Timely Schwann cell division drives peripheral myelination in vivo via the laminin/cAMP pathway

Abstract

ABSTRACT Schwann cells (SCs) 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, is required for temporal mitotic exit of SCs. In sil-deficient cassiopeia (csp−/−) mutants, SCs 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 Laminin 2 expression in csp−/− fully restores the ability of SCs to myelinate. Thus, we demonstrate an essential role for timely SC division in mediating laminin expression to orchestrate radial sorting and peripheral myelination in vivo.