Insulinoma-Associated 1 Has a Panneurogenic Role and Promotes the Generation and Expansion of Basal Progenitors in the Developing Mouse Neocortex
Insulinoma-Associated 1 Has a Panneurogenic Role and Promotes the Generation and Expansion of Basal Progenitors in the Developing Mouse Neocortex
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DOI：
10.1016/j.neuron.2008.09.020
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发表时间：
2008-10-09
期刊：
影响因子：
16.2
通讯作者：
Huttner, Wieland B.
中科院分区：
文献类型：
--
作者：
Farkas, Lilla M.;Haffner, Christiane;Huttner, Wieland B.
基底（中间）祖细胞是哺乳动物新皮层神经元的主要来源。控制基底祖细胞生物发生的分子机制尚不清楚。在这里，我们表明，锌指转录因子Insm1（胰岛素瘤相关1）是在经历神经原性分裂的祖细胞中特异性表达的，在整个大脑中具有泛神经原性作用，并促进新皮层中的基础祖细胞形成。缺乏Insm1的小鼠胚胎含有一半数量的基底祖细胞，并显示皮质板径向厚度显着减少。在神经上皮细胞中的Insm1的强制过早表达导致其有丝分裂发生在心室区的基底侧（而不是顶端），并诱导基底祖细胞标记Tbr 2的表达。值得注意的是，这些细胞对神经原性祖细胞的标志物Tis21保持阴性，并且不产生神经元，而是进行自我扩增。我们的数据表明，Insm1参与了基础祖细胞的产生和扩展，这是新皮层进化的标志。
Basal (intermediate) progenitors are the major source of neurons in the mammalian neocortex. The molecular machinery governing basal progenitor biogenesis is unknown. Here, we show that the zinc-finger transcription factor Insm1 (insulinoma-associated 1) is expressed specifically in progenitors undergoing neurogenic divisions, has a panneurogenic role throughout the brain, and promotes basal progenitor formation in the neocortex. Mouse embryos lacking Insm1 contained half the number of basal progenitors and showed a marked reduction in cortical plate radial thickness. Forced premature expression of Insm1 in neuroepithelial cells resulted in their mitosis occurring at the basal (rather than apical) side of the ventricular zone and induced expression of the basal progenitor marker Tbr2. Remarkably, these cells remained negative for Tis21, a marker of neurogenic progenitors, and did not generate neurons but underwent self-amplification. Our data imply that Insm1 is involved in the generation and expansion of basal progenitors, a hallmark of neocortex evolution.