Some old and some new observations on myelin formation

David R. COLMAN
Montreal Neurological Institute, Montreal, Quebec, Canada


The mechanisms by which the myelin sheath is generated remain elusive, although the widely accepted textbook “windowshade” model accounts for much of the data. When this model was introduced, it was unequivocally state-of-the-art in terms of novelty of the data, and insightful, articulate and compelling interpretation. However, there is now a substantial literature that is incompatible with the conclusions of this work. Taking current data into consideration, we have developed a comprehensive model for the generation of the myelin sheath.

Our model - we term it the "ribbon model" - proposes that: (a) Myelinating cells first elongate one or two exploratory cytoplasmic ribbons of membrane along the presumptive internode, closely apposed to the axon. These structures act as guides for the subsequent myelination process. (b) The distal terminus of each ribbon encircles the axon and seals to itself, via strong cadherin-mediated interactions. A stable, transbilayer scaffold of interacting glial/axonal proteins is then set up at each end of the sealed ribbon, providing adhesion between the axon and glial cell, while generating a "molecular sieve" that organizes ion channels along the axonal microdomain. (c) New membrane surface, added via vesicular fusion to the glial ribbons, flatten and extend them against the axon at all non-compact zones; the net result is the expansion of the ribbons to form the myelin helix, but one that is produced with very little actual rotation of membrane around the axon.


Session VIII -- Multiple Sclerosis Seminar
Monday, 28 June 2004, 11:00 am - 1:00 pm

Ninth Annual Meeting of the International Society for the History of the Neurosciences (ISHN)

Montreal, Quebec, Canada