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

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

Research output: Contribution to journalArticlepeer-review

28 Scopus citations

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.

Original languageEnglish (US)
Article numbere14264
JournaleLife
Volume5
Issue numberMAY2016
DOIs
StatePublished - May 25 2016
Externally publishedYes

Bibliographical note

Funding Information:
National Institutes of Health NIH R01 NS34389 Robert B Darnell, National Institutes of Health NS069473 Robert B Darnell, National Institutes of Health NS081706 Robert B Darnell, Howard Hughes Medical Institute Robert B Darnell, National Institutes of Health R01EY024261 Harald J Junge, Boettcher Foundation New Investigator Award Zhe Chen, Boettcher Foundation OCG5499B Zhe Chen

Publisher Copyright:
© Leggere et al.

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