Schwann cells (SC) migrate along peripheral axons and divide intensively to generate the right number of cells prior to axonal ensheathment; however, little is known regarding the temporal and molecular control of their division and its impact on myelination. We report that Sil, a spindle pole protein associated with autosomal recessive primary microcephaly (MCPH), is required for temporal mitotic exit of SC. In sil-deficient cassiopeia (csp−/-) mutants, SC fail to radially sort and myelinate peripheral axons. Elevation of cAMP, but not Rac1 activity in csp−/- restores myelin ensheathment. Most importantly, we show a significant decrease in Laminin expression within csp−/- posterior lateral line nerve and that forcing Laminin2 expression in csp−/- fully restores SC ability to myelinate. Thus, we unravel a novel and essential role for timely SC division in mediating Laminin expression to orchestrate radial sorting and peripheral myelination in vivo.
Timely Schwann cell division drives peripheral myelination in vivo via Laminin/cAMP pathway
Present address: UMR 3215 – U934, Institut Curie, 75005 Paris, France
These authors contributed equally to the work
- Award Group:
- Funder(s): Institut National de la Santa et de la Recherche Medicale
- Funder(s):
- Award Group:
- Funder(s): Universitat Paris-Saclay
- Funder(s):
Currently Viewing Accepted Manuscript - Newer Version Available
Aya Mikdache, Marie-José Boueid, Emilie Lesport, Brigitte Delespierre, Julien Loisel-Duwattez, Cindy Degerny, Marcel Tawk; Timely Schwann cell division drives peripheral myelination in vivo via Laminin/cAMP pathway. Development 2022; dev.200640. doi: https://doi.org/10.1242/dev.200640
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