inflammatory responses. In humans, various diseases have been linked to the mutation of the TGF-beta RII gene and SMAD4 mutation is genetically responsible for familial juvenile polyposis, an autosomal dominant disease characterized by predisposition to gastrointestinal polyps and cancers.&lt;br /&gt;
&lt;br /&gt;
====Cancer====&lt;br /&gt;
Alterations of this signalling pathway are common in cancer. Accessory proteins such as soluble or membrane-bound regulators or co-receptors can also affect TGF-beta signalling. A normal acting cell has a functional TGF-β signalling pathway, in which TGF- β stops proliferation of cells at G1 stage to either encourage apoptosis or induce differentiation. If the TGF-β signaling pathway becomes mutated these cells can become cancerous as the TGF-β no longer controls the cell. Uncontrolled, these cancer cells proliferate and cause surrounding fibroblasts, immune cells, endothelial and smooth-muscle cells to proliferate as well. From this increased production of TGF-β it causes angiogenesis and immunosuppression, further propogating the cancer. &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;10793168&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;The human body has an regulation against this, which is called effector T-cells which destroy cancer cells via an inflammatory reaction. However, TGF-β converts them into regulatory T-cells, which reduce the inflammatory reaction.&lt;br /&gt;
 Blobe GC, Schiemann WP, Lodish HF (May 2000). &amp;quot;Role of transforming growth factor beta in human disease&amp;quot;. N. Engl. J. Med. 342 (18): 1350–8. doi:10.1056/NEJM200005043421807. PMID &lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
 &lt;br /&gt;
====Marfan syndrome====&lt;br /&gt;
It is also suggested that TGF-β signaling has a large part to play in the pathogenesis of Marfan syndrome. This disease causes disproportionate height, abnormally long fingers and toes, displaced crystalline lens of the eye. Not only this but heart complications can also occur, like mitral valve prolapse or aortic enlargement. Marfan syndrome is generally known to be caused by defective creation of elastic fibres, more specifically of the glycoprotein fibrillin I. In a study done it was observed that by adding TGF-β antagonist in mice who were affected by Marfan syndrome phenotype, their symptoms were alleviated.[3] From this, we can see that the mechanism involved in Marfan syndrome most likely has an underlying relation with lowered sequestration of TGF-β by fibrillin.[4] &lt;br /&gt;
 &lt;br /&gt;
Habashi JP, Judge DP, Holm TM, et al. (April 2006). &amp;quot;Losartan, an AT1 antagonist, prevents aortic aneurysm in a mouse model of Marfan syndrome&amp;quot;. Science. 312 (5770): 117–21. doi:10.1126/science.1124287. PMC 1482474. PMID 16601194.&lt;br /&gt;
Jump up^Robinson PN, Arteaga-Solis E, Baldock C, et al. (October 2006). &amp;quot;The molecular genetics of Marfan syndrome and related disorders&amp;quot;. J. Med. Genet. 43 (10): 769–87. doi:10.1136/jmg.2005.039669. PMC 2563177. PMID 16571647.&lt;br /&gt;
&lt;br /&gt;
====Heart disease====&lt;br /&gt;
https://www.ncbi.nlm.nih.gov/pubmed/21059352 &lt;br /&gt;
The TGF-B pathway has many effects on cardiomyocytes, mesenchymal and immune cells. Not only this, but it plays a vital role in the pathogenesis of cardiac remodeling and fibrosis. Abnormalities in this pathway can cause an overexpression of TGF-β which has been associated with fibrosis and hypertrophy in mice hearts. We see that endogenous TGF-β is capable of varying matrix metabolism in a pressure-overloaded heart. In a heart which has undergone great stress, such as myocardial infarction, TGF-β is seen to inactivate inflammatory macrophages. This allows for less of an immune response but further done by it encouraging myofibroblast transdifferentiation and matrix synthesis. Thus higher levels of TGF-β is causing more inflammatory damage and further propagating the heart disease. &lt;br /&gt;
&lt;br /&gt;
====Loeys–Dietz syndrome====&lt;br /&gt;
Abnormalities of the TGF-β signaling can also cause Loeys–Dietz syndrome via mutations in the TGF-β receptor. Loeys-Deitz syndrome connective tissue disorder, mainly in children where there are aneurisms in the aorta. Not only this, but the aorta can undergo dissection in weakened layers of the aortic wall. Further, the disease is labelled into four different types, since it is an autosomal dominant genetic connective tissue disorder, the groups are categorized by their genetic cause. TGFB1 and TGFB2 cause type I and II. Normally these genes allow for the fruition of the body’s development and growth. However, when defective they create non-functioning proteins.&lt;br /&gt;
&lt;br /&gt;
====Obesity, Diabetes and Hepatic Steatosis====&lt;br /&gt;
Normally, TGF-β signaling pathway has a major role in maintaining a regulated level of glucose and energy under homeostatic conditions. Not only this, but TGF-B could also have a vital task in diabetic kidney disease.  &lt;br /&gt;
Abnormalities in TGF-β signaling in obesity is one of the reasons why there is so much inflammatory damage in the human body by obesity. [5]&lt;br /&gt;
This was shown again in a study done where mice affected were given a systemic blockade drug for the TGF-B pathway and it was observed that they were protected from obesity, diabetes and hepatic steatosis. &lt;br /&gt;
https://www.ncbi.nlm.nih.gov/pubmed/21723505 &lt;br /&gt;
Wu, Davina; Molofsky, Ari B.; Liang, Hong-Erh; Ricardo-Gonzalez, Roberto R.; Jouihan, Hani A.; Bando, Jennifer K.; Chawla, Ajay; Locksley, Richard M. (2011-04-08). &amp;quot;Eosinophils Sustain Adipose Alternatively Activated Macrophages Associated with Glucose Homeostasis&amp;quot;. Science. 332 (6026): 243–247. doi:10.1126/science.1201475. ISSN 0036-8075. PMC 3144160. PMID 21436399.&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
====Multiple Sclerosis====&lt;br /&gt;
In Multiple Sclerosis (MS) a common observation is that patients will generally have lower levels of TGF-β, which is suspected to prevent remylentation of neurons. The reason why this is of significance is because MS results in demylentation of neurons causing severe neurological problems. TGF-β is normally responsible for regulating apoptosis of Th17 cells.[6] Thus when TGF-β levels decrease due to abnormalities, they are not able to be regulating Th17 cells apoptosis.[6] This then causes Th17 cells to secrete TNF-α, finally causing a demylenation of the oliodendroglial (neurons).[7] By having a lower amount of TGF-β we get a higer level of Th17 cells and therefore more TNFα and neuronal damage. Thus we can observe that this pathway is vital in maintaining neuronal health.  &lt;br /&gt;
&lt;br /&gt;
Dobolyi A, Vincze C, Pál G, Lovas G (July 2012). &amp;quot;The neuroprotective functions of transforming growth factor Beta proteins&amp;quot;. Int J Mol Sci. 13 (7): 8219–58. doi:10.3390/ijms13078219. PMC 3430231. PMID 22942700.&lt;br /&gt;
&lt;br /&gt;
 Nakahara J, Maeda M, Aiso S, Suzuki N (February 2012). &amp;quot;Current concepts in multiple sclerosis: autoimmunity versus oligodendrogliopathy.&amp;quot;. Clinical reviews in allergy &amp;amp; immunology. 42 (1): 26–34. doi:10.1007/s12016-011-8287-6. PMID 22189514.&lt;br /&gt;
&lt;br /&gt;
==Further Reading==&lt;br /&gt;
&lt;br /&gt;
==Glossary==&lt;br /&gt;
{| class=&amp;quot;pretty table&amp;quot;&lt;br /&gt;
|-&lt;br /&gt;
| '''Apoptosis'''&lt;br /&gt;
| Cell death which occurs as a normal and controlled part of an organism's growth or development&lt;br /&gt;
|-&lt;br /&gt;
| '''Avian system'''&lt;br /&gt;
| Respiratory system that delivers oxygen and removes carbon dioxide&lt;br /&gt;
|-&lt;br /&gt;
| '''CCL-64'''&lt;br /&gt;
|  - mink lung epithelial cell&lt;br /&gt;
|-&lt;br /&gt;
| '''Cytokine'''&lt;br /&gt;
| A broad and loose category of small proteins that are important in cell signalling&lt;br /&gt;
|-&lt;br /&gt;
| '''Cushion Formation'''&lt;br /&gt;
| Cells in development that play a role in the formation of the heart septa&lt;br /&gt;
|-&lt;br /&gt;
| '''Dimer'''&lt;br /&gt;
| An oligomer consisting of two structurally similar monomers joined by bonds that can be either strong or weak, covalent or intermolecular&lt;br /&gt;
|-&lt;br /&gt;
| '''Homodimers'''&lt;br /&gt;
| A protein composed of two polypeptide chains that are identical in the order, number, and kind of their amino acid residues&lt;br /&gt;
|-&lt;br /&gt;
| '''Isoform'''&lt;br /&gt;
| A protein that has the same function as another protein but which is encoded by a different gene and may have small differences in its sequence&lt;br /&gt;
|-&lt;br /&gt;
| '''Ligands'''&lt;br /&gt;
| A molecule that binds to a larger molecule&lt;br /&gt;
|-&lt;br /&gt;
| '''Looping'''&lt;br /&gt;
| A morphogenetic process when the heart shape is formed by looping the embryonic tube&lt;br /&gt;
|-&lt;br /&gt;
| '''Pleiotropic'''&lt;br /&gt;
| To produce more than one type of effect&lt;/div&gt;</summary>
		<author><name>Z5020466</name></author>
	</entry>
	<entry>
		<id>https://embryology.med.unsw.edu.au/embryology/index.php?title=2016_Group_Project_6&amp;diff=255324</id>
		<title>2016 Group Project 6</title>
		<link rel="alternate" type="text/html" href="https://embryology.med.unsw.edu.au/embryology/index.php?title=2016_Group_Project_6&amp;diff=255324"/>
		<updated>2016-10-27T12:34:42Z</updated>

		<summary type="html">&lt;p&gt;Z5020466: /* Abnormalities of the TGF-Beta Pathway */&lt;/p&gt;
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&amp;lt;!-- Do not delete the above template from the Group project page. --&amp;gt;&lt;br /&gt;
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=Transforming Growth Factor-Beta (TGF-β) Signalling Pathway=&lt;br /&gt;
&lt;br /&gt;
==Introduction==&lt;br /&gt;
&lt;br /&gt;
The transforming growth factor beta (TGF-β) is a multifunctional and pleiotropic cytokine &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;26555259&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;.&lt;br /&gt;
The TGF-β signalling pathway is crucial to the control of different biological and pathological processes, such as cellular proliferation and differentiation, angiogenesis, immune regulation/inflammation, apoptosis and cell survival. &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;17896911&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
TGF-β belongs to the Transforming Growth Factor superfamily - a large group of structually connected cell regulatory proteins. It consists of TGF-β 1, 2 AND 3, Growth Differentiation Factors (GDFs), Activins, Inhibins, Bone Morphogenetic Proteins (BMPs), Glial-derived Neurotrophic Factors (GDNFs) and Mullierian Inhibiting Substance (MIS). &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;24270394&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
Most importantly, TGF-β plays a dominant part in the development of the embryo and adult organism. &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;23926286&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
This wiki aims to present a helpful overview of the TGF-β signalling pathway, but is in no means a complete resource on all information regarding the topic. We focus on ________________&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
&amp;lt;br&amp;gt;&amp;lt;br&amp;gt;&lt;br /&gt;
&amp;lt;div align=&amp;quot;center&amp;quot;&amp;gt;&amp;lt;html5media width=&amp;quot;560&amp;quot; height=&amp;quot;315&amp;quot;&amp;gt;https://www.youtube.com/watch?v=GuKjUearIUI&amp;lt;/html5media&amp;gt;&amp;lt;/div&amp;gt;&lt;br /&gt;
&amp;lt;br&amp;gt;&lt;br /&gt;
&lt;br /&gt;
==History==&lt;br /&gt;
Since the early stages of the TGF beta-signaling pathway, plenty of in-depth research and studies have been conducted that have no doubt contributed to our knowledge of the pathway today.&lt;br /&gt;
&lt;br /&gt;
SMAD signaling and the three receptors for TGF-beta are two of the many fields of interest regarding the topic. In medicine and specific areas such as cancer, cardiovascular disease and inflammatory bowel disease, there are numerous alternatives for drugs that can either heighten or suppress the activity of TGF-beta.&lt;br /&gt;
&lt;br /&gt;
{| class=&amp;quot;pretty table&amp;quot;&lt;br /&gt;
| '''1988'''&lt;br /&gt;
| The process of maturation of follicle-enclosed oocytes and cumulus-oocyte complexes was sped up by TGF beta. It was discovered that TGF beta and other growth factors are effective in vitro stimulators of oocyte maturation in the rat&lt;br /&gt;
&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;3275534&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
|-&lt;br /&gt;
| '''1989'''&lt;br /&gt;
| It was already known that TGF-beta 1 is a strong autocrine growth inhibitor of lymphocytes. Ellingsworth and colleagues found that TGF-beta 1 binds to all three cell surface-binding proteins (280-200 kD, 95-85 kD, 65 kD).&lt;br /&gt;
It was also found that these binding proteins are required for signal transduction. Overall, they discovered that the regulation of the expression of the TGF-beta 1 receptor is controlled by T cell mitogenic signals.&lt;br /&gt;
&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;2785999&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
|-&lt;br /&gt;
| '''1989'''&lt;br /&gt;
| It was made known that the properties of R mutants classify TGF-beta type I binding protein as the receptor involved in mediating TGF-beta actions on cell adhesion and proliferation&lt;br /&gt;
&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;2536702&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
|-&lt;br /&gt;
| '''1989'''&lt;br /&gt;
| Drosophil was the only member of the TGF-beta family to be identified in invertebrates &lt;br /&gt;
&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;2699859&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
|-&lt;br /&gt;
| '''1990'''&lt;br /&gt;
| It was already known that the rapid increase in number response of mink lung epithelial cells to serum and to epidermal growth factor was inhibited by TGF beta 1. A necessary component of TGF-beta 1 mediated growth inhibition in CCL64 epithelial cells is the coupling of TGF beta 1 receptor binding to G-protein activation&lt;br /&gt;
&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;2156499&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
|-&lt;br /&gt;
| '''2000'''&lt;br /&gt;
| VegT function was found to be involved in sequence with the TGF beta pathway. Therefore, TGF beta signaling may be activated by the maternally expressed VegT to participate in endoderm determination&lt;br /&gt;
&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;10640706&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
|-&lt;br /&gt;
| '''2005'''&lt;br /&gt;
| Within the TGF beta superfamily, it was found that a limited number of type I and type II receptors worked together to produce specificity of action &lt;br /&gt;
&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;15483083&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
|-&lt;br /&gt;
| '''2010'''&lt;br /&gt;
| Deregulation of TGF beta signaling was reported in human psoriasis&lt;br /&gt;
&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;19710682&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
|-&lt;br /&gt;
| '''2015'''&lt;br /&gt;
| It was known that TGF is required in the tumorigenicity and metastasis of bone tumour. A significant event in the activation of the TGF beta signaling pathway is the binding of transcription coactivator Yes-associated protein (YAP) to Smad transcription factors&lt;br /&gt;
&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;27491038&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
|}&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
[[File:Canonical and non-canonical signalling TGF beta pathways.png|thumb|500px|Flowchart showing the Canonical and Non-Canonical pathways of TGF-β signalling pathway.&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;24393789&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;]] &lt;br /&gt;
===Canonical pathway===&lt;br /&gt;
In the canonical pathway, the dormant TGF-β complex is formed when the three TGF-β ligand isoforms - TGF-B1, TGF-B2 and TGF-B3 - bind once it is synthesized as precursors. After secretion and extracellular activation, TGF-β ligands can bind to two types of receptors: the membranous TGF-β type III receptor or the TGF-β type II receptor (TGF-βRII) homodimers with high affinity. &lt;br /&gt;
TGF-βRII binding enables dimerization with TGF-β type I receptor (TGF-βRI) homodimers, as well as activation of the TGF-βRI kinase domain and signal transduction across phosphorylation of the C-terminus of receptor-regulated SMADs, SMAD2 and SMAD3.&lt;br /&gt;
A heterotrimeric complex is formed by the TGF-βR dimer and SMAD4, which moves and assemblies in the nucleus.&lt;br /&gt;
TGF-β dependent signalling can operate or subdue numerous target genes through the communication of SMADs with multiple transcription factors. There are many structures in which SMAD activities are regulated, such as SMAD2/3 nucleocytoplasmic shuttling, binding to anchor proteins, phosphorylation and Smurf (SMAD-ubiquitination-regulatory factor).  &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;24393789 &amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
&lt;br /&gt;
===Non-Canonical pathway===&lt;br /&gt;
In the non-canonical pathway, SMAD-independent pathways such as PI3K/AKT and MAPK pathways like ERK, JNK, and p38 MAPK are activated by TGF-β signalling. In addition, transversal signalling, especially at the SMAD level, allows TGF-β pathway activation to incorporate signals from integrins, Notch and Wnt dependent pathways as well as signals from cellular processes like the cell cycle or apoptosis machineries. Thus, the TGF-β signalling pathway has pleiotropic functions regulating cell growth, differentiation, apoptosis, cell motility, extracellular matrix production, angiogenesis and cellular immune response.&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;24393789 &amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
&lt;br /&gt;
==Process of TGF-β signalling pathway==&lt;br /&gt;
&lt;br /&gt;
TGF-β signalling pathway is required for regulation of a large number of cellular processes such as cell proliferation, invasion and inflammation. It is also activated mitogen activated protein kinase signalling. There are two main routes in TGF-β signalling; the SMAD Dependent pathway and SMAD Independent pathway.&lt;br /&gt;
&lt;br /&gt;
===SMAD Dependent TGF-β signalling pathway===&lt;br /&gt;
&lt;br /&gt;
[[File:TGF-B Signalling - Formation of Receptor Hetero-Tetramers.png|thumb|350px|SMAD Dependent TGF-β signalling pathway: Formation of Receptor Hetero-Tetramers&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;16446785&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;]]&lt;br /&gt;
&lt;br /&gt;
The ligands of the TGF-β superfamily form dimers that bind to heterodimeric receptor complexes composed of two type I and two type II transmembrane receptor subunits with serine/threonine kinase domains.&lt;br /&gt;
Following ligand binding on TGF-β1, the dimerized TGF-β type II receptors phosphorylates and activates the TGF-β type I receptors. In most cell types, this leads to recruitment and phosphorylation of the receptor-regulated SMAD2 and SMAD3, presented by the SMAD anchor for receptor activation. SMAD1 and SMAD5 can be activated by the TGF-β signaling depending on the Type I receptor that is expressed.&lt;br /&gt;
Heterologous complexes are formed by the phosphorylated receptor-regulated SMAD with the common-mediator SMAD, SMAD4, and successively move into the nucleus, where they accumulate and act as transcription factors participating in the regulation of target gene expression. &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;21302608&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
In addition, they recruit extra transcriptional regulators, such as DNA-binding transcription factors, co-activators and co-repressors. These control the expression of several target genes and ultimately initiates a SMAD-dependent signaling cascade that induces or represses transcriptional activity. SMADs are widely expressed in most adult tissue and cell types, indicating that the TGF-β signaling pathway is ubiquitous.&lt;br /&gt;
&lt;br /&gt;
===SMAD independent TGF-β signalling pathway===&lt;br /&gt;
&lt;br /&gt;
Rather than SMAD-mediated transciption TGF-β also has the potential to activate other signalling cascades for example the Erk, JNK and p38 MAPK kinase pathways. In some cases these pathways exhibit activation with slow kinetics which indicates SMAD-dependant mechanics, however there has also been rapid activation cases (5-15mins) suggesting independence from transcription mechanisms. Studies carried out with SMAD4 deficient cells and dominant-negative SMADS provide evidence that the MAPK pathway activation is independent from SMADS, as well as this it has be found that p38 MAPK signalling  was activated in response to mutated TGF- β type 1 receptors, which were defective in SMAD activation&amp;lt;ref name=&amp;quot;PMID14534577&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;14534577&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;.&lt;br /&gt;
&lt;br /&gt;
The precise mechanisms and biological consequences of these SMAD-Independent pathways (Erk, JNK, p38 MAPK) are currently poorly characterized. Ras is implicated in TGF- β induced Erk signalling as there is rapid activation of Ras by TGF- β in epithelial cells. The JNK and p38 MAPK signalling are activated by various MAPK kinase kinases (MAPKKK) TGF- β kinase 1 (TAK 1) receptor is a MAPKKK family member. Further research and identification of various interactions between the small signalling molecules and receptor proteins will provide additional insight into the precise mechanism behind the activation of MAPK pathways by TGF- β ligands &amp;lt;ref name=&amp;quot;PMID14534577&amp;quot;/&amp;gt;.&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
==Regulation of the pathway and factors affecting it==&lt;br /&gt;
&lt;br /&gt;
Signalling mechanisms by TGF-β like factors are regulated in both negative and positive fashions, these are all tightly controlled through a multitude of mechanisms at extracellular, membrane, cytoplasmic and all the way to nuclear levels. Positive regulation is required to amplify signalling from TGF-β like factors, while negative regulation is important for the termination and restriction of signalling usually occurring through the mechanism of a feedback loop. There is also additional regulation of TGF-β like factors via cross-talk with other signal transduction pathways such as MAPK and JAK/STAT pathways.&amp;lt;ref name=&amp;quot;PMID10704361&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;10704361&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
===Positive Regulation===&lt;br /&gt;
The positive regulation of TGF-β specifically the induction of ligands and their signalling components often is triggered by the action TGF-β-like factors themselves. For example NODAL, a secretory protein of the TGF-β superfamily which plays a role in early embryogenesis and acts through activin receptors and SMAD2 is induced by nodal signalling itself. In other types of cells TGF-β receptors as well as transcription factors which serve as targets for TGF-β like factors can be induced by ligand stimulation, as identified in case of transcription factor Runx3 which is induced by TGF-β and forms a complex with SMAD3 to be further activated by TGF-β. The mechanism of SMAD signalling is also positively modulated via the &amp;quot;cross-talk&amp;quot; (and hence the process of SMAD dependant TGF-β signalling) with other signalling pathways, SMADS may be activated by the tyrosine kinase receptor under specific circumstances and further positively regulate TGF-β like factors &amp;lt;ref name=&amp;quot;PMID10704361&amp;quot;/&amp;gt;.&lt;br /&gt;
&lt;br /&gt;
===Negative Regulation===&lt;br /&gt;
&lt;br /&gt;
Signalling is regulated at the cell membrane level as well as within the cytoplasm of the cell, specifically by BAMBI, a pseudo-receptor for serine/threonine kinase receptors (in Xenopus embryos however displays a high degree of sequence similarity to human BAMBI gene). This BAMBI receptor is structurally alike to the type 1 serine/threonine kinase receptor, the only difference being that it lacks an intracellular domain. BAMBI  has shown a similar expression profile to that of BMP-4 a growth factor from the TGF-β super family, and has been found to require BMP signalling for expression. BAMBI when goes on to interact with both type 1 and type 2 serine/threonine receptors and works to abolish their abilities to signal via BMPs, activins and TGF-βs, therefore it is postulated that BAMBI can be inductively expressed by BMPS to self regulate BMP signalling as well as cross-regulate signalling from other members of the TGF-β super family. &amp;lt;ref name=&amp;quot;PMID10704361&amp;quot;/&amp;gt;&lt;br /&gt;
&lt;br /&gt;
==Significance in Embryonic Development==&lt;br /&gt;
&lt;br /&gt;
TGF betas are involved in embryogenesis. During development of the embryo, members of the TGF-beta family are essential for bone and cartilage formation, mesoderm induction and patterning and dorso-ventral patterning.&lt;br /&gt;
&lt;br /&gt;
[[File:TGF in Cardiovascular.jpg|thumb|500px|Expression of TGF-β2 and TGF-β3 in wildtype embryonic hearts.&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;12948523&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;]]&lt;br /&gt;
===Cardiovascular Development===&lt;br /&gt;
&lt;br /&gt;
Genetic engineering and tissue explanation studies have revealed many roles for TGF-β ligands and their signaling molecules in development. In the embryo, TGF-β appear to be involved in epithelial-mesenchymal transformations (EMT) during the formation of endocardial cushions, and in epicardial epithelial-mesenchymal transformations essential for coronary vasculature, ventricular myocardial development and compaction. It must be noted that in the normal function of the cardiovascular system in the adult, TGF-β play significant roles in cardiac hypertrophy, vascular remodeling and regulation of the renal renin-angiotensin system.&lt;br /&gt;
&lt;br /&gt;
TGF-β1 is expressed in the endocardium of the developing mouse. TGF-β(-/-) mice have been found with obvious congenital cardiovascular defects, so it’s important to review its expression in the developing heart. In the blood vessels, TGF-β1 is in the intima whereas TGF-β2 and TGF-β3 are in the media and adventitia. TGF-β2 signals are found as early as embryonic day 7.25 (E7.25) &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;7687212&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; in the cardiogenic plate of the precardiac mesoderm and is later prominent in the myocardium of the aortic sac and outflow track regions. TGF-β2 protein is also found in the entire myocardium of the heart at the time when looping occurs. From E8.5-9.5 when the cushion formation process occurs, there is a particularly strong TGF-β2 expression localised to the myocardium as displayed in A, B, D and E in the figure. After cushion formation and EMT, and before myocardialization of the endocardial cushion begins, there is also strong TGF-β2 expression in the OT myocardium and in the adjacent developing cushion mesenchym. However, as myocardialization occurs, TGF-β2 expression is reduced in the myocardium so that from E12.5 onwards, it is only expressed mainly in the mesenchyme of the cushion and OT septum. As can be seen in 2GH, TGF-β2 expression remains high in the cushion mesenchyme of the OT septum. By E15.5, TGF-β1 s now the most highly expressed isoform in the endocardial cells of the myocardium. It is seen in M, N, O of the figure that the epidcardium TGF-β1 and TGF-β3 expression is higher than that of TGF-β2. Thus, it can be seen that all three TGF-β are expressed in the epicardium, and they are not expressed in an overlapping fashion.&lt;br /&gt;
&lt;br /&gt;
Cross talk between mesoderm and underlying endoderm is needed to form the early tubular heart. This cellular and molecular induction in the primary heart forming regions is important for the specification and differentiation of myocardial and endocardial precursor cells &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;10767078&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;. Other endoderm-derived growth factors such as BMP2, FGF2 as well as TGFBS have been implicated in this process in the avian system &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;11322300&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;. TGFB2 and TGFB receptors are expressed in the precardiac mesoderm along with BMP2 &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;7687212&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;10767078&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;10340759&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;. Members of the TGG family can serve as inductive signals at the heart forming fields for the formation of myocardial and endocardial precursor cells. Members such as Activin, BMP, Nodal, Left and others have been found to be crucial for the establishment of embryonic asymmetry &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;11836504&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;, and this asymmetry is in turn critical for heart development &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;11752633&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;.&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
===Mammary Gland Development===&lt;br /&gt;
Similarly, all three TGF-β isoforms are expressed during all stages in the development of the mammary gland except lactation. Specifically, mouse studies have indicated key roles for TGF-β in organizing the architecture of the mammary gland, regulating stem cell kinetics, inducing apoptosis in the involuting gland and maintaining the epithelium in a functionally undifferentiated state. The TGF-β isoforms are expressed in the ductal epithelium at all stages of development and some reviews have found that there may be some isoform specificity for temporal and spatial expression patterns &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;10887507&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;. For example, TGF-β3 is the only isoform present in the endbup cap cells and myoepithelial cells. Additionally, TGF-β1 is present at high levels in the extracellular matrix that surrounds growth-quiescent ducts. As for its effect, TGF-β have been to have induce multiple responses such as inhibiting the proliferation of mammillary epithelial cells. The nature of the target cell of plays a role as TGF-β also induced apoptosis without the inhibiting the proliferation. This highlights the highly variable actions of TGF-β that are affected by cell type, environmental and cell history to name a few. Interestingly, TGF-β have been implicated as both tumour suppressors and oncogenes in mammary tumorigenesis. For example, the overexpression of TGF-β1 inhibits tumorigenesis whilst interfering with its receptor function enhances tumorigenesis, thus hinting at its tumor suppressor role &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;7753792&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;9407968&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;. On the contrary, TGF-β has exhibited the enhancement of tumorigenesis as the TGF-β ligand expression is increased in late human breast cancer. Thus, TGF-β further proves its pleiotropic behaviour as prevalent to the mammary gland as it potentially suppresses and/or promotes tumorigenesis.&lt;br /&gt;
&lt;br /&gt;
===Maintenance of pluripotency in hESC===&lt;br /&gt;
Many of the members within the TGF-β superfamily are enriched within stem cells suggesting they play an important role in these cells, specifically relation to their pluripotency. The ability for a cell to self renew and differentiate is known as  'stemness', the stemness of human as well as mouse embryonic stem cells can be maintained by growing a combined culture with feed cells for example, bone morphogenic protein 4 (BMP4) induces a helix-loophelix-protein known as Id which is a potent inhibitor of differentiation, since this BMP (a member of the TGF-β  superfamily) is a potent inhibitor of neural differentiation in vertebrate embryos it is thought to maintain the stemness of hESCs and thus maintain their pluripotency.&amp;lt;ref name=&amp;quot;PMID24298330 &amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;24298330 &amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
[[File:Flowchart_for_maintenance_of_pluripotency_in_hESCs.png|550px|Flowchart for mechanism of maintenance of pluripotency in hESCs|]]&lt;br /&gt;
&lt;br /&gt;
The nodal secretory protein from the TGF-β superfamily were found to also contribute to mESC pluripotency, this was evidenced by microarray of Nodal deficient mice which were found to have diminished  levels of Oct3/4 (transcription factors)expression, which are markers of undifferentiated stem cells. More importantly a nuclear localization of SMAD2 was found in hESCs, this is generally induced by TGF-β, activin or nodal signalling. Further microarray analysis identified that activin supposedly maintains the pluripotency of hESCs through inducing the expression of Oct4 as well as Nanog both transcription factors which are heavily involved in the self renewal of undifferentiated embryonic stem cells. Consistent with this finding, the subsequent inhibition of SMAD2 phosphorylation resulted in the decrease of expression of the markers of undifferentiated ESCs (Oct3/4, Nanog), suggesting that these were a product of SMAD2 phosphorylation and because SMAD2 is a product of activin/nodal signalling further suggesting that activin or nodal proteins produced by ESCs function to promote the maintenance of pluripotency in hESCs.&amp;lt;ref name=&amp;quot;PMID24298330 &amp;quot;/&amp;gt;.&lt;br /&gt;
&lt;br /&gt;
===Formation of the palate===&lt;br /&gt;
The formation of the palate is a complex procedure which involves a multitude of events including palatal shelf growth, elevation as well as left and right side fusion, as a result of genetic defects this procedure can sometimes result in formation of a cleft palate, one of the most common genetic birth defects. There have been recent findings which indicate TGF-β signalling plays a prime role in regulating the development of the palate in regards to both the palatal mesenchyme and epithelium. In humans the palate develops from two primordiuims, the primary and secondary palate, these progress to develop into palatal shelves which are positioned vertically against each other along the sides of the tongue. Following jaw growth and descent of the tongue these primordial palates orientate themselves horizontally and begin to fuse, in the case of the hard palate the mesenchyme cells are replaced by intramembranous bone as opposed to the soft palate which remains muscular and does not undergo ossification. Alike to humans mice have a similar embryological process of palate formation with the stage of palatal fusion resulting in the formation of a medial edge epithelium (MEE) seam which eventually degrades via apoptosis, thus the mouse serves as a strong candidate to fulfil the role of a reliable animal model. &amp;lt;ref name=&amp;quot;PMID21395922 &amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;21395922&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
With this model being established, it has been identified that TGF-β1 is strongly expressed in MEE cells just prior to adherence of the opposing palatal shelves, following this adherence the level of TGF-β1 gradually decreased until it ceased to be expressed in the mesenchymal cells, TGF-β. TGF-β2 and TGF-β3 were also expressed in the palatal mesenchymal cells during adherence and TGF-β3 was found to be continually expressed during the fusion process, it is further found that TGF-β3 played a crucial role in the cell degradation of MEE cells in addition to palatal fusion. It was found that when TGF-β3 deficient mice developed they expressed defects in MEE seam degradation and fusion.&amp;lt;ref name=&amp;quot;PMID21395922&amp;quot;/&amp;gt;.&lt;br /&gt;
&lt;br /&gt;
The use of these animal models to explore the role of TGF-β in cleft palate formation is fruitful in terms of identifying contributing factors and subtypes of TGF-β family members however there still remains much to discover of the molecular and cellular mechanisms  associated with palate formation.&lt;br /&gt;
&lt;br /&gt;
==Animal Studies==&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
===Wound healing===&lt;br /&gt;
Animal studies have served as a useful way in providing pivotal information regarding the mechanisms of TGF-β action in wound healing. In fact, much of the current information on the action of TGF-β in wound healing has been acquired from animal studies using incisional and/or excisional wounding models and manipulation of TGF-β signalling by adding the exogenous TGF-β protein or anti-TGF-β neutralizing antibodies, or by genetic alteration in components of the TGF-β signalling pathway. This is due to the fact that animal models provide outstanding experimental methods for explaining molecular mechanisms by which TGF-β regulates wound-healing responses. Ultimately, it has led the development of therapeutic strategies focusing on how the TGF-β pathway can improve wound healing and scarring outcome.&lt;br /&gt;
&lt;br /&gt;
[[File:Destination filename.jpeg|thumb|550px|Excisional wound healing in Smad 3 KO mice.&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;24761336&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;]] &lt;br /&gt;
Wound healing is an intricate physiological process distinguished by the successive overlapping stages of inflammation, proliferation and maturation. It that requires numerous growth factors, one of which includes TGF-β, which has the widest range of effects. TGF-β is a multifunctional growth factor that employs pleiotropic effects on wound healing by regulating cell differentiation, extracellular matrix production and immune modulation. The role of TGF-β signalling in wound healing was explored through examination of the development of tissue-specific expression systems for overexpression or knockout of TGF-b signalling pathway components. This study also classified that molecules might serve as molecular targets for the treatment of pathological skin conditions such as chronic wounds and excessive scarring (fibrosis). &lt;br /&gt;
&lt;br /&gt;
Exogenously added TGF-β has the potential to promote wound healing by stimulating angiogenesis, immune cell infiltration, and ECM production, and that diminishing endogenous TGF-β action reduces scarring without adversely affecting wound-healing quality.&lt;br /&gt;
====Direct modulation of TGF-β levels====&lt;br /&gt;
Injecting TGF-β into normal skin of newborn mice led to resilient initiation of angiogenesis and fibrosis. This consisted of important new collagen synthesis combined into the matrix. As a result of these observations, people were encouraged to further study the administration of TGF-β to incisional wounds in rats. It proved that TGF-β treatment resulted in better dermal healing, as showed by prominent collagen deposition and significantly increased wound strength.&lt;br /&gt;
&lt;br /&gt;
Interpreting wound-healing results obtained from the animals brought about its limitations. For instance, an underlying skin abnormality was found on many of the mouse models with genetic alterations in the TGF-β signalling pathway. Also, the pleiotropic effects of TGF-β on many different cell types throughout stages of wound healing highlighted a challenge in designing particular methods in which the TGF-β signalling pathway can assist wound healing or reduce scarring. &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;24761336&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;
==Current Research==&lt;br /&gt;
&lt;br /&gt;
==Abnormalities of the TGF-Beta Pathway==&lt;br /&gt;
Mutations or deletion of the TGF-beta 1 or TGF-beta RII gene have been associated with multiple syndromes. In mice, defects have been found in haematopoiesis, vasculogenesis and endothelial differentiation of extra embryonic tissues, while knockout mice for SMAD2 or SMAD4 genes are more likely to have spontaneous tumour development and excessive inflammatory responses. In humans, various diseases have been linked to the mutation of the TGF-beta RII gene and SMAD4 mutation is genetically responsible for familial juvenile polyposis, an autosomal dominant disease characterized by predisposition to gastrointestinal polyps and cancers.&lt;br /&gt;
&lt;br /&gt;
====Cancer====&lt;br /&gt;
Alterations of this signalling pathway are common in cancer. Accessory proteins such as soluble or membrane-bound regulators or co-receptors can also affect TGF-beta signalling. A normal acting cell has a functional TGF-β signalling pathway, in which TGF- β stops proliferation of cells at G1 stage to either encourage apoptosis or induce differentiation. If the TGF-β signaling pathway becomes mutated these cells can become cancerous as the TGF-β no longer controls the cell. Uncontrolled, these cancer cells proliferate and cause surrounding fibroblasts, immune cells, endothelial and smooth-muscle cells to proliferate as well. From this increased production of TGF-β it causes angiogenesis and immunosuppression, further propogating the cancer. [1] The human body has an regulation against this, which is called effector T-cells which destroy cancer cells via an inflammatory reaction. However, TGF-β converts them into regulatory T-cells, which reduce the inflammatory reaction.&lt;br /&gt;
 Blobe GC, Schiemann WP, Lodish HF (May 2000). &amp;quot;Role of transforming growth factor beta in human disease&amp;quot;. N. Engl. J. Med. 342 (18): 1350–8. doi:10.1056/NEJM200005043421807. PMID 10793168.&lt;br /&gt;
 &lt;br /&gt;
====Marfan syndrome====&lt;br /&gt;
It is also suggested that TGF-β signaling has a large part to play in the pathogenesis of Marfan syndrome. This disease causes disproportionate height, abnormally long fingers and toes, displaced crystalline lens of the eye. Not only this but heart complications can also occur, like mitral valve prolapse or aortic enlargement. Marfan syndrome is generally known to be caused by defective creation of elastic fibres, more specifically of the glycoprotein fibrillin I. In a study done it was observed that by adding TGF-β antagonist in mice who were affected by Marfan syndrome phenotype, their symptoms were alleviated.[3] From this, we can see that the mechanism involved in Marfan syndrome most likely has an underlying relation with lowered sequestration of TGF-β by fibrillin.[4] &lt;br /&gt;
 &lt;br /&gt;
Habashi JP, Judge DP, Holm TM, et al. (April 2006). &amp;quot;Losartan, an AT1 antagonist, prevents aortic aneurysm in a mouse model of Marfan syndrome&amp;quot;. Science. 312 (5770): 117–21. doi:10.1126/science.1124287. PMC 1482474. PMID 16601194.&lt;br /&gt;
Jump up^Robinson PN, Arteaga-Solis E, Baldock C, et al. (October 2006). &amp;quot;The molecular genetics of Marfan syndrome and related disorders&amp;quot;. J. Med. Genet. 43 (10): 769–87. doi:10.1136/jmg.2005.039669. PMC 2563177. PMID 16571647.&lt;br /&gt;
&lt;br /&gt;
====Heart disease====&lt;br /&gt;
https://www.ncbi.nlm.nih.gov/pubmed/21059352 &lt;br /&gt;
The TGF-B pathway has many effects on cardiomyocytes, mesenchymal and immune cells. Not only this, but it plays a vital role in the pathogenesis of cardiac remodeling and fibrosis. Abnormalities in this pathway can cause an overexpression of TGF-β which has been associated with fibrosis and hypertrophy in mice hearts. We see that endogenous TGF-β is capable of varying matrix metabolism in a pressure-overloaded heart. In a heart which has undergone great stress, such as myocardial infarction, TGF-β is seen to inactivate inflammatory macrophages. This allows for less of an immune response but further done by it encouraging myofibroblast transdifferentiation and matrix synthesis. Thus higher levels of TGF-β is causing more inflammatory damage and further propagating the heart disease. &lt;br /&gt;
&lt;br /&gt;
====Loeys–Dietz syndrome====&lt;br /&gt;
Abnormalities of the TGF-β signaling can also cause Loeys–Dietz syndrome via mutations in the TGF-β receptor. Loeys-Deitz syndrome connective tissue disorder, mainly in children where there are aneurisms in the aorta. Not only this, but the aorta can undergo dissection in weakened layers of the aortic wall. Further, the disease is labelled into four different types, since it is an autosomal dominant genetic connective tissue disorder, the groups are categorized by their genetic cause. TGFB1 and TGFB2 cause type I and II. Normally these genes allow for the fruition of the body’s development and growth. However, when defective they create non-functioning proteins.&lt;br /&gt;
&lt;br /&gt;
====Obesity, Diabetes and Hepatic Steatosis====&lt;br /&gt;
Normally, TGF-β signaling pathway has a major role in maintaining a regulated level of glucose and energy under homeostatic conditions. Not only this, but TGF-B could also have a vital task in diabetic kidney disease.  &lt;br /&gt;
Abnormalities in TGF-β signaling in obesity is one of the reasons why there is so much inflammatory damage in the human body by obesity. [5]&lt;br /&gt;
This was shown again in a study done where mice affected were given a systemic blockade drug for the TGF-B pathway and it was observed that they were protected from obesity, diabetes and hepatic steatosis. &lt;br /&gt;
https://www.ncbi.nlm.nih.gov/pubmed/21723505 &lt;br /&gt;
Wu, Davina; Molofsky, Ari B.; Liang, Hong-Erh; Ricardo-Gonzalez, Roberto R.; Jouihan, Hani A.; Bando, Jennifer K.; Chawla, Ajay; Locksley, Richard M. (2011-04-08). &amp;quot;Eosinophils Sustain Adipose Alternatively Activated Macrophages Associated with Glucose Homeostasis&amp;quot;. Science. 332 (6026): 243–247. doi:10.1126/science.1201475. ISSN 0036-8075. PMC 3144160. PMID 21436399.&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
====Multiple Sclerosis====&lt;br /&gt;
In Multiple Sclerosis (MS) a common observation is that patients will generally have lower levels of TGF-β, which is suspected to prevent remylentation of neurons. The reason why this is of significance is because MS results in demylentation of neurons causing severe neurological problems. TGF-β is normally responsible for regulating apoptosis of Th17 cells.[6] Thus when TGF-β levels decrease due to abnormalities, they are not able to be regulating Th17 cells apoptosis.[6] This then causes Th17 cells to secrete TNF-α, finally causing a demylenation of the oliodendroglial (neurons).[7] By having a lower amount of TGF-β we get a higer level of Th17 cells and therefore more TNFα and neuronal damage. Thus we can observe that this pathway is vital in maintaining neuronal health.  &lt;br /&gt;
&lt;br /&gt;
Dobolyi A, Vincze C, Pál G, Lovas G (July 2012). &amp;quot;The neuroprotective functions of transforming growth factor Beta proteins&amp;quot;. Int J Mol Sci. 13 (7): 8219–58. doi:10.3390/ijms13078219. PMC 3430231. PMID 22942700.&lt;br /&gt;
&lt;br /&gt;
 Nakahara J, Maeda M, Aiso S, Suzuki N (February 2012). &amp;quot;Current concepts in multiple sclerosis: autoimmunity versus oligodendrogliopathy.&amp;quot;. Clinical reviews in allergy &amp;amp; immunology. 42 (1): 26–34. doi:10.1007/s12016-011-8287-6. PMID 22189514.&lt;br /&gt;
&lt;br /&gt;
==Further Reading==&lt;br /&gt;
&lt;br /&gt;
==Glossary==&lt;br /&gt;
{| class=&amp;quot;pretty table&amp;quot;&lt;br /&gt;
|-&lt;br /&gt;
| '''Apoptosis'''&lt;br /&gt;
| Cell death which occurs as a normal and controlled part of an organism's growth or development&lt;br /&gt;
|-&lt;br /&gt;
| '''Avian system'''&lt;br /&gt;
| Respiratory system that delivers oxygen and removes carbon dioxide&lt;br /&gt;
|-&lt;br /&gt;
| '''CCL-64'''&lt;br /&gt;
|  - mink lung epithelial cell&lt;br /&gt;
|-&lt;br /&gt;
| '''Cytokine'''&lt;br /&gt;
| A broad and loose category of small proteins that are important in cell signalling&lt;br /&gt;
|-&lt;br /&gt;
| '''Cushion Formation'''&lt;br /&gt;
| Cells in development that play a role in the formation of the heart septa&lt;br /&gt;
|-&lt;br /&gt;
| '''Dimer'''&lt;br /&gt;
| An oligomer consisting of two structurally similar monomers joined by bonds that can be either strong or weak, covalent or intermolecular&lt;br /&gt;
|-&lt;br /&gt;
| '''Homodimers'''&lt;br /&gt;
| A protein composed of two polypeptide chains that are identical in the order, number, and kind of their amino acid residues&lt;br /&gt;
|-&lt;br /&gt;
| '''Isoform'''&lt;br /&gt;
| A protein that has the same function as another protein but which is encoded by a different gene and may have small differences in its sequence&lt;br /&gt;
|-&lt;br /&gt;
| '''Ligands'''&lt;br /&gt;
| A molecule that binds to a larger molecule&lt;br /&gt;
|-&lt;br /&gt;
| '''Looping'''&lt;br /&gt;
| A morphogenetic process when the heart shape is formed by looping the embryonic tube&lt;br /&gt;
|-&lt;br /&gt;
| '''Pleiotropic'''&lt;br /&gt;
| To produce more than one type of effect&lt;/div&gt;</summary>
		<author><name>Z5020466</name></author>
	</entry>
	<entry>
		<id>https://embryology.med.unsw.edu.au/embryology/index.php?title=2016_Group_Project_6&amp;diff=255320</id>
		<title>2016 Group Project 6</title>
		<link rel="alternate" type="text/html" href="https://embryology.med.unsw.edu.au/embryology/index.php?title=2016_Group_Project_6&amp;diff=255320"/>
		<updated>2016-10-27T12:32:18Z</updated>

