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

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 sp...

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Autores principales: Leggere, Janelle C, Saito, Yuhki, Darnell, Robert B, Tessier-Lavigne, Marc, Junge, Harald J, Chen, Zhe
Formato: Online Artículo Texto
Lenguaje:English
Publicado: eLife Sciences Publications, Ltd 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4930329/
https://www.ncbi.nlm.nih.gov/pubmed/27223328
http://dx.doi.org/10.7554/eLife.14264
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author Leggere, Janelle C
Saito, Yuhki
Darnell, Robert B
Tessier-Lavigne, Marc
Junge, Harald J
Chen, Zhe
author_facet Leggere, Janelle C
Saito, Yuhki
Darnell, Robert B
Tessier-Lavigne, Marc
Junge, Harald J
Chen, Zhe
author_sort Leggere, Janelle C
collection PubMed
description 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. DOI: http://dx.doi.org/10.7554/eLife.14264.001
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spelling pubmed-49303292016-07-05 NOVA regulates Dcc alternative splicing during neuronal migration and axon guidance in the spinal cord Leggere, Janelle C Saito, Yuhki Darnell, Robert B Tessier-Lavigne, Marc Junge, Harald J Chen, Zhe eLife Developmental Biology and Stem Cells 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. DOI: http://dx.doi.org/10.7554/eLife.14264.001 eLife Sciences Publications, Ltd 2016-05-25 /pmc/articles/PMC4930329/ /pubmed/27223328 http://dx.doi.org/10.7554/eLife.14264 Text en © 2016, Leggere et al http://creativecommons.org/licenses/by/4.0/ This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited.
spellingShingle Developmental Biology and Stem Cells
Leggere, Janelle C
Saito, Yuhki
Darnell, Robert B
Tessier-Lavigne, Marc
Junge, Harald J
Chen, Zhe
NOVA regulates Dcc alternative splicing during neuronal migration and axon guidance in the spinal cord
title NOVA regulates Dcc alternative splicing during neuronal migration and axon guidance in the spinal cord
title_full NOVA regulates Dcc alternative splicing during neuronal migration and axon guidance in the spinal cord
title_fullStr NOVA regulates Dcc alternative splicing during neuronal migration and axon guidance in the spinal cord
title_full_unstemmed NOVA regulates Dcc alternative splicing during neuronal migration and axon guidance in the spinal cord
title_short NOVA regulates Dcc alternative splicing during neuronal migration and axon guidance in the spinal cord
title_sort nova regulates dcc alternative splicing during neuronal migration and axon guidance in the spinal cord
topic Developmental Biology and Stem Cells
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4930329/
https://www.ncbi.nlm.nih.gov/pubmed/27223328
http://dx.doi.org/10.7554/eLife.14264
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