Division of Developmental Neuroscience, United Centers for Advanced Research and Translational Medicine (ART), Graduate School of Medicine, Tohoku University, Seiryo-Machi, Aoba-ku, Sendai, Miyagi, Japan.
Mech Dev. 2011 May-Jun;128(5-6):289-302. doi: 10.1016/j.mod.2011.04.001. Epub 2011 Apr 9.
The vertebrate neuroepithelium can be subdivided into non-boundary and boundary regions. The boundary regions act as signaling centers for regional specification and neurogenesis in the neighboring non-boundary regions. An important question is how boundary regions are specified and maintained during brain development. In this study, we report that Pax6, a homeodomain transcription factor, regulates boundary-cell specification between rhombomeres of the developing rat hindbrain. We compared expression patterns of four boundary-cell markers, including PLZF (Zbtb16), Ring1A (Ring1), Wnt5a, and cadherin7 (Cdh7), in wild-type and Pax6 loss-of-function mutant hindbrains and found that the expression of Zbtb16, Ring1, and Wnt5a was down-regulated in the rhombomere boundaries, while Cdh7 expression was up-regulated in the non-boundary regions of the Pax6 mutant hindbrain. Morphological observations revealed that the boundary regions were larger and that the interface between the boundary and non-boundary regions was obscured in the Pax6 mutant hindbrain. We also found ectopic neuronal differentiation in the boundary cells of the Pax6 mutant hindbrain. In addition, we observed that Hes5 was down-regulated and that Neurogenin2 (Neurog2) was up-regulated in the boundary regions of the Pax6 mutant hindbrain. Because Hes genes have been shown to inhibit neuronal differentiation by repressing proneural genes, Pax6 may act through this pathway to prevent neurogenesis in the boundary cells. Taken together, Pax6 seems to be required for coordinating boundary-cell specification and reducing neurogenesis within the hindbrain boundary region.
脊椎动物神经上皮可细分为非边界区和边界区。边界区充当信号中心，为邻近非边界区的区域特化和神经发生提供信号。一个重要的问题是，在大脑发育过程中，边界区是如何被特化和维持的。在这项研究中，我们报告 Pax6（一种同源域转录因子）调节发育中大鼠后脑的菱脑节边界细胞的特化。我们比较了四个边界细胞标志物（包括 PLZF（Zbtb16）、Ring1A（Ring1）、Wnt5a 和 cadherin7（Cdh7））在野生型和 Pax6 功能缺失突变体后脑中的表达模式，发现 Zbtb16、Ring1 和 Wnt5a 的表达在菱脑节边界下调，而 Cdh7 的表达在 Pax6 突变体后脑的非边界区上调。形态学观察显示，边界区更大，边界和非边界区之间的界面在 Pax6 突变体后脑中变得模糊。我们还发现 Pax6 突变体后脑的边界细胞中存在异位神经元分化。此外，我们观察到 Hes5 在 Pax6 突变体后脑的边界区下调，Neurogenin2（Neurog2）上调。因为 Hes 基因已被证明通过抑制原神经基因来抑制神经元分化，所以 Pax6 可能通过这条途径来防止边界细胞中的神经发生。综上所述，Pax6 似乎需要协调边界细胞的特化和减少后脑边界区的神经发生。