		<summary type="html">&lt;p&gt;Z5020466: /* Abnormalities of the TGF-Beta Pathway */&lt;/p&gt;
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=Transforming Growth Factor-Beta (TGF-β) Signalling Pathway=&lt;br /&gt;
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==Introduction==&lt;br /&gt;
&lt;br /&gt;
The transforming growth factor beta (TGF-β) is a multifunctional and pleiotropic cytokine &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;26555259&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;.&lt;br /&gt;
The TGF-β signalling pathway is crucial to the control of different biological and pathological processes, such as cellular proliferation and differentiation, angiogenesis, immune regulation/inflammation, apoptosis and cell survival. &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;17896911&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
TGF-β belongs to the Transforming Growth Factor superfamily - a large group of structually connected cell regulatory proteins. It consists of TGF-β 1, 2 AND 3, Growth Differentiation Factors (GDFs), Activins, Inhibins, Bone Morphogenetic Proteins (BMPs), Glial-derived Neurotrophic Factors (GDNFs) and Mullierian Inhibiting Substance (MIS). &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;24270394&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
Most importantly, TGF-β plays a dominant part in the development of the embryo and adult organism. &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;23926286&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&lt;br /&gt;
This wiki aims to present a helpful overview of the TGF-β signalling pathway, but is in no means a complete resource on all information regarding the topic. We focus on ________________&lt;br /&gt;
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==History==&lt;br /&gt;
Since the early stages of the TGF beta-signaling pathway, plenty of in-depth research and studies have been conducted that have no doubt contributed to our knowledge of the pathway today.&lt;br /&gt;
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SMAD signaling and the three receptors for TGF-beta are two of the many fields of interest regarding the topic. In medicine and specific areas such as cancer, cardiovascular disease and inflammatory bowel disease, there are numerous alternatives for drugs that can either heighten or suppress the activity of TGF-beta.&lt;br /&gt;
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{| class=&amp;quot;pretty table&amp;quot;&lt;br /&gt;
| '''1988'''&lt;br /&gt;
| The process of maturation of follicle-enclosed oocytes and cumulus-oocyte complexes was sped up by TGF beta. It was discovered that TGF beta and other growth factors are effective in vitro stimulators of oocyte maturation in the rat&lt;br /&gt;
&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;3275534&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
|-&lt;br /&gt;
| '''1989'''&lt;br /&gt;
| It was already known that TGF-beta 1 is a strong autocrine growth inhibitor of lymphocytes. Ellingsworth and colleagues found that TGF-beta 1 binds to all three cell surface-binding proteins (280-200 kD, 95-85 kD, 65 kD).&lt;br /&gt;
It was also found that these binding proteins are required for signal transduction. Overall, they discovered that the regulation of the expression of the TGF-beta 1 receptor is controlled by T cell mitogenic signals.&lt;br /&gt;
&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;2785999&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
|-&lt;br /&gt;
| '''1989'''&lt;br /&gt;
| It was made known that the properties of R mutants classify TGF-beta type I binding protein as the receptor involved in mediating TGF-beta actions on cell adhesion and proliferation&lt;br /&gt;
&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;2536702&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
|-&lt;br /&gt;
| '''1989'''&lt;br /&gt;
| Drosophil was the only member of the TGF-beta family to be identified in invertebrates &lt;br /&gt;
&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;2699859&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
|-&lt;br /&gt;
| '''1990'''&lt;br /&gt;
| It was already known that the rapid increase in number response of mink lung epithelial cells to serum and to epidermal growth factor was inhibited by TGF beta 1. A necessary component of TGF-beta 1 mediated growth inhibition in CCL64 epithelial cells is the coupling of TGF beta 1 receptor binding to G-protein activation&lt;br /&gt;
&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;2156499&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
|-&lt;br /&gt;
| '''2000'''&lt;br /&gt;
| VegT function was found to be involved in sequence with the TGF beta pathway. Therefore, TGF beta signaling may be activated by the maternally expressed VegT to participate in endoderm determination&lt;br /&gt;
&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;10640706&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
|-&lt;br /&gt;
| '''2005'''&lt;br /&gt;
| Within the TGF beta superfamily, it was found that a limited number of type I and type II receptors worked together to produce specificity of action &lt;br /&gt;
&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;15483083&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
|-&lt;br /&gt;
| '''2010'''&lt;br /&gt;
| Deregulation of TGF beta signaling was reported in human psoriasis&lt;br /&gt;
&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;19710682&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
|-&lt;br /&gt;
| '''2015'''&lt;br /&gt;
| It was known that TGF is required in the tumorigenicity and metastasis of bone tumour. A significant event in the activation of the TGF beta signaling pathway is the binding of transcription coactivator Yes-associated protein (YAP) to Smad transcription factors&lt;br /&gt;
&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;27491038&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
|}&lt;br /&gt;
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[[File:Canonical and non-canonical signalling TGF beta pathways.png|thumb|500px|Flowchart showing the Canonical and Non-Canonical pathways of TGF-β signalling pathway.&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;24393789&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;]] &lt;br /&gt;
===Canonical pathway===&lt;br /&gt;
In the canonical pathway, the dormant TGF-β complex is formed when the three TGF-β ligand isoforms - TGF-B1, TGF-B2 and TGF-B3 - bind once it is synthesized as precursors. After secretion and extracellular activation, TGF-β ligands can bind to two types of receptors: the membranous TGF-β type III receptor or the TGF-β type II receptor (TGF-βRII) homodimers with high affinity. &lt;br /&gt;
TGF-βRII binding enables dimerization with TGF-β type I receptor (TGF-βRI) homodimers, as well as activation of the TGF-βRI kinase domain and signal transduction across phosphorylation of the C-terminus of receptor-regulated SMADs, SMAD2 and SMAD3.&lt;br /&gt;
A heterotrimeric complex is formed by the TGF-βR dimer and SMAD4, which moves and assemblies in the nucleus.&lt;br /&gt;
TGF-β dependent signalling can operate or subdue numerous target genes through the communication of SMADs with multiple transcription factors. There are many structures in which SMAD activities are regulated, such as SMAD2/3 nucleocytoplasmic shuttling, binding to anchor proteins, phosphorylation and Smurf (SMAD-ubiquitination-regulatory factor).  &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;24393789 &amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
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===Non-Canonical pathway===&lt;br /&gt;
In the non-canonical pathway, SMAD-independent pathways such as PI3K/AKT and MAPK pathways like ERK, JNK, and p38 MAPK are activated by TGF-β signalling. In addition, transversal signalling, especially at the SMAD level, allows TGF-β pathway activation to incorporate signals from integrins, Notch and Wnt dependent pathways as well as signals from cellular processes like the cell cycle or apoptosis machineries. Thus, the TGF-β signalling pathway has pleiotropic functions regulating cell growth, differentiation, apoptosis, cell motility, extracellular matrix production, angiogenesis and cellular immune response.&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;24393789 &amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; &lt;br /&gt;
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==Process of TGF-β signalling pathway==&lt;br /&gt;
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TGF-β signalling pathway is required for regulation of a large number of cellular processes such as cell proliferation, invasion and inflammation. It is also activated mitogen activated protein kinase signalling. There are two main routes in TGF-β signalling; the SMAD Dependent pathway and SMAD Independent pathway.&lt;br /&gt;
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===SMAD Dependent TGF-β signalling pathway===&lt;br /&gt;
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[[File:TGF-B Signalling - Formation of Receptor Hetero-Tetramers.png|thumb|350px|SMAD Dependent TGF-β signalling pathway: Formation of Receptor Hetero-Tetramers&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;16446785&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;]]&lt;br /&gt;
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The ligands of the TGF-β superfamily form dimers that bind to heterodimeric receptor complexes composed of two type I and two type II transmembrane receptor subunits with serine/threonine kinase domains.&lt;br /&gt;
Following ligand binding on TGF-β1, the dimerized TGF-β type II receptors phosphorylates and activates the TGF-β type I receptors. In most cell types, this leads to recruitment and phosphorylation of the receptor-regulated SMAD2 and SMAD3, presented by the SMAD anchor for receptor activation. SMAD1 and SMAD5 can be activated by the TGF-β signaling depending on the Type I receptor that is expressed.&lt;br /&gt;
Heterologous complexes are formed by the phosphorylated receptor-regulated SMAD with the common-mediator SMAD, SMAD4, and successively move into the nucleus, where they accumulate and act as transcription factors participating in the regulation of target gene expression. &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;21302608&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
In addition, they recruit extra transcriptional regulators, such as DNA-binding transcription factors, co-activators and co-repressors. These control the expression of several target genes and ultimately initiates a SMAD-dependent signaling cascade that induces or represses transcriptional activity. SMADs are widely expressed in most adult tissue and cell types, indicating that the TGF-β signaling pathway is ubiquitous.&lt;br /&gt;
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===SMAD independent TGF-β signalling pathway===&lt;br /&gt;
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Rather than SMAD-mediated transciption TGF-β also has the potential to activate other signalling cascades for example the Erk, JNK and p38 MAPK kinase pathways. In some cases these pathways exhibit activation with slow kinetics which indicates SMAD-dependant mechanics, however there has also been rapid activation cases (5-15mins) suggesting independence from transcription mechanisms. Studies carried out with SMAD4 deficient cells and dominant-negative SMADS provide evidence that the MAPK pathway activation is independent from SMADS, as well as this it has be found that p38 MAPK signalling  was activated in response to mutated TGF- β type 1 receptors, which were defective in SMAD activation&amp;lt;ref name=&amp;quot;PMID14534577&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;14534577&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;.&lt;br /&gt;
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The precise mechanisms and biological consequences of these SMAD-Independent pathways (Erk, JNK, p38 MAPK) are currently poorly characterized. Ras is implicated in TGF- β induced Erk signalling as there is rapid activation of Ras by TGF- β in epithelial cells. The JNK and p38 MAPK signalling are activated by various MAPK kinase kinases (MAPKKK) TGF- β kinase 1 (TAK 1) receptor is a MAPKKK family member. Further research and identification of various interactions between the small signalling molecules and receptor proteins will provide additional insight into the precise mechanism behind the activation of MAPK pathways by TGF- β ligands &amp;lt;ref name=&amp;quot;PMID14534577&amp;quot;/&amp;gt;.&lt;br /&gt;
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==Regulation of the pathway and factors affecting it==&lt;br /&gt;
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Signalling mechanisms by TGF-β like factors are regulated in both negative and positive fashions, these are all tightly controlled through a multitude of mechanisms at extracellular, membrane, cytoplasmic and all the way to nuclear levels. Positive regulation is required to amplify signalling from TGF-β like factors, while negative regulation is important for the termination and restriction of signalling usually occurring through the mechanism of a feedback loop. There is also additional regulation of TGF-β like factors via cross-talk with other signal transduction pathways such as MAPK and JAK/STAT pathways.&amp;lt;ref name=&amp;quot;PMID10704361&amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;10704361&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
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===Positive Regulation===&lt;br /&gt;
The positive regulation of TGF-β specifically the induction of ligands and their signalling components often is triggered by the action TGF-β-like factors themselves. For example NODAL, a secretory protein of the TGF-β superfamily which plays a role in early embryogenesis and acts through activin receptors and SMAD2 is induced by nodal signalling itself. In other types of cells TGF-β receptors as well as transcription factors which serve as targets for TGF-β like factors can be induced by ligand stimulation, as identified in case of transcription factor Runx3 which is induced by TGF-β and forms a complex with SMAD3 to be further activated by TGF-β. The mechanism of SMAD signalling is also positively modulated via the &amp;quot;cross-talk&amp;quot; (and hence the process of SMAD dependant TGF-β signalling) with other signalling pathways, SMADS may be activated by the tyrosine kinase receptor under specific circumstances and further positively regulate TGF-β like factors &amp;lt;ref name=&amp;quot;PMID10704361&amp;quot;/&amp;gt;.&lt;br /&gt;
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===Negative Regulation===&lt;br /&gt;
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Signalling is regulated at the cell membrane level as well as within the cytoplasm of the cell, specifically by BAMBI, a pseudo-receptor for serine/threonine kinase receptors (in Xenopus embryos however displays a high degree of sequence similarity to human BAMBI gene). This BAMBI receptor is structurally alike to the type 1 serine/threonine kinase receptor, the only difference being that it lacks an intracellular domain. BAMBI  has shown a similar expression profile to that of BMP-4 a growth factor from the TGF-β super family, and has been found to require BMP signalling for expression. BAMBI when goes on to interact with both type 1 and type 2 serine/threonine receptors and works to abolish their abilities to signal via BMPs, activins and TGF-βs, therefore it is postulated that BAMBI can be inductively expressed by BMPS to self regulate BMP signalling as well as cross-regulate signalling from other members of the TGF-β super family. &amp;lt;ref name=&amp;quot;PMID10704361&amp;quot;/&amp;gt;&lt;br /&gt;
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==Significance in Embryonic Development==&lt;br /&gt;
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TGF betas are involved in embryogenesis. During development of the embryo, members of the TGF-beta family are essential for bone and cartilage formation, mesoderm induction and patterning and dorso-ventral patterning.&lt;br /&gt;
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[[File:TGF in Cardiovascular.jpg|thumb|500px|Expression of TGF-β2 and TGF-β3 in wildtype embryonic hearts.&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;12948523&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;]]&lt;br /&gt;
===Cardiovascular Development===&lt;br /&gt;
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Genetic engineering and tissue explanation studies have revealed many roles for TGF-β ligands and their signaling molecules in development. In the embryo, TGF-β appear to be involved in epithelial-mesenchymal transformations (EMT) during the formation of endocardial cushions, and in epicardial epithelial-mesenchymal transformations essential for coronary vasculature, ventricular myocardial development and compaction. It must be noted that in the normal function of the cardiovascular system in the adult, TGF-β play significant roles in cardiac hypertrophy, vascular remodeling and regulation of the renal renin-angiotensin system.&lt;br /&gt;
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TGF-β1 is expressed in the endocardium of the developing mouse. TGF-β(-/-) mice have been found with obvious congenital cardiovascular defects, so it’s important to review its expression in the developing heart. In the blood vessels, TGF-β1 is in the intima whereas TGF-β2 and TGF-β3 are in the media and adventitia. TGF-β2 signals are found as early as embryonic day 7.25 (E7.25) &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;7687212&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt; in the cardiogenic plate of the precardiac mesoderm and is later prominent in the myocardium of the aortic sac and outflow track regions. TGF-β2 protein is also found in the entire myocardium of the heart at the time when looping occurs. From E8.5-9.5 when the cushion formation process occurs, there is a particularly strong TGF-β2 expression localised to the myocardium as displayed in A, B, D and E in the figure. After cushion formation and EMT, and before myocardialization of the endocardial cushion begins, there is also strong TGF-β2 expression in the OT myocardium and in the adjacent developing cushion mesenchym. However, as myocardialization occurs, TGF-β2 expression is reduced in the myocardium so that from E12.5 onwards, it is only expressed mainly in the mesenchyme of the cushion and OT septum. As can be seen in 2GH, TGF-β2 expression remains high in the cushion mesenchyme of the OT septum. By E15.5, TGF-β1 s now the most highly expressed isoform in the endocardial cells of the myocardium. It is seen in M, N, O of the figure that the epidcardium TGF-β1 and TGF-β3 expression is higher than that of TGF-β2. Thus, it can be seen that all three TGF-β are expressed in the epicardium, and they are not expressed in an overlapping fashion.&lt;br /&gt;
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Cross talk between mesoderm and underlying endoderm is needed to form the early tubular heart. This cellular and molecular induction in the primary heart forming regions is important for the specification and differentiation of myocardial and endocardial precursor cells &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;10767078&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;. Other endoderm-derived growth factors such as BMP2, FGF2 as well as TGFBS have been implicated in this process in the avian system &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;11322300&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;. TGFB2 and TGFB receptors are expressed in the precardiac mesoderm along with BMP2 &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;7687212&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;10767078&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;10340759&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;. Members of the TGG family can serve as inductive signals at the heart forming fields for the formation of myocardial and endocardial precursor cells. Members such as Activin, BMP, Nodal, Left and others have been found to be crucial for the establishment of embryonic asymmetry &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;11836504&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;, and this asymmetry is in turn critical for heart development &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;11752633&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;.&lt;br /&gt;
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===Mammary Gland Development===&lt;br /&gt;
Similarly, all three TGF-β isoforms are expressed during all stages in the development of the mammary gland except lactation. Specifically, mouse studies have indicated key roles for TGF-β in organizing the architecture of the mammary gland, regulating stem cell kinetics, inducing apoptosis in the involuting gland and maintaining the epithelium in a functionally undifferentiated state. The TGF-β isoforms are expressed in the ductal epithelium at all stages of development and some reviews have found that there may be some isoform specificity for temporal and spatial expression patterns &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;10887507&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;. For example, TGF-β3 is the only isoform present in the endbup cap cells and myoepithelial cells. Additionally, TGF-β1 is present at high levels in the extracellular matrix that surrounds growth-quiescent ducts. As for its effect, TGF-β have been to have induce multiple responses such as inhibiting the proliferation of mammillary epithelial cells. The nature of the target cell of plays a role as TGF-β also induced apoptosis without the inhibiting the proliferation. This highlights the highly variable actions of TGF-β that are affected by cell type, environmental and cell history to name a few. Interestingly, TGF-β have been implicated as both tumour suppressors and oncogenes in mammary tumorigenesis. For example, the overexpression of TGF-β1 inhibits tumorigenesis whilst interfering with its receptor function enhances tumorigenesis, thus hinting at its tumor suppressor role &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;7753792&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;9407968&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;. On the contrary, TGF-β has exhibited the enhancement of tumorigenesis as the TGF-β ligand expression is increased in late human breast cancer. Thus, TGF-β further proves its pleiotropic behaviour as prevalent to the mammary gland as it potentially suppresses and/or promotes tumorigenesis.&lt;br /&gt;
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===Maintenance of pluripotency in hESC===&lt;br /&gt;
Many of the members within the TGF-β superfamily are enriched within stem cells suggesting they play an important role in these cells, specifically relation to their pluripotency. The ability for a cell to self renew and differentiate is known as  'stemness', the stemness of human as well as mouse embryonic stem cells can be maintained by growing a combined culture with feed cells for example, bone morphogenic protein 4 (BMP4) induces a helix-loophelix-protein known as Id which is a potent inhibitor of differentiation, since this BMP (a member of the TGF-β  superfamily) is a potent inhibitor of neural differentiation in vertebrate embryos it is thought to maintain the stemness of hESCs and thus maintain their pluripotency.&amp;lt;ref name=&amp;quot;PMID24298330 &amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;24298330 &amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
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[[File:Flowchart_for_maintenance_of_pluripotency_in_hESCs.png|550px|Flowchart for mechanism of maintenance of pluripotency in hESCs|]]&lt;br /&gt;
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The nodal secretory protein from the TGF-β superfamily were found to also contribute to mESC pluripotency, this was evidenced by microarray of Nodal deficient mice which were found to have diminished  levels of Oct3/4 (transcription factors)expression, which are markers of undifferentiated stem cells. More importantly a nuclear localization of SMAD2 was found in hESCs, this is generally induced by TGF-β, activin or nodal signalling. Further microarray analysis identified that activin supposedly maintains the pluripotency of hESCs through inducing the expression of Oct4 as well as Nanog both transcription factors which are heavily involved in the self renewal of undifferentiated embryonic stem cells. Consistent with this finding, the subsequent inhibition of SMAD2 phosphorylation resulted in the decrease of expression of the markers of undifferentiated ESCs (Oct3/4, Nanog), suggesting that these were a product of SMAD2 phosphorylation and because SMAD2 is a product of activin/nodal signalling further suggesting that activin or nodal proteins produced by ESCs function to promote the maintenance of pluripotency in hESCs.&amp;lt;ref name=&amp;quot;PMID24298330 &amp;quot;/&amp;gt;.&lt;br /&gt;
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===Formation of the palate===&lt;br /&gt;
The formation of the palate is a complex procedure which involves a multitude of events including palatal shelf growth, elevation as well as left and right side fusion, as a result of genetic defects this procedure can sometimes result in formation of a cleft palate, one of the most common genetic birth defects. There have been recent findings which indicate TGF-β signalling plays a prime role in regulating the development of the palate in regards to both the palatal mesenchyme and epithelium. In humans the palate develops from two primordiuims, the primary and secondary palate, these progress to develop into palatal shelves which are positioned vertically against each other along the sides of the tongue. Following jaw growth and descent of the tongue these primordial palates orientate themselves horizontally and begin to fuse, in the case of the hard palate the mesenchyme cells are replaced by intramembranous bone as opposed to the soft palate which remains muscular and does not undergo ossification. Alike to humans mice have a similar embryological process of palate formation with the stage of palatal fusion resulting in the formation of a medial edge epithelium (MEE) seam which eventually degrades via apoptosis, thus the mouse serves as a strong candidate to fulfil the role of a reliable animal model. &amp;lt;ref name=&amp;quot;PMID21395922 &amp;quot;&amp;gt;&amp;lt;pubmed&amp;gt;21395922&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
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With this model being established, it has been identified that TGF-β1 is strongly expressed in MEE cells just prior to adherence of the opposing palatal shelves, following this adherence the level of TGF-β1 gradually decreased until it ceased to be expressed in the mesenchymal cells, TGF-β. TGF-β2 and TGF-β3 were also expressed in the palatal mesenchymal cells during adherence and TGF-β3 was found to be continually expressed during the fusion process, it is further found that TGF-β3 played a crucial role in the cell degradation of MEE cells in addition to palatal fusion. It was found that when TGF-β3 deficient mice developed they expressed defects in MEE seam degradation and fusion.&amp;lt;ref name=&amp;quot;PMID21395922&amp;quot;/&amp;gt;.&lt;br /&gt;
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The use of these animal models to explore the role of TGF-β in cleft palate formation is fruitful in terms of identifying contributing factors and subtypes of TGF-β family members however there still remains much to discover of the molecular and cellular mechanisms  associated with palate formation.&lt;br /&gt;
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==Animal Studies==&lt;br /&gt;
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===Wound healing===&lt;br /&gt;
Animal studies have served as a useful way in providing pivotal information regarding the mechanisms of TGF-β action in wound healing. In fact, much of the current information on the action of TGF-β in wound healing has been acquired from animal studies using incisional and/or excisional wounding models and manipulation of TGF-β signalling by adding the exogenous TGF-β protein or anti-TGF-β neutralizing antibodies, or by genetic alteration in components of the TGF-β signalling pathway. This is due to the fact that animal models provide outstanding experimental methods for explaining molecular mechanisms by which TGF-β regulates wound-healing responses. Ultimately, it has led the development of therapeutic strategies focusing on how the TGF-β pathway can improve wound healing and scarring outcome.&lt;br /&gt;
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[[File:Destination filename.jpeg|thumb|550px|Excisional wound healing in Smad 3 KO mice.&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;24761336&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;]] &lt;br /&gt;
Wound healing is an intricate physiological process distinguished by the successive overlapping stages of inflammation, proliferation and maturation. It that requires numerous growth factors, one of which includes TGF-β, which has the widest range of effects. TGF-β is a multifunctional growth factor that employs pleiotropic effects on wound healing by regulating cell differentiation, extracellular matrix production and immune modulation. The role of TGF-β signalling in wound healing was explored through examination of the development of tissue-specific expression systems for overexpression or knockout of TGF-b signalling pathway components. This study also classified that molecules might serve as molecular targets for the treatment of pathological skin conditions such as chronic wounds and excessive scarring (fibrosis). &lt;br /&gt;
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Exogenously added TGF-β has the potential to promote wound healing by stimulating angiogenesis, immune cell infiltration, and ECM production, and that diminishing endogenous TGF-β action reduces scarring without adversely affecting wound-healing quality.&lt;br /&gt;
====Direct modulation of TGF-β levels====&lt;br /&gt;
Injecting TGF-β into normal skin of newborn mice led to resilient initiation of angiogenesis and fibrosis. This consisted of important new collagen synthesis combined into the matrix. As a result of these observations, people were encouraged to further study the administration of TGF-β to incisional wounds in rats. It proved that TGF-β treatment resulted in better dermal healing, as showed by prominent collagen deposition and significantly increased wound strength.&lt;br /&gt;
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Interpreting wound-healing results obtained from the animals brought about its limitations. For instance, an underlying skin abnormality was found on many of the mouse models with genetic alterations in the TGF-β signalling pathway. Also, the pleiotropic effects of TGF-β on many different cell types throughout stages of wound healing highlighted a challenge in designing particular methods in which the TGF-β signalling pathway can assist wound healing or reduce scarring. &amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;24761336&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
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==Current Research==&lt;br /&gt;
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==Abnormalities of the TGF-Beta Pathway==&lt;br /&gt;
Mutations or deletion of the TGF-beta 1 or TGF-beta RII gene have been associated with multiple syndromes. In mice, defects have been found in haematopoiesis, vasculogenesis and endothelial differentiation of extra embryonic tissues, while knockout mice for SMAD2 or SMAD4 genes are more likely to have spontaneous tumour development and excessive inflammatory responses. In humans, various diseases have been linked to the mutation of the TGF-beta RII gene and SMAD4 mutation is genetically responsible for familial juvenile polyposis, an autosomal dominant disease characterized by predisposition to gastrointestinal polyps and cancers.&lt;br /&gt;
&lt;br /&gt;
Cancer&lt;br /&gt;
Alterations of this signalling pathway are common in cancer. Accessory proteins such as soluble or membrane-bound regulators or co-receptors can also affect TGF-beta signalling. A normal acting cell has a functional TGF-β signalling pathway, in which TGF- β stops proliferation of cells at G1 stage to either encourage apoptosis or induce differentiation. If the TGF-β signaling pathway becomes mutated these cells can become cancerous as the TGF-β no longer controls the cell. Uncontrolled, these cancer cells proliferate and cause surrounding fibroblasts, immune cells, endothelial and smooth-muscle cells to proliferate as well. From this increased production of TGF-β it causes angiogenesis and immunosuppression, further propogating the cancer. [1] The human body has an regulation against this, which is called effector T-cells which destroy cancer cells via an inflammatory reaction. However, TGF-β converts them into regulatory T-cells, which reduce the inflammatory reaction.&lt;br /&gt;
 Blobe GC, Schiemann WP, Lodish HF (May 2000). &amp;quot;Role of transforming growth factor beta in human disease&amp;quot;. N. Engl. J. Med. 342 (18): 1350–8. doi:10.1056/NEJM200005043421807. PMID 10793168.&lt;br /&gt;
 &lt;br /&gt;
Marfan syndrome&lt;br /&gt;
It is also suggested that TGF-β signaling has a large part to play in the pathogenesis of Marfan syndrome. This disease causes disproportionate height, abnormally long fingers and toes, displaced crystalline lens of the eye. Not only this but heart complications can also occur, like mitral valve prolapse or aortic enlargement. Marfan syndrome is generally known to be caused by defective creation of elastic fibres, more specifically of the glycoprotein fibrillin I. In a study done it was observed that by adding TGF-β antagonist in mice who were affected by Marfan syndrome phenotype, their symptoms were alleviated.[3] From this, we can see that the mechanism involved in Marfan syndrome most likely has an underlying relation with lowered sequestration of TGF-β by fibrillin.[4] &lt;br /&gt;
 &lt;br /&gt;
Habashi JP, Judge DP, Holm TM, et al. (April 2006). &amp;quot;Losartan, an AT1 antagonist, prevents aortic aneurysm in a mouse model of Marfan syndrome&amp;quot;. Science. 312 (5770): 117–21. doi:10.1126/science.1124287. PMC 1482474. PMID 16601194.&lt;br /&gt;
Jump up^Robinson PN, Arteaga-Solis E, Baldock C, et al. (October 2006). &amp;quot;The molecular genetics of Marfan syndrome and related disorders&amp;quot;. J. Med. Genet. 43 (10): 769–87. doi:10.1136/jmg.2005.039669. PMC 2563177. PMID 16571647.&lt;br /&gt;
&lt;br /&gt;
Heart disease&lt;br /&gt;
https://www.ncbi.nlm.nih.gov/pubmed/21059352 &lt;br /&gt;
The TGF-B pathway has many effects on cardiomyocytes, mesenchymal and immune cells. Not only this, but it plays a vital role in the pathogenesis of cardiac remodeling and fibrosis. Abnormalities in this pathway can cause an overexpression of TGF-β which has been associated with fibrosis and hypertrophy in mice hearts. We see that endogenous TGF-β is capable of varying matrix metabolism in a pressure-overloaded heart. In a heart which has undergone great stress, such as myocardial infarction, TGF-β is seen to inactivate inflammatory macrophages. This allows for less of an immune response but further done by it encouraging myofibroblast transdifferentiation and matrix synthesis. Thus higher levels of TGF-β is causing more inflammatory damage and further propagating the heart disease. &lt;br /&gt;
&lt;br /&gt;
Loeys–Dietz syndrome&lt;br /&gt;
Abnormalities of the TGF-β signaling can also cause Loeys–Dietz syndrome via mutations in the TGF-β receptor. Loeys-Deitz syndrome connective tissue disorder, mainly in children where there are aneurisms in the aorta. Not only this, but the aorta can undergo dissection in weakened layers of the aortic wall. Further, the disease is labelled into four different types, since it is an autosomal dominant genetic connective tissue disorder, the groups are categorized by their genetic cause. TGFB1 and TGFB2 cause type I and II. Normally these genes allow for the fruition of the body’s development and growth. However, when defective they create non-functioning proteins.&lt;br /&gt;
Obesity, Diabetes and Hepatic Steatosis &lt;br /&gt;
Normally, TGF-β signaling pathway has a major role in maintaining a regulated level of glucose and energy under homeostatic conditions. Not only this, but TGF-B could also have a vital task in diabetic kidney disease.  &lt;br /&gt;
Abnormalities in TGF-β signaling in obesity is one of the reasons why there is so much inflammatory damage in the human body by obesity. [5]&lt;br /&gt;
This was shown again in a study done where mice affected were given a systemic blockade drug for the TGF-B pathway and it was observed that they were protected from obesity, diabetes and hepatic steatosis. &lt;br /&gt;
https://www.ncbi.nlm.nih.gov/pubmed/21723505 &lt;br /&gt;
Wu, Davina; Molofsky, Ari B.; Liang, Hong-Erh; Ricardo-Gonzalez, Roberto R.; Jouihan, Hani A.; Bando, Jennifer K.; Chawla, Ajay; Locksley, Richard M. (2011-04-08). &amp;quot;Eosinophils Sustain Adipose Alternatively Activated Macrophages Associated with Glucose Homeostasis&amp;quot;. Science. 332 (6026): 243–247. doi:10.1126/science.1201475. ISSN 0036-8075. PMC 3144160. PMID 21436399.&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
Multiple Sclerosis&lt;br /&gt;
In Multiple Sclerosis (MS) a common observation is that patients will generally have lower levels of TGF-β, which is suspected to prevent remylentation of neurons. The reason why this is of significance is because MS results in demylentation of neurons causing severe neurological problems. TGF-β is normally responsible for regulating apoptosis of Th17 cells.[6] Thus when TGF-β levels decrease due to abnormalities, they are not able to be regulating Th17 cells apoptosis.[6] This then causes Th17 cells to secrete TNF-α, finally causing a demylenation of the oliodendroglial (neurons).[7] By having a lower amount of TGF-β we get a higer level of Th17 cells and therefore more TNFα and neuronal damage. Thus we can observe that this pathway is vital in maintaining neuronal health.  &lt;br /&gt;
&lt;br /&gt;
Dobolyi A, Vincze C, Pál G, Lovas G (July 2012). &amp;quot;The neuroprotective functions of transforming growth factor Beta proteins&amp;quot;. Int J Mol Sci. 13 (7): 8219–58. doi:10.3390/ijms13078219. PMC 3430231. PMID 22942700.&lt;br /&gt;
&lt;br /&gt;
 Nakahara J, Maeda M, Aiso S, Suzuki N (February 2012). &amp;quot;Current concepts in multiple sclerosis: autoimmunity versus oligodendrogliopathy.&amp;quot;. Clinical reviews in allergy &amp;amp; immunology. 42 (1): 26–34. doi:10.1007/s12016-011-8287-6. PMID 22189514.&lt;br /&gt;
&lt;br /&gt;
==Further Reading==&lt;br /&gt;
&lt;br /&gt;
==Glossary==&lt;br /&gt;
{| class=&amp;quot;pretty table&amp;quot;&lt;br /&gt;
|-&lt;br /&gt;
| '''Apoptosis'''&lt;br /&gt;
| Cell death which occurs as a normal and controlled part of an organism's growth or development&lt;br /&gt;
|-&lt;br /&gt;
| '''Avian system'''&lt;br /&gt;
| Respiratory system that delivers oxygen and removes carbon dioxide&lt;br /&gt;
|-&lt;br /&gt;
| '''CCL-64'''&lt;br /&gt;
|  - mink lung epithelial cell&lt;br /&gt;
|-&lt;br /&gt;
| '''Cytokine'''&lt;br /&gt;
| A broad and loose category of small proteins that are important in cell signalling&lt;br /&gt;
|-&lt;br /&gt;
| '''Cushion Formation'''&lt;br /&gt;
| Cells in development that play a role in the formation of the heart septa&lt;br /&gt;
|-&lt;br /&gt;
| '''Dimer'''&lt;br /&gt;
| An oligomer consisting of two structurally similar monomers joined by bonds that can be either strong or weak, covalent or intermolecular&lt;br /&gt;
|-&lt;br /&gt;
| '''Homodimers'''&lt;br /&gt;
| A protein composed of two polypeptide chains that are identical in the order, number, and kind of their amino acid residues&lt;br /&gt;
|-&lt;br /&gt;
| '''Isoform'''&lt;br /&gt;
| A protein that has the same function as another protein but which is encoded by a different gene and may have small differences in its sequence&lt;br /&gt;
|-&lt;br /&gt;
| '''Ligands'''&lt;br /&gt;
| A molecule that binds to a larger molecule&lt;br /&gt;
|-&lt;br /&gt;
| '''Looping'''&lt;br /&gt;
| A morphogenetic process when the heart shape is formed by looping the embryonic tube&lt;br /&gt;
|-&lt;br /&gt;
| '''Pleiotropic'''&lt;br /&gt;
| To produce more than one type of effect&lt;/div&gt;</summary>
		<author><name>Z5020466</name></author>
	</entry>
	<entry>
		<id>https://embryology.med.unsw.edu.au/embryology/index.php?title=User:Z5020466&amp;diff=249816</id>
		<title>User:Z5020466</title>
		<link rel="alternate" type="text/html" href="https://embryology.med.unsw.edu.au/embryology/index.php?title=User:Z5020466&amp;diff=249816"/>
		<updated>2016-10-07T02:53:55Z</updated>

