Transcription factor RBP-J-mediated signaling represses the differentiation of neural stem cells into intermediate neural progenitors
Transcription factor RBP-J-mediated signaling represses the differentiation of neural stem cells into intermediate neural progenitors
复制标题
DOI：
10.1016/j.mcn.2008.12.008
复制
发表时间：
2009-04-01
影响因子：
3.5
通讯作者：
Ju, Gong
中科院分区：
文献类型：
--
作者：
Gao, Fang;Zhang, Qi;Ju, Gong
Notch信号对于神经发生的多个方面都至关重要，但它如何调节神经干细胞（NSC）和中间神经祖细胞（INP）的增殖和分化尚未得到很好的阐明，尤其是在体内。在这项研究中，我们使用 RBP-J-floxed 小鼠和新建立的 Nestin-Cre 小鼠，有条件地消除了基底前脑和腹侧中脑中介导所有四种哺乳动物 Notch 受体信号传导的转录因子 RBP-J。我们发现，在神经发生早期（E11.5），RBP-J 失活区域中神经球的频率显着增加。大多数 RBP-J 缺陷神经球由 INP 组成，表明 NSC 过早分化为 INP。同时，在 E11.5 时，同一区域的神经元分化减少，这与大多数 Notch 相关突变体的早熟分化表型不一致。在神经发生晚期（E17.5 和新生儿），正如从早熟耗尽的 NSC 库中所预期的那样，RBP-J 减弱区域的神经球频率和 NSC 减少，同时神经元和神经胶质细胞显着增加。这些结果表明，RBP-J 介导的信号传导可能抑制 NSCS 分化为 INP，并支持早期神经发生阶段某些早期神经元的生成。 （三）； 2008 Elsevier Inc. 保留所有权利。
Notch signaling is critical for multiple aspects of neurogenesis, but how it regulates the proliferation and differentiation of neural stem cells (NSCs) and intermediate neural progenitors (INPs) has not been well elucidated, especially in vivo. In this study, we conditionally ablated the transcription factor RBP-J, which mediates signalling from all four mammalian Notch receptors, in the basal forebrain and ventral midbrain using the RBP-J-floxed mouse and a newly established Nestin-Cre mouse. We found that at early stage neurogenesis (E11.5), the frequency of neurospheres increased significantly in the RBP-J-inactivated regions. The majority of the RBP-J deficient neurospheres were composed of INPs, suggesting the precocious differentiation of NSCs into INPs. Meanwhile, neuronal differentiation was reduced in the same regions at E11.5, inconsistent with the precocious differentiation phenotype in most Notch-related mutants. At late neurogenic stages (E17.5 and neonatal), as expected from precociously exhausted NSC pool, neurosphere frequency and NSCs decreased in the RBP-J-albated regions, accompanied by a significant increase of both neurons and glial cells. These results indicated that the RBP-J-mediated signaling might inhibit the differentiation of NSCS into INPs and support the generation of certain early born neurons at early neurogenic stages. (C); 2008 Elsevier Inc. All rights reserved.