Hes genes and neurogenin regulate non-neural versus neural fate specification in the dorsal telencephalic midline
Hes genes and neurogenin regulate non-neural versus neural fate specification in the dorsal telencephalic midline
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DOI：
10.1242/dev.021535
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发表时间：
2008-08-01
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：
Imayoshi, Itaru;Shimogori, Tomomi;Kageyama, Ryoichiro
大脑中的脉络丛是独一无二的，因为它是一种非神经分泌组织。它分泌脑脊液，起血脑屏障的作用，但这种非神经组织的确切机制尚未确定。利用小鼠胚胎和谱系追踪分析，我们发现预期的脉络丛区域最初产生Cajal-Retzius细胞，这是指导神经元迁移的专门神经元。BHLH抑制基因Hes1、Hes3和Hes5的失活上调了神经原基因Ngn2的表达，并过早地耗尽了表达BMP的祖细胞，导致Cajal-Retzius细胞的形成增强和脉络丛上皮细胞的完全丧失。过表达Ngn2也有类似的作用。这些数据表明，Hes基因通过拮抗端脑中线背侧区域的Ngn2来促进脉络丛上皮细胞的命运指定，而不是Cajal-Retzius细胞的命运的指定，因此本研究确定了bHLH基因在决定哪些细胞将具有非神经或神经命运的过程中发挥了新的作用。
The choroid plexus in the brain is unique because it is a non-neural secretory tissue. It secretes the cerebrospinal fluid and functions as a blood-brain barrier, but the precise mechanism of specification of this non-neural tissue has not yet been determined. Using mouse embryos and lineage-tracing analysis, we found that the prospective choroid plexus region initially gives rise to Cajal-Retziuscells, specialized neurons that guide neuronal migration. Inactivation of the bHLH repressor genes Hes1, Hes3 and Hes5 upregulated expression of the proneural gene neurogenin 2 (Ngn2) and prematurely depleted Bmp-expressing progenitor cells, leading to enhanced formation of Cajal-Retzius cells and complete loss of choroid plexus epithelial cells. Overexpression of Ngn2 had similar effects. These data indicate that Hes genes promote specification of the fate of choroid plexus epithelial cells rather than the fate of Cajal-Retzius cells by antagonizing Ngn2 in the dorsal telencephalic midline region, and thus this study has identified a novel role for bHLH genes in the process of deciding which cells will have a non-neural versus a neural fate.