		<summary type="html">&lt;p&gt;Z5020466: /* Lab Attendance */&lt;/p&gt;
&lt;hr /&gt;
&lt;div&gt;{{ANAT2341Student2016}}&lt;br /&gt;
&lt;br /&gt;
==Lab Attendance==&lt;br /&gt;
[[User:Z5020466|Z5020466]] ([[User talk:Z5020466|talk]]) 14:42, 12 August 2016 (AEST)&lt;br /&gt;
[[User:Z5020466|Z5020466]] ([[User talk:Z5020466|talk]]) 13:46, 26 August 2016 (AEST)&lt;br /&gt;
[[User:Z5020466|Z5020466]] ([[User talk:Z5020466|talk]]) 13:53, 7 October 2016 (AEDT)&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
===Belbin Team Roles===&lt;br /&gt;
If I’m completely honest, I think my role in group work is generally the “Co-ordinator”. I’m not too sure about my ability to step back from the ‘nitty gritty’ details and see the bigger picture. But rather I generally like to take on leadership roles and assign people tasks. That way I can do things how I like to and place people in roles that I think they would be suited to. But not only that I think to be a good leader you have to be a good worker. So I try to lead by example and not really depend on others too much so that if something has messed up, I have no one to blame but myself. This part about Co-ordinators made me chuckle. “Sometimes perceived to be manipulative and will tend to delegate all work” which is unfortunately a little true. But at the same time I’ve been open to working an equal amount as others previously as well.&lt;br /&gt;
&lt;br /&gt;
===Lecture 1: Fertilisation===&lt;br /&gt;
In my previous years in attending university I’ve completed many courses which have gone through the fertilization process such as: Evolutionary Biological Sciences, Physiology, Histology and Pathology. From having done these courses already, there were parts which were familiar to me and that I have understood before in the past. However, I still was amazed by the new refreshing things I have not yet encounter which I did during this lecture. Such as polar bodies and their role in fertilization in disposing of extra DNA. It also clarified a point which I was previously confused about on whether or not polar bodies were gametes or not. Cementing all this information and weaving it in with new learnt information has really been a beneficial experience for me, in that I’m building up on topics I thoroughly enjoy.&lt;br /&gt;
&lt;br /&gt;
==New SubHeading==&lt;br /&gt;
===External Link===&lt;br /&gt;
[http://www.smh.com.au/ SMH]&lt;br /&gt;
&lt;br /&gt;
===Internal Link===&lt;br /&gt;
[[ANAT2341 Lab 1]]&lt;br /&gt;
&lt;br /&gt;
[[ANAT2341 Lab 1|Fertilization Lab]]&lt;br /&gt;
 &lt;br /&gt;
[[Student Page]]&lt;br /&gt;
&lt;br /&gt;
==Referencing==&lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/sites/entrez?db=pubmed&amp;amp;cmd=search&amp;amp;term=fertilization fertilization]&lt;br /&gt;
&lt;br /&gt;
PMID 27486480&lt;br /&gt;
&lt;br /&gt;
==Assessment 1==&lt;br /&gt;
&amp;lt;pubmed&amp;gt;PMC3528851&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&lt;br /&gt;
The research article called &amp;quot; Tet1 controls meiosis by regulating meiotic gene expression&amp;quot; by Yamaguchi et al. (2012) aims to determine the role of ten-eleven translocation methylcytosine dioxygenase 1 (TET1) which is a member of the TET family of enzymes, in regulating meiotic gene expression and thus meiosis in mice. This study was highly useful since little is known about how the expression of meiotic genes is regulated and how their expression contributes to normal meiosis. &lt;br /&gt;
In the study they performed a whole-genome bisulphite sequencing (WGBS) analysis using an ultra-low input so that they would be able to see how Tet1 is used in the activation of meiotic genes. &lt;br /&gt;
&lt;br /&gt;
Results showed that a decreased functioning of Tet1 caused an increase in the unpaired synaptonemal complex at zygotene-stage oocyte, suggesting a synapsis-formation defect. The meiotic defects seen from Tet1 loss of function included: formation of univalent chromosome, but also homologous recombination and DNA double-strand breaks (DSBs) repair defects. These in turn caused defective meiotic prophase which caused decreased amount of oocytes and in turn reduced litter size and lowering in fertility. The study done was pivotal as it built upon past studies which have already established that DNA methylation levels of certain meiotic genes are lowered with genomic reprogramming.&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
{| width=95%&lt;br /&gt;
|-bgcolor=&amp;quot;FAF5FF&amp;quot;&lt;br /&gt;
| [mailto:m.hill@unsw.edu.au Mark Hill] 18 August 2016 - You have added the citation correctly and written a good brief summary of the article findings. &lt;br /&gt;
TET1 is part of the family of methylcytosine dioxygenases that involved in cytosine demethylation and gene activation, interesting that it has a meiotic-specific role.&lt;br /&gt;
&lt;br /&gt;
| width=100px| Assessment 5/5&lt;br /&gt;
|}&lt;/div&gt;</summary>
		<author><name>Z5020466</name></author>
	</entry>
	<entry>
		<id>https://embryology.med.unsw.edu.au/embryology/index.php?title=Talk:2016_Group_Project_5&amp;diff=249780</id>
		<title>Talk:2016 Group Project 5</title>
		<link rel="alternate" type="text/html" href="https://embryology.med.unsw.edu.au/embryology/index.php?title=Talk:2016_Group_Project_5&amp;diff=249780"/>
		<updated>2016-10-07T02:13:41Z</updated>

		<summary type="html">&lt;p&gt;Z5020466: &lt;/p&gt;
&lt;hr /&gt;
&lt;div&gt;{{ANAT2341Project2016discussionheader}}&lt;br /&gt;
=Peer Review=&lt;br /&gt;
&lt;br /&gt;
===Group 5 Peer Review===&lt;br /&gt;
Congrats Group 5 on producing a really great looking page so far! Straightaway I like that you have an introduction paragraph and that I can immediately see inclusion of tables, images, and some correct referencing. Explaining the origin of the T-box name is a great piece of background info to include (maybe make it a proper subheading though?). You’ve also touched on some of the history of the gene/signalling pathway in your paragraphs but it might be good to also present that in a brief timeline/table. Your table for T-box family features is really great - especially because of inclusion of main expression sites and the related abnormalities. Also, you have references to primary research articles so it’s good to see you’re backing up your content with accurate and relevant sources. You’ve done a really great job on exploring the animal models as well.&lt;br /&gt;
&lt;br /&gt;
Ultimately you guys have done great work so my suggestions for improving your page are mostly minor! You have a lot of PMID links just left at the end of some paragraphs so make sure you get those properly listed at the end in your reference section. If you change your pictures to thumbnails then I think they would integrate into your text better (because at the moment where they are placed breaks up the text). Also, I’m not sure if there’s a particular reason why you did this in the first place but I wouldn’t capitalise all the subheadings in the abnormalities section. And I suggest moving the ‘Ancient origins and evolution of the T-box gene family’ near the top of your page, because at the moment it seems out of place and doesn’t really flow on from discussing the abnormalities. The other thing I would say is that - if it’s possible - it would be great if you could explain more about the actual molecular pathway and include a picture of the molecules/factors involved, because at the moment you’ve only described it in the context of different TBX genes being expressed in each developmental role. I think especially if you have an image of the structure of some of the different proteins, transcription factors, etc. then it would really help to visualise the molecular aspects of the pathway. Hope my comments are helpful!&lt;br /&gt;
&lt;br /&gt;
===Group 5 Review===&lt;br /&gt;
&lt;br /&gt;
Your team has a very impressive wiki page, well done! The key points relating to T-Box as well as your choice of subheadings and headings are very good, however I would advise removing 'Good places to look'. In terms of diagrams, tables and graphs, these are present and augment the information presented quite well. The content presented is cited mostly correctly however care must be taken with pictures, which have to be checked for copyright reuse as well as ensuring that they are cited correctly in the first place, I would advise that your team checks each of your pictures to make sure that they are correctly cited. &lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
In the context of peer level education, your content is understandable and written well even though the topic is complex. What is lacking however are using your own explanations as well as interesting hand drawn visual stimuli to present information, this can be easily remedied. Also, completion of the glossary section so that someone can understand complex terms would be useful. With the information that has been provided and the depth of research that has went into the meticulous presentation of information regarding T-box, it is clear that your team has went beyond formal teaching activities, however, perhaps the inclusion of some interactive features on your page such as a video with voice over or a quiz would help augment this criterion. The learning aims of the Embryology course are mostly in line with the information on the wiki page, but there is no section for current research/technologies, which is important to address the second criteria of the course aims. &lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
Overall, you guys did a very nice job that requires only minor touch ups and the addition of a few pieces of information. Don't forget the current research section though, that is pretty important to include in my opinion. Well done! &lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
===Group 5 Peer Review===&lt;br /&gt;
&lt;br /&gt;
'''Positive Factors'''&lt;br /&gt;
&lt;br /&gt;
Group 5 have introduced their topic really well, I think it could be improved by putting the second half of their intro under the ‘History’ subheading though and maybe it could be moved up so it is straight after the introduction. The table they have included shows they have considered addressing criteria 4 as I think it makes it easy for students to quickly take in a lot of information. Furthermore, they have addressed criteria 1 and 2 by organising the subheadings and sub-subheadings in a way that gives the page a logical flow. The amount of references already incorporated in their project shows that they have already completed extensive research on the topic area, which addresses criteria 5. Criteria 6 has clearly been addressed in the ‘development’ subsections. &lt;br /&gt;
&lt;br /&gt;
'''Points for Improvement'''&lt;br /&gt;
&lt;br /&gt;
Some improvements that Group 5 could make to their already extensive effort include: changing some of the headings in the table to bold so that they are clearer/easier to read; they could also uncapitalise the subheadings under ‘Abnormalities’ to make the page more uniform; and also formatting the images to incorporate them around the text (rather than breaking up the page each time) would improve the flow of information. &lt;br /&gt;
&lt;br /&gt;
'''Overall'''&lt;br /&gt;
&lt;br /&gt;
Overall Group 5 have already done extensive research as evidenced by the volume of information and various images included in their page, I can see that they have made an effort to address most of the criteria already. The improvements they need to make mainly involve formatting to make the page more student-friendly.&lt;br /&gt;
&amp;lt;br&amp;gt;&lt;br /&gt;
&amp;lt;br&amp;gt;&lt;br /&gt;
&amp;lt;u&amp;gt;Group 5: &amp;lt;/u&amp;gt;&lt;br /&gt;
&amp;lt;br&amp;gt;&lt;br /&gt;
&amp;lt;br&amp;gt;&lt;br /&gt;
&lt;br /&gt;
&amp;lt;b&amp;gt;Positive aspects of the project and suggested improvements:&amp;lt;/b&amp;gt;&lt;br /&gt;
&amp;lt;br&amp;gt;&lt;br /&gt;
&amp;lt;br&amp;gt;&lt;br /&gt;
Upon reviewing this page, it is clear that group 5 has provided numerous headings and subheadings related to Tbx-genes ranging from origins of the genes, their function in embryonic development, abnormalities, history and animal models (criteria 1 and 6). In doing so, the group has also ventured to provide an in-depth explanation of each subheading. Take for example the subheading named, “limb development”, the authors have provided an in-depth description into the role of T-box transcription factors in limb development whilst utilising a diagram to reinforce this description (criteria 2). It also appears that in-text citations have been correctly used to reference the sources of data in most cases (criteria 3). The authors have utilised diagrams and a table to describe various components of the T-box gene ranging from the different types of T-box genes to its mechanisms in embryonic development (criteria 4). The extensive use of diagrams allows the audience to develop a holistic understanding of the various subheadings included, as these diagrams convey the description provided in a visual manner (criteria 5). It is also evident that the group has conducted research into animal models and evolution of the T-box gene, thus demonstrating that the group has investigated areas of research beyond formal teaching activities (criteria 5).&lt;br /&gt;
&amp;lt;br&amp;gt;&lt;br /&gt;
&amp;lt;br&amp;gt;&lt;br /&gt;
Improvements which may be made to this page would be to include a timeline regarding the history of the T-box family, as this will display the information in a much more organised and appealing manner. Another improvement which may be made would be to include a YouTube video to introduce the signalling process in development, such as in cardiac and limb development for example. In order to make the wikipage interactive, a further improvement which may be made would be to include a set of multiple choice questions at the end of the page which ask questions about the content covered. &lt;br /&gt;
&amp;lt;br&amp;gt;&lt;br /&gt;
&amp;lt;br&amp;gt;&lt;br /&gt;
&amp;lt;b&amp;gt;Negative aspects of the project and suggested improvements:&amp;lt;/b&amp;gt;&lt;br /&gt;
&amp;lt;br&amp;gt;&lt;br /&gt;
&amp;lt;br&amp;gt;&lt;br /&gt;
&lt;br /&gt;
Alongside the various positive aspects of this project, there are few negative aspects. A negative aspect identified includes the use of images from Wikipedia pages more than once. It was stated that only one Wikipedia page was allowed to be included as a source. Therefore a suggestion would be to obtain images and data from research articles rather than from Wikipedia pages, as research articles are often a more reliable source of data. It was also noticed that images were not utilised to describe different abnormalities associated with the TBX gene, hence a possible improvement would be to include images depicting such abnormalities. These images may make this section of the page more appealing and engaging to audiences. &lt;br /&gt;
&amp;lt;br&amp;gt;&lt;br /&gt;
&amp;lt;br&amp;gt;&lt;br /&gt;
&lt;br /&gt;
It was also noticed that the image titled “Evolution of the T box gene family”, was incorrectly referenced. Therefore, it is suggested that the authors of the project ensure that the original author of the image are correctly referenced to ensure that copyright laws are not breached. The final negative aspect of the project was that the “Ancient origins and evolution of the T-box gene family” subheading appeared out of place in the page. Therefore a possible improvement would be to include evolution of the T-box gene under the “Origins of the T-box gene” subheading at the beginning of the page as this will create a sense of consistency in the page.&lt;br /&gt;
&amp;lt;br&amp;gt;&lt;br /&gt;
&amp;lt;br&amp;gt;&lt;br /&gt;
&lt;br /&gt;
===Group 5===&lt;br /&gt;
&lt;br /&gt;
First of all, well done on making significant progress on your project! You have addressed all aspects of the pathway involving T-Box genes through subdivision into various headings and subheadings. I particularly liked how there was an inclusion of the specific T-Box gene affected in each of the abnormalities in the subheading itself. The only suggestion I would make is to combine the ‘Ancient origins and evolution of the T-Box gene family’ section with the origins of the ‘T-Box genes’ section to provide a more coherent description of the history of these pathway. You could even form a table to create a timeline of events. In addition, I think it would be beneficial to include the ‘What does T-Box mean?’ as an introduction to the ‘origins of the T-box genes’ section as there is overlap between these sections. &lt;br /&gt;
&lt;br /&gt;
The use of a table to describe the main T-box genes was helpful in providing a brief overview of the components of the pathway and their influence in embryological development. In addition, the link between T-Box genes and embryonic development has been explored considerably. In saying this, greater attention to detail must be paid to explaining abbreviations to aid one’s understanding of the concepts being discussed. For example, what is NKX2-5, Shh and OFT? Though you’ve explained that RA stands for retinoic acid in the ‘Organisms used in animal models for T-Box’ section, this same explanation is not provided in the ‘Limb development’ section where you have discussed that ‘RA and Shh both induced Tbx2’. These small changes will significantly improve the quality of your work. &lt;br /&gt;
&lt;br /&gt;
The inclusion of abnormalities provides great insight into the role of T-Box genes in development. In saying this, though you have explored the effect of the mutation of these genes in animal models, more information is required to explain the effect of these mutations in humans and how they come about. Furthermore, under the heading of ‘Animal models’ there has been discussion mainly of the ‘brachyury gene’ which seems unrelated to animal models due to the lack of a proper introduction. I found the following section (organisms used in animal models for T-Box) to be a better introduction to the topic of animal models. In addition, there has been mention of a number of animal models ‘Drosophila, Xenopus, zebrafish, avians, and mice’ yet only marsupials and amphioxus has been discussed. This could be potentially misleading to readers. &lt;br /&gt;
&lt;br /&gt;
Overall, a fantastic effort has been made. Not only have you touched upon nearly every section of the project, but have included some excellent diagrams and tables which aid understanding of this pathway. In saying this, it is noted that two Wikipedia images have been used though it has been suggested that only one of the images utilised can be from Wikipedia. All information provided was also appropriately referenced and cited. In addition, I think it would be useful to utilise the discussion page to encourage interaction between group members as it allows individuals to provide feedback and suggestions. Hope this helps!&lt;br /&gt;
&lt;br /&gt;
===Group 5 Critical Assessment===&lt;br /&gt;
Well done on constructing a thorough Wiki page on the topic of T-box Genes and their Signalling! Viewing the page it is evident numerous headings and subheadings have been provided to accommodate for the large amount of information gathered. Starting off with the introduction I like how you have included a section on what T’-box exactly means, however the information provided in this section talks about the history significantly, hence to turn this into a positive I would suggest adding a table or timeline outlining the major events and discoveries in the past to present this information in a complete, meaningful way. This issue is also seen with the section ‘Origins of the T-box genes’ where major discoveries are highlighted and in which year they occurred. This information can also merge with the history timeline/table. &lt;br /&gt;
&lt;br /&gt;
Within the ‘What does T-box mean?’ section you have also added information on which animal studies were undertaken for the discoveries. To avoid spreading of information and causing confusion for the reader, you could either construct a table to show which animal study was completed in which year, and what discovery it led to as 3 columns, or bring this information down to the section ‘Animal Models’. In saying that, you have attempted to utilize a table and the table works very well with the topic of the different T-box genes, and would prove great help for the viewer. &lt;br /&gt;
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It is great to see T-box genes and Signalling has been explored further in the field of embryonic development. Extensive information is provided with good use of in- text citations, allowing the reader to navigate to relevant articles. The ability to navigate could be further improved by providing an accessible link to the ‘Abnormalities’ section in a case where you are directing the reader to the section for further information, instead of plain text. Beneath each section for e.g. ‘Limb Development’ Pubmed links have been provided to relevant articles, which is a fantastic idea, however the links have no indication whatsoever of what the article is about. You could add a sentence each next to the links briefly stating what the article is exploring in relation to limb development. &lt;br /&gt;
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Overall with a few more images, possibly some interactive components such as clips, and a knowledge testing short exam or quiz this Wiki page will stand out. Remember to ensure your information flows well by placing it within appropriate sections!&lt;br /&gt;
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===Group 5 Peer Assessment===&lt;br /&gt;
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It is quite clear that what has been provided in your wiki page is extensive and well researched. The inclusion of tables summarizing the different T-box genes although extensive, is very concise and easy to read. I feel that this table really links all the elements of your page together, where you have included its function and related it to embryological development and abnormalities which you go on later to elaborate in other sections. I feel this really complements the introduction and gives a good feel for what’s to come in the rest of the page. The addition of what the term T-box means also is a nice touch, giving context and some history regarding the name. &lt;br /&gt;
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Your origins section of T-box is quite well outlined, but as mentioned in your page, having a timeline with critical points of discovery with regards to the genes would probably be more beneficial as it would be a lot easier to read a see the time points as a whole. That being said, having the timeline alongside your outline would probably work well, as your outline can serve to elaborate on the timeline. With regards to your subheadings, it seems to they are quite extensive and cover practically all the key components of the T-box genes, and it is also good to see that there is a glossary subheading in place. Content wise there seems to be limited to no issues, but with regards to abbreviations, I have found that the usage hasn’t always been after the fact of providing the full name first. For example, bone morphogenic protein’s abbreviation is used consistently throughout the first part of the wiki page, but it is only described by its full name and then abbreviation later on. This is something you should check out and fix by either adding the full name the first time the abbreviation is used, or adding all these terms to the glossary. &lt;br /&gt;
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With regards to the pictures they all seem to compliment the sections well and are quite plentiful. That being said though the picture in the “Marsupial forelimb development” does not appear to have the copyright information regarding to its usage, and referencing does not appear to be in full. This is also the same for the picture under the subheading “Organisms used in animal models for T-box”.  Other than that the referencing is perfectly fine within the text.&lt;br /&gt;
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Overall this project is really good and without any major flaws when it comes to the content. A few touch ups here and there with regards to my suggestion above, and your project should be good to go along as the quality is kept at this level.&lt;br /&gt;
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===Group 5 – T-Box===&lt;br /&gt;
First impressions alone it is extremely clear that Group 5 has thoroughly researched this topic have tried hard to include many diagrams and tables to help separate their information up in order to more successfully convey the information across to the reader. Positive aspects of this project include the well-defined subheadings, making the navigation through the page very easy. The introduction is informative and introduces the following subheadings of the project well. The inclusion of what does T-Box mean is also interesting, setting you apart from the other projects. One of the best aspects of the project would have to be the summary table of the main T-box genes, which includes its main expression sites, its function and abnormalities relevant to the specific gene. You have made a note to include a timeline for the history of the T-Box gene, which I think would be successful in summarizing the scientific advances since its discovery, and also help to break up paragraphs of writing. The project appears to be referenced correctly using in-text citations, only query is whether the links to the PMID articles say in the bottom of cardiac and limb development are references or just articles in which you haven’t written on yet and will be referenced appropriately when you do later. The inclusion of a glossary is also a good idea just to help define and explain some of the more difficult terms mentioned. &lt;br /&gt;
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As for negative aspects of the project, there wasn’t too many. Like for every project, in terms of making it more interactive it might be a good idea to include a YouTube video or animation of the signaling pathway or its role in a specific developmental process, as well as your own hand-drawn image just to fulfill the necessary criteria of this assignment. Furthermore, with some of the smaller images that don’t go the full width of the page, it might be a nice idea to align them to the right as a thumbnail next to their relevant text, so readers see them whilst reading about it. Also remember to make a reference the image you have chosen in your text to emphasise its importance to what you are actually talking about. Although the subheading “good places to look” might just be something for you guys while researching, I think that you could utilize this by including various links with more information on the relevant topics of which you have discussed. This would help to make you page more interactive as well.&lt;br /&gt;
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This project appears to be extremely well done and is definitely one of the strongest. Most of the criticisms are regarding the formatting of the page and making it more interactive for the reader. All in all this is very well researched project! &lt;br /&gt;
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===Group 5 Peer Assessment===&lt;br /&gt;
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Positive aspects of the project and improvements:&lt;br /&gt;
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Upon reviewing the page, it is evident that there has been a lot of research put in this project. Initially, there is evidence of a range of headings and subheadings which allowed the navigation from one aspect of the project to another extremely easy. This allowed me to confirm that the project is about T-box genes and their signalling. Secondly, it was excellent to see a range of images, tables and graphs as they provided visual aids to learn more about the topic and in general made it easier to accumulate information. Also it was good to see that these tables and images were correctly cited and referenced at the end which meant that there was no breach of copyright laws. &lt;br /&gt;
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Also, throughout the project there was sufficient amount of information in each subheading which meant that the reader gained all relevant information pertaining to the section that they are reading. It was also great to see a range of abnormalities being added to the project. This meant that you have went above and beyond the scope of the assessment and researched that extra bit to provide additional information about the signalling pathway and complications arising from any mutations. This meant that you successfully satisfied criteria 5 and thus a more rounded project.  &lt;br /&gt;
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Negative aspects of the project and improvements:&lt;br /&gt;
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This project certainly contains a range of positives but there were minimal negatives that can easily be amended in order to achieve a very high mark. I noticed that there was more than 1 image being used from Wikipedia and the criterion clearly says that a maximum of 1 was allowed. This is not a big deal but just in case there is harsh marking and penalties, it is advised to replace the additional image with another image. In addition, it would be useful to add a glossary of all the terms that one may find confusing such as “homologues”, “heterozygous”, “homology”, “notochord” etc. This in turn will provide the reader with enough information to understand the context of the project and in turn keep them engaged.&lt;br /&gt;
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Another negative aspect of the project was that the subheading “Ancient origins and evolution of the T-box gene family” randomly appearing nearing the end of the project. This looked a bit out of place and not flowing with the rest of the passage. To correct this it would be advised to add this to the start of the page with the “Origin of the T-box genes” section just so the information clearly flows from one topic to another without creating confusion. Overall, this project is coming along quite nicely. It is evident that a lot of research has been put into constructing a coherent and succinct project but also have the visual cues to back up the main aspects. To maximise marks, it is recommended to reflect on the feedback and correct the minor mistakes. &lt;br /&gt;
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===Group 5 Peer Assessment===&lt;br /&gt;
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Positive feedback:&lt;br /&gt;
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This is a very well, put together and organised page. Everything is very simple and straight-forward make it extremely student friendly and something I would definitely use to learn about T-Box genes.&lt;br /&gt;
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The introduction along with explanation of the actual meaning of T-box is both informative and also interesting and gives students a good chance to take a break from the heavy load of information and actually indulge in some interesting facts.Following this, the table is one of the most useful things on the entire page and is extremely concise and structurally pleasing. It provides the key and relevant information and allowed me to make connections with T-box genes and their functions straight away.&lt;br /&gt;
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There is also the use of many pictures throughout the page which definitely aids in visual learning and the more the used the better. The chronological structuring of the page is also very impressive. As I was reading the page I felt like the information that I was gathering was carrying on and helping me understand what was talked about in the next sections.&lt;br /&gt;
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Critical Assessment:&lt;br /&gt;
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The chronological structuring although very impressive did fall a little out of place when the sub-headings “Ancient origins and evolution of the T-box gene family” appeared at the end of the page when it seems like this is something that should be included in the start. It would be thoroughly recommended to utilised hand drawings to explain some of the concepts, especially when introducing the signalling because this would really compliment your  already easy to understand introductions and really enhance learning/understanding.&lt;br /&gt;
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Lastly I think it would be a good addition to your project to include some information on the current research that is being conducted on t-box genes and also if there are treatments for the abnormalities. This page is looking amazing so far so keep up the good work!&lt;br /&gt;
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GROUP 5&lt;br /&gt;
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From reading through Group 5’s project I can see that they having clearly and effectively talked about topics relating to Tbx genes. Their subheadings include animal models, history, function in embryonic development, as well as abnormalities. This provides evidence to me that they have obviously considered and addressed both criteria’s 6 and 1. Group 5 has done a fantastic job with criteria 2, in that they provide many visual representations of information with different forms. For examples they provide a table of the main T-box genes, but then also have many visual diagrams relating to the Tbx development. Even though criteria 2 is very well done, it could be improved by having a timeline of the history of the T-box family. Also, I have seen in some other groups that they have included multiple choice questions to test the audience on their knowledge, I think this is a good idea since it makes the learning experience more interactive.&lt;br /&gt;
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Some searches to get us started:&lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/sites/gquery?term=t-box ''T-box'']&lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/sites/gquery?term=tbx ''tbx'']&lt;br /&gt;
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[[User:Z5020373|Z5020373]] ([[User talk:Z5020373|talk]]) 14:44, 26 August 2016 (AEST)&lt;br /&gt;
PMID 25294936 - a relatively recent article that provides background info on the T-box gene family&lt;br /&gt;
PMID 16285859&lt;br /&gt;
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[[User:Z3516832|Z3516832]] ([[User talk:Z3516832|talk]]) 14:52, 26 August 2016 (AEST)&lt;br /&gt;
http://www.columbia.edu/itc/hs/medical/humandev/2007/HD15/HD15.pdf&lt;br /&gt;
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[[User:Z5020373|Z5020373]] ([[User talk:Z5020373|talk]]) 11:32, 16 September 2016 (AEST) Does anyone know how to draw up a table on the page? Thanks.&lt;/div&gt;</summary>
		<author><name>Z5020466</name></author>
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	<entry>
		<id>https://embryology.med.unsw.edu.au/embryology/index.php?title=Talk:2016_Group_Project_4&amp;diff=249778</id>
		<title>Talk:2016 Group Project 4</title>
		<link rel="alternate" type="text/html" href="https://embryology.med.unsw.edu.au/embryology/index.php?title=Talk:2016_Group_Project_4&amp;diff=249778"/>
		<updated>2016-10-07T02:13:17Z</updated>

