Cells encounter countless external cues and the specificity of their responses is translated through a myriad of tightly regulated intracellular signals. For this, Rho GTPases play a central role and transduce signals that contribute to fundamental cell dynamic and survival events. Here, we review our knowledge on how zebrafish helped us understand the role of some of these proteins in a multitude of in vivo cellular behaviors. Zebrafish studies offer a unique opportunity to explore the role and more specifically the spatial and temporal dynamic of Rho GTPases activities within a complex environment at a level of details unachievable in any other vertebrate organism.

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.