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Publication : Functional Genome-wide Screen Identifies Pathways Restricting Central Nervous System Axonal Regeneration.

First Author  Sekine Y Year  2018
Journal  Cell Rep Volume  23
Issue  2 Pages  415-428
PubMed ID  29642001 Mgi Jnum  J:270948
Mgi Id  MGI:6278353 Doi  10.1016/j.celrep.2018.03.058
Citation  Sekine Y, et al. (2018) Functional Genome-wide Screen Identifies Pathways Restricting Central Nervous System Axonal Regeneration. Cell Rep 23(2):415-428
abstractText  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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