Profilin 1 is required for peripheral nervous system myelination.

Myelination allows rapid saltatory propagation of action potentials along the axon and is an essential prerequisite for the normal functioning of the nervous system. During peripheral nervous system (PNS) development, myelin-forming Schwann cells (SCs) generate radial lamellipodia to sort and ensheath axons. This process requires controlled cytoskeletal remodeling, and we show that SC lamellipodia formation depends on the function of profilin 1 (Pfn1), an actin-binding protein involved in microfilament polymerization.

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

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.

Cdc42 and Rac1 signaling are both required for and act synergistically in the correct formation of myelin sheaths in the CNS.

The formation of myelin sheaths in the CNS is the result of a complex series of events involving oligodendrocyte progenitor cell (OPC) proliferation, directed migration, and the morphological changes associated with axon ensheathment and myelination. To examine the role of Rho GTPases in oligodendrocyte biology, we have used a conditional tissue-specific gene-targeting approach. Ablation of Cdc42 in cells of the oligodendrocyte lineage did not affect OPC proliferation, directed migration, or in vitro differentiation, but it led to the formation of a unique and stage-specific myelination phenotype.

Beta1-integrin signaling mediates premyelinating oligodendrocyte survival but is not required for CNS myelination and remyelination.

Previous reports, including transplantation experiments using dominant-negative inhibition of beta1-integrin signaling in oligodendrocyte progenitor cells, suggested that beta1-integrin signaling is required for myelination. Here, we test this hypothesis using conditional ablation of the beta1-integrin gene in oligodendroglial cells during the development of the CNS. This approach allowed us to study oligodendroglial beta1-integrin signaling in the physiological environment of the CNS, circumventing the potential drawbacks of a dominant-negative approach.