Tawk, M. | Search bioRxiv

bioRxiv2024

Schwann cells have a limited window of time in which to initiate myelination program 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 activate the Laminin/Gpr126/cAMP signaling required for radial sorting and myelination at later stages in vivo.

developmental biology↗

bioRxiv2022

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

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.

developmental biology↗