The T-box transcription factor Eomes/Tbr2 regulates neurogenesis in the cortical subventricular zone
The T-box transcription factor Eomes/Tbr2 regulates neurogenesis in the cortical subventricular zone
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DOI：
10.1101/gad.475408
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发表时间：
2008-09-15
影响因子：
10.5
通讯作者：
Groszer, Matthias
中科院分区：
文献类型：
--
作者：
Arnold, Sebastian J.;Huang, Guo-Jen;Groszer, Matthias
胚胎脑室下区（SVZ）是产生皮质投射神经元的关键部位；然而，特异性调控SVZ神经发生的分子机制在很大程度上是未知的。转录因子Eomes/Tbr2在皮质SVZ祖细胞中瞬时表达。在此我们证明，在早期大脑发育过程中Tbr2的条件性失活会导致小头畸形和严重的行为缺陷。在Tbr2突变体中，SVZ祖细胞的数量减少，大脑皮质上层神经元的分化受到干扰。成年齿状回的神经发生被消除，但室管膜下区的神经发生未受影响。这些研究确立了Tbr2作为SVZ神经发生的关键调节因子。
The embryonic subventricular zone (SVZ) is a critical site for generating cortical projection neurons; however, molecular mechanisms regulating neurogenesis specifically in the SVZ are largely unknown. The transcription factor Eomes/Tbr2 is transiently expressed in cortical SVZ progenitor cells. Here we demonstrate that conditional inactivation of Tbr2 during early brain development causes microcephaly and severe behavioral deficits. In Tbr2 mutants the number of SVZ progenitor cells is reduced and the differentiation of upper cortical layer neurons is disturbed. Neurogenesis in the adult dentate gyrus but not the subependymal zone is abolished. These studies establish Tbr2 as a key regulator of neurogenesis in the SVZ.