In vertebrate organisms, the electrical conduction properties of axons are greatly enhanced by the presence of myelin. Glia form myelin by wrapping axons with multiple layers of specialized cell membrane. An essential feature of myelinated axons is the presence of nodes of Ranvier, short unmyelinated gaps in the axon membrane with a high density of Na+ channels. The importance of myelin to normal nervous system function is underscored by demyelinating diseases such as multiple sclerosis and Charcot-Marie-Tooth syndrome. Studies of demyelination suggest that the effects on node morphology and the dynamics of node assembly during remyelination are contributors to the pathogenesis of and recovery from demyelinating conditions. Using the zebrafish as a vertebrate model, I have performed the first forward genetic screen to identify mutants with defects in node assembly and I will use these mutants to identify new molecules involved in this process. I will also use Schwann cell-deficient mutants to directly test the importance of Schwann cells in the clustering of Na+ channels to the nodes. Lastly, I will perform live imaging of Nan- channel clustering to determine if the dynamics of Na+ channel movement matches theoretical predictions.
| Voas, Matthew G; Lyons, David A; Naylor, Stephen G et al. (2007) alphaII-spectrin is essential for assembly of the nodes of Ranvier in myelinated axons. Curr Biol 17:562-8 |
