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Essential and distinct roles for cdc42 and rac1 in the regulation of Schwann cell biology during peripheral nervous system development

¹ Institute of Cell Biology, Department of Biology, Eidgenössische Technische Hochschule Zurich, CH-8093 Zurich, Switzerland
² Department of Molecular Pathology, University of Copenhagen, 2100 Copenhagen, Denmark
³ Department of Molecular Medicine, Max Planck Institute of Biochemistry, D-82152 Martinsried, Germany
⁴ Department of Neurogenetics, Max Planck Institute of Experimental Medicine, 37075 Goettingen, Germany
⁵ Cambridge Centre for Brain Repair and Neuroregeneration Laboratory, Department of Veterinary Medicine, University of Cambridge, Cambridge CB3 0ES, England, UK
⁶ Department of Cell Biology and Genetics, Erasmus MC University Medical Centre, 3000 DR Rotterdam, Netherlands

Correspondence to João B. Relvas: joao.relvas{at}cell.biol.ethz.ch

During peripheral nervous system (PNS) myelination, Schwann cells must interpret extracellular cues to sense their environment and regulate their intrinsic developmental program accordingly. The pathways and mechanisms involved in this process are only partially understood. We use tissue-specific conditional gene targeting to show that members of the Rho GTPases, cdc42 and rac1, have different and essential roles in axon sorting by Schwann cells. Our results indicate that although cdc42 is required for normal Schwann cell proliferation, rac1 regulates Schwann cell process extension and stabilization, allowing efficient radial sorting of axon bundles.

Abbreviations used in this paper: BL, basal lamina; CNP, 2',3'-cyclic nucleotide 3'-phosphodiesterase; E, embryonic day; NRG1, neuregulin-1; P, postnatal day; PNS, peripheral nervous system; SC, Schwann cell.

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