OLIGODENDROCYTE-TYPE-2 ASTROCYTE PROGENITORS USE A METALLOENDOPROTEASE TO SPREAD AND MIGRATE ON CNS MYELIN

Oligodendrocyte-type 2 astrocyte (O-2A) progenitors are highly motile cells which migrate in the developing and adult central nervous system (CNS). Adult CNS myelin, however, contains inhibitory proteins, the n eurite growth inhibitors NI 35/250, which block neurite outgrowth and spreading of many different cell types, such as astrocytes and fibrobl asts. In the present study we investigated the spreading of dissociate d cells and migration out of aggregates ('spheres') of primary O-2A cu ltures and of a glial precursor cell line (CG-4) on purified CNS myeli n and on CNS tissue. Primary O-2A progenitors and CG-4 cells quickly a ttached to and spread on CNS myelin-coated culture dishes, showing no inhibition by the neurite growth inhibitors. CG-4 cells migrated with a velocity of 30 mu m/h on a CNS myelin protein extract and at 5.7 mu m/h on adult spinal cord tissue. Both cell spreading and migration on a CNS substrate could be specifically blocked by metalloprotease block ers like o-phenanthroline and the tetrapeptide carbobenzoxy-phe-ala-ph e-tyr-amide, whereas blockers of the serine, aspartyl and cysteine pro teases had no effect, On differentiation to astrocytes, the O-2A proge nitors lost their ability to spread on CNS myelin. These results sugge st the crucial involvement of a metalloprotease in the mechanism of mi gration on a CNS substrate. In vivo, migration of oligodendrocyte prog enitors may be an important aspect of myelin repair following local tr aumatic, inflammatory or toxin-induced myelin loss.