A novel function of the proneural factor Ascl1 in progenitor proliferation identified by genome-wide characterization of its targets.
Genes & Development. 2011-05-01; 25(9): 930-945
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1. Genes Dev. 2011 May 1;25(9):930-45. doi: 10.1101/gad.627811.
A novel function of the proneural factor Ascl1 in progenitor proliferation
identified by genome-wide characterization of its targets.
Castro DS(1), Martynoga B, Parras C, Ramesh V, Pacary E, Johnston C, Drechsel D,
Lebel-Potter M, Garcia LG, Hunt C, Dolle D, Bithell A, Ettwiller L, Buckley N,
(1)Medical Research Council National Institute for Medical Research, Division of
Molecular Neurobiology, The Ridgeway, Mill Hill, London NW7 1AA, United Kingdom.
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
PMID: 21536733 [Indexed for MEDLINE]