Oligodendrocytes repel axons and cause axonal growth cone collapse

Abstract

We have examined the interactions between axons regenerating from dorsal root ganglia (DRGs) derived from newborn rats and oligodendrocytes cultured by three different techniques. Cultures examined after 2 days have a profuse outgrowth of axons from the DRGs, forming a dense mat on the culture surface. However, the axons avoid growing on oligodendrocytes; axons are seen all around these cells, but do not grow over them. We have also performed time-lapse video studies of the interactions between axonal growth cones and oligodendrocytes. Axons grow normally until their growth cone comes into direct contact with an oligodendrocyte, following which the growth cone remains motile for 30–60 min, but without making any progress over the cell. The growth cone then suddenly collapses, and the axon retracts, leaving a thin strand in contact with the cell. After this a new growth cone is usually elaborated and the process repeated. Oligodendrocytes are therefore inhibitory to axonal growth, and this may partially explain the failure of axons to regenerate in the mammalian central nervous system.

NI-35/250/nogo-a: A neurite growth inhibitor restricting structural plasticity and regeneration of nerve fibers in the adult vertebrate CNS

“…Differentiated oligodendrocytes in culture and CNS myelin exerted a strong inhibitory effect on adhesion and outgrowth for primary neurons, neuroblastoma cells, and also for spreading of nonneuronal cells (Caroni and Schwab, 1988b;McKerracher et al, 1994;Ng et al, 1996;Schwab and Thoenen, 1985). It was further shown that growth cones interacting with differentiated oligodendrocytes were inhibited in their fiber growth and forced to collapse (Bandtlow et al, 1990;Fawcett et al, 1989;Moorman and Gould 1997). In vivo experiments demonstrated that elongation of axons over long distances could be observed in myelin-free spinal cord or optic nerve, which has been produced by killing the dividing oligodendrocyte precursors by repeated X-irradiation of newborn rats (Savio and Schwab 1990;Weibel et al, 1994) or by immunocytolysis in chicken (Hasan et al, 1993;Keirstead et al, 1992).…”