Schwann cells have a limited window of time in which to initiate myelination signaling during early migration in vivo.

The temporal control of mitotic exit of individual Schwann cells (SCs) is essential for radial sorting and peripheral myelination. However, it remains unknown when, during their multiple rounds of division, SCs initiate myelin signaling in vivo. By manipulating SC division during development, we report that when SCs skip their division during migration, but not during radial sorting, they fail to myelinate peripheral axons. This coincides with a sharp decrease in Laminin expression within the posterior lateral line nerve. Interestingly, elevating cAMP levels or forcing Laminin 2 expression within individual SCs restore their ability to myelinate, despite missing mitosis during migration. Our results demonstrate a limited time window during which migrating SCs initiate Laminin expression to gradually activate the Laminin/Gpr126/cAMP signaling required for radial sorting and myelination at later stages in vivo.