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Functional Genome-wide Screen Identifies Pathways Restricting Central Nervous System Axonal Regeneration
Abstract
Axonal regrowth is crucial for recovery from CNS injury but is severely restricted in adult mammals. We used a genome-wide loss-of-function screen for factors limiting axonal regeneration from cerebral cortical neurons in vitro. Knockdown of 16,007 individual genes identified 580 significant phenotypes. These molecules share no significant overlap with those suggested by previous expression profiles. There is enrichment for genes in pathways related to transport, receptor binding, and cytokine signaling, including Socs4 and Ship2. Among transport-regulating proteins, Rab GTPases are prominent. In vivo assessment with C. elegans validates a cell-autonomous restriction of regeneration by Rab27. Mice lacking Rab27b show enhanced retinal ganglion cell axon regeneration after optic nerve crush and greater motor function and raphespinal sprouting after spinal cord trauma. Thus, a comprehensive functional screen reveals multiple pathways restricting axonal regeneration and neurological recovery after injury.
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“Paradoxically, a genome-wide screening identified Rab27 and Rab3 as negative regulators of neuronal regeneration.72”
From Endosomal protein DENND10 promotes developmental competence of neurite extension (2025) · cites this paper as [72]
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Metadata
- Authors
- Sekine, Y., Lin-Moore, A., Chenette, D. M., Wang, X., Jiang, Z., Cafferty, W. B., Hammarlund, M., & Strittmatter, S. M.
- Venue
- Cell Reports
- Publisher
- Elsevier BV
- Published
- 2018-04
- Volume
- 23
- Issue
- 2
- Pages
- 415-428
- ISSN
- 2211-1247
- PMC
- PMC5937716
- Cited by
- 52
- References
- 61
- Language
- en
- Update notices
- erratum (2018-07-03)
- Licence
- www.elsevier.com/tdm/userlicense/1.0/ (tdm)
- www.elsevier.com/legal/tdmrep-license (tdm)
- creativecommons.org/licenses/by/4.0/ (vor)
- Funders
- National Institutes of Health (R01NS098817, R35NS097283)
- Dr. Ralph and Marian Falk Medical Research Trust
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