May 4, 2011

A novel function of the proneural factor Ascl1 in progenitor proliferation identified by genome-wide characterization of its targets

Genes & Development
Diogo S CastroFrancois Guillemot

Abstract

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 mol...Continue Reading

Mentioned in this Paper

Embryo
Cell Cycle Progression
Genome-Wide Association Study
Gene Knockdown Techniques
Neurite Outgrowth
Ascl1 protein, mouse
Transcription, Genetic
Molecular Profiling
Cell Proliferation
Neural Stem Cells

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