2016 Group Project 1: Difference between revisions

From Embryology
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**During vertebrate gastrulation, the mesodermal and ectodermal cells undergo convergent extension. Polarized cells will thus intercalate along the mediolateral axis, resulting in mediolateral narrowing (convergent) and anteroposterior elongation (extension).  
**During vertebrate gastrulation, the mesodermal and ectodermal cells undergo convergent extension. Polarized cells will thus intercalate along the mediolateral axis, resulting in mediolateral narrowing (convergent) and anteroposterior elongation (extension).  
**The non-canonical Wnt pathway regulates cell polarity and movements of dorsal mesodermal cells during convergent extension and later during neural tube closure.
**The non-canonical Wnt pathway regulates cell polarity and movements of dorsal mesodermal cells during convergent extension and later during neural tube closure.


<pubmed>19279717</pubmed>
<pubmed>19279717</pubmed>

Revision as of 15:38, 16 September 2016

2016 Student Projects 
Signalling: 1 Wnt | 2 Notch | 3 FGF Receptor | 4 Hedgehog | 5 T-box | 6 TGF-Beta
2016 Group Project Topic - Signaling in Development

OK you are now in a group, add a topic with your student signature to the group page.

This page is an undergraduate science embryology student project and may contain inaccuracies in either descriptions or acknowledgements.
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Topic: WnT Signaling Pathway in skin of fetus

Things to do/ Reference

Friday 9/9/16: 1. Identify all the components of each pathway. (Can possibly look into the similarities vs differences/ interactions between the pathways. 2. Research into how each pathway contributes to fetal devleopment in different body. (Can look into which fetal part we can focus on e.g. skin) 3. Look for picture/diagrams/graphs etc.

Let's get some more information up by next Thursday, 15/9/16

Friday 16/9/16: Good resource: Omim.org (Contains alot of information about different genes and every signalling pathways. How to reference?)

The signalling pathways:

Canonical Pathway - Gloria

    • The Wnt family of secreted glycolipoproteins play an important role in the role of embryonic development and adult homeostasis.
    • They do so via the transcription of β-catenin, which accumulates in the cytoplasm and eventually gets translocated into the nucleus to act as a transcriptional coactivator of transcription factors that belong to the TCF/LEF family.
    • The canonical Wnt pathway of (Wnt/ β-catenin pathway) is the Wnt pathway that causes β-catenin to stay in the cytoplasm rather than be degraded through ubiquitination which is induced by destruction complexes. The destruction complexes which sends β-catenin to proteasome for digestion are proteins such as: Axin, adenomatosis, polyposiscoli (APC), protein phosphatase 2A (PP2A), glycogen synthase kinase 3 (GSK3) and casein kinase 1α (CK1α).
    • Once the stabilised β-catenin enters the cell nucleus it acts as a transcriptional coactivator for transcription of Wnt-target genes. The primary family of transcription factor which β-catenin associates with is the TCF/LEF family. Activation through β-catenin is mediated with compounds such as histone acetyl transferase CBP, the chromatin-remodeling SWI/SNF complex and Bcl9 bound to pygopus (Pyg).
    • This signalling pathway is crucial for deciding the fate of cells during early embryogenesis.


<pubmed>19279717 </pubmed>

Canonical Pathway: How it works - Gloria
    • Wnt family of signalling proteins plays various roles in fetus development of embryogenesis.
    • Wnt signals are pleiotropic (when a gene has effects on two or more seemingly unrelated phenotypic traits). The signals have effects on mitogenic stimulation, cell fate specification and differentiation.
    • In the canonical pathway, Wnt ligands bind to frizzle receptors that are at the cell surface.
    • Due to this activation of Wnt signalling, B-catenin, which is normally degraded within the cell, starts to accumulate in the cell and ultimately the nucleus.
    • At normal levels of B-catenin, the protein binds at the intracellular side of the membrane with cadherins to promote cell adhesion and also controls cell shape through actin microfilament cytoskeletal network.
    • However at elevated level of this protein, activation of transcription occurs alongside co-transcription factors such as action of Lefs/Tcfs.

<pubmed>15473860 </pubmed>

Canonical Pathway & Embryogenesis - Gloria

Non-Canonical Pathway - Caroline

    • The non-canonical pathway can also be referred to as the beta-catenin independent pathway. It can be divided into two pathways known as the Planar Call Polarity pathway or the PCP pathway.
    • The PCP pathway was discovered through genetic studies in Drosophila. It was found that mutations in Wnt signaling resulted in a randomised orientation of epithelial structures.
    • During vertebrate gastrulation, the mesodermal and ectodermal cells undergo convergent extension. Polarized cells will thus intercalate along the mediolateral axis, resulting in mediolateral narrowing (convergent) and anteroposterior elongation (extension).
    • The non-canonical Wnt pathway regulates cell polarity and movements of dorsal mesodermal cells during convergent extension and later during neural tube closure.


