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Dmrta1 regulates proneural gene expression downstream of P ax6 in the mammalian telencephalon
Author(s) -
Kikkawa Takako,
Obayashi Takeshi,
Takahashi Masanori,
FukuzakiDohi Urara,
NumayamaTsuruta Keiko,
Osumi Noriko
Publication year - 2013
Publication title -
genes to cells
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.912
H-Index - 115
eISSN - 1365-2443
pISSN - 1356-9597
DOI - 10.1111/gtc.12061
Subject(s) - biology , proneural genes , pax6 , cerebrum , neurogenesis , transcription factor , progenitor cell , neocortex , microbiology and biotechnology , progenitor , neural stem cell , gene , genetics , stem cell , neuroscience , central nervous system
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.