		<summary type="html">&lt;p&gt;Z5020466: &lt;/p&gt;
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=Peer review=&lt;br /&gt;
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===Group 4 Peer Review===&lt;br /&gt;
First off you guys have chosen great headings and subheadings! It’s really helpful in breaking down your information to be better understood and I like all the aspects you’ve chosen to explore. Your content so far is clear and concise and most of it is correctly referenced - well done particularly on the info for animal models. The examples of primary research you’ve included are also a great addition. The information you’ve presented is also written well and in a way that’s not too scientific so it’s easy to understand.&lt;br /&gt;
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It would be great if you included an introduction paragraph to just give a brief overview of Hedgehog signalling. While your animal model content is good, I think you need a lot more info for human embryonic development (considering that it should be the focus of the project) - you’ve mentioned organogenesis very briefly, but I think if you explored each of the systems in greater detail then it would really improve your page. I would strongly recommend including a glossary as well. Make sure you have captions for your images so the reader understands why the image is relevant to your text. Also you should fully define all the abbreviations somewhere (either in your glossary on the image’s page) for the reader’s benefit. If you have some more images in the signalling/animal model sections I think that would break up the paragraphs a bit more and make it easier to read. And you might want to include a summary table, maybe of the molecular pathway factors, somewhere. But overall you’ve started off really well as a team - keep working hard to finish off/improve each section.&lt;br /&gt;
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===Group 4 Review===&lt;br /&gt;
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Nice effort group 4. Key points that relate to the Hedgehog signalling pathway are very succinctly described. Your choice of headings, albeit brief, provides a sense that you guys understand the topic generally but I feel as if you could improve on your subheadings, for example of the Clinical Significances section, I feel as if the diagnosis subheading could be altered. I also feel as if the information in the Organogenesis section could be reworked into an introduction which would allow you to then focus on Organogenesis on its own in more detail. Also, you guys only have one image so far which seems to be slightly lacklustre, you guys definitely need more images. The relevant content is mostly cited correctly, albeit the odd reference located below the marking criteria, I feel as if that is more of a small accident. &lt;br /&gt;
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The information presented is relatively peer friendly. Perhaps more explanation, for example in the Processing of precursor section as I felt well and truly lost in that area. You guys could do with some hand drawn diagrams or analogies to help explain the information provided. A glossary section would be very helpful in understanding the wiki page, by defining the complex terms such as proteasome(which is misspelt on your page as proteosome). The research that has been done has indicated that you guys have went beyond the formal teaching activities, however, you guys could do more research in the sections that have no information for example 'History', you could even put a timeline in there! In the context of the course aims, he embryological relevance of the Hedgehog pathway is addressed to an extent but as you have missing sections under human disease, there is still work to be done in this section. Also, you should try to complete your current research section to address the second criterion of the course aims regarding new technologies and research.&lt;br /&gt;
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Overall you guys have had a good start and really just need to start filling in the blanks so to speak. Your team researches information well, just ensure that you fill in your missing sections and think of innovative ways to present information. Nice job!&lt;br /&gt;
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===Group 4 Peer Review===&lt;br /&gt;
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'''Positive Factors'''&lt;br /&gt;
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Group 4 have provided well-written information that I found was easy to follow despite not having an extensive understanding of the topic (covering criteria 1). Another positive aspect of this Group’s effort is the integration of the references, which makes it easy for students to access the resources they have used; already it seems that they have done extensive research on the topic (covering criteria 5). From looking at the subheadings it appears that the scope of the topic will be covered well (which will address criteria 2). Furthermore, the image at the top of the page provides a great visual to aid students’ understanding of and engagement in the topic (showing they have begun to address criteria 4). They have also directly related subsections to embryology, which covers criteria 6.  &lt;br /&gt;
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'''Points for Improvement'''&lt;br /&gt;
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Some aspects of Group 4’s page that would improve their project include: the image at the top of the page could be better if a title and short explanatory caption accompanied it on the page; use of more diagrams throughout the page would also better address criteria 4; and under the ‘Animal Models’ heading, maybe shortening all the sub headings just to the animal name would make it a little more succinct and clear. &lt;br /&gt;
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'''Overall'''&lt;br /&gt;
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Overall this page has shown efforts at addressing a few of the assessment criteria, however still needs some improvements to make the page more suitable to engaging and informing students. &lt;br /&gt;
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&amp;lt;u&amp;gt;Group 4:&amp;lt;/u&amp;gt;&lt;br /&gt;
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&amp;lt;b&amp;gt;Positive aspects of the project and suggested improvements:&amp;lt;/b&amp;gt;&lt;br /&gt;
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Group 4 has provided numerous headings related to the Hedgehog pathway, such as its involvement in organ development, neural development as well as its mechanism of signalling during embryonic development (criteria 1). The group has also used an image of the signalling pathway to help provide a visual description of the different components of Hedgehog signalling (criteria 2). The authors of this project have also provided in-text citations for all information utilised and have also included a list of references at the end of their page (criteria 3). It is also evident that the group has investigated the involvement of the Shh signalling pathway outside of the scope of human embryonic development by exploring its role in mice, chicks and fruit flies, which is excellent (criteria 5 and 6). The authors have also began to include new research and abnormalities related to the Shh pathway (criteria 1).&lt;br /&gt;
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In order to further improve these positive aspects, the authors may provide a written description of the signalling pathway alongside the diagram utilised. This is because it is difficult to understand the signalling pathway just by looking at a diagram. Also, a suggestion would be to include a greater variety of diagrams and tables to support the descriptions already provided. Diagrams may relate to the animal models or the abnormalities described. A table may be utilised to summarise the history of the signalling pathway, such as different components of the pathway that were discovered and the year in which they were discovered. Additionally, whilst it appears that most of the information is correctly referenced, the authors have not correctly referenced the diagram that has been utilised to describe the signalling pathway, which is a breach of copyright laws. Therefore, a suggestion would be to ensure that all diagrams are referenced when added to the page.&lt;br /&gt;
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&amp;lt;b&amp;gt;Negative aspects of the project and suggested improvements: &amp;lt;/b&amp;gt;&lt;br /&gt;
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Whilst there were positive aspects to this project, a key negative aspect of the project is that the authors have not provided an introduction describing what the Hedgehog signalling pathway is. The introduction may include an overview of the nature and role of the hedgehog signalling pathway in embryonic development, thereby introducing headings in your page. It is also evident that the authors have not met criteria 2 completely, in that a small number of subheadings were utilised. Take for example the heading, “organogenesis”, no subheadings have been created under this heading. A suggested improvement would be to include subheadings relating to specific organs formed by the actions of the Shh pathway, accompanied by an in-depth description and diagrams. It is also evident that the authors utilise complex terminology within their description that often make it difficult to grasp certain concepts. Terms include “knockout”, “autocrine”, “appendage” and “paracrine” for example. A suggestion for improvement would be to include a table of glossary terms at the end of the page, defining these terms.&lt;br /&gt;
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It also appears that the authors have not provided a history regarding the Hedgehog signalling pathway and its discovery. A suggestion would be to include a timeline regarding the discovery of this signalling pathway, as it provides the audience with a background of how Shh came to be known. &lt;br /&gt;
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===Group 4===&lt;br /&gt;
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A good start has been made to the project with the appropriate selection of headings and subheadings which provide a brief overview of what is to be discussed in terms of the Hedgehog signalling pathway. By breaking down the mechanism of the pathway, it made the foreign concept much easier to understand. In saying this, this section is quite text-heavy and may benefit with the relocation of the included diagram or even inclusion of other diagrams and flowcharts to engage readers. With the introduction of a fairly new concept, the inclusion of visual or audio stimuli and maybe even a short quiz may encourage interaction with readers.  &lt;br /&gt;
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The discussion of this pathway in mammals exposed readers to the diversity of the Hh signalling pathway but in saying this, the inclusion of a table may be useful to compare and contrast the differences between the pathways in mammals and insects. Overall, this section was well written. On the other hand, when considering the section on animal models, it provided insight into the role of Hh signalling pathway on embryological development and offered a brief introduction to the abnormalities caused by disruptions of this pathway. Once again, the inclusion of diagrams would be useful in this section to provide visual insight into the research being performed. &lt;br /&gt;
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Though there has been significant exploration of the mechanism and animal models utilised in this pathway, more work is needed to link this pathway to embryological development and this could provide a good leeway into understanding the abnormalities associated with disruption of this pathway. This project can be significantly improved simply by focusing on making it more interactive ad engaging with the inclusion of a variety of stimuli like tables, diagrams, quizzes and even videos. In addition, all information has been well cited and referenced and there has been substantial communication between group members, allowing team members to provide feedback and suggestions thus, ultimately increasing the quality of the work produced. &lt;br /&gt;
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===Group 4 – Hedgehog Pathway ===&lt;br /&gt;
Positive aspects of this project include that Group 4 appear to have well defined subheadings, which function well to help the reader navigate through the page. The information is appropriately referenced using in-text citations, appearing to be from both primary and review articles. There is a significant amount of research on the mechanisms of the pathway but less of a focus on the role of this pathway in embryonic development, which I think is really important in order to relate it back to what we are leaning in both the lectures and tutorials. I think the inclusion of current research is a very important aspect to include in this project, as it identifies the current direction in which this research is heading. This might be also interesting to link to its clinical significance and abnormalities in the signaling pathway. &lt;br /&gt;
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However, some negative aspects of the page include the lack of an introduction as this essentially establishes your page. You need to include a brief outline of the signaling pathway, a summary of its role in development and the other aspects of it you are looking to discuss. Furthermore, the inclusion of an image outlining the signaling pathway without any information inducing or explaining it should be corrected. The project appears to be very informative but isn’t very interactive and lacks images. Perhaps sourcing images of results from some of the primary articles, which you have referenced or include videos outlining the signaling pathway, might be a useful addition. It might be a good idea to include a glossary at the bottom of the page to help readers to better understand some of these more difficult terms. Also under the subheading of history, like in some of the other projects, a table could be a useful addition, just summarizing all the scientific advances regarding this pathway since it was first discovered, this helps set up how far we have come and then may be helpful when talking about the direction in which we are heading under current research. &lt;br /&gt;
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In conclusion, this looks like it’s on its way to being a successful project. In summary though, a greater emphasis on its role in embryonic development and conscious effort to make the page more interactive and engaging for the reader will go a long way.  &lt;br /&gt;
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===Group 4 Peer Assessment===&lt;br /&gt;
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Positive aspects of the project and improvements:&lt;br /&gt;
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At initial glance I can see a range of headings and subheadings which just made it easier to navigate from one aspect of the project to another. This satisfied the requirements for criteria 1 and 2. This also allowed me to recognise the main topic of the project is the Hedgehog signalling pathway. There is also an addition of an image of the pathway which was great to see as it outlines the main components of the pathway and in general educates the reader about the signalling pathway. This provided a visual stimulus/ description which in turn engaged the reader to find out more about the topic.&lt;br /&gt;
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It was also good to see correct in text citations and a references list at the end which in turn satisfied criteria 3. To satisfy criteria 5 it was excellent to see information that was well beyond the required information. An example of this is when discussing the role of the pathway in not only humans but also in mice, chicks and fruit flies. The group also began to include new research and abnormalities related to the Shh pathway which aided in rounding off criteria 1. &lt;br /&gt;
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In order to improve the already positives of this project it would be advised to add a description to the image just so the reader can have some sort of summary about the main points of the image/ pathway. Also, addition of diagrams or tables in some of the subheadings would be good as it will keep the reader interested and in general provide a visual aid. Also it is necessary to cite and provide a reference of the image as it breaches the copyright laws. &lt;br /&gt;
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Negative aspects of the project and improvements:&lt;br /&gt;
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Although there are positives to the project, there are a few negatives that can easily be fixed. It is crucial to put in an “Introduction” heading and providing relevant information. This in turn will create a coherent project as it flows from one aspect to another whilst simultaneously providing a brief overview of the Sonic Hedgehog Pathway. Although you have explored the mechanism in animal models it is imperative to link this to embryological development. Also, addition of diagrams, interactive quizzes and tables is necessary to satisfy criteria 3, since 1 image is not enough. &lt;br /&gt;
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Adding a glossary of terms at the end of the project is needed to clarify any words or phrases that have not been previously encountered such as “organogenesis”, “paracrine”, “dephosphorylation” etc. Overall, the project is coming along nicely and with the recommended amendments, a high mark is definitely in order. &lt;br /&gt;
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===Group 4 Peer Assessment===&lt;br /&gt;
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Positive Assessment:&lt;br /&gt;
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I am very impressed with the level and depth of information provided in this page so far. It is quite evident that you guys have gone to great effort and lengths to research and find relevant information regarding hedgehog signalling. The research conducted is also further solidified with the correct use of citations which link the information with their articles and allow the user to learn more if required. There is almost 34 references already provided which is a testament to the work that has been put in by the group. Well done!&lt;br /&gt;
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I love the very detailed explanation of animal models used to investigate hedgehog signalling and there is an abundance of information provided for this where as I’ve noticed other groups tend to very lightly touch this topic.&lt;br /&gt;
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Critical Assessment:&lt;br /&gt;
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The page is looking very good so far but in my opinion there are a few ways in which it can be improved.&lt;br /&gt;
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Although the information is in-depth and thorough it can be a little intense at times. I would recommend using more dot points or look into using tables to categorise information into a more user friendly structure. This can also be achieved by using more subheadings to further dissect the information and make it less imposing when reading as this content can be difficult to understand at first. I would also have a nice and clear introduction at the beginning of your page as it essential for the students entering your page to be able to familiarise themselves with Hedgehog signalling before diving into the more complicated information.&lt;br /&gt;
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I would also make better use of the subheadings, so that they reflect more of the marking criteria in particular hedgehog signalling role in embryology. I didn’t see too much content outlining and explaining this and this is a major part of the project. It would also be a good idea to draw a picture rather than using one to explain the mechanism as simplified visual aids always help. Lastly, try including a glossary as there were many terms that I was very unfamiliar with, such as organogenesis.&lt;br /&gt;
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===Peer Assessment: Project 4: Hedgehog signalling pathway===&lt;br /&gt;
====1. The key points relating to the topic are clearly described. ====&lt;br /&gt;
The key points related to the topic are clearly described however the introduction is a little limited , as there is no information just a figure without any text related to the figure. &lt;br /&gt;
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====2.The choice of content, headings and sub-headings, diagrams, tables, graphs show a good understanding of the topic area. ====&lt;br /&gt;
This wiki does seem to have a very extensive list of contents, which demonstrate that the topic is divided into clear interesting sections.  However it is not finished and there are empty headings with no text underneath. There is only one figure but there is no text related to these figures so it makes it hard for the reader to know what this means. There are no tables and no other illustrative diagrams. This wiki would benefit a great deal with more figures, table and perhaps a you tube video.&lt;br /&gt;
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====3. Content correctly cited. ====&lt;br /&gt;
Yes it seems the content is cited correctly. There is an extensive list of references. However there is some information that is not cited at all e.g. under Organogenesis. This needs to be cited.&lt;br /&gt;
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====4. The wiki has an element of teaching at a peer level using the student's own innovative diagrams, tables or figures and/or using interesting examples or explanations. ====&lt;br /&gt;
There are no graphs, or tables and one figure that is floating in the introduction and start of the topic. Clearly this can be improved. The wiki does use examples with Drosophilia and Mammals which is great and interesting. &lt;br /&gt;
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====5. Evidence of significant research relating to basic and applied sciences that goes beyond the formal teaching activities. ====&lt;br /&gt;
This is evident that the students have done a lot of research in this topic and are innovative with their examples using Drosophilia and Mammalia however there is still headings without content that needs to be filled.&lt;br /&gt;
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====6. Relates the topic and content of the Wiki entry to learning aims of embryology. ====&lt;br /&gt;
There is a heading on neural development but no text and some information on organogenesis which does correspond to learning aims in Embryology. However more information is clearly needed.&lt;br /&gt;
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====7. Clearly reflects on editing/feedback from group peers and articulates how the Wiki could be improved (or not) based on peer comments/feedback. Demonstrates an ability to review own work when criticised in an open edited wiki format. Reflects on what was learned from the process of editing a peer's wiki. ====&lt;br /&gt;
There seems to be editing in this Wiki however the students need to come together to talk about what is missing: i.e. introduction is missing.  &lt;br /&gt;
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====8. Evaluates own performance and that of group peers to give a rounded summary of this wiki process in terms of group effort and achievement. ====&lt;br /&gt;
This is hard to tell. There seems to be an overall group effort but some sections have missing content and it either seems one student is not pulling weight or that section will be a group effort and the group has not worked on it yet.&lt;br /&gt;
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====9. The content of the wiki should demonstrate to the reader that your group has researched adequately on this topic and covered the key areas necessary to inform your peers in their learning. ====&lt;br /&gt;
Yes so far there is adequate research, a lot of references cited but some key sections are empty. It seems that the group has used the Discussion section to communicate between each other.&lt;br /&gt;
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====10. Develops and edits the wiki entries in accordance with the above guidelines. ====&lt;br /&gt;
Yes this group has edited the wiki using the guidelines. &lt;br /&gt;
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[[User:Z5019880|Z5019880]] ([[User talk:Z5019880|talk]]) 14:58, 26 August 2016 (AEST) Hey guys, I have added some sub-headings for the hedgehog signalling pathway, feel free to add any headings that might be useful for the topic, or suggest a different topic.&lt;br /&gt;
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Hey guys, I've started doing some research on the animal models for the Hedgehog signalling pathway. I'm currently finding it a little difficult understanding some of the terms when researching the experiments done on Drosophila melanogaster so I was wondering if you had any suggestions as to how much detail to include. Also I have included some links that maybe useful for those researching mechanism and history:&lt;br /&gt;
&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;17925578&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
&amp;lt;ref&amp;gt;&amp;lt;pubmed&amp;gt;26839340&amp;lt;/pubmed&amp;gt;&amp;lt;/ref&amp;gt;&lt;br /&gt;
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Also, I thought I would just put in writing here that we want everyone to have completed their parts by the end of mid semester break so that we can meet up the following week to fix any issues with formatting and work on the introduction, conclusion etc. Thanks guys!! &lt;br /&gt;
P.S. Did Mark mention that we shouldn't use research articles?&lt;br /&gt;
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[[User:Z5019880|Z5019880]] ([[User talk:Z5019880|talk]]) 23:30, 12 September 2016 (AEST) Hey, what you have added is really good! To be honest I'm not completely sure about how technical we have to be, because I have also found my self that there is a lot of chemistry when it comes to the signalling pathways etc. which makes it incredibly difficult for me to understand. At this point I reckon what you have now is enough, but we can always revisit it when we have added more to the page, to keep the content at a consistent depth. Also with regards to the research articles, I'm not entirely sure what Mark said, but I'm sure it would be alright to see what is written, and click into the citations to get further information, and just cite that. Anyway I've added a small piece on the processing of the Hh protein, but am unsure if It would be necessary to go more into the chemistry behind how the auto-cleavage occurs.&lt;br /&gt;
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So I've read what you have written and I think it sounds coherent and it's also very easy to understand so good job! I think I'll do a little more research, I think it might be a little tedious to add information of Shh knockout mice considering the experiments on the chick embryo were quite similar but I'm open to suggestions. I was also thinking it would be useful to include a link to a short youtube video of some sort that would be able to visually explain the Hh signalling pathway (something like this https://www.youtube.com/watch?v=w1xXD9kss2w but unfortunately this video has no audio but has some good visual and written cues). In regards to an image, I actually found a pretty decent image of this pathway but I'm not too sure if we can use it due to copyright. It says we can if it's not for commercial use so I think we should be ok.&lt;br /&gt;
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Please let me know what you think of the diagram. I've just added something that looks like it could be helpful but feel free to edit/remove it if you don't think it is appropriate :)&lt;br /&gt;
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[[User:Z5019880|Z5019880]] ([[User talk:Z5019880|talk]]) 22:28, 26 September 2016 (AEST) The diagram looks great! I reckon as long as we include all the copyright it should be fine. We can probably eventually move the image next to the mechanism of signalling section when it is finished. I have started it, and will continue finishing it tomorrow, so if there are any issues with how I'm going about it, please don't hesitate to tell me.&lt;br /&gt;
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Good idea! I've added some information on Shh Knockout mice so any feedback on what I have written will be greatly appreciated! I'm also thinking of looking into videos that we could link as part of our assignment to make the concept easier to understand.&lt;br /&gt;
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[[User:Z5019880|Z5019880]] ([[User talk:Z5019880|talk]]) 21:30, 28 September 2016 (AEST) Hey, I've read your section on Shh and it seems good. In terms of what you could add, do you reckon it is appropriate to talk about the advantage of using each of the models over one another, and possible problems you might encounter with each model. I get that it's probably hard to find material on that, so don't worry if that's the case. Also a video would be a great idea, although we should first check with Mark with regards to what sources would be appropriate. Anyway I have finished the first part of the mechanism part regarding the general pathway for Hh proteins that have specifically been studied in the fruit fly, and will continue onto vertebrates later. I was wondering from what you guys have studied on this pathway if I have covered most of the areas sufficiently and in a coherent matter. Any other feedback is also appreciated.&lt;br /&gt;
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I've read what you've written and you've successfully made it really easy to understand. From the knowledge I've gained through reading articles on this pathway, I don't think you have missed anything thus far. The only improvement I could suggest is maybe referencing an image in your explanation so that readers have a visual stimulus to refer to to ease understanding of the pathway. In regards to looking at the differences between the models, I genuinely tried to find a comparison between the animal models but was met with no such information unfortunately. I'll try and have a look sometime soon. Also, I was thinking maybe we could include a quiz of some sort to make our project more interactive. We could do this by adding a quiz after each section or just one quiz at the very end. Our project is also quite text heavy so I think we should find more images and other stimuli to make it more interesting. We should create a timeline of events for the history of the pathway in the form of a table. Also, should we create a glossary?&lt;br /&gt;
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Also, quick question, who's handling history, function and current research?&lt;br /&gt;
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=== Group 4===&lt;br /&gt;
This web page is developing well, but has many areas that need completion. Starting the web page with the flowchart of the hedgehog signalling pathway is not recommended, as the reader has not been introduced to the topic at all and does not know what any of the terms and abbreviations mean. This image would serve better further down in the web page where the reader has knowledge of this signalling process and what is involved to then apply and consolidate in the image. More images can also be included in this web page, such as an image of a hedgehog at the top of the page, which would be an interesting and humorous way to grab the reader’s attention, which is required to fulfil the criteria for this assessment. Images in the animal model section would also enhance the reader’s understanding. &lt;br /&gt;
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Many subheadings have been included, but could be improved on their clarity. For example, the heading “Mechanism” is not very specific and thus could be improved to identify which mechanisms are being spoken about. A “History” subheading has also been included with no information. A timeline of the history of research associated with the hedgehog signalling pathway would be very comprehensive, including where future research is headed. This research should include why there are question marks (“?”) in yellow in the diagram at the top of the web page, as these could be areas where future research is heading. Ensure this table/timeline is well referenced, including names of researchers for depth of information. A glossary section should also be included to enable to reader to keep track of the different terms and abbreviations used in this web page. Terms in this list could include information on the abbreviations in the diagram included: Cos2, PKA, Slimb and a range of other terms. &lt;br /&gt;
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A “Human disease” heading has also been included. No information has been added to this section as more research by the group members must be carried out. This heading could be more specific, such as titling it as “abnormalities” as “Human disease” can be in reference to a wide range of issues, whereas “abnormalities” or something similar is more topic specific. Images of the effects of these abnormalities would also be an interesting addition, including treatments for the diseases and their symptoms as well as future research areas.  The “Animal Models” section contains substantial textual information. Images would enhance this section, such as images of the animals being studied and short videos of their embryological development. A greater focus on human embryology is needed throughout the entire web page as there is a substantial amount of information on the hedgehog signalling pathway in animals. &lt;br /&gt;
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In text referencing has been carried out throughout the web page which is commended, and an extensive reference list is developing well. Be sure to reference information twice (using the same reference number) when they are being mentioned, so that the reader has a direct link to where this is being sourced from. For example, another reference for when “Chiang et al., 2001” is mentioned would be appropriate, as the preceding paragraph referenced this work without specifically mentioning Chiang. More in-text referencing in the “Blockage of Shh Signalling in Forebrain Neuroectoderm of Chick Embryos” section would also be appropriate, even if the same references are being re-used. This would make it easier for the readers of the web page to easily access further information at any point in the web page.&lt;br /&gt;
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GROUP 4&lt;br /&gt;
From reading through Group 4’s project I can see they are clearly and succinctly describing the topic at hand, which is related to the hedgehog pathway. They explore things such as the mechanism of signalling during embryonic development as well as neural and organ development. From reading their research I can see they have carefully written it according it to criteria 1. Unfortunately, their use of headings and sub-headings, diagrams, tables, graphs is not as good as it could be. They have used an imagine of the Hedgehog signaling pathway, which is a good start, but to improve and further fulfil this criterion I would suggest having more media. The referencing has been done quite well as it has its own section and is easy to find, but also there are quite regular in text citations, fulfilling criteria 3.&lt;/div&gt;</summary>
		<author><name>Z5020466</name></author>
	</entry>
	<entry>
		<id>https://embryology.med.unsw.edu.au/embryology/index.php?title=Talk:2016_Group_Project_3&amp;diff=249776</id>
		<title>Talk:2016 Group Project 3</title>
		<link rel="alternate" type="text/html" href="https://embryology.med.unsw.edu.au/embryology/index.php?title=Talk:2016_Group_Project_3&amp;diff=249776"/>
		<updated>2016-10-07T02:12:34Z</updated>

