Nova2 Regulates Neuronal Migration through an RNA Switch in Disabled-1 Signaling
Open accessAbstract
Neuronal migration leads to a highly organized laminar structure in the mammalian brain, and its misregulation causes lissencephaly and behavioral and cognitive defects. Reelin signaling, which is mediated in part by a key adaptor, disabled-1 (Dab1), plays a critical but incompletely understood role in this process. We found that the neuron-specific RNA-binding protein Nova2 regulates neuronal migration in late-generated cortical and Purkinje neurons. An unbiased HITS-CLIP and exon junction array search for Nova-dependent reelin-pathway RNAs at E14.5 revealed only one candidate-an alternatively spliced isoform of Dab1 (Dab1.7bc). In utero electroporation demonstrated that Dab1.7bc was sufficient to induce neuronal migration defects in wild-type mice and exacerbate defects when Dab1 levels were reduced, whereas Dab1 overexpression mitigates defects in Nova2 null mice. Thus, Nova2 regulates an RNA switch controlling the ability of Dab1 to mediate neuronal responsiveness to reelin signaling and neuronal migration, suggesting new links between splicing regulation, brain disease, and development.
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Pleurobrachia has more RNA-binding proteins, especially RRM/ELAV, KH and NOVAs, than any basal metazoan or choanoflagellate examined.
“Matching the expansion of RNA regulatory mechanisms, Pleurobrachia has more RNA-binding proteins (especially RRM/ELAV, KH and NOVAs 26,27 , Supplementary Table 21) thananybasalmetazoanorchoanoflagellateexamined.”
From The ctenophore genome and the evolutionary origins of neural systems (2014) · cites this paper as [26]
The Introduction discusses RNA-binding proteins in mammalian neuronal development, and the Results examine Nova2 in mouse brain. Searches for Pleurobrachia, choanoflagellates, and the named protein families found no passage comparing their RNA-binding-protein counts across species. (LLM, conf=0.75)
Experimental — accuracy not yet measuredIn Nova2-null mice, neurons of cortical layers II/III and IV are mislocalized to lower layers without altering the layer-specific molecular markers.
“In Nova2-null mice, neurons of cortical layers II/III and IV are mislocalized to lower layers without altering the layer-specific molecular markers39”
From The neurogenetics of alternative splicing (2016) · cites this paper as [39]
Progenitor cell proliferation and radial glia morphology are largely unaffected in Nova2-null mice, suggesting a defect in neuronal migration rather than subtype specification.
“Progenitor cell proliferation and radial glia morphology are largely unaffected, suggesting a defect in neuronal migration rather than subtype specification.”
From The neurogenetics of alternative splicing (2016) · cites this paper as [39]
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- Authors
- Yano, M., Hayakawa-Yano, Y., Mele, A., & Darnell, R. B.
- Affiliations
- Howard Hughes Medical Institute (US)
- Corresponding author
- Darnell, Robert B.
- Venue
- Neuron
- Publisher
- Elsevier BV
- Published
- 2010-06
- Volume
- 66
- Issue
- 6
- Pages
- 848-858
- ISSN
- 0896-6273 (ISSN-L)
- PMC
- PMC2965850
- OpenAlex
- W1971147333
- Cited by
- 176
- References
- 64
- Citations by year
- 2026: 2 · 2025: 5 · 2024: 12 · 2023: 11 · 2022: 13 · 2021: 11 · 2020: 9 · 2019: 12 · 2018: 13 · 2017: 15 · 2016: 13 · 2015: 4 · 2014: 13 · 2013: 13 · 2012: 12
- FWCI
- 4.35
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Neuron (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Howard Hughes Medical Institute
- National Institute of Neurological Disorders and Stroke (RC2NS069473, R01NS034389)
- National Center for Research Resources (UL1RR024143)
- Topics
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Axon Guidance and Neuronal Signaling
- Keywords
- NOVA2, neuronal migration, Disabled-1, Dab1, Reelin signaling, RNA switches, alternative splicing, RNA-binding proteins, cortical neurons, Purkinje cells, lissencephaly, HITS-CLIP, brain development
- MeSH terms
- Neuro-Oncological Ventral Antigen, Reelin Protein, Animals, Antigens, Neoplasm, Bromodeoxyuridine, Cell Movement, Embryo, Mammalian, Nerve Tissue Proteins, Neurons, RNA Splicing, Signal Transduction, RNA-Binding Proteins, Mice, Knockout, Neocortex, Mice
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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