A screen for mutations in zebrafish that affect myelin gene expression in Schwann cells and oligodendrocytes

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.ydbio.2006.03.020 Byline: Natalia Kazakova (a), Huiliang Li (b), Ana Mora (b), Kristjan R. Jessen (a), Rhona Mirsky (a), William D. Richardson (b), Hazel K. Smith (b) Keywords: Myelin; Zebrafish; Schwann cells; Oligodendrocytes; Genetic screen; Retinoic acid Abstract: Myelin is the multi-layered glial sheath around axons in the vertebrate nervous system. Myelinating glia develop and function in intimate association with neurons and neuron-glial interactions control much of the life history of these cells. However, many of the factors that regulate key aspects of myelin development and maintenance remain unknown. To discover new molecules that are important for glial development and myelination, we undertook a screen of zebrafish mutants with previously characterized neural defects. We screened for myelin basic protein (mbp) mRNA by in situ hybridization and identified four mutants (neckless, motionless, iguana and doc) that lacked mbp expression in parts of the peripheral and central nervous systems (PNS or CNS), despite the presence of axons. In all four mutants electron microscopy revealed that myelin-forming glia were present and had formed loose wraps around axons but did not form compact myelin. We found that addition of exogenous retinoic acid (RA) rescued mbp expression in neckless mutant embryos, which lack endogenous RA synthesis. Timed application of the RA synthesis inhibitor DEAB to wild type embryos showed that RA signalling is required at least 48 h before the onset of myelin protein synthesis in both CNS and PNS. Author Affiliation: (a) Department of Anatomy and Developmental Biology, University College London, Gower Street, London WC1E 6BT, UK (b) Wolfson Institute for Biomedical Research and Department of Biology, University College London, Gower Street, London WC1E 6BT, UK Article History: Received 28 October 2005; Revised 13 March 2006; Accepted 15 March 2006