Lecture 4: Development of the Hypothalamus 2 Flashcards
What happens in PM signalling after the induction of shh?
Wnt, BMP, FGF10 and Tbx2 are all upregulated in the fan-shaped cells above the PM.
How do we know that these TFs are being expressed and why is it very unusual that they are?
By doing a double in-situ hybridisation it is revealed that the fan-shaped cells are co-expressing these TFs but shh & BMP7 usually repress each others transcription.
How was the hypothesised hypothalamic stem cell that expresses shh, BMP7 & FGF10 tested?
By performing fate mapping studies using dye injected into the area above the PM and leaving the embryo to develop in the egg.
Allowed identification of whether cells positive for these TFs gave rise to many other hypothalamic cells (i.e. multipotent) and whether they self renewed.
What is thought to have happened to the early patterning effect of the shh?
It was thought to be obscured by the growth of cells from the FGF10+ progenitors
How does differentiation of the hypothalamic progenitors occur?
The anterior & mammillary regions grow sequentially from the edges of the centrally retained FGF10+ progenitors.
FGF is expressed in one cell and shh in the other daughter.
However, shh is a secreted factor so diffuses from the shh expressing cell & acts on the FGF cell to maintain it’s shh expression.
What is the working hypothesis for hypothalamic development?
A cellular homeostatic mechanism involving FGF & shh signalling ensures an appropriate balance of FGF10+/shh+ progenitors and differentiating cells
