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bioRxiv · 10.1101/2022.02.11.480035

Timely Schwann cell division during migration drives peripheral myelination in vivo via Laminin/cAMP pathway

Mikdache, A.·Boueid, M.-J.·Lesport, E.·Delespierre, B.·Loisel-Duwattez, J.·Degerny, C.·Tawk, M.
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Abstract

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, particularly during migration, 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. We also discovered that SC have a restricted time window during which they have to divide, while migrating, in order to trigger myelination. Thus, we unravel a novel and essential role for timely SC division during migration in mediating Laminin expression to orchestrate radial sorting and peripheral myelination in vivo.

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Mikdache, A., Boueid, M.-J., Lesport, E., Delespierre, B., Loisel-Duwattez, J., Degerny, C., Tawk, M.. 2022-02-11. Timely Schwann cell division during migration drives peripheral myelination in vivo via Laminin/cAMP pathway. https://doi.org/10.1101/2022.02.11.480035

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