Centre for Neuroscience Research, University of Edinburgh
Chancellor´s Building
49 Little France Crescent

EH16 4SB - Edinburgh
United Kingdom

+44-(0)131-242-7980
+44-(0)131-242-7981
peter.brophy@ed.ac.uk

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Oligodendrocytes and Schwann cells ensheath nerves with a myelin sheath which is essential for the normal function of the vertebrate nervous system. These glial cells also play a vital role in promoting neuron survival, a fact underscored by the debilitating consequences of demyelination in multiple sclerosis (CNS) and in peripheral neuropathies of the Charcot-Marie-Tooth (PNS) type. We are now identifying the molecules on the cell surfaces of glial cells that signal axon contact. In one project we are building on our discovery of the Periaxin (Prx) gene in Schwann cells and its role in the formation of Cajal bands. Mice lacking a functional Prx gene ensheath and myelinate peripheral nerve axons in an apparently normal manner but the sheath later destabilizes and the mice develop a severe demyelinating neuropathy. In collaboration with colleagues in Paris we have identified a human disease caused by similar mutations. In a second project we are studying how myelinating glial cells induce the assembly of axonal domains. We have shown that isoforms of neurofascin play distinct and crucial roles in the assembly of the nodes of Ranvier in myelinated nerves. The role of these proteins in the assembly of the myelin sheath during normal development and repair is the subject of current work.

Camara, J., Z. Wang, C. Nunes-Fonseca, H.C. Friedman, M. Grove, D.L. Sherman, N.H. Komiyama, S.G. Grant, P.J. Brophy, A. Peterson, and C. ffrench-Constant. (2009). Integrin-mediated axoglial interactions initiate myelination in the central nervous system. J Cell Biol. 185:699-712.

Zonta, B., S. Tait, S. Melrose, H. Anderson, S. Harroch, J. Higginson, D.L. Sherman and P.J. Brophy (2008). Glial and neuronal isoforms of Neurofascin have distinct roles in the assembly of nodes of Ranvier in the CNS. J. Cell Biol. 181: 1169-1170.

Grove, M., N.H. Komiyama, K.A. Nave, K.A. S.G. Grant, D.L. Sherman, P.J. Brophy (2007):FAK is required for axonal sorting by Schwann cells. J. Cell Biol: 176: 277-282

Sherman, D.L. and P.J. Brophy (2005):Mechanisms of axon ensheathment and myelin growth. Nat. Rev. Neurosci.: 6: 683-690

Sherman, D.L., S. Tait, S. Melrose, R. Johnson, B. Zonta, F.A. Court, W.B. Macklin, S. Meek, A.J. Smith, D.F. Cottrell, and P.J. Brophy (2005):Organization of axonal domains for saltatory conduction requires the neurofascins. Neuron: 48: 737-742 (Cover).

Court, F.A., D.L. Sherman, T. Pratt, E.M. Garry, R.R. Ribchester, D.F. Cottrell, S.M. Fleetwood-Walker, P.J. Brophy (2004):Restricted growth of Schwann cells lacking Cajal bands slows conduction in myelinated nerves.  Nature: 431: 191-195 (Cover)

Charles, P., S. Tait, C. Faivre-Sarrailh, G. Barbin, F. Gunn-Moore, N. Denisenko-Nehrbass, A-M. Guennoc, J-A. Girault, P.J. Brophy, C. Lubetzki (2002):Neurofascin is a glial receptor for the paranodin/caspr-contactin axonal complex at the axoglial junction. Current Biology: 12: 217-220. (Featured Article).

Sherman, D.L., C. Fabrizi, C.S. Gillespie, P.J. Brophy (2001):Specific disruption of a Schwann cell dystrophin-related protein complex in a demyelinating neuropathy..Neuron: 30: 677-687. (also see commentary: Wrabetz, L. and M.L. Feltri. (2001), Do Schwann cells stop, DR(o)P2, and roll? Neuron. 30, 642-644).