<pubmed>19279717</pubmed>

<pubmed>27101101</pubmed>

<pubmed>26989192 </pubmed>

<pubmed>26680417</pubmed>

WnT-Calcium Ion Pathway - Tony

  • PMID 21903638
    • WNT5 ligands were specifically studied since calcium ions are secondary signaling molecules of wnt5. During gastrulation, wnt/beta-catenin pathway is switched on to promote migration of cells, while wnt/calcium pathway is later turned on to stop its effect. Wnt signalling pathway is especially important in guiding the movement of embryonic cells, and wnt/calcium pathway is especially active during gastrulation process.
    • Drosophila and zebrafish models are frequently used to study wnt singalling pathway, due to the fact that wnt signaling is quite conserved across species.
    • Wnt/calcium pathway has also been know to be able to alter the signalling transduction of wnt ligand through other receptors.
  • PMID 17881570
    • It is suggested that wnt3a is identified as a wnt canonical pathway ligand in hematopoietic stem cells. However, wnt5a functions in the same cell line mainly as a wnt canonical pathway antagonist since the intracellular catenin level was significantly decreased. Wnt 5a is able to increase the transcription of BCL-2 in the HSC cells and therefore, increase their life span. It seems that in HSCs, wnt5a can also induce the transcription of hes-1 gene which then activates Notch signalling pathway. Notch signalling pathway has been reported to be able to increase the re-productivity of the HSCs. Therefore, it can be seen that wnt5a also possesses a positive effect on HSCs reproduction. wnt5a induces the self-renewal of HSCs, while wnt3a induction increases the amount of c-myc whcih inhibits this action.

How does it work in a foetus (skin formation) - Arsalan

Wnt signalling is an important component of skin formation in the very early stages of foetus development. Once the embryo undergoes gastrulation, cells of the ectoderm will form differentiate to form the epidermis and the mesoderm will form the dermis.

WnT signalling strongly influences the decision of the ectoderm layer specifying as nervous system or skin epithelium. WnT signalling inhibits the ectoderm’s responsiveness to the fibroblast growth factors. This inhibition is essential for the ectodermal cells to be able to express bone morphogenetic proteins that result in blocking neural induction and directing the cells to differentiate into keratin expressing cells that form the epidermis.

In terms of the mesoderm WnT signals are important for the process of somitogenesis, in which the mesoderm segments into somites that eventually form the dermis. WnT signals will also instruct the lateral plate mesoderm and somite derived cells to create mesenchymal cells which are essential cells within the dermis.

<pubmed>PMC3552514</pubmed>

===What can go wrong?=== z341763

Cells need to communicate with each other so they can act in a coordinated manner in response to the environment. Communication occurs through signalling pathways which, stimulate, inhibit and coordinate the behaviour of cells to grow or divide during the appropriate times. This can hence become a very pedantic and intricate process and little changes can interrupt the entire system. When things go wrong in signalling, cancer can happen.

In most normal cells the Wnt pathway is inactive and the beta catenin is destroyed and gene transcription is inhibited. In tumour cells, the Wnt pathway may be activated despite the absence of a Wnt signal. This is a result of a mutation of a gene that carries code for a protein complex and hence disintegrates the protein complex. The beta catenin is now no longer tagged for destruction and its cellular level continues to increase. This is very similar to a normal cell where the pathway was actually activated by the Wnt Signal. Beta catenin reaches the nucleus and activates the TCF and LEF transcription factors which activates an RNA polymerase and transcription of several genes begin. This however is inappropriate and uncontrolled and hence leads to cancer. One of the most common mutations is the mutation of the APC protein and is directly linked with the development of colon cancer. People who inherit defective APC alleles’ develop large numbers of polyps which become malignant adenocarcinoma(insertfootnote). People who have mutant APC have nearly a 100% chance of developing colon cancer by the age of 40 years.

Reference(im not sure how to reference things that arent from pubmed) http://www.cell.com/cell/fulltext/S0092-8674(06)01344-4 Wnt/β-Catenin Signaling in Development and Disease Clevers, Hans Cell , Volume 127 , Issue 3 , 469 - 480

References

PMID 21903638