Neural stem cells are defined by their capacity to proliferate and self-renew indefinitely and their ability to differentiate into various neuronal and glial progeny. One of the signaling pathways involved in neural stem cells' decision between proliferation and differentiation is the Notch pathway. Members of the Hes and Hey families of transcription factors are regarded as Notch target genes which generally inhibit the differentiation of neural stem cells and maintain them in cell cycle. One of the Hey family members, HeyL, appears to have the unique ability to promote neuronal differentiation of neural stem cells in vitro, suggesting a similar role in vivo. This proposal seeks to assess the neurogenic potential of HeyL in vivo and to identify the target genes regulated by HeyL that may mediate this effect.
These aims will be achieved through a series of experiments entailing overexpression or knock-down of HeyL in the nervous system of developing mouse embryos and analyzing the effects on neurogenesis. Additionally, chromatin immunoprecipitation assays and promoter reporter assays will be utilized to identify the putative transcriptional targets of HeyL. These studies will further our understanding of the underlying biology of neural stem cells and nervous system development.
|Jalali, Ali; Bassuk, Alexander G; Kan, Lixin et al. (2011) HeyL promotes neuronal differentiation of neural progenitor cells. J Neurosci Res 89:299-309|
|Jalali, Ali; Aldinger, Kimberly A; Chary, Ajit et al. (2008) Linkage to chromosome 2q36.1 in autosomal dominant Dandy-Walker malformation with occipital cephalocele and evidence for genetic heterogeneity. Hum Genet 123:237-45|
|Kan, Lixin; Jalali, Ali; Zhao, Li-Ru et al. (2007) Dual function of Sox1 in telencephalic progenitor cells. Dev Biol 310:85-98|