Identification of a novel basic helix-loop-helix gene, Heslike, and its role in GABAergic Neurogenesis
Identification of a novel basic helix-loop-helix gene, Heslike, and its role in GABAergic Neurogenesis
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DOI：
10.1523/jneurosci.5327-03.2004
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发表时间：
2004-04-07
影响因子：
5.3
通讯作者：
Kageyama, R
中科院分区：
文献类型：
--
作者：
Miyoshi, G;Bessho, Y;Kageyama, R
神经元亚型的确定取决于多种转录因子，如基本螺旋-环-螺旋（bHLH）因子。然而，大多数神经元的转录因子编码仍有待确定。在这里，我们报道了一种新的小鼠bHLH因子的鉴定，称为Heslike，具有hes1样bHLH结构域和转录抑制因子活性。Heslike与bHLH因子Mash1在产生gaba能神经元的脑区共表达。在中脑和尾间脑中，Heslike和Mash1的共表达最初局限于小区域，但从胚胎第9.5天起，Heslike和Mash1的共表达在背侧扩展，这种共表达的扩展随后发生gaba能神经发生。Heslike在小鼠胚胎中的错误表达仅在Mash1（+）区域产生异位gaba能神经元。相比之下，在mash1缺失小鼠的中脑和尾间脑中，gaba能神经元几乎完全缺失，取而代之的是产生其他神经元，尽管Heslike仍然表达。此外，在神经前体细胞培养中，与单独表达Heslike和Mash1基因相比，Heslike和Mash1基因的共表达显著促进gaba能神经元的形成。因此，仅Heslike或Mash1是不够的，但它们的共表达可能对gaba能神经元的产生很重要。这些结果表明不同bHLH因子的组合促进了不同神经元亚型的形成，从而增加了神经元的多样性。
Neuronal subtype specification depends on multiple transcription factors such as basic helix-loop-helix (bHLH) factors. However, transcription factor codes for most neurons remain to be determined. Here, we report identification of a novel mouse bHLH factor, termed Heslike, that has Hes1-like bHLH domain and transcriptional repressor activity. Heslike is coexpressed with the bHLH factor Mash1 in brain regions that give rise to GABAergic neurons. In the mesencephalon and the caudal diencephalon, coexpression of Heslike and Mash1 is initially restricted to small regions but expanded dorsally from embryonic day 9.5 onward, and this expansion of coexpression is followed by GABAergic neurogenesis. Misexpression of Heslike in mouse embryos generates ectopic GABAergic neurons only from the Mash1(+) region. In contrast, in the mesencephalon and the caudal diencephalon of Mash1-null mice, GABAergic neurons are almost completely missing and, instead, other neurons are generated, although Heslike is still expressed. Furthermore, coexpression of Heslike and Mash1 significantly promotes formation of GABAergic neurons, compared with each gene alone, in neural precursor cell culture. Thus, Heslike or Mash1 alone is not sufficient, but their coexpression may be important for generation of GABAergic neurons. These results suggest that combinations of distinct bHLH factors promote formation of distinct neuronal subtypes, thereby increasing neuronal diversity.