During myelination, Schwann cells and oligodendrocytes, undergo dramatic morphological changes in order to generate their large specialized membrane extensions that warp axons in multiple layers. In the CNS for example, oligodendrocyte progenitors are settled along the fiber tracts that will be myelinated, where they differentiate into immature oligodendrocytes that send multiple filopodia which contact and ensheath axons. Following this early, rather loose ensheathment, non-ensheathing processes are removed and spiral wrapping of the axon commences, eventually forming the compact myelin. Studies in our labs are aimed at understanding what are the intrinsic glial mechanisms required for membrane wrapping? Given that the substantial morphological changes of Schwann cells and oligodendrocytes are likely controlled by cytoskeletal reorganization, we are studying the role of several regulators of the actomyosin cytoskeleton (e.g., Ermin, and the Neural Wiskott–Aldrich syndrome protein; N-WASP) during the different stages of myelination. We are using proteomic and protein tagging experiments, combined with functional experiments in glia/neurons co-cultures to understand how these proteins operate in myelinating glia.