Axons and myelinating glia exhibit a series of striking cell interactions during development. Axons promote gliogenesis and glial differentiation, most dramatically formation of the myelin sheath that spirals around axons. Glial cells promote the survival of neurons and direct the reorganization of the entire length of the axon into a series of specialized domains. These domains are centered around nodes of Ranvier and consist of distinct multiprotein complexes of cell adhesion molecules, ion channels, and scaffolding molecules. This organization promotes saltatory conduction, synchronizes presynaptic inputs, and is crucial for axon function and integrity. Elucidation of the signaling between axons and glia is providing important insights into formation of myelinated nerves and the pathogenesis of neurologic disorders such as Multiple Sclerosis in which axo-glial interactions are disrupted.

Our current studies focus on three aspects of axo-glial interactions. We are characterizing growth factors on axons, and the signaling pathways they activate in glia, that promote glial differentiation and myelination. We are investigating the morphogenetic events mediated by the cytoskeleton that drive spiral formation of the myelin sheath. Lastly, we have identified novel components of the domains of myelinated axons and are studying how they are targeted to and assemble at their precise locations along the axon. As experimental approaches, we utilize tissue culture models of myelination, molecular genetic approaches and mouse mutants deficient in specific domain components.