Current Research and Scholarly Interests
Our research focuses on the development of myelinated axons in the vertebrate nervous system. The myelin sheath allows for rapid axonal conduction in vertebrates. Disruption of myelin underlies important human diseases, including Multiple Sclerosis and peripheral neuropathies. The formation of myelin, which involves reciprocal signaling between neurons and glial cells, a dramatic morphological transformation of the glial cells, and organization of the axon into different specialized domains, is fascinating but nonetheless poorly understood.
Our goal is to define new genes with essential functions in the development of myelinated axons using genetic approaches in zebrafish. In genetic screens, we have identified mutations in at least 15 different genes that have specific functions in the development of myelinated axons. By characterizing the mutant phenotypes, we are working to define the functions of these genes at the cellular level. Through genetic mapping and positional cloning, we identify the mutated genes and analyze their functions at the molecular level. This project will discover new genes with essential functions in myelination, define new zebrafish models of important myelin disorders in humans, and provide new avenues toward therapies for myelin repair and prevention of axonal damage after demyelination.
Examples of essential proteins defined in the screen include a novel G-protein coupled receptor that instructs Schwann cells to make myelin in peripheral nerves (Monk et al. 2009, Science 325: 1402), receptors that control migration of glial cells along growing axons (Lyons et al. 2005, Current Biology 15: 513), and a kinesin motor protein that is essential for mRNA localization and normal membrane compaction in myelinating oligodendrocyes (Lyons et al. 2009, Nature Genetics 41: 854).