N-cadherin is involved in axon-oligodendrocyte contact and myelination

We have analyzed the influence of the calcium-dependent cell adhesion molec ule, N-cadherin, on events leading to CNS myelination, Interactions between axons and oligodendrocyte progenitor (OP) cells and the CG4 OP cell line w ere examined by video-microscopy. OPs cocultured with dorsal root ganglia e xplants migrated around the culture and formed numerous contacts with axons . The duration of these contacts depended on the morphology of the OF, with OPs containing four or more processes forming long-lasting contacts and OP s with three or fewer processes forming short-termed contacts. Treatment wi th N-cadherin function blocking peptides approximately halved the duration of contacts made by cells with four or more processes but contact times for cells with three or less processes were unaffected. The L7 cadherin-blocki ng antibody and calcium withdrawal had similar effects. Contacts with axons regenerating from explants of adult retina, which do not have N-cadherin o n their surface was examined. The contact duration of OPs to adult retina a xons was short and similar in length to those formed between OPs and dorsal root ganglion axons in the presence of cadherin blocking reagents. Oligode ndrocyte myelination was examined in organotypic rat cerebellar slice cultu res, taken before myelination at postnatal day 10 and then allowed to myeli nate in vitro over 7 days. When incubated with an N-cadherin function-block ing peptide, myelination of Purkinje cell axons was reduced to about half o f control levels, while control peptides were without effect. Cadherin-bloc kade did not prevent maturation of OPs, since oligodendrocytes showing myel in basic protein immunostaining were still found in these cultures. However , many of the cell processes did not colocalize with calbindin-positive axo ns. From these data we conclude that N-cadherin is important for the initia l contact between a myelinating oligodendrocyte and axons and significantly contributes to the success of myelination.