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Insm1 Induces Neural Progenitor Delamination in Developing Neocortex via Downregulation of the Adherens Junction Belt-Specific Protein Plekha7
Neuron ( IF 14.7 ) Pub Date : 2018-03-01 , DOI: 10.1016/j.neuron.2018.01.052
Stefania Tavano , Elena Taverna , Nereo Kalebic , Christiane Haffner , Takashi Namba , Andreas Dahl , Michaela Wilsch-Bräuninger , Judith T.M.L. Paridaen , Wieland B. Huttner

Delamination of neural progenitor cells (NPCs) from the ventricular surface is a crucial prerequisite to form the subventricular zone, the germinal layer linked to the expansion of the mammalian neocortex in development and evolution. Here, we dissect the molecular mechanism by which the transcription factor Insm1 promotes the generation of basal progenitors (BPs). Insm1 protein is most highly expressed in newborn BPs in mouse and human developing neocortex. Forced Insm1 expression in embryonic mouse neocortex causes NPC delamination, converting apical to basal radial glia. Insm1 represses the expression of the apical adherens junction belt-specific protein Plekha7. CRISPR/Cas9-mediated disruption of expression suffices to cause NPC delamination. Plekha7 overexpression impedes the intrinsic and counteracts the Insm1-induced, NPC delamination. Our findings uncover a novel molecular mechanism underlying NPC delamination in which a BP-genic transcription factor specifically targets the integrity of the apical adherens junction belt, rather than adherens junction components as such.

中文翻译:

Insm1 通过下调粘附连接带特异性蛋白 Plekha7 诱导新皮质发育中的神经祖细胞分层

神经祖细胞(NPC)从脑室表面分层是形成脑室下区的关键先决条件,脑室下区是与哺乳动物新皮质在发育和进化过程中的扩张相关的生发层。在这里,我们剖析了转录因子 Insm1 促进基底祖细胞(BP)生成的分子机制。Insm1 蛋白在小鼠和人类发育新皮质的新生儿 BP 中表达最高。Insm1 在胚胎小鼠新皮质中的强制表达会导致 NPC 分层,将顶端胶质细胞转变为基底放射状胶质细胞。Insm1 抑制顶端粘附连接带特异性蛋白 Plekha7 的表达。CRISPR/Cas9 介导的表达破坏足以导致 NPC 分层。Plekha7 过度表达会阻碍内在现象并抵消 Insm1 诱导的 NPC 分层。我们的研究结果揭示了 NPC 分层背后的一种新的分子机制,其中 BP 基因转录因子专门针对顶端粘附连接带的完整性,而不是粘附连接组件本身。
更新日期:2018-03-01
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