Myelin is the lipid rich sheath that surrounds axons and promotes rapid action potential propagation in the vertebrate nervous system. Myelin is made by specialized glial cells called oligodendrocytes (OLs) in the central nervous system (CNS) and Schwann Cells (SCs) in the peripheral nervous system (PNS). Loss of or disruption to the myelin sheath can result in debilitating human conditions including multiple sclerosis and Charcot-Marie-Tooth disease, and understanding glial cell development is critical for development of therapies to treat myelin diseases. Our lab therefore performed a large-scale forward genetic screen in zebrafish to look for novel regulators of myelination and identified a mutant, stl83, that exhibits both axon and myelin defects. Using whole genome sequencing, it was determined that the stl83 phenotype results from a missense mutation in the gene actr10, which encodes the protein Arp11. This was confirmed by a complementation cross using a previously identified mutant actr10 allele, llg22, which results in a point mutation in the start site. Arp11 is a component of the dynactin complex, which is necessary for retrograde transport by the molecular motor dynein. In-situ hybridization (ISH) for myelin basic protein (mbp) mRNA to mark mature glial cells showed that both actr10stl83/stl83 and actr10llg22/llg22 mutants have drastically reduced mbp expression in the CNS and PNS at 5 dpf. Transmission electron microscopy analysis revealed that many fewer axons are myelinated in the CNS and PNS of both mutants. In addition, those axons that are myelinated have a thinner myelin sheath. We are currently teasing out the mechanism resulting in reduced mbp expression and transport by marker analysis for different molecular makers of oligodendrocyte and Schwann cell development, cell death and cell proliferation assays, live imaging using fluorescent transgenic reporter lines, and chimera analysis to determine autonomy of the myelin defects.