NOVA regulates Dcc alternative splicing during neuronal migration and axon guidance in the spinal cord
Open accessAbstract
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.
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NOVA1 and RASA1 are known to interact with DCC.
“are known to interact with DCC [111, 112]”
From Self-domestication in Homo sapiens: Insights from comparative genomics (2017) · cites this paper as [111]
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- Authors
- Leggere, J. C., Saito, Y., Darnell, R. B., Tessier-Lavigne, M., Junge, H. J., & Chen, Z.
- Affiliations
- University of Colorado Boulder (US)
- Howard Hughes Medical Institute (US)
- Laboratory of Brain Development and Repair, The Rockefeller University, New York, United States
- Corresponding author
- Junge, Harald J
- Chen, Zhe
- Venue
- eLife
- Publisher
- eLife Sciences Publications, Ltd
- Published
- 2016-05-25
- Volume
- 5
- ISSN
- 2050-084X (ISSN-L)
- PMC
- PMC4930329
- OpenAlex
- W2395185061
- Cited by
- 67
- References
- 83
- Citations by year
- 2026: 2 · 2025: 6 · 2024: 5 · 2023: 3 · 2022: 8 · 2021: 7 · 2020: 9 · 2019: 11 · 2018: 6 · 2017: 8 · 2016: 1 · 2015: 1
- FWCI
- 4.88
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- eLife (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- CU Scholar (University of Colorado Boulder) (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Japan Society for the Promotion of Science (Postdoctoral Fellowship for Research Abroad)
- National Institutes of Health (NIH R01 NS34389, NS069473, NS081706, R01EY024261)
- Howard Hughes Medical Institute
- Boettcher Foundation (New Investigator Award, OCG5499B)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Axon Guidance and Neuronal Signaling
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Keywords
- nova, DCC, alternative splicing, RNA-binding proteins, neuronal migration, axon guidance, axon growth, commissural neurons, post-transcriptional regulation, RNAi screen
- MeSH terms
- Axon Guidance, DCC Receptor, Neuro-Oncological Ventral Antigen, Animals, Antigens, Neoplasm, Genetic Testing, Spinal Cord, RNA-Binding Proteins, Alternative Splicing, Mice, Knockout, Gene Expression Regulation, Developmental, RNA Interference, Mice, Commissural Interneurons
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