Axoglial interactions during myelination in the CNS.

Identification of the repertoire of axoglial signalling molecules that initiates myelination in the CNS will be required if we are to understand the developmental biology of myelination and devise strategies to promote remyelination in MS. The previous work of our two labs on the survival signalling in oligodendrocytes that precedes initiation (ffrench-Constant) and on the formation of the node of Ranvier that follows initiation (Brophy) has identified sets of glial adhesion molecules that play essential roles in each process neurofascin in node formation and integrins and contactin in survival signalling. Here we hypothesize that these same adhesion molecules also make an essential contribution to the initiation of myelination. To test this we will, i) determine the localization and function of integrin, contactin and neurofascin during the initial stages of myelination using both cell culture assays and transgenic mice, ii) reveal the signalling complexes downstream of these adhe sion molecules, focussing on the Src Family kinase Fyn, iii) elucidate the mechanisms that drive extension and myelin formation in each oligodendrocyte process, (iv) identify new signalling and adhesion molecules in proteomic studies of oligodendrocytes using the mouse lines generated earlier, and initiate studies of their function.