The basic helix-loop-helix genes Hesr1/Hey1 and Hesr2/Hey2 regulate maintenance of neural precursor cells in the brain
The basic helix-loop-helix genes Hesr1/Hey1 and Hesr2/Hey2 regulate maintenance of neural precursor cells in the brain
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DOI：
10.1074/jbc.m300448200
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发表时间：
2003-11-07
影响因子：
4.8
通讯作者：
Kageyama, R
中科院分区：
文献类型：
--
作者：
Sakamoto, M;Hirata, H;Kageyama, R
神经前体细胞在脑室区域增殖，首先在脑室产生深层神经元，然后是浅层神经元，最后是大脑中的神经胶质细胞。因此，保持神经前体细胞直到神经发育的后期阶段对于产生各种各样的细胞类型是至关重要的。在这里，我们发现Hes相关的碱性螺旋-环-螺旋(BHLH)基因Hesr1/Hey1和Hesr2/Hey2在含有神经前体细胞的脑室区域表达。在胚胎13.5天，通过电穿孔在小鼠脑中错误表达Hesr1和Hesr2，可以暂时维持神经前体细胞，从而增加位于浅层的晚出生神经元。相反，基因在后期的错误表达会抑制神经发生，促进星形胶质细胞的生成。在培养细胞的瞬时转染实验中，Hesr1和Hesr2都抑制了神经元bHLH基因Mash1和Math3诱导的转录。这些结果表明，Hesr1和Hesr2负性调节神经元bHLH基因，促进神经前体细胞的维持，并增加发育中大脑中晚出生细胞的类型。
Neural precursor cells proliferate in the ventricular zone while giving rise to neurons of deep layers first, then those of the superficial layers, and lastly, glial cells in the brain. Thus, it is essential to maintain neural precursor cells until late stages of neural development for generation of a wide variety of cell types. Here, we found that the Hes-related basic helix-loop-helix (bHLH) genes Hesr1/Hey1 and Hesr2/Hey2 are expressed in the ventricular zone, which contains neural precursor cells. Misexpression of Hesr1 and Hesr2 by electroporation in mouse brain at embryonic day 13.5 transiently maintains neural precursor cells and thereby increases late-born neurons, which are located in the superficial layers. In contrast, misexpression of the genes at later stages inhibits neurogenesis and promotes generation of astroglial cells. In transient transfection assay with cultured cells, both Hesr1 and Hesr2 inhibit transcription induced by the neuronal bHLH genes Mash1 and Math3. These results indicate that Hesr1 and Hesr2 negatively regulate neuronal bHLH genes, promote maintenance of neural precursor cells, and increase late-born cell types in the developing brain.