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[P2.38]: Vasculature guides migrating neuronal precursors in the adult mammalian forebrain
Author(s) -
Snapyan M.,
Lemasson M.,
Saghatelayn A.
Publication year - 2008
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.2008.09.163
Subject(s) - forebrain , library science , citation , art history , sociology , art , psychology , neuroscience , computer science , central nervous system
humans.We found that ZFP423 cooperates dose-dependently with NICD to upregulate Hes5 and Blbp in P19 cells. In C2C12 cells, that do not express the gene, Hes5 gene transcription is strictly dependent upon the addition of exogenous Zfp423. In cells transfected with Zfp423, unlike untransfected controls, treatment with exogenous BMP4 further activates NICD-dependent Hes5 transcription. In keeping with the above findings, ZFP423 knockdown, achieved through specific shRNAs, reduces the level of Hes5 expression in response to NICD. Finally, in gain-of-function experiments, co-transfection of cells with Ebf genes counteracts the cooperative effect of ZFP423 andNICD onHes5 gene regulation. Our results, achieved in cellular systems, suggest that, by cooperating with NICD and nuclear SMAD1–SMAD4, ZFP423 may boost the activity of Notch signaling in maintaining and expanding the pool of cerebellar progenitors, to support the birth of successive waves of glial and/or neuronal progenitors. In vivo studies of Zfp423 mutants are in progress to test this hypothesis.