Persistent and high levels of Hes1 expression regulate boundary formation in the developing central nervous system
Persistent and high levels of Hes1 expression regulate boundary formation in the developing central nervous system
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DOI：
10.1242/dev.02403
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发表时间：
2006-07-01
期刊：
影响因子：
4.6
通讯作者：
Kageyama, Ryoichiro
中科院分区：
文献类型：
--
作者：
Baek, Joung Hee;Hatakeyama, Jun;Kageyama, Ryoichiro
发育中的中枢神经系统被边界细胞划分成不同的区室，边界细胞与区室细胞具有不同的特性，如形成无神经元区，增殖较慢，并作为组织中心。我们现在报道，在小鼠中，bHLH因子Hes1在边界细胞中持续高水平表达，但在非边界细胞中表达水平不同。Hes1的表达水平与原膜bHLH因子Mash1的表达水平呈负相关，表明Hes1的下调会导致非边界区Mash1的上调，而Hes1的持续高表达则会组成性地抑制边界区Mash1。在缺乏Hes1及其相关基因Hes3和Hes5的情况下，原神经bHLH基因在边界上异位表达，导致异位神经发生和组织中心的破坏。相反，从隔室区制备的神经祖细胞中持续表达Hes1会阻碍神经发生并降低细胞增殖率。这些结果表明，Hes1在边界细胞和非边界细胞中的表达方式是不同的，持续高水平的Hes1表达会组成性地抑制原膜bHLH基因的表达，降低细胞增殖率，从而形成作为组织中心的边界。
The developing central nervous system is partitioned into compartments by boundary cells, which have different properties than compartment cells, such as forming neuron-free zones, proliferating more slowly and acting as organizing centers. We now report that in mice the bHLH factor Hes1 is persistently expressed at high levels by boundary cells but at variable levels by non-boundary cells. Expression levels of Hes1 display an inverse correlation to those of the proneural bHLH factor Mash1, suggesting that downregulation of Hes1 leads to upregulation of Mash1 in non-boundary regions, whereas persistent and high Hes1 expression constitutively represses Mash1 in boundary regions. In agreement with this notion, in the absence of Hes1 and its related genes Hes3 and Hes5, proneural bHLH genes are ectopically expressed in boundaries, resulting in ectopic neurogenesis and disruption of the organizing centers. Conversely, persistent Hes1 expression in neural progenitors prepared from compartment regions blocks neurogenesis and reduces cell proliferation rates. These results indicate that the mode of Hes1 expression is different between boundary and non-boundary cells, and that persistent and high levels of Hes1 expression constitutively repress proneural bHLH gene expression and reduce cell proliferation rates, thereby forming boundaries that act as the organizing centers.