Mentions CMT: genetic screen identifies genes essential for development of myeli

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Dev Biol. 2006 Jun 15

A genetic screen identifies genes essential for development of

myelinated axons in zebrafish.

Pogoda HM, Sternheim N, Lyons DA, Diamond B, Hawkins TA, Woods IG,

Bhatt DH, Franzini-Armstrong C, Dominguez C, Arana N, s J, Nix

R, Fetcho JR, Talbot WS.

Department of Developmental Biology, Stanford University School of

Medicine, Stanford, CA 94305, USA.

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.