Dmrta1 regulates proneural gene expression downstream of P ax6 in the mammalian telencephalon

The transcription factor P ax6 balances cell proliferation and neuronal differentiation in the mammalian developing neocortex by regulating the expression of target genes. Using microarray analysis, we observed the down‐regulation of Dmrta1 ( doublesex and mab‐3 ‐related transcription factor‐like fa...

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Published in:Genes to cells : devoted to molecular & cellular mechanisms 2013-08, Vol.18 (8), p.636-649
Main Authors: Kikkawa, Takako, Obayashi, Takeshi, Takahashi, Masanori, Fukuzaki‐Dohi, Urara, Numayama‐Tsuruta, Keiko, Osumi, Noriko
Format: Article
Language:English
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Summary:The transcription factor P ax6 balances cell proliferation and neuronal differentiation in the mammalian developing neocortex by regulating the expression of target genes. Using microarray analysis, we observed the down‐regulation of Dmrta1 ( doublesex and mab‐3 ‐related transcription factor‐like family A1) in the telencephalon of Pax6 homozygous mutant rats ( rS ey 2 / rS ey 2 ). Dmrta1 expression was restricted to the neural stem/progenitor cells of the dorsal telencephalon. Overexpression of Dmrta1 induced the expression of the proneural gene Neurogenin2 ( Neurog2 ) and conversely repressed Ascl1 ( Mash1 ), a proneural gene expressed in the ventral telencephalon. We found that another Dmrt family molecule, Dmrt3 , induced Neurog2 expression in the dorsal telencephalon. Our novel findings suggest that dual regulation of proneural genes mediated by Pax6 and Dmrt family members is crucial for cortical neurogenesis.
ISSN:1356-9597
1365-2443
DOI:10.1111/gtc.12061