Zic1 promotes the expansion of dorsal neural progenitors in spinal cord by inhibiting neuronal differentiation
Zic1 promotes the expansion of dorsal neural progenitors in spinal cord by inhibiting neuronal differentiation
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DOI：
10.1006/dbio.2002.0598
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发表时间：
2002-04-15
影响因子：
2.7
通讯作者：
Mikoshiba, K
中科院分区：
文献类型：
--
作者：
Aruga, J;Tohmonda, T;Mikoshiba, K
通过改变其在发育中的脊髓中的表达状态来研究Zic 1的作用。Zic基因编码与果蝇Odd配对同源的锌指蛋白。在脊椎动物神经发育中，它们通常在背神经管中表达。鸡Zic 1最初沿着背腹轴均匀表达，在神经胚形成过程中，其表达在背侧变得越来越受限制。Zic1的背侧表达受Sonic hedgehog、BMP 4和BMP 7的调节，正如它们在脊髓中的过度表达所揭示的那样。当Zic1在鸡脊髓腹侧错误表达时，无论背腹侧位置如何，神经元分化都受到抑制。此外，背腹属性没有受到严重影响，所揭示的分子标记。一致地，当Zic1在转基因小鼠的背侧脊髓中过表达时，我们观察到背侧脊髓中的细胞过多。与截短突变Zic1荷瘤小鼠相比，转基因表达细胞增加。相反，我们观察到一个显着的细胞数量减少，而没有损失的背侧属性Zic1缺陷小鼠的背侧脊髓。综上所述，这些发现表明，Zic1通过抑制神经元分化的进展来控制神经元前体的扩张。Notch介导的神经元分化抑制可能作用于Zic基因的下游，因为Notch 1在小鼠和鸡的Zic 1过表达脊髓中上调。(C)2002 Elsevier Science（美国）。
The role of Zic1 was investigated by altering its expression status in developing spinal cords. Zic genes encode zinc finger proteins homologous to Drosophila Odd-paired. In vertebrate neural development, they are generally expressed in the dorsal neural tube. Chick Zic1 was initially expressed evenly along the dorsoventral axis and its expression became increasingly restricted dorsally during the course of neurulation. The dorsal expression of Zic1 was regulated by Sonic hedgehog, BMP4, and BMP7, as revealed by their overexpressions in the spinal cord. When Zic1 was misexpressed on the ventral side of the chick spinal cord, neuronal differentiation was inhibited irrespective of the dorsoventral position. In addition, dorsoventral properties were not grossly affected as revealed by molecular markers. Concordantly, when Zic1 was overexpressed in the dorsal spinal cord in transgenic mice, we observed hypercellularity in the dorsal spinal cord. The transgene-expressing cells were increased in comparison to those of truncated mutant Zic1-bearing mice. Conversely, we observed a significant cell number reduction without loss of dorsal properties in the dorsal spinal cords of Zic1-deficient mice. Taken together, these findings suggest that Zic1 controls the expansion of neuronal precursors by inhibiting the progression of neuronal differentiation. Notch-mediated inhibition of neuronal differention is likely to act downstream of Zic genes since Notch1 is upregulated in Zic1-overexpressing spinal cords in both the mouse and the chick. (C) 2002 Elsevier Science (USA).