Novel gene crucial for myelin maintenance in zebrafish embryos

Centre for neuroregeneration, University of Edinburgh

Myelin is a plasma membrane extension of specialised glial cells (called oligodendrocytes in the CNS and Schwann cells in the PNS) that wraps around the axons of neurons in order to allow rapid conduction of neural impulses and to provide metabolic and trophic support to those axons. Disruption to myelin contributes to the symptoms of numerous devastating conditions of the nervous system, including the demyelinating disease multiple sclerosis, MS. We currently have a relatively limited understanding of the molecular and cellular mechanisms that specifically regulate myelination, which limits our ability to provide therapeutic interventions to aid myelin repair.

Zebrafish are a great model to study myelination. The small size, optical transparency, relative simplicity, and rapid development of zebrafish embryos are properties that allow direct observation of biological events as they occur in living animals. Our group has developed a set of tools to visualise myelination at high-resolution in live zebrafish.

The aim of this project is to identify new genes that are crucial for myelination in order to understand how oligodendrocytes and Schwann cells function during myelination and remyelination. Importantly, these genes, and the proteins they encode, might be future drug targets to enhance myelin repair.

In order to do this we have carried out an ENU-based forward genetic screen using a zebrafish transgenic mbp: eGFP-caax reporter line that allows high-resolution analyses of myelination in vivo. One very interesting mutant we identified is UE58 which has a mutation in a newly identified gene “Slc12a2-Like” that encodes Na-K-Cl cotransporter 1-Like. We are currently characterizing the mutation and phenotype. Here we show that in UE58 long term maintenance of the oligodendrocyte and Schwann cell myelin sheaths is affected.

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