Generation of astrocytes within the developing cerebral cortex is a tightly regulated process, which bursts after neuronogenesis completion and precedes the bulk of oligodendrogenesis. Astrocytic outputs depend on two primary factors: progression of multipotent precursors towards astroglial lineages and proliferation of astrocyte‐committed progenitors. Molecular mechanisms controlling lineage choice have been investigated and reconstructed to large extent. On the contrary, very little is known about control of astroblast population kinetics. In this study we show that Emx2 inhibits astrocyte progenitors proliferation by repressing EgfR and Fgf9, and report details of molecular mechanisms mediating such repression. Indeed we demonstrated that Emx2 overexpression in cortico‐cerebral stem cells decreased proliferation within the astrogenic lineage, resulting in a severe reduction of the astroglial outcome. We also showed that this was caused by EgfR and Fgf9 downregulation. The former originated from exaggerated Bmp signalling. The latter was due to Emx2-dependent suppression of the Sox2 activation elicited by Brn2. Finally, we provided evidence that temporal progression of Emx2 levels in neural stem cells confines astrogenesis to postnatal life.
|Autori interni:||Filippis, Carol|
|Titolo:||Emx2 expression levels in NSCs modulate astrogenesis rates by downregulating EgfR and Fgf9|
|Data di pubblicazione:||nov-2013|
|Appare nelle tipologie:||8.1 PhD thesis|