Dlx1/2 are Central and Essential Components in the Transcriptional Code for Generating Olfactory Bulb Interneurons
Dlx1/2 are Central and Essential Components in the Transcriptional Code for Generating Olfactory Bulb Interneurons
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Dlx1/2 是生成嗅球中间神经元的转录代码的核心和重要组成部分。
DOI：
10.1093/cercor/bhz018
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发表时间：
2019-11-01
期刊：
影响因子：
3.7
通讯作者：
Yang, Zhengang
中科院分区：
文献类型：
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作者：
Guo, Teng;Liu, Guoping;Yang, Zhengang
嗅球(OB)中间神经元的产生需要神经干/祖细胞的规范、增殖、分化以及幼年间神经元的迁移和成熟。在这里，我们证明了同源框转录因子Dlx1/2是产生OB中间神经元的转录密码的中心和必要组件。在D1x1/2结构性缺失突变体中，GSX2+和ASCL1+神经干/祖细胞在背外侧神经节隆起的分化受阻，导致OB中间神经元的生成失败。在Dlx1/2条件突变体(hGFAP-CRE；Dlx1/2F/-小鼠)中，出生后脑室下区的GSX2+和ASCL1+神经干/祖细胞也不能分化为OB中间神经元。相反，Dlx1和Dlx2在胚胎小鼠皮质中的过度表达导致异位产生表达Gad1、SP8、SP9、Arx、Pbx3、Etw1、Tshz1和PROKR2的OB样中间神经元。Pax6突变体与OB样中间神经元发生皮质异位，但在复合Pax6；Dlx1/2突变体中不这样做。我们认为DLX1/2主要通过激活SP8/9的表达，进而促进Tshz1和PROKR2的表达，从而促进OB间神经元的发育。在此基础上，结合前人的研究，我们提出了OB中间神经元发育过程的转录网络。
Generation of olfactory bulb (OB) interneurons requires neural stem/progenitor cell specification, proliferation, differentiation, and young interneuron migration and maturation. Here, we show that the homeobox transcription factors Dlx1/2 are central and essential components in the transcriptional code for generating OB interneurons. In Dlx1/2 constitutive null mutants, the differentiation of GSX2+ and ASCL1+ neural stem/progenitor cells in the dorsal lateral ganglionic eminence is blocked, resulting in a failure of OB interneuron generation. In Dlx1/2 conditional mutants (hGFAP-Cre; Dlx1/2F/- mice), GSX2+ and ASCL1+ neural stem/progenitor cells in the postnatal subventricular zone also fail to differentiate into OB interneurons. In contrast, overexpression of Dlx1&2 in embryonic mouse cortex led to ectopic production of OB-like interneurons that expressed Gad1, Sp8, Sp9, Arx, Pbx3, Etv1, Tshz1, and Prokr2. Pax6 mutants generate cortical ectopia with OB-like interneurons, but do not do so in compound Pax6; Dlx1/2 mutants. We propose that DLX1/2 promote OB interneuron development mainly through activating the expression of Sp8/9, which further promote Tshz1 and Prokr2 expression. Based on this study, in combination with earlier ones, we propose a transcriptional network for the process of OB interneuron development.