First cell fate choice in the mammalian embryo and the hippo pathway Flashcards
What is the first cell fate in mammalian embryo controlled by?
Controlled by the position of the cell in the embryo and its polarity
What transcription factors are expressed in inner cell mass?
Oct3/4, Sox2, Sall4, Nanog expressed in ICM
What transcription factors are expressed in trophectoderm cells?
Cdx2, Gata4 expressed in TE
What is the Tead4 transcription factor a crucial regulator of?
-Tead4 is a crucial regulator of TE formation
What is Tead4 transcription factor expressed in and what type of cell is it activated in and by what pathway?
- Tead4 is expressed in TE and ICM
- Activated only in TE by hippo pathway
What is Hippo identified as?
Hippo identified as a tumour suppressor in drosophila
What does a hippo mutation cause?
-Mutation causes overgrowth
What type of surface do trophectoderm cells have and comment on the polarity?
-Outer surface cells, trophectoderm cells, have a free surface and are therefore polar
What type of surface do inner cell mass have and comment on the polarity?
-Inner surface cells, inner cell mass, don’t have a free surface and are therefore non polar.
What happens in hippo active cells?
- Occurs in inner cell mass
- A complex of kinases are activated and one of them are Mst.
- This complex of kinases lead to the phosphorylation of the Yap protein
- Yap protein is a coactivator
- When its phosphorylated, it can’t translocate into the nucleus, therefore unable to activate the Tead4 transcription factor
What happens in hippo inactive cells?
- In trophectoderm cells, the complex of kinases isn’t activated, hence the Yap protein isn’t phosphorylated.
- Unphosphorylated Yap protein is able to translocate into the nucleus and interact with the Tead4 transcription factor.
- This ultimately leads to the expression of the trophectoderm specific genes
What has recent studies shown to be necessary in order to inactivate the hippo pathway?
-Recent studies have proposed the presence of an apical surface on the polar cells that form the trophectoderm is necessary to inactivate the hippo pathway
How does an apical surface inactivate the hippo pathway?
-Molecules in the apical surface will sequester the kinase complexes, therefore preventing the phosphorylation of the Yap protein. This will allow the Yap protein to translocate into the nucleus and binds with Tead4.
How is the binding of Yap to Tead4 mediated?
-The binding ofYAPto TEAD4 is mediated by the N-terminal domain ofYAPand the C-terminal domain ofTEAD4
Why do inner cell mass not have an apical surface?
-Inner cell mass are not polar , therefore do not have an apical surface.
