Premium
[P1.52]: Roles of notch signaling in adult neural stem cells
Author(s) -
Imayoshi I.,
Kageyama R.
Publication year - 2010
Publication title -
international journal of developmental neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.761
H-Index - 88
eISSN - 1873-474X
pISSN - 0736-5748
DOI - 10.1016/j.ijdevneu.2010.07.092
Subject(s) - library science , citation , neural crest , notch signaling pathway , neural stem cell , cognitive science , neuroscience , stem cell , biology , computer science , psychology , genetics , signal transduction , embryo
Every year, a significant numbers of Canadians are affected by psychiatric and neurological disorders such as depression, autism and schizophrenia. The possibility of promoting neurogenesis following the onset of these diseases is an extremely appealing therapeutic option. The functionally intertwined Retinoblastoma (pRb) and E2F protein families are well known for their essential roles in regulating cell cycle entry; however we have described expanded roles for these proteins in regulating multiple aspects of neural development. Determining the mechanism that regulates these processes is essential for our understanding of how neural development proceeds. We show that the absence of the cell cycle regulatory protein E2F4 leads to a deficit in neural stem cell numbers and a severe impairment of self renewal. Additionally, E2F4 deficiency results in a loss of ventral telencephalic structures, a phenotype with striking similarity to animals lacking the Sonic Hedgehog (Shh) gene. We have previously shown that loss of both Shh expression and ventral telencephalic structures are rescued by interbreeding E2F4 s mutant with mice heterozygous for Gli3, a negative regulator of the Shh pathway. Preliminary data using ChIP-on Chip has identified Gli3 as a regulatory target for the E2F4 transcription factor. These findings suggest that E2F4 negatively regulates Gli3 expression and that in the absence of E2F4, Gli3 aberrantly represses Shh expression, consequently impeding ventral telencephalic patterning. In conclusion, these findings suggest that E2F4 is an essential regulator of neural stem cell renewal and telencephalic patterning by regulating the activity of the Shh pathway through repression of Gli3 expression. This work was funded by CMM travel grants, OGSST, FGPS to DDT, CIHR grant to RSS.