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NOVA在脊髓神经元迁移和轴突导向过程中调节Dcc可变剪接。

NOVA regulates Dcc alternative splicing during neuronal migration and axon guidance in the spinal cord.

作者信息

Leggere Janelle C, Saito Yuhki, Darnell Robert B, Tessier-Lavigne Marc, Junge Harald J, Chen Zhe

机构信息

Department of Molecular, Cellular, and Developmental Biology, University of Colorado, Boulder, United States.

Laboratory of Molecular Neuro-Oncology, Howard Hughes Medical Institute, The Rockefeller University, New York, United States.

出版信息

Elife. 2016 May 25;5:e14264. doi: 10.7554/eLife.14264.

DOI:10.7554/eLife.14264
PMID:27223328
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4930329/
Abstract

RNA-binding proteins (RBPs) control multiple aspects of post-transcriptional gene regulation and function during various biological processes in the nervous system. To further reveal the functional significance of RBPs during neural development, we carried out an in vivo RNAi screen in the dorsal spinal cord interneurons, including the commissural neurons. We found that the NOVA family of RBPs play a key role in neuronal migration, axon outgrowth, and axon guidance. Interestingly, Nova mutants display similar defects as the knockout of the Dcc transmembrane receptor. We show here that Nova deficiency disrupts the alternative splicing of Dcc, and that restoring Dcc splicing in Nova knockouts is able to rescue the defects. Together, our results demonstrate that the production of DCC splice variants controlled by NOVA has a crucial function during many stages of commissural neuron development.

摘要

RNA结合蛋白（RBPs）在神经系统的各种生物过程中控制转录后基因调控和功能的多个方面。为了进一步揭示RBPs在神经发育过程中的功能意义，我们在包括连合神经元在内的背脊髓中间神经元中进行了体内RNA干扰筛选。我们发现RBPs的NOVA家族在神经元迁移、轴突生长和轴突导向中起关键作用。有趣的是，Nova突变体表现出与Dcc跨膜受体敲除类似的缺陷。我们在此表明，Nova缺乏会破坏Dcc的可变剪接，并且在Nova基因敲除中恢复Dcc剪接能够挽救这些缺陷。总之，我们的结果表明，由NOVA控制的DCC剪接变体的产生在连合神经元发育的许多阶段具有关键功能。

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