Stem Cell Biology Laboratory, Institute of Molecular Biology and Genetics, Vari-Attica, Greece.
Stem Cells. 2011 Jan;29(1):89-98. doi: 10.1002/stem.554.
Neural stem/progenitor cells maintain their identity via continuous self-renewal and suppression of differentiation. Gain-of-function experiments in the chick revealed an involvement for Sox1-3 transcription factors in the maintenance of the undifferentiated neural progenitor (NP) identity. However, the mechanism(s) employed by each factor has not been resolved. Here, we derived cortical neural/stem progenitor cells from wild-type and Sox1-null mouse embryos and found that Sox1 plays a key role in the suppression of neurogenic cell divisions. Loss of Sox1 leads to progressive depletion of self-renewing cells, elongation of the cell cycle of proliferating cells, and significant increase in the number of cells exiting the cell cycle. In proliferating NP cells, Sox1 acts via a prospero-related homeobox 1 (Prox1)-mediated pathway to block cell cycle exit that leads to neuronal differentiation in vivo and in vitro. Thus, our results demonstrate that Sox1 regulates the size of the cortical NP pool via suppression of Prox1-mediated neurogenic cell divisions.
神经干细胞/祖细胞通过持续的自我更新和抑制分化来维持其特性。鸡的功能获得实验表明 Sox1-3 转录因子参与维持未分化的神经祖细胞（NP）特性。然而，每个因子所采用的机制尚未解决。在这里，我们从野生型和 Sox1 基因敲除小鼠胚胎中分离出皮质神经/干细胞祖细胞，发现 Sox1 在抑制神经发生细胞分裂中起关键作用。Sox1 的缺失导致自我更新细胞逐渐耗竭，增殖细胞的细胞周期延长，以及退出细胞周期的细胞数量显著增加。在增殖的 NP 细胞中，Sox1 通过 Prospero 相关同源盒蛋白 1（Prox1）介导的途径发挥作用，阻止导致体内和体外神经元分化的细胞周期退出。因此，我们的结果表明 Sox1 通过抑制 Prox1 介导的神经发生细胞分裂来调节皮质 NP 池的大小。
