Pard3 regulates contact between neural crest cells and the timing of Schwann cell differentiation but is not essential for neural crest migration or myelination.

Abstract

Schwann cells, which arise from the neural crest, are the myelinating glia of the peripheral nervous system. During development neural crest and their Schwann cell derivatives engage in a sequence of events that comprise delamination from the neuroepithelium, directed migration, axon ensheathment, and myelin membrane synthesis. At each step neural crest and Schwann cells are polarized, suggesting important roles for molecules that create cellular asymmetries. In this work we investigated the possibility that one polarity protein, Pard3, contributes to the polarized features of neural crest and Schwann cells that are associated with directed migration and myelination. We analyzed mutant zebrafish embryos deficient for maternal and zygotic pard3 function. Time-lapse imaging revealed that neural crest delamination was normal but that migrating cells were disorganized with substantial amounts of overlapping membrane. Nevertheless, neural crest cells migrated to appropriate peripheral targets. Schwann cells wrapped motor axons and, although myelin gene expression was delayed, myelination proceeded to completion. Pard3 mediates contact inhibition between neural crest cells and promotes timely myelin gene expression but is not essential for neural crest migration or myelination.