		<summary type="html">&lt;p&gt;Z5020466: &lt;/p&gt;
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&lt;div&gt;{{ANAT2341Project2016discussionheader}}&lt;br /&gt;
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==Peer Review==&lt;br /&gt;
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===Group 3 Peer Review===&lt;br /&gt;
At first glance, your page looks well structured with lots of information present so well done! Your introduction is concise but effective and it provides a good outline of the topic. It’s also good that you’ve started to explain the history - I think the timeline will be really helpful once it’s finished. All your referencing looks to be correct and most of the abbreviations are all defined. The table of subtypes of FGFR is a great way to present this info briefly and clearly, and I really like that you’ve also listed the associated abnormalities. Also, your hand-drawn image is a great effort but it would be better to clearly explain all the abbreviations (at least on the actual image summary page, or maybe in the glossary) since it’s not all defined in the text. You guys have done a really great job so far in explaining the different roles in embryonic development and it’s especially good that you’ve included descriptions of primary research. And your image for bone development is a really helpful addition to your info.&lt;br /&gt;
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Obviously your group still has some research and info to fill out in your sections but you’ve done really well so far. For your abnormalities section, I think it would be good if you can find some related pictures to include. In general I think you should add more content and explain your sections in some more detail - particularly the overview of the pathway and the signal transduction section. At the moment it’s more of a description/listing of the components and factors, rather than a full explanation of how they interact and the responses they induce. So as long as you guys get fill out your content a bit more and make sure to finish off your quiz, history, animal models, and new/current research sections then I think you will have a great page by the end.&lt;br /&gt;
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===Group 3 Peer Review===&lt;br /&gt;
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'''Positive Factors'''&lt;br /&gt;
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Overall Group 3 has made a really comprehensive effort at addressing the assessment criteria so far. The flow and amount of information covered by this Group is really impressive, showing that they have begun to cover criteria 1, 2, 3 and 5. The range of tools used to convey information (tables, diagrams, the quiz) make this Group’s page a lot more engaging, particularly for a student audience (covering criteria 4). The use of in-text links to wiki pages describing certain terms is also a positive aspect, which lets the readers gain a better understanding of relevant areas of embryology (covering criteria 6). &lt;br /&gt;
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'''Points for Improvement'''&lt;br /&gt;
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Some improvements that could be made to this page include: the use of in-text links directly to the glossary to better aid students’ understanding of specific terms used throughout the explanations (this would better address criteria 4); using more succinct headings in some areas such as that under the ‘New and Emerging Research Into FGF’ section; and also a more extensive timeline could be used.&lt;br /&gt;
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'''Overall'''&lt;br /&gt;
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In conclusion, Group 3 have a lot of strengths in their work so far, particularly the volume of information they have provided that is formatted in an engaging and logical way. Only a few improvements are necessary for this Group’s project as it seems they have already begun to address most of the assessment criteria.&lt;br /&gt;
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===Group 3===&lt;br /&gt;
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You guys have made a good start on your project! I particularly liked how the headings were subdivided appropriately into smaller subheadings as it effectively broke down the FGFR pathway and made the page easy to navigate. Though you have included a short and succinct introduction, I think it should address all the sections being discussed to give the reader a better overview of your project. In addition, the use of a table to explore the timeline of research of the FGF pathway was an excellent idea but I think the text above the table could be incorporated into the table itself and a more extensive timeline could be provided. &lt;br /&gt;
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Though it was good that you provided a brief overview of the FGFR pathway, you’ve only discussed the components of the pathway rather than the pathway itself. Furthermore, when discussing signal transduction, I think you should be more specific when explaining the process, for example when you mentioned ‘which leads to changes in gene transcription through interactions with DNA’, it causes changes in transcription in which genes and through interactions with which DNA? In saying this, it was wonderful to see the inclusion of a hand-drawn diagram which represents not only your understanding of the pathway but also aids readers understanding of the FGFR pathway. &lt;br /&gt;
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A good overview has been provided to explain the role of FGFs in embryonic development. The only suggestion I can make is to provide explanations or full names of the abbreviations to aid understanding of the concepts explored. For example, what is ETV1 and EWSR1? By explaining what these abbreviations are the reader will gain better understanding on how they function to help maintain FGF10 expression. In terms of the section on abnormalities, a succinct and coherent introduction was provided. There was a good description of the morphological changes produced by these mutations along with the cause of these abnormalities. There isn’t much I would change in this section except for maybe explaining FGFR2 mutation. &lt;br /&gt;
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Overall, you guys have done a fantastic job! I thought the inclusion of a quiz was particularly innovative as it makes your project interactive and thus, aids the learning process. Everything was well cited and referenced and it was wonderful to see the use of an original diagram. It was also good to see all groups members contributing to the discussion page which indicates effective communication within the team. &lt;br /&gt;
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===Group 3 Critical Assessment===&lt;br /&gt;
A great introduction to the topic, allowing the reader to slowly transition into the more in-depth points! I particularly like how you have broken down the different constituents of the pathway such as the receptors and protein subtypes and provided a succinct table outlining their function and clinical significance before moving onto the mechanism. Although the ‘FGF Subtype’ table has proven to be effective and helpful, the table on ‘History’ does not seem to be thorough and is very limited. Possibly extending the table by researching more developments in the field of FGF Signalling could make it appear more complete. &lt;br /&gt;
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Effort has been made to include a hand drawn image of the signalling pathway, which serves as a great source of aid in understanding how the pathway works whilst reading the text beside it. In saying that, effort should be further made to include a complete glossary and ensure terms such as ‘receptor dimerization’ ‘morphogenesis’ are broken down for the reader in order to satisfy criteria 4. This is not only seen in the ‘Signal Transduction’ section but also throughout the other sections. As you have included a fantastic image on bone development to represent the information visually, it would also be a good idea to post up images covering the other areas of embryonic development, such as kidney and inner ear development! You could even consider including short clips explaining these processes to make the page more interactive. &lt;br /&gt;
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It is clear a decision has been made to talk about ‘Animal Models’. As well as including text on the topic, a possible option could be including a table briefly outlining which animal model has contributed to what knowledge in relation to the pathway in order to simplify the information.  &lt;br /&gt;
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A particular highlight of the Wiki page is the use of a quiz. It is great to see viewers can test their understanding of the topic towards the end and challenge themselves! For the correct option to each question a link to a supporting article or particular section of the page can be provided so the viewer can revisit the information should they have answered the question incorrectly. Overall a great use of tables, images and interactive components!&lt;br /&gt;
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===Group 3 Peer Assessment=== &lt;br /&gt;
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With regards to your project I have noticed there are many forms of educational tools employed or being planned other than text, which to me is a big plus with regards to your project. The usage of the table to summarises the different FGFR sub-types is really easy to read and understand, and presents the information in a better way than you could’ve with just a wall of text. Your planned multiple choice section seems like it would be a nice addition to your page where it should help solidify the knowledge of the reader, allowing to check what they know. When doing the quiz section not only would it be good if you added explanations for the correct answers, but maybe also if possible explanations of why the other answers are wrong. There seems to be no issues with your citations given that all of them are in-text and multiple. Also the link between signal transduction, embryonic development and abnormalities is quite smooth and within context of their respective preceding parts, making the page read very well. &lt;br /&gt;
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With regards to your usage of images, it seems mostly good and compliments the passages well, but I feel that it would benefit with adding more information to the legend, possibly by moving some of the description when clicking into the image into the legend. Also since your first image contains mainly abbreviations, maybe it would be good to collate all abbreviations and add it to the glossary such that the reader can easily refer to what the abbreviations mean. &lt;br /&gt;
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With respect to your signal transduction section, all the components of the pathway seem to have been included, but for the most part how each factor interacts with one another has been left out. Elaborating on how each factor interacts and activates one another such as how FRS2 recruits GRB2 and SHP2, and how those events actually promote activation of RAS. I feel adding this will really improve the depth of this section, and make it less about a bunch of different components and more about how the work together in the context of their individual functions. Also I feel that the history section could be expanded on, maybe to include more time points or critical areas of discovery for the FGFR pathway.&lt;br /&gt;
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Overall I think your project is shaping up quite well, and that with the addition of the suggestions made above, would make your project quite good. Having used many images, a table, and including the quiz has really made your page quite interactive and engaging which has really benefited your page. Also your subheadings and included passages have appeared to cover most important topics within your signalling pathway. &lt;br /&gt;
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===Group 3 Peer Assessment=== &lt;br /&gt;
Positive aspects of the project and improvements:&lt;br /&gt;
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The group project looks terrific at the initial glance. You can clearly see all the headings and subheadings. In particular, it is great to see a range of subheadings such as “limb bud formation”, “bone development”, “kidney development”. This shows that there was a lot of research put into this project. Also by doing so you have made it clear that your project is about the Fibroblast Growth Factor Receptor Pathway (FGFR). The page is also very easy to navigate as well which was nice to see. &lt;br /&gt;
It is also great to see that there is addition of tables, images, and diagrams as it kept the read a lot more interesting and captivating. This allowed you to successfully satisfy criteria 2. It is also good to see correct in text citations and references as this allowed the reader to search for additional information if interested or necessary. Although you haven’t made up any multiple choice questions it is excellent to see a MCQ section. This is a great way to test the readers’ knowledge and in turn you can reflect if you have provided accurate and sufficient information to answer these questions. &lt;br /&gt;
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It was great to see that you added an abnormalities section and in particular different types of syndromes and disorders. This meant that you went over the minimum information required and put in extra effort to create a coherent project. This satisfied criteria 5 and thus a better project. Overall there are many positives in this report and with minor amendments such as adding information to sections such as “Apert syndrome”, “Animal models”, “Kidney development”, “external genitalia development” etc, a very articulate and well rounded project will be created.&lt;br /&gt;
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Negative aspects of the project and improvements:&lt;br /&gt;
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Although there are many positives in the project, there should be some amendments to the project just to ensure all bases are covered. Firstly, it would be advised to increase the amount of information to the introduction and history sections. As these sections are lacking information, the reader may not have enough information to carry on reading as their base on this topic isn’t really strong and lacks information. This can easily turn off new readers and inhibit further exploration of the topic/ project. By adding additional dates in the history section, a better overall knowledge and background of the signalling pathway can be developed which can only enhance learning.  &lt;br /&gt;
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Overall, there are not many negatives and I believe as a reader your project was a great example of progress so far and with the aforementioned minor tweaks, your group is well on their way to achieving extremely high marks.&lt;br /&gt;
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===Group 3 Peer Assessment=== &lt;br /&gt;
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Positive Assessment&lt;br /&gt;
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Wow this is a very professional looking page and one that I was immediately drawn to. The introduction is very clear and simple and I was able to understand the basic of FGFR  straight away which made it so much easier for me to try to understand the rest of the information. I absolutely love the use of the tables to introduce the sub-types of FGFR as this is so much easier to read than blobs of information. The dot points are concise and to the point and introduce each sub-type along with its abnormality. &lt;br /&gt;
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The signal transduction in any signalling pathway is probably the most confusing and hard to understand part. However this part of your project is my favourite and I was surprised as to how quickly I managed to understand the molecular mechanisms of FGFR. The hand drawn diagram is amazing and really clearly displays all the key elements in play for FGFR. What I really like about your page is that it is really user and student friendly. It really invites learning and encourages it. The use of a quiz is a great example of this and really does allow the student to reflect on their knowledge.&lt;br /&gt;
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Critical Assessment:&lt;br /&gt;
 &lt;br /&gt;
The page is absolutely amazing but in my opinion there are a few ways that it could be made even more amazing.&lt;br /&gt;
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Sometimes the information is a bit overwhelming, in that there is too much of it. For example in the sections Limb Bud formation and Bone development, for information that complicated it would probably be better to employ the use of dot points or tables just to make the information more digestible. Although the hand drawing of the signal induction is extremely useful, I think it could be made even better by being accompanied with some specific step by step commentary which matches with the drawing. As a student this would make learning about FGFR a lot more engaging and easier. 	&lt;br /&gt;
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The section on bone development although very informative could be more relevant to embryology and lastly a section outlining the treatments available for the abnormalities would be very interesting.&lt;br /&gt;
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Overall great work guys !&lt;br /&gt;
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===Peer Assessment: Project 3: Fibroblast Growth Factor Receptor (FGFR) Pathway===&lt;br /&gt;
====1. The key points relating to the topic are clearly described.====&lt;br /&gt;
The key points related to the topic are clearly described however the introduction is a little limited and further information is needed with examples.&lt;br /&gt;
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====2.The choice of content, headings and sub-headings, diagrams, tables, graphs show a good understanding of the topic area. ====&lt;br /&gt;
The fibroblast growth factor receptor pathway wiki does overall seem to have a very extensive list of contents, which demonstrate that the topic is divided into clear interesting sections.  This wiki has a good use of a table to demonstrate history (be it small) and subtypes of FGFR pathways.&lt;br /&gt;
In the history section it is not clear if they first discovered FGFR in human pituitary or pig or mouse. Please be more explicit. The history table does not seem to be finished as from 1999 to present there is no information at all added. Also there is no reference to the History information and this needs to be referenced.&lt;br /&gt;
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====3. Content correctly cited. ====&lt;br /&gt;
The content is cited correctly. However as mentioned there are some sections which are not referenced at all: History, Bone Development (there is a large paragraph which says a lot of what is known but it is not referenced.&lt;br /&gt;
Some of the references are repeated in the reference list: see below in wiki guidelines.&lt;br /&gt;
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====4. The wiki has an element of teaching at a peer level using the student's own innovative diagrams, tables or figures and/or using interesting examples or explanations. ====&lt;br /&gt;
There 2 small tables  and two diagrams which are educational.  I am very impressed that one of the members of the group re drew the first diagram. It is quite artistic but it is a bit confusing as to what each abbreviation in the figure means. If this sort of figure is added I think that some abbreviations or an explanation in the text needs  to be added to allow the reader to understand what is actually happening . If not it looks like a figure with some sort of pathway but not very clear as to what It represents. &lt;br /&gt;
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====5. Evidence of significant research relating to basic and applied sciences that goes beyond the formal teaching activities. ====&lt;br /&gt;
This is evident that the students have done a lot of research in this topic.&lt;br /&gt;
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====6.Relates the topic and content of the Wiki entry to learning aims of embryology. ====&lt;br /&gt;
Yes there are some headings which relate to the learning aims of embryology such as limb bud formation and bone formation. But there are some sections which are not finished at all  Kidney development, External Genitalia development, Inner Ear Development and Animal Models.&lt;br /&gt;
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====7. Clearly reflects on editing/feedback from group peers and articulates how the Wiki could be improved (or not) based on peer comments/feedback. Demonstrates an ability to review own work when criticised in an open edited wiki format. Reflects on what was learned from the process of editing a peer's wiki. ====&lt;br /&gt;
It does seem that that the members of the group have had some communication and worked together well.  It does seem that they have learnt to edit a wiki, making a online quiz, making tables, adding figures and content. Well done!&lt;br /&gt;
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====8. Evaluates own performance and that of group peers to give a rounded summary of this wiki process in terms of group effort and achievement.====&lt;br /&gt;
This is a very interesting and well-researched wiki. There is still information lacking and more figures are needed as well as explanations for the figures. It is clear that a lot of effort has been carried out with the quiz, the figure that was re drawn from a publication.&lt;br /&gt;
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====9. The content of the wiki should demonstrate to the reader that your group has researched adequately on this topic and covered the key areas necessary to inform your peers in their learning. ====&lt;br /&gt;
The key areas on this wiki have been  researched adequately. There is still information missing.&lt;br /&gt;
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====10. Develops and edits the wiki entries in accordance with the above guidelines. ====&lt;br /&gt;
Yes this wiki is in accordance with the guidelines. In terms of the reference list, some references have been re cited and added as new references, please see editing guidelines to avoid this- as so the reference is only listed once in the reference list and not  multiple times.&lt;br /&gt;
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===Group 3===&lt;br /&gt;
This page is developing well, as extensive headings have been well organised, with substantial written and visual information. A fantastic student produced image has been included, showing the different steps in the signalling pathway in a flowchart. It is very clear and neat, and the group is highly commended for this. An interesting and potentially humorous image can be included at the beginning of the web page to attract the reader’s attention and add interest to the page. Another image showing the ‘FGF and FGFR expression patterns during endochondral and intramembranous bone development’ has been included and is very clear and relevant. Another flowchart in the “Limb Bud formation” section would also help the reader summarise the different processes and the FGFR subtypes involved in each step. Adding short animations or movies would also be very helpful in aiding the reader understand these processes, particularly in the ‘Patterning Of The Embryonic Axis’ subheading. Images in the abnormalities sections, such as what the hands, broad thumbs, feet and medially deviated broad great toes of those with Pfeiffer Syndrome look like would also add depth to the web page. &lt;br /&gt;
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Extensive and well organised headings have been included in this project, although some headings are still incomplete. A history section has been included in this web page. The timeline in this section requires more information as only two years, 1973 and 1999, have been included. More information is needed on the research carried out over the last decade, as well as gaps in this research, where future studies are heading and what is currently being researched in relation to this signalling process. The naming of researchers and where this research took place would also show depth of knowledge and extensive research, as required in the criteria. A heading at the bottom of the web page has been included titled “New and Emerging Research Into FG” and needs more information added to it. A summary of the current findings and research should also be added to the timeline higher up on the page when this section is further worked on. &lt;br /&gt;
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Other sections including the glossary and “Animal models” sections have been started. Further terms to define in the glossary should include full names of terms such as RAS and AER included in the web page. The “Animal models” section is a comprehensive addition to the web page but is empty and requires further research. Ensure images of the animal models being explored are included in this section to enhance the textual information and to improve the readers’ understanding of these animal models. A table of the FGFR Subtypes has been included which is commended, however, needs much more elaboration as it is still quite bare. Images of these different FGFR Subtypes would also add depth to this web page. &lt;br /&gt;
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In text referencing has been carried out well so far in this project. The writers often need to use references again when researchers and their research is mentioned again. For example, Mathias et al. (2001) is mentioned in the Subheading “Patterning Of The Embryonic Axis”. This research was referenced in the paragraph before the researchers were specifically mentioned, and thus should be referenced again with the same reference number. In the Limb Bud formation heading, a link to the lecture notes for Limb Development has been included. This is a very good way to allow the readers to easily access more information relevant to the topic.&lt;br /&gt;
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GROUP 3&lt;br /&gt;
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Overall from analysing through Group 3’s project I can starkly see that they have made a good attempt at addressing the marking criteria. The flow and clarity of the information in this project shows some serious thought and is showing a promising coverage of criteria 1. Not only this, but the group has excellently covered criteria 2 by having a plethora of headings, subheadings, tables and diagrams. Not only this but they have included a quiz which really shows an extra level of understanding and effort. One improvement that I might suggest is that they could extend the table by researching more developments in the field of FGF Signaling. Furthermore, this group has covered criteria 3 quite well as well but having a thorough amount of references and in text citations. Also, I have been able to learn a great amount of information from this project which means they have successfully achieved criteria 4. Overall, this project has done very well in presenting their project. &lt;br /&gt;
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==&amp;lt;u&amp;gt;&amp;lt;font size=&amp;quot;4.5&amp;quot;&amp;gt;Comments by Group 3&amp;lt;/font&amp;gt;&amp;lt;/u&amp;gt;==&lt;br /&gt;
[[User:Z5015686|Z5015686]] ([[User talk:Z5015686|talk]]) 12:36, 19 August 2016 (AEST) I thought looking into how prenatal cannabis exposure influences signalling during development might be interesting&lt;br /&gt;
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[[User:Z5017002|Z5017002]] ([[User talk:Z5017002|talk]]) 12:47, 19 August 2016 (AEST) Ooh cool idea, I agree that looks really interesting, there seems to be a lot of literature about its influence on brain development&lt;br /&gt;
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[[User:Z5015544|Z5015544]] ([[User talk:Z5015544|talk]])z5015544[[User:Z5015544|Z5015544]] ([[User talk:Z5015544|talk]]) Thats excellent, what about the sonic hedgehog pathway?&lt;br /&gt;
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[[User:Z5015544|Z5015544]] ([[User talk:Z5015544|talk]])Other ideas[[User:Z5015544|Z5015544]] ([[User talk:Z5015544|talk]]) 	WNT Signaling Pathway is another one to look at&lt;br /&gt;
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How can we harvest stem cells from the embyro for use in later life - z5015337&lt;br /&gt;
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[[User:Z5015544|Z5015544]] ([[User talk:Z5015544|talk]])z5015544[[User:Z5015544|Z5015544]] ([[User talk:Z5015544|talk]]) Ok guys I created a couple of subheadings and provided a brief history. Make sure to use primary research articles that are peer-reviewed because I just spoke to Dr Hill and noticed he stressed that a lot.&lt;br /&gt;
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[[User:Z5015337|Z5015337]] ([[User talk:Z5015337|talk]]) I have scoured through the projects of old to get a better idea about what is expected from us for this project - [[User:Z5015337|Z5015337]] ([[User talk:Z5015337|talk]])&lt;br /&gt;
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[[User:Z5015337|Z5015337]] ([[User talk:Z5015337|talk]])I found this giant slab of text regarding the structures of the receptors involved from a journal article and I am working through culling it down for a usable structure definition: FGF receptors and FGF signal transduction. FGFRs are modular proteins comprising 3 immunoglobulin domains (IgI, IgII and IgIII). IgI and IgII are separated by an acidic box (AD). IgII contains a heparin binding domain (HBD). The IgIII domain is followed by a unique transmembrane (TM), a juxtamembrane (JM) and a kinase domain (KD) interrupted by an interkinase domain (IKD). FGF ligands linked to heparin sulfate proteoglycan (HSPG) bind to IgII and IgIII of FGFR. This results in the dimerization and the subsequent transactivation by phosphorylation of specific tyrosine residues. The main two transduction pathways involve the phospholipase C-γ (PLCγ) and the Ras/MAP kinase. The SH2 domain of the PLCγ interacts with the phosphorylated Y766 of the activated receptor. The activated PLCγ hydrolyzes the phosphatidyl-inositol-4,5-diphosphate (PIP2) to inositol-1,4,5-triphophate (IP3) and the diacylglycerol (DAG). IP3 releases Ca2+ while DAG activates the protein kinase C-δ (PKCδ). Activated PKCδ activates Raf by phosphorylating its S338 and stimulates the downstream pathway in a Ras independent manner. The main pathway involves the interaction of the docking protein FRS2α with the amino-acid residues 407–433 (Xu et al., 1998). This protein is activated by phosphorylation on multiple tyrosine residues and subsequently interacts and activates Grb2 linked to Sos, a nucleotide exchange factor involved in the activation of Ras. Activated Ras then activates Raf which stimulates MEK which in turn phosphorylates the MAP kinase ERK. This last activated component translocates to the nucleus and phosphorylates specific transcription factors of the Ets family which in turn activate expression of specific FGF target genes. P: phosphorylation&lt;br /&gt;
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[[User:Z5015686|Z5015686]] ([[User talk:Z5015686|talk]]) 18:31, 14 September 2016 (AEST) Hey guys I've just changed our subheadings so we can better allocate something for each of us to write on this week. More then happy to change them! Just came across these while I was researching. Did everyone maybe want to put their name next to something they are able to research or chuck in new subheadings that interest them?&lt;br /&gt;
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[[User:Z5015544|Z5015544]] ([[User talk:Z5015544|talk]]) 14:31, 16 September 2016 (AEST)Hey guys, here is the link for omim. Type in the name of the gene and it will give you different articles about it: http://www.omim.org/[[User:Z5015544|Z5015544]] ([[User talk:Z5015544|talk]]) 14:31, 16 September 2016 (AEST)&lt;br /&gt;
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[[User:Z5015544|Z5015544]] ([[User talk:Z5015544|talk]]) 14:41, 16 September 2016 (AEST)Things to include: Flow diagram of the FGFR pathway, 3D diagram of the FGF protein (can be hand-drawn)[[User:Z5015544|Z5015544]] ([[User talk:Z5015544|talk]]) 14:41, 16 September 2016 (AEST)&lt;br /&gt;
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[[User:Z5015544|Z5015544]] ([[User talk:Z5015544|talk]]) 23:22, 28 September 2016 (AEST)Hey guys, hope you're all enjoying the break. Just thought I would let you know I've added a hand drawn diagram and a table too. If anyone finds more information about specific receptor functions in embryo development please add it to the table.[[User:Z5015544|Z5015544]] ([[User talk:Z5015544|talk]]) 23:22, 28 September 2016 (AEST)&lt;br /&gt;
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[[User:Z5015686|Z5015686]] ([[User talk:Z5015686|talk]]) 12:35, 29 September 2016 (AEST) '''just moved this from our main page''' Extra Resources&lt;br /&gt;
Useful review articles that may be worth a read through: &lt;br /&gt;
http://onlinelibrary.wiley.com/doi/10.1002/wdev.176/full&lt;br /&gt;
http://www.nature.com.wwwproxy0.library.unsw.edu.au/nrd/journal/v8/n3/pdf/nrd2792.pdf &lt;br /&gt;
http://www.sciencedirect.com.wwwproxy0.library.unsw.edu.au/science/article/pii/S0012160605006184&lt;br /&gt;
http://www.nature.com.wwwproxy0.library.unsw.edu.au/nrm/journal/v14/n3/full/nrm3528.html&lt;br /&gt;
http://onlinelibrary.wiley.com.wwwproxy0.library.unsw.edu.au/doi/10.1002/jcp.24649/full &lt;br /&gt;
http://genesdev.cshlp.org/content/29/14/1463.full (FGF signalling and skeletogenesis, specifically how mutations to the FGF signalling pathway may be responsible for skeletal diseases)&lt;br /&gt;
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[[User:Z5015544|Z5015544]] ([[User talk:Z5015544|talk]]) 01:14, 4 October 2016 (AEDT)Looking really good guys, I think we should try and expand beyond what has been covered in the lectures. Maybe we can look at new research involving FGF. We can also look at FGF in animals and how it affects limb development. Let me know what you guys think&lt;/div&gt;</summary>
		<author><name>Z5020466</name></author>
	</entry>
	<entry>
		<id>https://embryology.med.unsw.edu.au/embryology/index.php?title=Talk:2016_Group_Project_2&amp;diff=249774</id>
		<title>Talk:2016 Group Project 2</title>
		<link rel="alternate" type="text/html" href="https://embryology.med.unsw.edu.au/embryology/index.php?title=Talk:2016_Group_Project_2&amp;diff=249774"/>
		<updated>2016-10-07T02:11:37Z</updated>

