title: A genetic screen identifies genes essential for development of myelinated axons in zebrafish.
abstract: The myelin sheath insulates axons in the vertebrate nervous system, allowing rapid propagation of action potentials via saltatory conduction. Specialized glial cells, termed Schwann cells in the PNS and oligodendrocytes in the CNS, wrap axons to form myelin, a compacted, multilayered sheath comprising specific proteins and lipids. Disruption of myelinated axons causes human diseases, including multiple sclerosis and Charcot-Marie-Tooth peripheral neuropathies. Despite the progress in identifying human disease genes and other mutations disrupting glial development and myelination, many important unanswered questions remain about the mechanisms that coordinate the development of myelinated axons. To address these questions, we began a genetic dissection of myelination in zebrafish. Here we report a genetic screen that identified 13 mutations, which define 10 genes, disrupting the development of myelinated axons. We present the initial characterization of seven of these mutations, defining six different genes, along with additional characterization of mutations that we have described previously. The different mutations affect the PNS, the CNS, or both, and phenotypic analyses indicate that the genes affect a wide range of steps in glial development, from fate specification through terminal differentiation. The analysis of these mutations will advance our understanding of myelination, and the mutants will serve as models of human diseases of myelin.
authors.affiliation: Department of Developmental Biology, Stanford University School of Medicine, Stanford, CA 94305, USA.
authors.forename: Hans-Martin
authors.initials: HM
authors.lastname: Pogoda
authors.forename: Nitzan
authors.initials: N
authors.lastname: Sternheim
authors.forename: David A
authors.initials: DA
authors.lastname: Lyons
authors.forename: Brianne
authors.initials: B
authors.lastname: Diamond
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Hawkins
authors.forename: Ian G
authors.initials: IG
authors.lastname: Woods
authors.forename: Dimple H
authors.initials: DH
authors.lastname: Bhatt
authors.forename: Clara
authors.initials: C
authors.lastname: Franzini-Armstrong
authors.forename: Claudia
authors.initials: C
authors.lastname: Dominguez
authors.forename: Naomi
authors.initials: N
authors.lastname: Arana
authors.forename: Jennifer
authors.initials: J
authors.lastname: Jacobs
authors.forename: Rebecca
authors.initials: R
authors.lastname: Nix
authors.forename: Joseph R
authors.initials: JR
authors.lastname: Fetcho
authors.forename: William S
authors.initials: WS
authors.lastname: Talbot
mesh_terms: D000818:Animals; D001369:Axons / Q000378:metabolism*; D019521:Body Patterning; D002490:Central Nervous System / Q000378:metabolism; D004625:Embryo, Nonmammalian; D018507:Gene Expression Regulation, Developmental; D008297:Male; D009154:Mutation; D009186:Myelin Sheath / Q000378:metabolism*; D009413:Nerve Fibers, Myelinated / Q000378:metabolism*; D017933:Peripheral Nervous System / Q000378:metabolism; D010641:Phenotype; D015027:Zebrafish / Q000196:embryology / Q000235:genetics / Q000378:metabolism*; D029961:Zebrafish Proteins / Q000235:genetics* / Q000378:metabolism
chemical_list: D029961:Zebrafish Proteins