Laboratory of Molecular Neuroscience, School of Biomedical Science and Medical Research Institute, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo, Japan.
Dev Biol. 2011 Jun 1;354(1):44-54. doi: 10.1016/j.ydbio.2011.03.020. Epub 2011 Apr 2.
During brain development, neurons and glias are generated from neural stem cells and more limited intermediate neural progenitors (INPs). Numerous studies have revealed the mechanisms of development of neural stem cells. However, the signaling pathways that govern the development of INPs are largely unknown. The cerebellum is suitable for examining this issue because cerebellar cortical inhibitory neurons such as basket and stellate cells are derived from small Pax2(+) interneuronal progenitors. Here, we show that Sox2(-)/Pax2(+) and Sox2(+)/Pax2(-) progenitors, 2 types of interneuronal progenitors of basket and stellate cells, exist in the cerebellar white matter (WM) and that the former arise from the latter during the first postnatal week. Moreover, RBP-J promotes the neurogenesis of stellate and basket cells by converting Sox2(+)/Pax2(-) interneuronal progenitors to more mature Sox2(-)/Pax2(+) interneuronal progenitors. This study shows a novel RBP-J function that promotes INP differentiation.
在大脑发育过程中,神经元和神经胶质由神经干细胞和更有限的中间神经祖细胞(INP)产生。许多研究已经揭示了神经干细胞发育的机制。然而,调控 INP 发育的信号通路在很大程度上是未知的。小脑非常适合研究这个问题,因为小脑皮质抑制性神经元,如篮状细胞和星状细胞,均起源于小的 Pax2(+) 中间神经元祖细胞。在这里,我们发现 Sox2(-)/Pax2(+) 和 Sox2(+)/Pax2(-)祖细胞,即篮状细胞和星状细胞的两种中间神经元祖细胞,存在于小脑白质(WM)中,前者在出生后第一周内由后者产生。此外,RBP-J 通过将 Sox2(+)/Pax2(-) 中间神经元祖细胞转化为更成熟的 Sox2(-)/Pax2(+) 中间神经元祖细胞,促进星状细胞和篮状细胞的神经发生。这项研究展示了 RBP-J 促进 INP 分化的新功能。