		<summary type="html">&lt;p&gt;Z5020466: &lt;/p&gt;
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&lt;div&gt;{{ANAT2341Project2016discussionheader}}&lt;br /&gt;
=Peer Review=&lt;br /&gt;
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&amp;lt;u&amp;gt;Group 2:&amp;lt;/u&amp;gt;&lt;br /&gt;
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&amp;lt;b&amp;gt;Positive aspects of the project and suggested improvements: &amp;lt;/b&amp;gt;&lt;br /&gt;
Group 2 has provided a variety of different topics related to the Notch receptor, such as its molecular pathway, its role in embryonic developing both in humans and animals as well as abnormalities caused by disruption in the receptor’s normal function (criteria 6). This variety is excellent, as it informs the audience of various aspects of the Notch receptor ranging from normal to abnormal development as well as newly emerging research (criteria 1.). Group 2 has also utilised both tables and diagrams to represent Notch receptor’s history and signalling pathway respectively (criteria 2). The use of diagrams is a great idea as it allows peers to understand the complexity of the signalling pathway in a much simpler manner (criteria 4). &lt;br /&gt;
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In addition, the authors have correctly utilised in text citations when referencing all sources and have created a list of references at the conclusion of the page (criteria 3). Group 2 also investigated specific components of organ development which was another magnificent feature of their page, such that they divided cardiovascular development into different stages including “heart valve development” and “trabeculation” for example. This allows for an in-depth understanding of organ development with respect to the Notch receptor, rather than a general overview of the receptor’s involvement (criteria 5 and 6). The authors also have extended beyond Notch’s involvement in human embryonic development by exploring its role in animal embryonic development (criteria 5).&lt;br /&gt;
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Although there are many positives, a possible improvement to this outstanding wiki would be to include a table of the different types of Notch receptors that exist and their different roles in embryonic development. This will allow the audience to understand that there is not just a single receptor playing a role in embryonic development but multiple. Another suggestion would be to add more subheadings under the “Central nervous system” development, as this subheading appears to have a lot less information compared to others. Also, it is obvious that there are different pathways for this receptor such as “Canonical” and “Non-canonical”, therefore it would be a great idea to include a youtube video to summarise these pathways and reinforce the in-depth description already provided on the page. &lt;br /&gt;
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&amp;lt;b&amp;gt;Negative aspects of the project and suggested improvements:&amp;lt;/b&amp;gt;&lt;br /&gt;
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It was also noticed that a variety of terms were utilised which were not defined in the glossary such as “cyclins”, “pluripotent stem cells” and “ligands” for example. It is important to consider that the wiki should be able to teach at a peer level (criteria 4), as some students may not understand these terms. Therefore it is important to define them so audiences can develop a coherent understanding of the information. Another negative feature of the page was that it lacked interactivity. Indeed the page is very informative, however to further engage the audience, a suggestion would be to include a set of multiple choice questions at the end of the page which tests peers about the content covered.&lt;br /&gt;
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It was also noticed that the page had a very limited number of subheadings regarding Notch’s involvement in embryonic development. A possible improvement would be to investigate Notch’s involvement in organ systems other than Cardiovascular and central nervous system. This will add a greater variety to the page and provide a greater depth of understanding regarding the role of the Notch signalling pathway in embryonic development.&lt;br /&gt;
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===Group 2 Peer Review===&lt;br /&gt;
At first glance, I was blown away by your team's page. Definitely very impressive and understandable. The key points relating to the Notch signalling process are definitely clearly described however I may recall Dr Hill requesting that teams steer clear of clinical effects of genes(citation needed!). The choice of headings, sub-headings and diagrams show more than a good understanding of the topic area, it may be useful to include a table that summarises the various aspects of the Notch pathway so that readers realise there are different receptors. The content is cited correctly, however, I would not mind reading 'et al' instead of 'and colleagues' more often, I got sick of reading 'and colleagues'.&lt;br /&gt;
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The information presented is mostly peer friendly in the context of a simple introduction but your glossary certainly needs updating, there are a lot of terms that a lot of students would not understand and a comprehensive checking of your page will offer you a list of words that you need to define. Also lacking are sketches presented in your own hands, instead of reusing published images. There is plenty of evidence that suggests your team has went beyond the formal teaching activities. In the context of the aims of the embryology course, you guys have emphasised the embryonic role of Notch but the aspect of developing technologies appears to have been ignored to an extent.&lt;br /&gt;
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Overall, you guys have done a very impressive job that only requires minor tweaking, namely slight editing in the context of in text referencing, more comprehensive glossary as well as checking the course aims of embryology to incorporate the second criterion regarding technology. Excellent work!&lt;br /&gt;
===Group 2===&lt;br /&gt;
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Well done on the progress you have made thus far! You guys have chosen appropriate headings and subheadings that effectively break down the Notch signalling pathway. A coherent introduction has been provided, giving a taste of what is to be expected in this project. The use of a table to explore the history of this signalling pathway was particularly useful in making the information understandable and relevant. Though you have done an excellent job, was there any reason you stopped at 1989? It may even be useful to create a brief timeline of events, thus allowing you to better explore current areas of research by considering past studies that have been performed.&lt;br /&gt;
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You’ve provided a good overview of the canonical pathway with the appropriate use of a diagram which aids reader’s understanding of the information provided. In saying this, I think it would be useful to expand on how this pathway is tightly controlled, is it through transcriptional regulation or through other means? In addition, it may be useful to explain the differences in the non-canonical and canonical pathways in terms of their significance and role in embryonic development. I’ve noticed that you have provided a general overview of the role of Notch signalling pathway in embryonic development, do these roles differ between the canonical and non-canonical pathways?&lt;br /&gt;
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In addition, it’s good that you have included the role of the Notch signalling pathway in animal development as it explores the scope of this pathway beyond human embryology but it may also be useful to explore animal models in research, especially considering that the ‘first description of a “notch” defect’ was discovered in Drosophila. By combining the role of animal models in expanding our knowledge of the Notch signalling pathway with the effect of this pathway in animals, it provides a more rounded approach to explaining and discussing this signalling pathway. &lt;br /&gt;
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I particularly like how you have included statistics in the ‘Abnormalities of Notch signalling’ section as it provides insight into the importance of this pathway in embryological development. You have successfully described the type of mutation that results in the particularly disease in most cases except for Alagille syndrome. More detail in how the mutation causes the syndrome would be useful with an explanation of how the mutation is brought about. &lt;br /&gt;
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Overall, you guys have done a fantastic job! You have appropriately referenced and cited all the information provided and have included useful flowcharts, tables and diagrams that aid understanding of the text provided. Providing more detail to each of the sections and communicating with all your team members in the discussion page will ensure that you produce an excellent project! Good luck!&lt;br /&gt;
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===Group 2 Critical Assessment===&lt;br /&gt;
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A job well done with the introduction! The introduction is brief however manages to link the topic to embryonic development, different medical conditions, whilst also outlining the function and elements of the pathway. Being brief and succinct, it allows the viewer to continue exploring the page without experiencing confusion at the first lot of information. Further to this, the history of the pathway is formatted well and is not too overwhelming or boring. It is evident you have decided ‘Current Areas of Research’ will also be included in your page which is a great idea as you have included a section on History. This would ensure your Wiki flows well, and covers the pathway from start to finish. &lt;br /&gt;
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Images have been included to visually represent the elements of the general pathway, as well as the elements specific to the pathway in cardiac development, which forms a great aid for viewers in understanding the content. Videos explaining the different canonical and non- canonical pathways could also be included for viewers with a video learning preference. &lt;br /&gt;
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Use of in text citations neatens the layout of information and enables viewers to access the article should they find the point interesting. Numerous subheadings have been included which further break down the page into small sections of information. This is a fantastic positive as viewers can locate information in which they are interested in easily instead of having to read through long paragraphs of text. I feel as if linking the topic clinically is extremely important which you have done a great job in! Along with the text explaining the disease, you could possibly include a table stating the disease, the mutation, and the symptoms for viewers after a more easy, accessible format. &lt;br /&gt;
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Throughout the topics covered, a lot of jargon is utilized, however a full glossary has not been provided. A glossary should definitely be included for terms such as ‘gastrulation’, ‘kinases’ or ‘cardiogenesis’ in order to satisfy criteria 4. Additionally, the page does not cater for viewers interested in further reading up on the topic. To ensure criteria’s 4 and 5 are met, links to interesting facts or articles could be provided so the audience has access to more information if they would like to further their understanding. With a few improvements this Wiki page can definitely prove helpful in understanding the pathway! &lt;br /&gt;
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===Group 2 Peer Assessment===&lt;br /&gt;
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Your project is quite good and seems to be on the right track. All your references have been done in-text and have made it really easy to make one’s way to the research article to read more about certain points. Not only that, you have appropriately abbreviated your terms by using the full name initially, and I can see that you have a glossary section which should be beneficial in the future when more terms are added. Your history section is well presented but, it might be important to add references to the papers of the main points of discovery in your history section as to allow people to easily access and find the full article regarding the discovery. &lt;br /&gt;
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The fact that you have added pictures is quite handy when it comes to using it as an aid to accompanying passage. With regards to the image legend, maybe add more information to it or transfer the description of the image present when clicking into the image onto the legend as to better represent what the image is about while having the passage right next to it. Furthermore, maybe it would be beneficial to add other forms of media such as videos to compliment the passages as well, and help better engage the reader in the topic. &lt;br /&gt;
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With regards to your section on the canonical pathway, I’ve noticed that the specific genes that are targeted by Notch have been left out and I feel that it is important to mention those genes targets explicitly there as well. That being said, they are mentioned in the proceeding section so it isn’t imperative that you do this. Maybe also try seeing if there is any literature on how the NOTCH receptors come about, such as what genes transcribe it and how the protein is processed and expressed before signalling in the pathway can occur. &lt;br /&gt;
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I think for the most part there is very little to improve with your wiki page given the quality of it albeit a few minor corrections that I have mentioned above. It is very concise and at no times do I feel that I am reading a wall of text that is disengaging. Thus I feel that as long as such quality is maintained then your wiki page will be quite good when finished. &lt;br /&gt;
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===Group 2 – Notch Signaling Pathway ===&lt;br /&gt;
First impressions of Group 2’s page on the notch-signaling pathway are all positive. Subheadings are very well defined. They have chosen to include a brief yet informative introduction on the pathway, a simple table outlining the major scientific developments over the last 100 years, the molecular mechanisms of the pathway, its specific role in embryonic development (which they have further defined as cardiovascular and CNS), role in animal development, abnormalities relating to this pathway and a glossary. I think another positive aspect of this project, is that they have identified additional subheadings for which they are still to do research on; a particularly important one is current areas of research which not many groups have included. Furthermore, additional positive aspects of this project include the addition of images on the canonical notch signaling pathway and its role in cardiovascular development (which both appear also to be appropriately added to the website), which support the text nicely. It might also be useful to find a relevant video to include just to break up some of the text, and help make the page more interactive. It appears this group has widely researched their topic using both primary and review articles, which are all appropriately referenced using in-text citations. All of these aspects help to clearly convey the necessary information to the reader, and fulfill much of the required criteria of this project. In terms of their written information, Group 2 has included really detailed information on its role in embryonic cardiovascular development, as well as identifying some of the major research articles that have lead to these discoveries and a little bit about them (which then the reader if they are interested it can go read thanks to the inclusion of the in-text citations.) They do include a section of the roles of this pathway in animal development, which is really interesting and goes beyond the normal scope of this course.  &lt;br /&gt;
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Some negative aspects of the project include that, as part of the criteria being that the project has an “element of teaching at a peer level using the student's own innovative diagrams, tables or figures and/or using interesting examples or explanations” perhaps it would be useful to consider including a hand drawn image when researching the non-canonical pathway or transcriptional regulation of notch signaling, or even of some of the receptor/ligands involved in this signaling pathway. Furthermore, on a similar note it may be important to summarise the receptor subtypes involved in the different pathways, their role in embryonic development and abnormalities of the receptor subtype specifically relating to embryonic development in a table or dot point format. Additionally perhaps more information on its role in the CNS (or other systems during embryonic development) even if its not as detailed as cardiovascular, may help to inform the reader of all of its various roles. &lt;br /&gt;
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In conclusion, it appears that this project is one of the strongest, it has very clear and informative subheadings separating well researched written material, supported by images sourced from the Internet. The main criticisms were just including your own innovative diagrams or explanations, videos to help make it more interactive and table or dot points summarizing the different receptor subtypes involved in each pathway. Following the completion of this, and the subheadings yet to be researched (and glossary) it appears that this project is going to be very successful in informing peers about the said pathway. &lt;br /&gt;
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===Group 2 Peer Assessment===&lt;br /&gt;
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Positive Assessment:&lt;br /&gt;
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So far this page looks great and very organised. I am really impressed by the set out of the information and the way the headings are arranged. It made it really easy for me to navigate around for particular information and not have to look for around aimlessly when I was looking for something in particular.  Furthermore I think that the actual categories/sub headings used so far are very concise and effective. For example, I appreciate the brief introduction along with an overview of the molecular mechanisms involved in notch signalling before introducing its roles in embryonic development. This way I was able to have a understanding of what is really involved before understanding how it is important in embryonic development.&lt;br /&gt;
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The references are also very neatly and correctly done and many times when I did not fully understand a concept I clicked on the citations which took me to the relevant articles and my understanding was clarified. I also really enjoyed the commentary on the specific research papers, for example cardiomyocyte specification and differentiation where you guys actually compared information from separate studies to make the information more whole and relevant.&lt;br /&gt;
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In the abnormalities section, I think it was really awesome you guys included so many statistics and symptoms and not just a description of the abnormality.&lt;br /&gt;
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Critical Assessment:&lt;br /&gt;
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Although everything looks really amazing a couple of improvements that I personally think could be made would make this page really useful to students. &lt;br /&gt;
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The introduction, although very informative can be simplified a bit more to address criteria 4 and make it a bit easier to understand. This can be done through including an interesting or very simplified diagram to engage the student from the beginning. I would also generally include more diagrams and drawings that are personally drawn as the pictures used although effective, can be difficult to understand when you are learning for the first time. It would also be nice if more words are included in the glossary because there was a quite few words I did not know the meaning of. &lt;br /&gt;
Lastly I think it would be a great addition to your page to include another subheading which outlines how the abnormalities are treated as this is something that I was intrigued to discover.&lt;br /&gt;
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Overall I think your page is going great guys keep it going !&lt;br /&gt;
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===Project 2: Notch signalling pathway===&lt;br /&gt;
====1. The key points relating to the topic are clearly described.====&lt;br /&gt;
There are headings for key points and the information for these key points has clearly described. This information is laid out in a clear way beginning with an introduction, historical aspect of the topic and continues to more specific information (e.g. animal models) related to the overall topic. &lt;br /&gt;
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====2.The choice of content, headings and sub-headings, diagrams, tables, graphs show a good understanding of the topic area.====&lt;br /&gt;
The Notch singalling pathway has a very clear contents list. This demonstrates that a lot of thought and research has gone into the topic.  There are two figures which are very neat and well set out. These are referenced. There is one table which described the historical aspect of this topic and this is very clear and beneficial as it summerises a lot of information in a clear manner. &lt;br /&gt;
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====3. Content correctly cited.====&lt;br /&gt;
The content is cited correctly. If the refernces are used more than twice this has been cited in following the Wiki guidelines and the reference is not repeated in the list. &lt;br /&gt;
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====4. The wiki has an element of teaching at a peer level using the student's own innovative diagrams, tables or figures and/or using interesting examples or explanations.====&lt;br /&gt;
This wiki does have an element of teaching: It is clearly laid out, it is easy to read and the information is set up in a correct manner with a general overview, historical aspects and then more precise information is given. There is some interesting examples given which describes abnormalities in this pathway.&lt;br /&gt;
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====5. Evidence of significant research relating to basic and applied sciences that goes beyond the formal teaching activities. ====&lt;br /&gt;
This is very much evident.  There is evidence that research has been undertaken as the topic has been divided into sub topics and there is a lot of interesting clear information to educate the reader.&lt;br /&gt;
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====6.Relates the topic and content of the Wiki entry to learning aims of embryology. ====&lt;br /&gt;
Yes the topic does related to the learning aims of embryology and how Notch signalling pathway is involved in embryonic organ development through the regulation of cell-cell signalling&lt;br /&gt;
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====7. Clearly reflects on editing/feedback from group peers and articulates how the Wiki could be improved (or not) based on peer comments/feedback. Demonstrates an ability to review own work when criticised in an open edited wiki format. Reflects on what was learned from the process of editing a peer's wiki.====&lt;br /&gt;
This is still not as evident as there is no comments or feedback observed. There are still some sections that have information missing and perhaps comment or feedback could have been given here to ensure that the students fill in this missing information or remove the subheadings all together.&lt;br /&gt;
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====8. Evaluates own performance and that of group peers to give a rounded summary of this wiki process in terms of group effort and achievement.====&lt;br /&gt;
The way this Wiki is laid out clearly demonstrates that there has  been some feedback and communication between the group. It seems that each member of the group did write a section, yet the sections do come together and do not seem out of place. However there are sections with information missing and this needs to be addressed.&lt;br /&gt;
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====9. The content of the wiki should demonstrate to the reader that your group has researched adequately on this topic and covered the key areas necessary to inform your peers in their learning. ====&lt;br /&gt;
Yes the Wiki content does  demonstrate that the group has researched adqueately in this area. &lt;br /&gt;
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====10. Develops and edits the wiki entries in accordance with the above guidelines. ====&lt;br /&gt;
This has been achieved. This wiki entry does seem to be in accordance with the guidelines provided. &lt;br /&gt;
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[[User:Z3462474|Z3462474]] ([[User talk:Z3462474|talk]]) 07:15, 23 September 2016 (AEST) Hey no worries I hope you feel better soon! I won't be able to do as much during the midsem break which is why I've been doing lots this week. I'll have a look at that link thanks! Also I tried to make a Glossary but am having trouble with the coding side of it but I'll try fix it later to make it a proper glossary :)&lt;br /&gt;
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[[User:Z5015014|Z5015014]] ([[User talk:Z5015014|talk]]) 21:00, 22 September 2016 (AEST) I'm so sorry I've been terrible with putting stuff on our page!! I know I said I would get some done this week but I've been sick these past few days and still recovering so I probably won't make it to the lab tomorrow. I'm having some trouble finding an image that summarises Notch signalling that we can use (most of the good ones I've found don't allow reuse) but I'll keep looking. I'll definitely do a lot more during the midsem break. sorry again! I also found this link: http://www.omim.org/entry/190198 that looks like it has some really good references for different roles in development.&lt;br /&gt;
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[[User:Z5015014|Z5015014]] ([[User talk:Z5015014|talk]]) 14:27, 16 September 2016 (AEST) looks like a great picture so I think we can leave it. I just altered the formatting of the image a little bit, but feel free to change it back if you prefer the previous placement! also I think having the copyright info on the file page is enough. thanks for doing that, I'm still hunting out pictures as well. I've been busy this week with another group project but now that it's out of the way I should be able to do a lot more here. :)&lt;br /&gt;
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[[User:Z3462474|Z3462474]] ([[User talk:Z3462474|talk]]) 09:21, 16 September 2016 (AEST) I found one that didnt look too complicated and also found that it allowed unrestricted use so I've added it into the cardio section of our page (we can always delete it later if need be), not 100% about my formatting though and whether I should include the legend/copyright notice directly on our page? If you click the image though its all there :) &lt;br /&gt;
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[[User:Z5015014|Z5015014]] ([[User talk:Z5015014|talk]]) 23:08, 12 September 2016 (AEST) I've been looking around and found some images, but most of the time they involve a lot more detail than we need and I don't want to overcomplicate it. will keep researching this week and see if I can find some simpler diagrams. :) The images in that book look really good but yeah I'm not sure what the copyright details for that are. if it comes to it I think if we reproduce it by hand and credit the source then it's fine!&lt;br /&gt;
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[[User:Z3462474|Z3462474]] ([[User talk:Z3462474|talk]]) 13:50, 12 September 2016 (AEST) Has anyone found any good images to use for our page? I have found a couple of diagrams on cardiac development and Notch in this book chapter: http://www.sciencedirect.com.wwwproxy0.library.unsw.edu.au/science/article/pii/S0070215310920115 but am still looking to the copyright restrictions etc and thought I'd check everyone's opinion&lt;br /&gt;
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[[User:Z3462474|Z3462474]] ([[User talk:Z3462474|talk]]) 09:22, 9 September 2016 (AEST) Hey everyone, I have added some of my notes to the main page, they are still a work in progress though! I'll continue to research the roles of Notch in the development of the different systems&lt;br /&gt;
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[[User:Z3462474|Z3462474]] ([[User talk:Z3462474|talk]]) 10:04, 2 September 2016 (AEST) Just found this online textbook titled 'Notch Signaling : Methods and Protocols' http://www.springerprotocols.com.wwwproxy0.library.unsw.edu.au/BookToc/doi/10.1007/978-1-4939-1139-4&lt;br /&gt;
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This one also looks like it might be helpful: http://www.sciencedirect.com.wwwproxy0.library.unsw.edu.au/science/bookseries/00702153/92&lt;br /&gt;
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[[User:Z3462474|Z3462474]] ([[User talk:Z3462474|talk]]) 14:27, 26 August 2016 (AEST) Here are some reviews I have found that could be a helpful starting point: &lt;br /&gt;
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Notch signalling at a glance: http://jcs.biologists.org/content/joces/126/10/2135.full.pdf &lt;br /&gt;
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Signalling pathways for neural development: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4369499/pdf/WJSC-7-437.pdf&lt;br /&gt;
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Notch's role in diabetic neuropathy  https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3677813/pdf/nihms473246.pdf&lt;br /&gt;
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Notch in cardio development and disease http://circres.ahajournals.org/content/118/1/e1.full&lt;br /&gt;
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[[User:Z5015014|Z5015014]] ([[User talk:Z5015014|talk]]) 14:28, 26 August 2016 (AEST) here's the embryology site page for [[Developmental Signals - Notch|Notch signalling]]!&lt;br /&gt;
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[[User:Z5015014|Z5015014]] ([[User talk:Z5015014|talk]]) 14:31, 26 August 2016 (AEST) I also found a review article for Notch signalling in the common fruit fly, which could be a good idea for a subsection: PMID 12369105 ''General outlines of the molecular genetics of the Notch signalling pathway in Drosophila melanogaster: a review''.&lt;br /&gt;
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[[User:Z5015014|Z5015014]] ([[User talk:Z5015014|talk]]) 14:44, 26 August 2016 (AEST) and here's some more reviews: PMID 22397947 ''Non-canonical Notch signaling: emerging role and mechanism'' and PMID 21828089 ''Notch signaling: simplicity in design, versatility in function''.&lt;br /&gt;
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[[User:Z5014803|Z5014803]] ([[User talk:Z5014803|talk]])&lt;br /&gt;
https://www.researchgate.net/publication/264164124_Introduction_to_Notch_Signaling   This seems like a good link for the history and discovery of the pathway&lt;br /&gt;
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[[User:Z5014803|Z5014803]] ([[User talk:Z5014803|talk]])&lt;br /&gt;
https://embryo.asu.edu/pages/notch-signaling-pathway-embryogenesis    Can be used for introduction&lt;br /&gt;
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[[User:Z3462474|Z3462474]] ([[User talk:Z3462474|talk]]) 12:41, 19 August 2016 (AEST) Signalling in neural embryonic development looks interesting! Particularly the paper about NSCs and psychiatric disorders.&lt;br /&gt;
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[[User:Z5015014|Z5015014]] ([[User talk:Z5015014|talk]]) 21:59, 18 August 2016 (AEST): Hedgehog signalling (specifically SHH signalling) sounds really interesting!&lt;br /&gt;
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[[User:Z5014803|Z5014803]] ([[User talk:Z5014803|talk]]) 22:39, 18 August 2016 (AEST): Bone Morphogenetic Proteins (BMP) signalling in development looks interesting&lt;br /&gt;
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[[User:Z3491219|Z3491219]] ([[User talk:Z3491219|talk]]) I think looking at how in utero exposure to cigarette smoke affects fetal ovarian development signalling would be interesting.&lt;br /&gt;
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===Group 2===&lt;br /&gt;
This web page is developing very well, with comprehensive information and textual information. Relevant images and diagrams have been included and accurately referenced, which is to be commended. Student produced images, diagrams and flowcharts should also be included to reflect depth of knowledge on this topic. More images would enhance the readers’ understanding of topics like the development of the Atrioventricular Canal, heart valve and outflow tract, all of which are subheadings. Short movies and animations should also be included to assist the readers in visualising these signalling pathways and embryological developments being discussed. An interesting and potentially humorous image could also be included at the beginning of the web page to attract the reader’s attention and add interest to the page, such as an image of an ordinary notch at the top of the page.&lt;br /&gt;
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The subheadings included in this web page are appropriate and have been well organised, ensuring consistency and cohesiveness in this project. The introduction is well written, as it covers a range of topics including an overview of the role of the Notch signalling pathway as well as an introduction to the abnormalities associated with mutations in the functional components of the pathway. The timeline could also be improved by including developments in research over the last 20 years, as well as the direction current research is moving in and where future research could be headed. An elaboration on 1914 by further explaining why this is called the “Notch signalling pathway” with the aid of an image would also be useful. More information on John S. Dexter and his research process, his team and initial findings would also add depth and interest to the web page. Another table could be included in this web page to help the readers differentiate between the four Notch genes in Mammals, including further information on each gene, their respective locations on chromosomes, functions and an image of each if possible. The location of the locus of the Notch gene on the 3C7 band of the X chromosome is included, as well as the NOTCH3 located on chromosome 19p13, showing detailed knowledge and extensive research by the group. Images, potentially student drawn, of where these locations physically are would also reflect a deeper understanding. &lt;br /&gt;
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The ‘Roles in Embryonic Development’ section and its respective subheadings have also been well organised and structured. There are several headings in this web page that require completion before the submission date, including the ‘non-canonical pathway’ and ‘transcriptional regulation of notch signalling’ headings. More animal models can also be included, with the subheadings in this section also requiring completion. An abnormalities section has also begun well and is detailed and well referenced. It still requires completion as some of the sub-headings are still empty. Images of symptoms of these abnormalities such as the rib and spine abnormalities associated with Spondylocostal Dysostosis, and the eye conditions and facial features associated with Alagille syndrome would add depth to this section. A glossary section has also been started, but can definitely be added to to improve the understanding of the readers. Terms to be added could include proteolytic reactions, ligands and descriptions of signalling molecules such as MyoD, Mash1 and GATA2. &lt;br /&gt;
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Referencing has been carried out well, with in-text referencing throughout the web page. The introduction was well referenced, as well as the “Roles in Embryonic development”, “Animal Models” and “Abnormalities” sections. However, no in-text referencing has been carried out for the “Overview of Molecular Mechanisms” section and the timeline. This should be resolved as soon as possible so that external links are easily accessed by the readers should they want to seek further information. Complete and proper referencing would also satisfy one of the criteria of this assessment, that the content is correctly cited and referenced.&lt;br /&gt;
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GROUP 2&lt;br /&gt;
Moving the the 2nd group I can see that their topic is mainly about the Notch receptor. They seem to elucidate upon different aspects of the receptor, like it’s role in embryonic development and molecular pathways. The aspect done especially well in this group is the vastness and breadth of their information. They explore numerous aspects of the Notch receptor, including the abnormalities that can arise in development. By showing such a vastness and clarity in their research they successfully achieve criteria 1. Furthermore, Group 2 has a phenomenal amount of tables, diagrams and figures describing canonical Notch signalling and the history of the discoveries for these receptors. This qualifies criteria 2 very well as they have included all these as well as headings and sub headings in a succinct manner. Moving onto referencing, this group has done a fantastic job in that aspect as they have a separate section for references, which is clear and easy to understand, fulfilling criteria 3. Overall, I have been able to learn from this group’s project and thus I believe that they fulfil an aspect of criteria 4, in that they have an element of teaching for peers. Improvements I might suggest would be having an even larger array of different learning outlets or media types. Examples could include maybe having a video included in your group project. In terms of improvements to specific information, maybe quickly glance over the different types of receptors and the different pathways they have.&lt;/div&gt;</summary>
		<author><name>Z5020466</name></author>
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	<entry>
		<id>https://embryology.med.unsw.edu.au/embryology/index.php?title=Talk:2016_Group_Project_1&amp;diff=249772</id>
		<title>Talk:2016 Group Project 1</title>
		<link rel="alternate" type="text/html" href="https://embryology.med.unsw.edu.au/embryology/index.php?title=Talk:2016_Group_Project_1&amp;diff=249772"/>
		<updated>2016-10-07T02:11:04Z</updated>

