Department of Neurological Surgery, University of Washington, Seattle, Washington 98101, USA.
J Neurosci. 2012 May 2;32(18):6275-87. doi: 10.1523/JNEUROSCI.0532-12.2012.
Neurogenesis in the dentate gyrus has been implicated in cognitive functions, including learning and memory, and may be abnormal in major neuropsychiatric disorders, such as depression. Dentate neurogenesis is regulated by interactions between extrinsic factors and intrinsic transcriptional cascades that are currently not well understood. Here we show that Tbr2 (also known as Eomes), a T-box transcription factor expressed by intermediate neuronal progenitors (INPs), is critically required for neurogenesis in the dentate gyrus of developing and adult mice. In the absence of Tbr2, INPs are depleted despite augmented neural stem cell (NSC) proliferation, and neurogenesis is halted as the result of failed neuronal differentiation. Interestingly, we find that Tbr2 likely promotes lineage progression from NSC to neuronal-specified INP in part by repression of Sox2, a key determinant of NSC identity. These findings suggest that Tbr2 expression in INPs is critical for neuronal differentiation in the dentate gyrus and that INPs are an essential stage in the lineage from NSCs to new granule neurons in the dentate gyrus.
齿状回中的神经发生与认知功能有关，包括学习和记忆，并且可能在重大神经精神疾病中异常，例如抑郁症。齿状回的神经发生受到外在因素和内在转录级联之间相互作用的调节，目前尚不完全清楚。在这里，我们表明 Tbr2（也称为 Eomes），一种由中间神经元祖细胞（INP）表达的 T 盒转录因子，对于发育中和成年小鼠齿状回中的神经发生至关重要。在缺乏 Tbr2 的情况下，尽管神经干细胞（NSC）增殖增加，但 INP 被耗尽，并且由于神经元分化失败而停止神经发生。有趣的是，我们发现 Tbr2 可能通过抑制 Sox2（NSC 身份的关键决定因素）来促进从 NSC 到神经元特异性 INP 的谱系进展，从而促进神经元分化。这些发现表明 INP 中的 Tbr2 表达对于齿状回中的神经元分化至关重要，并且 INP 是从 NSCs 到齿状回中新颗粒神经元的谱系中的一个重要阶段。
