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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...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
eLife Sciences Publications, Ltd
2016
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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 |
format | Online Article Text |
id | pubmed-4930329 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | eLife Sciences Publications, Ltd |
record_format | MEDLINE/PubMed |
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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