		<summary type="html">&lt;p&gt;Z5020466: &lt;/p&gt;
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=Peer Review=&lt;br /&gt;
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===Group 1 Peer Review===&lt;br /&gt;
Great job on all the content you’ve produced as a group so far. It’s clear you guys have done a lot of research into the topic and you’ve identified key aspects of Wnt signalling. The information you have is all relevant, everything is referenced, and all your abbreviations are defined. It’s really good that you have included some specific studies and explained the findings and what they discovered about Wnt signalling. It’s great you’ve also started to look into the abnormalities so if you put some more info into that I think it presents a really interesting topic for the reader to read about.&lt;br /&gt;
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The first things I would point out is mostly for the structure/layout of your page. Make sure you use the correct wiki formatting so the page looks uniform and clean. You should separate your references out from the main body of info and collate them properly at the end of the page. Also make sure that you have in-text referencing so the reader knows exactly where the information is from. And for your content, I think it would look more professional to present it in structured paragraphs instead of bullet points. I would suggest having a proper introduction paragraph so that the reader gets an immediate overview of Wnt signalling and which aspects you’ll be exploring, rather than going straight into explanation of the pathway. Also, while you do have good headings for each section I think putting in more specific subheadings will help both you and the reader to organise the information better. In terms of the info you have so far, I would just make a point that you should try and get most of the content from primary sources instead of review articles. Additionally, because you are focusing on Wnt signalling in skin development I don’t think you have enough explanation in that area. Since it’s your focal aspect then I think you should explore a lot more of the research and the related abnormalities that have been found. You could also just include some links to papers that describe Wnt signalling in other embryonic roles since you aren’t investigating those. Finally I would suggest making the page more interesting by including images, diagrams, tables, timeline, etc. so it’s not just paragraphs of text one after the other (and to fulfill the assessment criteria). But overall you guys have made great progress - I hope these comments will help you improve!&lt;br /&gt;
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===Peer Review - Group 1===&lt;br /&gt;
You guys have done really well to accumulate a lot of relevant information so far on your wiki page which is definitely a positive for your team. In the context of criterion 1 of the assessment criteria, I am not certain that the key points are clearly described as of yet, there is just a lot of information that is not presented to the reader in a targeted manner, so this definitely needs some work. As I have stated previously the choice of content appears to be adequate to address your topic however you guys need to work on increasing the number of subheadings as well as providing an introduction as the project aims remain unclear. Content is not completely correctly referenced yet, presumably due to the fact that you guys are still making your project page up but referencing is very easy to do correctly on this wiki and I implore you to make sure it is done correctly when it is time to submit the assignment.&lt;br /&gt;
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As I have alluded to previously, elements of teaching at a peer level were completely missing in this and these definitely need to be addressed, probably by putting entries into your glossary as well as creating a well structured introduction. It would also help if you guys drew some representations of information, such as sketches of pathways. There is certainly evidence of going above and beyond the formal learning activities, which is a major positive for your project. In the context of learning objectives of the course, you guys are addressing the aspect of embryological development but have not addressed the relevance of new technologies in the WnT Pathway.&lt;br /&gt;
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Overall, there is a lot of potential for you guys to put out a very good wiki page if you clean up your page so that it is more coherent and insert some information that is lacking so that a relatively uneducated reader could understand the WnT signalling pathway from the wiki page. Well done!&lt;br /&gt;
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===Group 1 Peer Review===&lt;br /&gt;
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'''Positive Factors'''&lt;br /&gt;
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Group 1 have a clear allocation of sub topics between members of their group which is shown under the subheadings. The pathways (e.g. canonical pathway) are all described clearly, I was able to follow easily despite not having extensive knowledge on the subject. I think this could be even more improved with some diagrams or flow charts to support the written explanations. Another positive aspect of this Group’s page is how they have included information from studies under a separate heading to emphasise their findings in regards to Wnt. Moreover, there is a subsection that directly and clearly relates Wnt to the developing fetus.&lt;br /&gt;
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'''Points for Improvement'''&lt;br /&gt;
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Some improvements I would suggest would be: the formatting on Group 1’s page be tidied a little but since this is a draft it is still in early stages (more specifically, Group 1 could use uniform subheading sizes and uniform subsections/subtopics for each pathway described); also it would be great if the references were sorted under one heading at the bottom of the page; and a short generalised introduction could be added to inform readers of the general role of the pathway and some information about relevant molecules. &lt;br /&gt;
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'''Overall'''&lt;br /&gt;
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Overall the main strength of Group 1’s page is the clear explanations they have provided, which I think is really important for meeting the assessment criteria for this project. More specifically, criteria 1, 5 and 6 have been addressed so far by this Group. With a few improvements to formatting and layout this page will provide a great resource for understanding the Wnt signalling pathway. &lt;br /&gt;
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&amp;lt;font size=&amp;quot;4&amp;quot;&amp;gt;&amp;lt;u&amp;gt;Group 1:&amp;lt;/u&amp;gt;&amp;lt;/font&amp;gt;&lt;br /&gt;
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&amp;lt;b&amp;gt;Positive aspects of the project and suggested improvements:&amp;lt;/b&amp;gt;&lt;br /&gt;
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Upon assessment of this project, it appears that the authors have devised a variety of subheadings related to the signalling pathway of the Wnt receptor in embryonic development which is excellent. The group has also began investigating the involvement of Wnt in numerous aspects of embryonic development such as skin formation. The use of subheadings and headings related to the Wnt receptor partially meets criteria 1 and 2 assessment. It also appears that the group has cited and referenced sources for some of the information utilised, particularly when describing the “Caronical Pathway”. This also partially meets criteria 3 for this assessment. The group has also attempted to explore abnormalities in the Wnt pathway by describing interruptions in the pathway and its relation to cancer which is very interesting. They have therefore attempted to research ideas related to this receptor that extend beyond formal teaching activities, by explaining the link between Wnt abnormalities and disease (criteria 5). &lt;br /&gt;
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Whilst there are the positive aspects of the page, improvements can still be made to ensure that the group satisfies the first five points of the marking criteria. Firstly, although there appears to be subheadings, there only appear to be few and therefore it would be excellent to add more subheadings. Subheadings may relate to the history of the Wnt signalling pathway or even subtypes of the receptor as well as their respective functions. In addition, whilst the group appear to have cited some of their sources, it is important to cite all sources, particularly when gathering data under the “Non-canonical pathway” subheading. Although a series of articles have been referred to, it is vital that the group includes in-text citations in order for the audience to determine the source for each segment of information. A suggestion would be to investigate more examples of diseases caused by abnormalities in the Wnt signalling pathway&lt;br /&gt;
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&amp;lt;b&amp;gt;Negative aspects of the project and suggested improvements:&amp;lt;/b&amp;gt;&lt;br /&gt;
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The group appeared to provide a general description of the abnormalities associated with disruption of the Wnt pathway; however they did not talk about abnormalities in the context of embryonic development. A suggestion would be to discuss Wnt abnormalities to the effect it has on embryonic development. It was also noticed that the group failed to include diagrams, tables or figures to reinforce the information. The use of diagrams would assist the audience in developing a visual understanding of the information presented and also makes the wiki page more appealing too. Therefore, a suggestion would be to use diagrams and figures. For example, a diagram of the signalling pathway would be a suggestion. It was noticed that the page appears to have no introduction or history describing the Wnt receptor. Therefore, a possible improvement would be to include a brief introduction and history at the beginning of the page as well as a few diagrams to provide the audience with an insight into what the receptor’s purpose is before exploring its function in embryonic developing.&lt;br /&gt;
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In addition, it appears that the group has focused on the role of Wnt in skin development of the embryo only. A possible improvement would be to investigate the involvement of Wnt in other areas of embryonic development, perhaps the development of specific organ systems or other structures.&lt;br /&gt;
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To all group members:&lt;br /&gt;
*More info on pathway focusing on fetus development, and which pathway it is majorly part of - focus research on those body parts&lt;br /&gt;
*Make your section presentable&lt;br /&gt;
*At least one picture per section&lt;br /&gt;
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===Group 1===&lt;br /&gt;
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You guys have made significant progress on your project, managing to touch briefly on each section of your assignment. There have been some good choices of subheadings but I think some improvement can be made. For example, I think it would be useful to breakdown the general heading of ‘introduction’ into smaller subheadings so readers are made aware of what will be discussed in this section. It would also be useful to touch upon the importance of this pathway and thus, highlighting its significance in embryological development. &lt;br /&gt;
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In terms of the content of the project, being only in the draft stage a considerable amount of editing is required. For example, there has been mention of the TCF/LEF family and though the use of this abbreviations is useful, I think it would be appropriate to initially include the full name and explain this term in brief detail. In addition, there has been discussion of the ‘canonical’ and ‘non-canonical’ pathways of WnT Signalling Pathway but you could consider discussing the significance of having these two separate pathways. Comparing and contrasting these two pathways may also assist in aiding one’s understanding of the topic. &lt;br /&gt;
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Though it is great that you have made progress, I think more detail is required in each section, particularly in linking the effect of these pathways on embryological development. Also, greater attention needs to paid to referencing and utilisation of studies that have dissected this signalling pathway. For example, greater emphasis can be placed on studies performed on ‘embryos of Xenopus laevis’ or the in vitro experiments on mice. Instead of saying ‘a study’ or ‘another study’ acknowledge the researchers of this study as it will increase the validity of your argument while providing readers with the opportunity to refer back to these papers for more information if required or interested. More detail is also required on the effect of this pathway on skin formation. One way this could be done is by expanding on the information already provided, for example, explain how ‘WnT signalling inhibits the ectoderm’s responsiveness to FGFs’ and provide a detailed explanation of the feedback mechanism. Though your topic is focusing on ‘WnT Signalling pathway in the skin of fetus’ It would be beneficial to explore the roles of Wnt signalling in other areas of embryological development as this could provide insight into the abnormalities caused by mutations in this pathway. In terms of the ‘what can go wrong’ section, try breaking this segment into the various embryological deficiencies that can develop through disruption of the WnT pathway and try and make it relevant by providing statistics. &lt;br /&gt;
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Overall, you guys have done a fantastic job! It was good to see that all group members had contributed to the project. The main thing that requires improvement is the lack of detail. Through editing and inclusion of appropriate references and citations you can significantly improve the quality of your work. It would be useful to add some diagrams or images to help explain the pathway. In addition, try utilising your discussion page and communicating with your other team members. By providing feedback and suggestions you can assist in efficiently producing an excellent project. I hope this helps!! &lt;br /&gt;
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===Group 1 Critical Assessment===&lt;br /&gt;
In terms of the topic of WnT signalling pathway, the page is beginning to come together with a great amount of information. What I particularly like is how the different concepts introduced in the page have been explained, for e.g. the different WnT pathways. However the content for each pathway does not seem to be consistent. While the canonical pathway addresses the mechanism, the non-canonical one doesn’t. I would suggest constructing a table to compare the similarities and differences between the various pathways, and adding images or shorts clips with audio to represent the elements of the pathways in a different form. This would not only enhance the look of your page but also make it more interactive for the audience. &lt;br /&gt;
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A great positive is to see links to research articles have been provided for the audience to access if they are interested to read on further. The links are short and easy to see, and direct you straight to the article on Pubmed, a reliable source. An effort has also been made to summarise the article, however the summary should be available as a simple breakdown so the audience can refer to it if they struggle to understand. The summaries include some jargon that can be further simplified. &lt;br /&gt;
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In relation to criteria 1, the key points have definitely been highlighted and the signalling pathway has been associated with the fetal development, however to make it more interesting and satisfy criteria 5, possibly construct a table or briefly outline how WnT signalling is involved in other areas such as Type 2 Diabetes and Cancer. Furthermore, to relate the topic back to embryological development explore the pathway in other areas such as gastrulation, rather than limiting discussion to skin development.&lt;br /&gt;
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Lastly to satisfy criteria 3, attempt to include in text citations within the paragraphs, instead of displaying references towards the end of the page. Overall, great job in gathering and highlighting key features, and backing up your information with relevant articles!&lt;br /&gt;
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===Group 1 Peer Assessment===&lt;br /&gt;
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The start you have made on your project appears to be quite decent. There seems to be a clear overview and scaffold of how your page will look and what it will discuss in the end. For the most part the usage of dot points has made understanding your points with regards to the signaling pathways (Canonical pathway section) a lot easier as opposed to having a wall of text. I would recommend possibly adopting dot points when explaining the pathway regarding the Wnt-Calcium Ion pathway to make it easier to digest. That being said though, there are areas within your wiki page that would most likely benefit from having complete paragraphs such as your sub sections labeled under the non-canonical pathway. It appears that each individual point in the sub section role appears to represent individual points that could be substantially elaborated on. In way I feel that it would make the ideas in the section less disjoint and more clear, given that writing in a paragraph format would be suitable for longer passages. Also for the part where there are there are research articles linked, and descriptions of such articles, it might be better to try integrate such ideas into other main components of your wiki page, because they seem quite out of context and out of nowhere. That being said you could also just put this under a current research heading and talk about it with respect to the current findings of the Wnt pathway. &lt;br /&gt;
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Another main aspect that should be corrected is that in some sections, there is the assumption in your wiki page that the reader fully understands all your abbreviations. I know it sounds silly but it is probably best that your group coordinates or finds where you first use an abbreviation such as CaMKII in your non canonical pathway section and change it to the unabbreviated name, with the abbreviated name in brackets, where from there you can just use the abbreviated name. Also maybe just providing a glossary of the abbreviated terms and their unabbreviated terms at the end of your page will do as well. Also its good to keep in mind that you may have already done this for some terms, so look out for that as well.&lt;br /&gt;
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With regards to your referencing, I see that it is quite extensive, but there seems to be a lack of in text citations. As a result, its quite hard for those who read your page to quickly find the appropriate citation with regards to the sentences or dot point being read. For the sections such as “Canonical Pathway: How it works” this isn’t too bad, as there is only one reference, but for the “Non-Canonical Pathway section” there are way too many for it to be easy to tell where the citations are associated to. So overall for this I recommend your group to use in-text citations. Also I’ve noticed that you have used a review to cite your whole “Canonical pathway: How it works” section, which for the most part most likely contains all your information you have stated, but doesn’t give credit to the specific or individual authors included in the review and also requires the reader to go and find the specific sections in the review that you have used to cite your text. It is such that it would be better to use research articles to site your individual points, maybe extracting such research articles from the review article itself. &lt;br /&gt;
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Overall the start made on your project is appearing to take shape, where I see that there are many subheadings yet to be filled below the “Wnt-Calcium Ion pathway” section. I’m sure if your groups keep up the quality of the work, your page should turn out fine with the addition of incorporating the feedback I have provided. &lt;br /&gt;
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===Group 1 – Wnt Signalling Pathway===&lt;br /&gt;
Positive aspects of the project include that fact that this group has included detailed information of the different WnT signaling pathways. It does seem however, that this information would perhaps be better conveyed to the audience if it were accompanied with images (either sourced from the internet or hand drawn) and/or videos/animations, as well as some information on the role of each signaling molecule/receptor subtype (perhaps in a table) just to provide a more thorough explanation of this pathway.  Furthermore, this group has made a conscious decision to include a glossary, although they have not yet started this, it is going to be something the group can add to whilst finishing the project and will help the reader better understand the concepts they discuss. This group has included a large amount of references throughout their project, including a significant amount of recent primary articles, which shows the reader that their information is well researched and very current. However, the only criticism here is that they aren't appropriately formatted for the purpose of this assignment. I would suggest that in text citations would be more appropriate, so the reader can clearly identify where this specific information is from and then go directly to said source if need be. &lt;br /&gt;
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Alternatively negative aspects of the project, which may need some revising before submitting the final version of this assignment, would be the formatting of the project as it appears relatively incomplete. Although there are some subheadings, which are helpful, it may be useful to add additional ones to these to make it a little clear for the reader. For example perhaps use a similar scaffold to the other group projects, which have included ones such as introduction, history, outline of the signaling pathway, its specific roles in embryonic development and then abnormalities specifically relating to embryonic development, as this would help break up the information better and make the projects more consistent for readers. Most of the work on this project seems to focus on explaining the signaling pathway so I assume its more the case of the group hasn’t got around to it yet, but I think more information on the role this signaling pathway specifically has in embryonic development is required, like the paragraph on early stages of skin formation, in order to tie in the assignment with what we have been learning in the labs and lectures. As mentioned I think the subheadings may need some revision, and the current ‘What can go wrong’ may be better described as ‘abnormalities’ that way you could also include a discussion of abnormalities to Wnt that specifically influence normal embryonic development, as well as still include the paragraphs on its influence on tumor cells which could perhaps be found using the ‘omim’ site searching by a receptor subtype or pathway. Also, although you have included more of a discussion of abnormalities that occur later in development, it is interesting for the reader and does go beyond our understanding from class, but the main focus probably should be on abnormalities in embryonic development. &lt;br /&gt;
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In conclusion this project is definitely on its way to being really good, the information on the signaling pathways appears to be well research. The major criticisms were mostly focused on presentational aspects of the project like subheadings, references and the inclusion of images/tables. With some more research on its role in early embryonic development and abnormalities this will be very successful. &lt;br /&gt;
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===Group 1 Peer Assessment===&lt;br /&gt;
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Positive aspects of the project and improvements:&lt;br /&gt;
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Upon initially glancing over the project you can clearly see a range on headings and subheadings and it is evident by these that the project is about the WnT signalling pathway in skin of fetus. This is sufficient for assessment criteria 1 and 2 as you can see the aspect of research they are targeting such as skin formation during embryonic development. Throughout the text you can see citations relating to the topic and a range of references at the end of the project. This satisfies the requirements for criteria 3 but just a small critique would be to put these references in the references section just to clear out the unnecessary area. It can also be commended that the group project goes above and beyond the curriculum of informing us about the background information of WnT signalling pathway in skin of fetus but also includes the complications and diseases arising due to abnormalities in the WnT pathway. This is excellent and satisfies the requirements for criteria 5&lt;br /&gt;
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There can be some improvements in the project but they are not necessarily of the utmost importance. Firstly, the group can add other specific subheadings and the relevant information under them such as the history or background of the signalling pathway. This is just so the reader has a more rounded knowledge of the pathway and can increase the interest and keep them engaged. It would also be good to see in the text and not just at the end of a paragraph. Such as, in the canonical and non canonical pathway heading it would be recommended to have in text citation and not just at the end just to show the reader where the information was gathered from.&lt;br /&gt;
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Negative aspects of the project and improvements:&lt;br /&gt;
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Although the project has a fair amount of positives there are some areas that are lacking. Firstly, the report requires additional information in each section and how this information can be linked to pathways in embryological development. It would also be recommended to put in diagrams, images, tables etc. This would engage the reader and make the read more interesting since at the moment there are no images or tables. Also doing so will satisfy one aspect of criteria 2. This way the audience can develop a visual understanding of the topic. It would be advisable to put tables in the history section in the form of relevant dates/years and the information corresponding to the year. &lt;br /&gt;
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Also, it would be good to see the role of WnT signalling pathway in something other than skin, for eg: an organ or tissue or cell. This would aid in achieving a higher mark for criteria 5 as you go above the required information. Overall it was great to see all group members contributing to the project but minor edits such as citations, images, tables, and adding additional information to sections would really captivate the reader and make it an enjoyable read. &lt;br /&gt;
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===Peer Assessment: Project 1: WnT Signaling Pathway in skin of fetus===&lt;br /&gt;
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====1. The key points relating to the topic are clearly described====&lt;br /&gt;
There are headings for key points but the information for these key points has not been added so far.&lt;br /&gt;
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====2.The choice of content, headings and sub-headings, diagrams, tables, graphs show a good understanding of the topic area.====&lt;br /&gt;
The WnT Signaling pathway wiki does have a list of contents, which demonstrate that the topic is divided into different section. However it is clear some thought has gone into this. However this is not finished, there are not tables, diagrams, graphs and a lot of work is needed.&lt;br /&gt;
There are sub headings but there is no clear concise information under these headings. There is no introduction on what the topic is about and this makes the reader a little confused. There are a lot of parts missing and not filled out. &lt;br /&gt;
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====3. Content correctly cited.====&lt;br /&gt;
The content is not cited correctly. There is a reference section but there are no publications that have been cited listed.&lt;br /&gt;
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====4. The wiki has an element of teaching at a peer level using the student's own innovative diagrams, tables or figures and/or using interesting examples or explanations====&lt;br /&gt;
There are no graphs, diagrams or tables and these clearly will help the reader have a better understanding of what the wiki is about. There does not seem to be any examples or explanations that show the students own innovation.&lt;br /&gt;
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====5. Evidence of significant research relating to basic and applied sciences that goes beyond the formal teaching activities.====&lt;br /&gt;
This is somewhat evident but there is not enough clear information and it makes it difficult for the reader to follow the topic.&lt;br /&gt;
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====6.Relates the topic and content of the Wiki entry to learning aims of embryology.====&lt;br /&gt;
There is a section on foetus skin formation and this will be interesting to read however it is still not finished. Figures and diagrams would aid a lot to visualize this section.&lt;br /&gt;
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====7. Clearly reflects on editing/feedback from group peers and articulates how the Wiki could be improved (or not) based on peer comments/feedback. Demonstrates an ability to review own work when criticised in an open edited wiki format. Reflects on what was learned from the process of editing a peer's wiki.====&lt;br /&gt;
Each section has been divided amongst the group but it seems that the members of the group have not really communicated or finished their own sections. This is not clear at all. The Wiki has a lot of room for improvement, the group needs to meet and decide who will do which section, the participants of the group need to find review publications and summarise this information for each section. Also it is a good idea to see how these projects were edited in the previous years and this will help with the layout.&lt;br /&gt;
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====8. Evaluates own performance and that of group peers to give a rounded summary of this wiki process in terms of group effort and achievement.====&lt;br /&gt;
This is not demonstrated and it seems that the key areas have not yet been researched adequately. There is still a lot of information missing and the overall flow of this wiki is muddled.&lt;br /&gt;
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====9. The content of the wiki should demonstrate to the reader that your group has researched adequately on this topic and covered the key areas necessary to inform your peers in their learning.====&lt;br /&gt;
The key areas on this wiki have been set up but there is no clear and adequate information that is correctly cited at all.  It is a very poor effort thus far in terms of group research.&lt;br /&gt;
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====10. Develops and edits the wiki entries in accordance with the above guidelines. ====&lt;br /&gt;
This still has not been achieved at all. There is no editing and it seems the group has put little effort in this project.&lt;br /&gt;
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==Notes==&lt;br /&gt;
Just trying to simplify and understand the process and these are some of my notes !(z3417363)&lt;br /&gt;
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The inactive Wnt Pathway In a normal cell:&lt;br /&gt;
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In most normal cells the Wnt pathway is inactive. In the cytosol , the destruction complex is formed from the proteins beta catenin, GSK3 beta, Axin,APC, Ck1-alpha. The ubiquitin ligase beta TRCP is able to bind to beta catenin and transfer short ubiquitin peptides to beta-catenin.  In other words the beta-catenin is phosphorolated and this beta catenin can then bound  and be by a complex of protease (proteasome) . Thus a low level of cellular beta catenin is achieved. &lt;br /&gt;
Therefore no beta catenin reaches the nucleus and the transcription factor of the TCF LEF family along with other proteins (groucho) binds to DNA and inhibits gene expression.&lt;br /&gt;
So essentially when WnT is inactive, beta canenin is destroyed and does not reach nucleus and transcription is inhibited. &lt;br /&gt;
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The Active Wnt Pathway in a normal cell.&lt;br /&gt;
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Extracellular(outside cell) Wnt binds with the membrane receptor frizzled (FZD). The wnt pathway is activated and activates the cytosolic protein &amp;quot;dishevelled&amp;quot;(DSH) which induces dissociation of  the protein destruction complex. Because the protein complex is destroyed beta- catenin is no longer modified by unbiquitin peptides/phosporolated and is not destroyed. Since the supply of beta catenin continues the level of beta catenin rises, first in the cytosol and later in the nucleus. Once the beta catenin reaches the nuclue it binds to the TCF LEF transcription factor which changes them from a transcriptional repressor into an activator. TCF itself activates an RNA polymerase which induces gene transcription.&lt;br /&gt;
So essentially WnT starts gene transcription by allowing beta catenin to reach the nucleus.&lt;br /&gt;
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This is actually very similar to a tumour cell where the mutation of the protein complex also inhibits the destruction of beta catenin and allows it to grow in quantity and reach the nucleus and start gene expression. However this is not uncontrolled and can be compared to a car travelling with no brakes. Ultimately this abnormal proliferation leads to malignant adenocarcinoma (cancer).&lt;br /&gt;
&lt;br /&gt;
 Use pubmed, biomedcentral journals==you can find it on pubmed just plug in the title and you will get the pubmed number&amp;gt;BMC developmental biology journal, journal of cell biology(cant use last 6months of research), proceeding national academy of science(can only use after 6months), public library of science omim&lt;br /&gt;
include research labs, animations&lt;br /&gt;
use the help tab&lt;br /&gt;
where the terminlogy came from &lt;br /&gt;
this is a student drawn image , based upon and give the reference&lt;br /&gt;
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=== Group 1===&lt;br /&gt;
GROUP 1&lt;br /&gt;
A great start to this group project has been made, with a substantial amount of textual information. No images have been included, limiting the visual engagement of the readers. The signalling pathways discussed extensively in the text would be easier to understand if images as well as diagrams and flowcharts were included. These flowcharts could summarise the processes in the Canonical and non-canonical pathways, as well as the Planar cell polarity pathway, the PCP pathway and the Wnt Calcium pathway. Since a range of pathways are described in this web page, it is essential that diagrams are included to simplify these, allowing the audience to consolidate their knowledge of these processes. Another addition could be short movies that would aid in the visualisation of these processes. Student drawn images should also be included to reflect the depth of knowledge of the individuals producing this web page. An interesting and potentially humorous image could also be included at the beginning of the web page to attract the reader’s attention and add interest to the page. One of the criteria to be fulfilled is that the wiki has an element of teaching at a peer level using the student's own innovative diagrams, tables or figures and/or using interesting examples or explanations. Hence, making these additions to the page would satisfy this criteria. &lt;br /&gt;
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An extensive list of references have been included throughout the paper. However, no in text referencing has been carried out. For example, at the end of Caroline’s sections, references including PMIDs have been included, but the lack of in text referencing means that the specific papers used for each piece of information can not be easily identified by the reader for further reading. Other members of the group have also placed their references at the end of their respective sections, rather than using in-text referencing. Compiling all the references at the end, after in-text referencing has been completed, will improve the cohesiveness of the paper, rather than having a separate list of references for each section. This would also improve the organisation and aestheticism of the page. One member of the group has commented “I’m not sure how to reference things that aren’t from pubmed” on the page. The solution to this problem would be to either ask fellow group members and colleagues from the class, or to ask Dr Hill as to how he would like these references to be made, ie. which style of referencing he would prefer. Other good resources such as OMIM have been identified, which is commended, and looking in places other than PubMed will create an extensive reference list and a range of information from various sources. This would fulfill the criteria that the page should demonstrate that the group has researched adequately on the topic.&lt;br /&gt;
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Subheadings have been included, organising the web page well. Names of the group members should be removed from subheadings when possible as these are visually distracting and unnecessary. Some subheadings also have not been formatted correctly, such as the “===What can go wrong?===” subheading, which needs to be fixed so that it is formatted in a similar manner to the other headings. More coherent formatting could also created in combining Tony’s “Abnormalities” and Arsalan’s “What can go wrong” sections. Many subheadings need completion with more information, including the “WnT-Calcium Ion Pathway - Tony”. In this section, the dot points “abnormalities”, “main components” and “functions” dot points should be made into subheadings and completed. The “Studies” section should also be elaborated on with more textual information, including specific researchers and dates. This section could be developed into a timeline of the history of the research associated with WnT signalling pathways, presenting this information in an accessible and interesting manner. A wide range of research has taken place, evident in the extensive list of references at the bottom of this section. This section can be enhanced by referencing other studies more specifically by naming the scientists involved, and when this research was carried out. This would be better than referring to research as “a study”. Ensure in-text referencing is carried out effectively in this section so the readers are able to easily find these research papers should they require more information. &lt;br /&gt;
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The “Things to do/reference” list at the top of the web page should be resolved as soon as possible so that these notes can be removed from the top of the web page so that the page can begin with relevant information. The comments and dates at the top of the web page shows a progression of this project over time as well as group communication, which is commended. The glossary section should also be developed at the bottom of the page to contain definitions for words like glycolipoproteins, the TCF/LEF family, abbreviations like CaMKII, Osteoprogenitor markers such as Alp, Opn, Ocn and Bsp in Tony’s sections and other terminology that may require a brief description to provide the readers with a more comprehensive understanding. Overall, this web page is developing well, but there are still many areas for improvement.&lt;br /&gt;
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GROUP 1&lt;br /&gt;
Through reading through and analysing group 1’s project it is starkly clear they have managed to relay some excellent information and present it in quite an easily digestible manner. That said though, there are some things which they could improve upon as well. I shall be dissecting what they have done well and what they could improve upon. The information they have regarding signalling pathways of the Wnt receptor in embryonic development is complex and intricate so they have done well by creating subheadings to more easily navigate the vastness of information displayed. This relates directly to criteria 2 in the “Group Assessment Criteria”. However, as seen in the criteria there are also other techniques such as diagrams, tables, graphs which could be employed to further add upon the excellence of this project. Moving onto criteria 3 we can see that there has been some referencing and citing, however it was hard to find and not clearly written. The part that was well referenced was under the “Non-Canonical Pathway – Caroline”. It’s starkly clear to me that these group members have truly gone beyond the formal teaching activities, as described in criteria 5, and have done some significant research exploring the abnormalities associated with the Wnt pathway be describing the interruptions in the pathway and its relation to cancer.&lt;/div&gt;</summary>
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		<updated>2016-08-26T03:46:38Z</updated>

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==Lab Attendance==&lt;br /&gt;
[[User:Z5020466|Z5020466]] ([[User talk:Z5020466|talk]]) 14:42, 12 August 2016 (AEST)&lt;br /&gt;
[[User:Z5020466|Z5020466]] ([[User talk:Z5020466|talk]]) 13:46, 26 August 2016 (AEST)&lt;br /&gt;
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&lt;br /&gt;
===Belbin Team Roles===&lt;br /&gt;
If I’m completely honest, I think my role in group work is generally the “Co-ordinator”. I’m not too sure about my ability to step back from the ‘nitty gritty’ details and see the bigger picture. But rather I generally like to take on leadership roles and assign people tasks. That way I can do things how I like to and place people in roles that I think they would be suited to. But not only that I think to be a good leader you have to be a good worker. So I try to lead by example and not really depend on others too much so that if something has messed up, I have no one to blame but myself. This part about Co-ordinators made me chuckle. “Sometimes perceived to be manipulative and will tend to delegate all work” which is unfortunately a little true. But at the same time I’ve been open to working an equal amount as others previously as well.&lt;br /&gt;
&lt;br /&gt;
===Lecture 1: Fertilisation===&lt;br /&gt;
In my previous years in attending university I’ve completed many courses which have gone through the fertilization process such as: Evolutionary Biological Sciences, Physiology, Histology and Pathology. From having done these courses already, there were parts which were familiar to me and that I have understood before in the past. However, I still was amazed by the new refreshing things I have not yet encounter which I did during this lecture. Such as polar bodies and their role in fertilization in disposing of extra DNA. It also clarified a point which I was previously confused about on whether or not polar bodies were gametes or not. Cementing all this information and weaving it in with new learnt information has really been a beneficial experience for me, in that I’m building up on topics I thoroughly enjoy.&lt;br /&gt;
&lt;br /&gt;
==New SubHeading==&lt;br /&gt;
===External Link===&lt;br /&gt;
[http://www.smh.com.au/ SMH]&lt;br /&gt;
&lt;br /&gt;
===Internal Link===&lt;br /&gt;
[[ANAT2341 Lab 1]]&lt;br /&gt;
&lt;br /&gt;
[[ANAT2341 Lab 1|Fertilization Lab]]&lt;br /&gt;
 &lt;br /&gt;
[[Student Page]]&lt;br /&gt;
&lt;br /&gt;
==Referencing==&lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/sites/entrez?db=pubmed&amp;amp;cmd=search&amp;amp;term=fertilization fertilization]&lt;br /&gt;
&lt;br /&gt;
PMID 27486480&lt;br /&gt;
&lt;br /&gt;
==Assessment 1==&lt;br /&gt;
&amp;lt;pubmed&amp;gt;PMC3528851&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&lt;br /&gt;
The research article called &amp;quot; Tet1 controls meiosis by regulating meiotic gene expression&amp;quot; by Yamaguchi et al. (2012) aims to determine the role of ten-eleven translocation methylcytosine dioxygenase 1 (TET1) which is a member of the TET family of enzymes, in regulating meiotic gene expression and thus meiosis in mice. This study was highly useful since little is known about how the expression of meiotic genes is regulated and how their expression contributes to normal meiosis. &lt;br /&gt;
In the study they performed a whole-genome bisulphite sequencing (WGBS) analysis using an ultra-low input so that they would be able to see how Tet1 is used in the activation of meiotic genes. &lt;br /&gt;
&lt;br /&gt;
Results showed that a decreased functioning of Tet1 caused an increase in the unpaired synaptonemal complex at zygotene-stage oocyte, suggesting a synapsis-formation defect. The meiotic defects seen from Tet1 loss of function included: formation of univalent chromosome, but also homologous recombination and DNA double-strand breaks (DSBs) repair defects. These in turn caused defective meiotic prophase which caused decreased amount of oocytes and in turn reduced litter size and lowering in fertility. The study done was pivotal as it built upon past studies which have already established that DNA methylation levels of certain meiotic genes are lowered with genomic reprogramming.&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
{| width=95%&lt;br /&gt;
|-bgcolor=&amp;quot;FAF5FF&amp;quot;&lt;br /&gt;
| [mailto:m.hill@unsw.edu.au Mark Hill] 18 August 2016 - You have added the citation correctly and written a good brief summary of the article findings. &lt;br /&gt;
TET1 is part of the family of methylcytosine dioxygenases that involved in cytosine demethylation and gene activation, interesting that it has a meiotic-specific role.&lt;br /&gt;
&lt;br /&gt;
| width=100px| Assessment 5/5&lt;br /&gt;
|}&lt;/div&gt;</summary>
		<author><name>Z5020466</name></author>
	</entry>
	<entry>
		<id>https://embryology.med.unsw.edu.au/embryology/index.php?title=User:Z5020466&amp;diff=242531</id>
		<title>User:Z5020466</title>
		<link rel="alternate" type="text/html" href="https://embryology.med.unsw.edu.au/embryology/index.php?title=User:Z5020466&amp;diff=242531"/>
		<updated>2016-08-19T04:01:32Z</updated>

		<summary type="html">&lt;p&gt;Z5020466: &lt;/p&gt;
&lt;hr /&gt;
&lt;div&gt;{{ANAT2341Student2016}}&lt;br /&gt;
&lt;br /&gt;
==Lab Attendance==&lt;br /&gt;
[[User:Z5020466|Z5020466]] ([[User talk:Z5020466|talk]]) 14:42, 12 August 2016 (AEST)&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
===Belbin Team Roles===&lt;br /&gt;
If I’m completely honest, I think my role in group work is generally the “Co-ordinator”. I’m not too sure about my ability to step back from the ‘nitty gritty’ details and see the bigger picture. But rather I generally like to take on leadership roles and assign people tasks. That way I can do things how I like to and place people in roles that I think they would be suited to. But not only that I think to be a good leader you have to be a good worker. So I try to lead by example and not really depend on others too much so that if something has messed up, I have no one to blame but myself. This part about Co-ordinators made me chuckle. “Sometimes perceived to be manipulative and will tend to delegate all work” which is unfortunately a little true. But at the same time I’ve been open to working an equal amount as others previously as well.&lt;br /&gt;
&lt;br /&gt;
===Lecture 1: Fertilisation===&lt;br /&gt;
In my previous years in attending university I’ve completed many courses which have gone through the fertilization process such as: Evolutionary Biological Sciences, Physiology, Histology and Pathology. From having done these courses already, there were parts which were familiar to me and that I have understood before in the past. However, I still was amazed by the new refreshing things I have not yet encounter which I did during this lecture. Such as polar bodies and their role in fertilization in disposing of extra DNA. It also clarified a point which I was previously confused about on whether or not polar bodies were gametes or not. Cementing all this information and weaving it in with new learnt information has really been a beneficial experience for me, in that I’m building up on topics I thoroughly enjoy.&lt;br /&gt;
&lt;br /&gt;
==New SubHeading==&lt;br /&gt;
===External Link===&lt;br /&gt;
[http://www.smh.com.au/ SMH]&lt;br /&gt;
&lt;br /&gt;
===Internal Link===&lt;br /&gt;
[[ANAT2341 Lab 1]]&lt;br /&gt;
&lt;br /&gt;
[[ANAT2341 Lab 1|Fertilization Lab]]&lt;br /&gt;
 &lt;br /&gt;
[[Student Page]]&lt;br /&gt;
&lt;br /&gt;
==Referencing==&lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/sites/entrez?db=pubmed&amp;amp;cmd=search&amp;amp;term=fertilization fertilization]&lt;br /&gt;
&lt;br /&gt;
PMID 27486480&lt;br /&gt;
&lt;br /&gt;
==Assessment 1==&lt;br /&gt;
&amp;lt;pubmed&amp;gt;PMC3528851&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&lt;br /&gt;
The research article called &amp;quot; Tet1 controls meiosis by regulating meiotic gene expression&amp;quot; by Yamaguchi et al. (2012) aims to determine the role of ten-eleven translocation methylcytosine dioxygenase 1 (TET1) which is a member of the TET family of enzymes, in regulating meiotic gene expression and thus meiosis in mice. This study was highly useful since little is known about how the expression of meiotic genes is regulated and how their expression contributes to normal meiosis. &lt;br /&gt;
In the study they performed a whole-genome bisulphite sequencing (WGBS) analysis using an ultra-low input so that they would be able to see how Tet1 is used in the activation of meiotic genes. &lt;br /&gt;
&lt;br /&gt;
Results showed that a decreased functioning of Tet1 caused an increase in the unpaired synaptonemal complex at zygotene-stage oocyte, suggesting a synapsis-formation defect. The meiotic defects seen from Tet1 loss of function included: formation of univalent chromosome, but also homologous recombination and DNA double-strand breaks (DSBs) repair defects. These in turn caused defective meiotic prophase which caused decreased amount of oocytes and in turn reduced litter size and lowering in fertility. The study done was pivotal as it built upon past studies which have already established that DNA methylation levels of certain meiotic genes are lowered with genomic reprogramming.&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
{| width=95%&lt;br /&gt;
|-bgcolor=&amp;quot;FAF5FF&amp;quot;&lt;br /&gt;
| [mailto:m.hill@unsw.edu.au Mark Hill] 18 August 2016 - You have added the citation correctly and written a good brief summary of the article findings. &lt;br /&gt;
TET1 is part of the family of methylcytosine dioxygenases that involved in cytosine demethylation and gene activation, interesting that it has a meiotic-specific role.&lt;br /&gt;
&lt;br /&gt;
| width=100px| Assessment 5/5&lt;br /&gt;
|}&lt;/div&gt;</summary>
		<author><name>Z5020466</name></author>
	</entry>
	<entry>
		<id>https://embryology.med.unsw.edu.au/embryology/index.php?title=User:Z5020466&amp;diff=242489</id>
		<title>User:Z5020466</title>
		<link rel="alternate" type="text/html" href="https://embryology.med.unsw.edu.au/embryology/index.php?title=User:Z5020466&amp;diff=242489"/>
		<updated>2016-08-19T03:40:17Z</updated>

