A genetic screen identifies genes essential for development of myelinated axons in zebrafish.
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.
Pogoda
Hans-Martin
HM
Department of Developmental Biology, Stanford University School of Medicine, Stanford, CA 94305, USA.
Sternheim
Nitzan
N
Lyons
David A
DA
Diamond
Brianne
B
Hawkins
Thomas A
TA
Woods
Ian G
IG
Bhatt
Dimple H
DH
Franzini-Armstrong
Clara
C
Dominguez
Claudia
C
Arana
Naomi
N
Jacobs
Jennifer
J
Nix
Rebecca
R
Fetcho
Joseph R
JR
Talbot
William S
WS
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
D029961:Zebrafish Proteins