Journal
GENES & DEVELOPMENT
Volume 25, Issue 9, Pages 930-945Publisher
COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT
DOI: 10.1101/gad.627811
Keywords
proneural factor; cell proliferation; genomic location analyses; target genes
Categories
Funding
- Wellcome Trust [082347/Z/07/Z]
- Medical Research Council (UK)
- Medical Research Council [U117570528]
- Wellcome Trust [082347/Z/07/Z] Funding Source: Wellcome Trust
- MRC [MC_U117570528] Funding Source: UKRI
- Medical Research Council [MC_U117570528] Funding Source: researchfish
Ask authors/readers for more resources
Proneural genes such as Ascl1 are known to promote cell cycle exit and neuronal differentiation when expressed in neural progenitor cells. The mechanisms by which proneural genes activate neurogenesis-and, in particular, the genes that they regulate-however, are mostly unknown. We performed a genome-wide characterization of the transcriptional targets of Ascl1 in the embryonic brain and in neural stem cell cultures by location analysis and expression profiling of embryos overexpressing or mutant for Ascl1. The wide range of molecular and cellular functions represented among these targets suggests that Ascl1 directly controls the specification of neural progenitors as well as the later steps of neuronal differentiation and neurite outgrowth. Surprisingly, Ascl1 also regulates the expression of a large number of genes involved in cell cycle progression, including canonical cell cycle regulators and oncogenic transcription factors. Mutational analysis in the embryonic brain and manipulation of Ascl1 activity in neural stem cell cultures revealed that Ascl1 is indeed required for normal proliferation of neural progenitors. This study identified a novel and unexpected activity of the proneural gene Ascl1, and revealed a direct molecular link between the phase of expansion of neural progenitors and the subsequent phases of cell cycle exit and neuronal differentiation.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available