		<summary type="html">&lt;p&gt;Z5020466: /* Lab Attendance */&lt;/p&gt;
&lt;hr /&gt;
&lt;div&gt;{{ANAT2341Student2016}}&lt;br /&gt;
&lt;br /&gt;
==Lab Attendance==&lt;br /&gt;
[[User:Z5020466|Z5020466]] ([[User talk:Z5020466|talk]]) 14:42, 12 August 2016 (AEST)&lt;br /&gt;
[[User:Z5020466|Z5020466]] ([[User talk:Z5020466|talk]]) 13:40, 19 August 2016 (AEST)&lt;br /&gt;
&lt;br /&gt;
===Belbin Team Roles===&lt;br /&gt;
If I’m completely honest, I think my role in group work is generally the “Co-ordinator”. I’m not too sure about my ability to step back from the ‘nitty gritty’ details and see the bigger picture. But rather I generally like to take on leadership roles and assign people tasks. That way I can do things how I like to and place people in roles that I think they would be suited to. But not only that I think to be a good leader you have to be a good worker. So I try to lead by example and not really depend on others too much so that if something has messed up, I have no one to blame but myself. This part about Co-ordinators made me chuckle. “Sometimes perceived to be manipulative and will tend to delegate all work” which is unfortunately a little true. But at the same time I’ve been open to working an equal amount as others previously as well.&lt;br /&gt;
&lt;br /&gt;
===Lecture 1: Fertilisation===&lt;br /&gt;
In my previous years in attending university I’ve completed many courses which have gone through the fertilization process such as: Evolutionary Biological Sciences, Physiology, Histology and Pathology. From having done these courses already, there were parts which were familiar to me and that I have understood before in the past. However, I still was amazed by the new refreshing things I have not yet encounter which I did during this lecture. Such as polar bodies and their role in fertilization in disposing of extra DNA. It also clarified a point which I was previously confused about on whether or not polar bodies were gametes or not. Cementing all this information and weaving it in with new learnt information has really been a beneficial experience for me, in that I’m building up on topics I thoroughly enjoy.&lt;br /&gt;
&lt;br /&gt;
==New SubHeading==&lt;br /&gt;
===External Link===&lt;br /&gt;
[http://www.smh.com.au/ SMH]&lt;br /&gt;
&lt;br /&gt;
===Internal Link===&lt;br /&gt;
[[ANAT2341 Lab 1]]&lt;br /&gt;
&lt;br /&gt;
[[ANAT2341 Lab 1|Fertilization Lab]]&lt;br /&gt;
 &lt;br /&gt;
[[Student Page]]&lt;br /&gt;
&lt;br /&gt;
==Referencing==&lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/sites/entrez?db=pubmed&amp;amp;cmd=search&amp;amp;term=fertilization fertilization]&lt;br /&gt;
&lt;br /&gt;
PMID 27486480&lt;br /&gt;
&lt;br /&gt;
==Assessment 1==&lt;br /&gt;
&amp;lt;pubmed&amp;gt;PMC3528851&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&lt;br /&gt;
The research article called &amp;quot; Tet1 controls meiosis by regulating meiotic gene expression&amp;quot; by Yamaguchi et al. (2012) aims to determine the role of ten-eleven translocation methylcytosine dioxygenase 1 (TET1) which is a member of the TET family of enzymes, in regulating meiotic gene expression and thus meiosis in mice. This study was highly useful since little is known about how the expression of meiotic genes is regulated and how their expression contributes to normal meiosis. &lt;br /&gt;
In the study they performed a whole-genome bisulphite sequencing (WGBS) analysis using an ultra-low input so that they would be able to see how Tet1 is used in the activation of meiotic genes. &lt;br /&gt;
&lt;br /&gt;
Results showed that a decreased functioning of Tet1 caused an increase in the unpaired synaptonemal complex at zygotene-stage oocyte, suggesting a synapsis-formation defect. The meiotic defects seen from Tet1 loss of function included: formation of univalent chromosome, but also homologous recombination and DNA double-strand breaks (DSBs) repair defects. These in turn caused defective meiotic prophase which caused decreased amount of oocytes and in turn reduced litter size and lowering in fertility. The study done was pivotal as it built upon past studies which have already established that DNA methylation levels of certain meiotic genes are lowered with genomic reprogramming.&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
{| width=95%&lt;br /&gt;
|-bgcolor=&amp;quot;FAF5FF&amp;quot;&lt;br /&gt;
| [mailto:m.hill@unsw.edu.au Mark Hill] 18 August 2016 - You have added the citation correctly and written a good brief summary of the article findings. &lt;br /&gt;
TET1 is part of the family of methylcytosine dioxygenases that involved in cytosine demethylation and gene activation, interesting that it has a meiotic-specific role.&lt;br /&gt;
&lt;br /&gt;
| width=100px| Assessment 5/5&lt;br /&gt;
|}&lt;/div&gt;</summary>
		<author><name>Z5020466</name></author>
	</entry>
	<entry>
		<id>https://embryology.med.unsw.edu.au/embryology/index.php?title=User:Z5020466&amp;diff=240793</id>
		<title>User:Z5020466</title>
		<link rel="alternate" type="text/html" href="https://embryology.med.unsw.edu.au/embryology/index.php?title=User:Z5020466&amp;diff=240793"/>
		<updated>2016-08-12T04:42:01Z</updated>

		<summary type="html">&lt;p&gt;Z5020466: &lt;/p&gt;
&lt;hr /&gt;
&lt;div&gt;{{ANAT2341Student2016}}&lt;br /&gt;
&lt;br /&gt;
==Lab Attendance==&lt;br /&gt;
[[User:Z5020466|Z5020466]] ([[User talk:Z5020466|talk]]) 14:42, 12 August 2016 (AEST)&lt;br /&gt;
&lt;br /&gt;
===Belbin Team Roles===&lt;br /&gt;
If I’m completely honest, I think my role in group work is generally the “Co-ordinator”. I’m not too sure about my ability to step back from the ‘nitty gritty’ details and see the bigger picture. But rather I generally like to take on leadership roles and assign people tasks. That way I can do things how I like to and place people in roles that I think they would be suited to. But not only that I think to be a good leader you have to be a good worker. So I try to lead by example and not really depend on others too much so that if something has messed up, I have no one to blame but myself. This part about Co-ordinators made me chuckle. “Sometimes perceived to be manipulative and will tend to delegate all work” which is unfortunately a little true. But at the same time I’ve been open to working an equal amount as others previously as well.&lt;br /&gt;
&lt;br /&gt;
===Lecture 1: Fertilisation===&lt;br /&gt;
In my previous years in attending university I’ve completed many courses which have gone through the fertilization process such as: Evolutionary Biological Sciences, Physiology, Histology and Pathology. From having done these courses already, there were parts which were familiar to me and that I have understood before in the past. However, I still was amazed by the new refreshing things I have not yet encounter which I did during this lecture. Such as polar bodies and their role in fertilization in disposing of extra DNA. It also clarified a point which I was previously confused about on whether or not polar bodies were gametes or not. Cementing all this information and weaving it in with new learnt information has really been a beneficial experience for me, in that I’m building up on topics I thoroughly enjoy.&lt;br /&gt;
&lt;br /&gt;
==New SubHeading==&lt;br /&gt;
===External Link===&lt;br /&gt;
[http://www.smh.com.au/ SMH]&lt;br /&gt;
&lt;br /&gt;
===Internal Link===&lt;br /&gt;
[[ANAT2341 Lab 1]]&lt;br /&gt;
&lt;br /&gt;
[[ANAT2341 Lab 1|Fertilization Lab]]&lt;br /&gt;
 &lt;br /&gt;
[[Student Page]]&lt;br /&gt;
&lt;br /&gt;
==Referencing==&lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/sites/entrez?db=pubmed&amp;amp;cmd=search&amp;amp;term=fertilization fertilization]&lt;br /&gt;
&lt;br /&gt;
PMID 27486480&lt;br /&gt;
&lt;br /&gt;
==Assessment 1==&lt;br /&gt;
&amp;lt;pubmed&amp;gt;PMC3528851&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&lt;br /&gt;
The research article called &amp;quot; Tet1 controls meiosis by regulating meiotic gene expression&amp;quot; by Yamaguchi et al. (2012) aims to determine the role of ten-eleven translocation methylcytosine dioxygenase 1 (TET1) which is a member of the TET family of enzymes, in regulating meiotic gene expression and thus meiosis in mice. This study was highly useful since little is known about how the expression of meiotic genes is regulated and how their expression contributes to normal meiosis. &lt;br /&gt;
In the study they performed a whole-genome bisulphite sequencing (WGBS) analysis using an ultra-low input so that they would be able to see how Tet1 is used in the activation of meiotic genes. &lt;br /&gt;
&lt;br /&gt;
Results showed that a decreased functioning of Tet1 caused an increase in the unpaired synaptonemal complex at zygotene-stage oocyte, suggesting a synapsis-formation defect. The meiotic defects seen from Tet1 loss of function included: formation of univalent chromosome, but also homologous recombination and DNA double-strand breaks (DSBs) repair defects. These in turn caused defective meiotic prophase which caused decreased amount of oocytes and in turn reduced litter size and lowering in fertility. The study done was pivotal as it built upon past studies which have already established that DNA methylation levels of certain meiotic genes are lowered with genomic reprogramming.&lt;/div&gt;</summary>
		<author><name>Z5020466</name></author>
	</entry>
	<entry>
		<id>https://embryology.med.unsw.edu.au/embryology/index.php?title=User:Z5020466&amp;diff=240729</id>
		<title>User:Z5020466</title>
		<link rel="alternate" type="text/html" href="https://embryology.med.unsw.edu.au/embryology/index.php?title=User:Z5020466&amp;diff=240729"/>
		<updated>2016-08-12T02:54:57Z</updated>

		<summary type="html">&lt;p&gt;Z5020466: &lt;/p&gt;
&lt;hr /&gt;
&lt;div&gt;{{ANAT2341Student2016}}&lt;br /&gt;
&lt;br /&gt;
==Lab Attendance==&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
===Belbin Team Roles===&lt;br /&gt;
If I’m completely honest, I think my role in group work is generally the “Co-ordinator”. I’m not too sure about my ability to step back from the ‘nitty gritty’ details and see the bigger picture. But rather I generally like to take on leadership roles and assign people tasks. That way I can do things how I like to and place people in roles that I think they would be suited to. But not only that I think to be a good leader you have to be a good worker. So I try to lead by example and not really depend on others too much so that if something has messed up, I have no one to blame but myself. This part about Co-ordinators made me chuckle. “Sometimes perceived to be manipulative and will tend to delegate all work” which is unfortunately a little true. But at the same time I’ve been open to working an equal amount as others previously as well.&lt;br /&gt;
&lt;br /&gt;
===Lecture 1: Fertilisation===&lt;br /&gt;
In my previous years in attending university I’ve completed many courses which have gone through the fertilization process such as: Evolutionary Biological Sciences, Physiology, Histology and Pathology. From having done these courses already, there were parts which were familiar to me and that I have understood before in the past. However, I still was amazed by the new refreshing things I have not yet encounter which I did during this lecture. Such as polar bodies and their role in fertilization in disposing of extra DNA. It also clarified a point which I was previously confused about on whether or not polar bodies were gametes or not. Cementing all this information and weaving it in with new learnt information has really been a beneficial experience for me, in that I’m building up on topics I thoroughly enjoy.&lt;br /&gt;
&lt;br /&gt;
==New SubHeading==&lt;br /&gt;
===External Link===&lt;br /&gt;
[http://www.smh.com.au/ SMH]&lt;br /&gt;
&lt;br /&gt;
===Internal Link===&lt;br /&gt;
[[ANAT2341 Lab 1]]&lt;br /&gt;
&lt;br /&gt;
[[ANAT2341 Lab 1|Fertilization Lab]]&lt;br /&gt;
 &lt;br /&gt;
[[Student Page]]&lt;br /&gt;
&lt;br /&gt;
==Referencing==&lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/sites/entrez?db=pubmed&amp;amp;cmd=search&amp;amp;term=fertilization fertilization]&lt;br /&gt;
&lt;br /&gt;
PMID 27486480&lt;br /&gt;
&lt;br /&gt;
==Assessment 1==&lt;br /&gt;
&amp;lt;pubmed&amp;gt;PMC3528851&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&lt;br /&gt;
The research article called &amp;quot; Tet1 controls meiosis by regulating meiotic gene expression&amp;quot; by Yamaguchi et al. (2012) aims to determine the role of ten-eleven translocation methylcytosine dioxygenase 1 (TET1) which is a member of the TET family of enzymes, in regulating meiotic gene expression and thus meiosis in mice. This study was highly useful since little is known about how the expression of meiotic genes is regulated and how their expression contributes to normal meiosis. &lt;br /&gt;
In the study they performed a whole-genome bisulphite sequencing (WGBS) analysis using an ultra-low input so that they would be able to see how Tet1 is used in the activation of meiotic genes. &lt;br /&gt;
&lt;br /&gt;
Results showed that a decreased functioning of Tet1 caused an increase in the unpaired synaptonemal complex at zygotene-stage oocyte, suggesting a synapsis-formation defect. The meiotic defects seen from Tet1 loss of function included: formation of univalent chromosome, but also homologous recombination and DNA double-strand breaks (DSBs) repair defects. These in turn caused defective meiotic prophase which caused decreased amount of oocytes and in turn reduced litter size and lowering in fertility. The study done was pivotal as it built upon past studies which have already established that DNA methylation levels of certain meiotic genes are lowered with genomic reprogramming.&lt;/div&gt;</summary>
		<author><name>Z5020466</name></author>
	</entry>
	<entry>
		<id>https://embryology.med.unsw.edu.au/embryology/index.php?title=User:Z5020466&amp;diff=240727</id>
		<title>User:Z5020466</title>
		<link rel="alternate" type="text/html" href="https://embryology.med.unsw.edu.au/embryology/index.php?title=User:Z5020466&amp;diff=240727"/>
		<updated>2016-08-12T02:53:31Z</updated>

		<summary type="html">&lt;p&gt;Z5020466: &lt;/p&gt;
&lt;hr /&gt;
&lt;div&gt;{{ANAT2341Student2016}}&lt;br /&gt;
&lt;br /&gt;
==Lab Attendance==&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
===Belbin Team Roles===&lt;br /&gt;
If I’m completely honest, I think my role in group work is generally the “Co-ordinator”. I’m not too sure about my ability to step back from the ‘nitty gritty’ details and see the bigger picture. But rather I generally like to take on leadership roles and assign people tasks. That way I can do things how I like to and place people in roles that I think they would be suited to. But not only that I think to be a good leader you have to be a good worker. So I try to lead by example and not really depend on others too much so that if something has messed up, I have no one to blame but myself. This part about Co-ordinators made me chuckle. “Sometimes perceived to be manipulative and will tend to delegate all work” which is unfortunately a little true. But at the same time I’ve been open to working an equal amount as others previously as well.&lt;br /&gt;
&lt;br /&gt;
===Lecture 1: Fertilisation===&lt;br /&gt;
In my previous years in attending university I’ve completed many courses which have gone through the fertilization process such as: Evolutionary Biological Sciences, Physiology, Histology and Pathology. From having done these courses already, there were parts which were familiar to me and that I have understood before in the past. However, I still was amazed by the new refreshing things I have not yet encounter which I did during this lecture. Such as polar bodies and their role in fertilization in disposing of extra DNA. It also clarified a point which I was previously confused about on whether or not polar bodies were gametes or not. Cementing all this information and weaving it in with new learnt information has really been a beneficial experience for me, in that I’m building up on topics I thoroughly enjoy.&lt;br /&gt;
&lt;br /&gt;
==New SubHeading==&lt;br /&gt;
===External Link===&lt;br /&gt;
[http://www.smh.com.au/ SMH]&lt;br /&gt;
&lt;br /&gt;
===Internal Link===&lt;br /&gt;
[[ANAT2341 Lab 1]]&lt;br /&gt;
&lt;br /&gt;
[[ANAT2341 Lab 1|Fertilization Lab]]&lt;br /&gt;
 &lt;br /&gt;
[[Student Page]]&lt;br /&gt;
&lt;br /&gt;
==Referencing==&lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/sites/entrez?db=pubmed&amp;amp;cmd=search&amp;amp;term=fertilization fertilization]&lt;br /&gt;
&lt;br /&gt;
PMID 27486480&lt;br /&gt;
&lt;br /&gt;
==Assessment 1==&lt;br /&gt;
&amp;lt;pubmed&amp;gt;3528851&amp;lt;/pubmed&amp;gt;&lt;br /&gt;
&lt;br /&gt;
The research article called &amp;quot; Tet1 controls meiosis by regulating meiotic gene expression&amp;quot; by Yamaguchi et al. (2012) aims to determine the role of ten-eleven translocation methylcytosine dioxygenase 1 (TET1) which is a member of the TET family of enzymes, in regulating meiotic gene expression and thus meiosis in mice. This study was highly useful since little is known about how the expression of meiotic genes is regulated and how their expression contributes to normal meiosis. &lt;br /&gt;
In the study they performed a whole-genome bisulphite sequencing (WGBS) analysis using an ultra-low input so that they would be able to see how Tet1 is used in the activation of meiotic genes. &lt;br /&gt;
&lt;br /&gt;
Results showed that a decreased functioning of Tet1 caused an increase in the unpaired synaptonemal complex at zygotene-stage oocyte, suggesting a synapsis-formation defect. The meiotic defects seen from Tet1 loss of function included: formation of univalent chromosome, but also homologous recombination and DNA double-strand breaks (DSBs) repair defects. These in turn caused defective meiotic prophase which caused decreased amount of oocytes and in turn reduced litter size and lowering in fertility. The study done was pivotal as it built upon past studies which have already established that DNA methylation levels of certain meiotic genes are lowered with genomic reprogramming.&lt;/div&gt;</summary>
		<author><name>Z5020466</name></author>
	</entry>
	<entry>
		<id>https://embryology.med.unsw.edu.au/embryology/index.php?title=User:Z5020466&amp;diff=240725</id>
		<title>User:Z5020466</title>
		<link rel="alternate" type="text/html" href="https://embryology.med.unsw.edu.au/embryology/index.php?title=User:Z5020466&amp;diff=240725"/>
		<updated>2016-08-12T02:49:43Z</updated>

		<summary type="html">&lt;p&gt;Z5020466: /* Assessment 1 */&lt;/p&gt;
&lt;hr /&gt;
&lt;div&gt;{{ANAT2341Student2016}}&lt;br /&gt;
&lt;br /&gt;
==Lab Attendance==&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
===Belbin Team Roles===&lt;br /&gt;
If I’m completely honest, I think my role in group work is generally the “Co-ordinator”. I’m not too sure about my ability to step back from the ‘nitty gritty’ details and see the bigger picture. But rather I generally like to take on leadership roles and assign people tasks. That way I can do things how I like to and place people in roles that I think they would be suited to. But not only that I think to be a good leader you have to be a good worker. So I try to lead by example and not really depend on others too much so that if something has messed up, I have no one to blame but myself. This part about Co-ordinators made me chuckle. “Sometimes perceived to be manipulative and will tend to delegate all work” which is unfortunately a little true. But at the same time I’ve been open to working an equal amount as others previously as well.&lt;br /&gt;
&lt;br /&gt;
===Lecture 1: Fertilisation===&lt;br /&gt;
In my previous years in attending university I’ve completed many courses which have gone through the fertilization process such as: Evolutionary Biological Sciences, Physiology, Histology and Pathology. From having done these courses already, there were parts which were familiar to me and that I have understood before in the past. However, I still was amazed by the new refreshing things I have not yet encounter which I did during this lecture. Such as polar bodies and their role in fertilization in disposing of extra DNA. It also clarified a point which I was previously confused about on whether or not polar bodies were gametes or not. Cementing all this information and weaving it in with new learnt information has really been a beneficial experience for me, in that I’m building up on topics I thoroughly enjoy.&lt;br /&gt;
&lt;br /&gt;
==New SubHeading==&lt;br /&gt;
===External Link===&lt;br /&gt;
[http://www.smh.com.au/ SMH]&lt;br /&gt;
&lt;br /&gt;
===Internal Link===&lt;br /&gt;
[[ANAT2341 Lab 1]]&lt;br /&gt;
&lt;br /&gt;
[[ANAT2341 Lab 1|Fertilization Lab]]&lt;br /&gt;
 &lt;br /&gt;
[[Student Page]]&lt;br /&gt;
&lt;br /&gt;
==Referencing==&lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/sites/entrez?db=pubmed&amp;amp;cmd=search&amp;amp;term=fertilization fertilization]&lt;br /&gt;
&lt;br /&gt;
PMID 27486480&lt;br /&gt;
&lt;br /&gt;
==Assessment 1==&lt;br /&gt;
The research article called &amp;quot; Tet1 controls meiosis by regulating meiotic gene expression&amp;quot; by Yamaguchi et al. (2012) aims to determine the role of ten-eleven translocation methylcytosine dioxygenase 1 (TET1) which is a member of the TET family of enzymes, in regulating meiotic gene expression and thus meiosis in mice. This study was highly useful since little is known about how the expression of meiotic genes is regulated and how their expression contributes to normal meiosis. &lt;br /&gt;
In the study they performed a whole-genome bisulphite sequencing (WGBS) analysis using an ultra-low input so that they would be able to see how Tet1 is used in the activation of meiotic genes. &lt;br /&gt;
&lt;br /&gt;
Results showed that a decreased functioning of Tet1 caused an increase in the unpaired synaptonemal complex at zygotene-stage oocyte, suggesting a synapsis-formation defect. The meiotic defects seen from Tet1 loss of function included: formation of univalent chromosome, but also homologous recombination and DNA double-strand breaks (DSBs) repair defects. These in turn caused defective meiotic prophase which caused decreased amount of oocytes and in turn reduced litter size and lowering in fertility. The study done was pivotal as it built upon past studies which have already established that DNA methylation levels of certain meiotic genes are lowered with genomic reprogramming.&lt;/div&gt;</summary>
		<author><name>Z5020466</name></author>
	</entry>
	<entry>
		<id>https://embryology.med.unsw.edu.au/embryology/index.php?title=User:Z5020466&amp;diff=240431</id>
		<title>User:Z5020466</title>
		<link rel="alternate" type="text/html" href="https://embryology.med.unsw.edu.au/embryology/index.php?title=User:Z5020466&amp;diff=240431"/>
		<updated>2016-08-11T08:44:44Z</updated>

		<summary type="html">&lt;p&gt;Z5020466: /* Belbin Team Roles */&lt;/p&gt;
&lt;hr /&gt;
&lt;div&gt;{{ANAT2341Student2016}}&lt;br /&gt;
&lt;br /&gt;
==Lab Attendance==&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
===Belbin Team Roles===&lt;br /&gt;
If I’m completely honest, I think my role in group work is generally the “Co-ordinator”. I’m not too sure about my ability to step back from the ‘nitty gritty’ details and see the bigger picture. But rather I generally like to take on leadership roles and assign people tasks. That way I can do things how I like to and place people in roles that I think they would be suited to. But not only that I think to be a good leader you have to be a good worker. So I try to lead by example and not really depend on others too much so that if something has messed up, I have no one to blame but myself. This part about Co-ordinators made me chuckle. “Sometimes perceived to be manipulative and will tend to delegate all work” which is unfortunately a little true. But at the same time I’ve been open to working an equal amount as others previously as well.&lt;br /&gt;
&lt;br /&gt;
===Lecture 1: Fertilisation===&lt;br /&gt;
In my previous years in attending university I’ve completed many courses which have gone through the fertilization process such as: Evolutionary Biological Sciences, Physiology, Histology and Pathology. From having done these courses already, there were parts which were familiar to me and that I have understood before in the past. However, I still was amazed by the new refreshing things I have not yet encounter which I did during this lecture. Such as polar bodies and their role in fertilization in disposing of extra DNA. It also clarified a point which I was previously confused about on whether or not polar bodies were gametes or not. Cementing all this information and weaving it in with new learnt information has really been a beneficial experience for me, in that I’m building up on topics I thoroughly enjoy.&lt;br /&gt;
&lt;br /&gt;
==New SubHeading==&lt;br /&gt;
===External Link===&lt;br /&gt;
[http://www.smh.com.au/ SMH]&lt;br /&gt;
&lt;br /&gt;
===Internal Link===&lt;br /&gt;
[[ANAT2341 Lab 1]]&lt;br /&gt;
&lt;br /&gt;
[[ANAT2341 Lab 1|Fertilization Lab]]&lt;br /&gt;
 &lt;br /&gt;
[[Student Page]]&lt;br /&gt;
&lt;br /&gt;
==Referencing==&lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/sites/entrez?db=pubmed&amp;amp;cmd=search&amp;amp;term=fertilization fertilization]&lt;br /&gt;
&lt;br /&gt;
PMID 27486480&lt;br /&gt;
&lt;br /&gt;
==Assessment 1==&lt;/div&gt;</summary>
		<author><name>Z5020466</name></author>
	</entry>
	<entry>
		<id>https://embryology.med.unsw.edu.au/embryology/index.php?title=User:Z5020466&amp;diff=240429</id>
		<title>User:Z5020466</title>
		<link rel="alternate" type="text/html" href="https://embryology.med.unsw.edu.au/embryology/index.php?title=User:Z5020466&amp;diff=240429"/>
		<updated>2016-08-11T08:44:30Z</updated>

		<summary type="html">&lt;p&gt;Z5020466: /* Lecture 1: Fertilisation */&lt;/p&gt;
&lt;hr /&gt;
&lt;div&gt;{{ANAT2341Student2016}}&lt;br /&gt;
&lt;br /&gt;
==Lab Attendance==&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
===Belbin Team Roles===&lt;br /&gt;
. &lt;br /&gt;
&lt;br /&gt;
===Lecture 1: Fertilisation===&lt;br /&gt;
In my previous years in attending university I’ve completed many courses which have gone through the fertilization process such as: Evolutionary Biological Sciences, Physiology, Histology and Pathology. From having done these courses already, there were parts which were familiar to me and that I have understood before in the past. However, I still was amazed by the new refreshing things I have not yet encounter which I did during this lecture. Such as polar bodies and their role in fertilization in disposing of extra DNA. It also clarified a point which I was previously confused about on whether or not polar bodies were gametes or not. Cementing all this information and weaving it in with new learnt information has really been a beneficial experience for me, in that I’m building up on topics I thoroughly enjoy.&lt;br /&gt;
&lt;br /&gt;
==New SubHeading==&lt;br /&gt;
===External Link===&lt;br /&gt;
[http://www.smh.com.au/ SMH]&lt;br /&gt;
&lt;br /&gt;
===Internal Link===&lt;br /&gt;
[[ANAT2341 Lab 1]]&lt;br /&gt;
&lt;br /&gt;
[[ANAT2341 Lab 1|Fertilization Lab]]&lt;br /&gt;
 &lt;br /&gt;
[[Student Page]]&lt;br /&gt;
&lt;br /&gt;
==Referencing==&lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/sites/entrez?db=pubmed&amp;amp;cmd=search&amp;amp;term=fertilization fertilization]&lt;br /&gt;
&lt;br /&gt;
PMID 27486480&lt;br /&gt;
&lt;br /&gt;
==Assessment 1==&lt;/div&gt;</summary>
		<author><name>Z5020466</name></author>
	</entry>
	<entry>
		<id>https://embryology.med.unsw.edu.au/embryology/index.php?title=User:Z5020466&amp;diff=240387</id>
		<title>User:Z5020466</title>
		<link rel="alternate" type="text/html" href="https://embryology.med.unsw.edu.au/embryology/index.php?title=User:Z5020466&amp;diff=240387"/>
		<updated>2016-08-11T03:51:15Z</updated>

		<summary type="html">&lt;p&gt;Z5020466: &lt;/p&gt;
&lt;hr /&gt;
&lt;div&gt;{{ANAT2341Student2016}}&lt;br /&gt;
&lt;br /&gt;
==Lab Attendance==&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
===Belbin Team Roles===&lt;br /&gt;
. &lt;br /&gt;
&lt;br /&gt;
===Lecture 1: Fertilisation===&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
==New SubHeading==&lt;br /&gt;
===External Link===&lt;br /&gt;
[http://www.smh.com.au/ SMH]&lt;br /&gt;
&lt;br /&gt;
===Internal Link===&lt;br /&gt;
[[ANAT2341 Lab 1]]&lt;br /&gt;
&lt;br /&gt;
[[ANAT2341 Lab 1|Fertilization Lab]]&lt;br /&gt;
 &lt;br /&gt;
[[Student Page]]&lt;br /&gt;
&lt;br /&gt;
==Referencing==&lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/sites/entrez?db=pubmed&amp;amp;cmd=search&amp;amp;term=fertilization fertilization]&lt;br /&gt;
&lt;br /&gt;
PMID 27486480&lt;br /&gt;
&lt;br /&gt;
==Assessment 1==&lt;/div&gt;</summary>
		<author><name>Z5020466</name></author>
	</entry>
	<entry>
		<id>https://embryology.med.unsw.edu.au/embryology/index.php?title=User:Z5020466&amp;diff=240385</id>
		<title>User:Z5020466</title>
		<link rel="alternate" type="text/html" href="https://embryology.med.unsw.edu.au/embryology/index.php?title=User:Z5020466&amp;diff=240385"/>
		<updated>2016-08-11T03:47:38Z</updated>

		<summary type="html">&lt;p&gt;Z5020466: /* Lab Attendance */&lt;/p&gt;
&lt;hr /&gt;
&lt;div&gt;{{ANAT2341Student2016}}&lt;br /&gt;
&lt;br /&gt;
==Lab Attendance==&lt;br /&gt;
[[User:Z5014803|Z5014803]] ([[User talk:Z5014803|talk]]) 18:29, 5 August 2016 (AEST)&lt;br /&gt;
&lt;br /&gt;
===Belbin Team Roles===&lt;br /&gt;
. &lt;br /&gt;
&lt;br /&gt;
===Lecture 1: Fertilisation===&lt;br /&gt;
&lt;br /&gt;
&lt;br /&gt;
==New SubHeading==&lt;br /&gt;
===External Link===&lt;br /&gt;
[http://www.smh.com.au/ SMH]&lt;br /&gt;
&lt;br /&gt;
===Internal Link===&lt;br /&gt;
[[ANAT2341 Lab 1]]&lt;br /&gt;
&lt;br /&gt;
[[ANAT2341 Lab 1|Fertilization Lab]]&lt;br /&gt;
 &lt;br /&gt;
[[Student Page]]&lt;br /&gt;
&lt;br /&gt;
==Referencing==&lt;br /&gt;
[http://www.ncbi.nlm.nih.gov/sites/entrez?db=pubmed&amp;amp;cmd=search&amp;amp;term=fertilization fertilization]&lt;br /&gt;
&lt;br /&gt;
PMID 27486480&lt;br /&gt;
&lt;br /&gt;
==Assessment 1==&lt;/div&gt;</summary>
		<author><name>Z5020466</name></author>
	</entry>
	<entry>
		<id>https://embryology.med.unsw.edu.au/embryology/index.php?title=User:Z5020466&amp;diff=240377</id>
		<title>User:Z5020466</title>
		<link rel="alternate" type="text/html" href="https://embryology.med.unsw.edu.au/embryology/index.php?title=User:Z5020466&amp;diff=240377"/>
		<updated>2016-08-11T03:40:31Z</updated>

		<summary type="html">&lt;p&gt;Z5020466: Created page with &amp;quot;==Lab Attendance== ~~~~  [http://www.smh.com.au/ SMH]  ANAT2341 Lab 1  Fertilization Lab&amp;quot;&lt;/p&gt;
&lt;hr /&gt;
&lt;div&gt;==Lab Attendance==&lt;br /&gt;
[[User:Z5020466|Z5020466]] ([[User talk:Z5020466|talk]]) 13:40, 11 August 2016 (AEST)&lt;br /&gt;
&lt;br /&gt;
[http://www.smh.com.au/ SMH]&lt;br /&gt;
&lt;br /&gt;
[[ANAT2341 Lab 1]]&lt;br /&gt;
&lt;br /&gt;
[[ANAT2341 Lab 1|Fertilization Lab]]&lt;/div&gt;</summary>
		<author><name>Z5020466</name></author>
	</entry>
</feed>