GUIDANCE OF OLIGODENDROCYTES AND THEIR PROGENITORS BY SUBSTRATUM TOPOGRAPHY

Oligodendrocyte progenitors arise in subventricular zones and migrate extensively during development before differentiating into mature olig odendrocytes, which myelinate nerve tracts in the central nervous syst em. We have used microfabricated substrata, containing periodic patter ns of contours similar to those of central nervous system axons to ass ess the influence in vitro of substratum topography on oligodendrocyte s isolated from 7 day rat optic nerve. Antiganglioside antibody A(2)B( 5) positive oligodendrocyte-type 2 astrocyte progenitors, and galactoc erebroside positive and myelin basic protein positive oligodendrocytes , were highly aligned by surface contours as small as 100 nm depth and 260 nm repeat spacing. Rat optic nerve astrocytes also aligned on sur face contours, but rat hippocampal and cerebellar neurons were unrespo nsive. Oligodendrocytes demonstrated enhanced parallel extension of th eir processes on narrow repeating topography in an arrangement similar to that found in the intact optic nerve. This is in marked contrast t o the phenotype displayed by this cell type on planar substrata. Neith er oligodendrocytes nor oligodendrocyte-type 2 astrocyte progenitors s howed high-order F-actin cytoskeletal networks; thus their alignment o n gratings is unlikely to result from deformation of actin cables and focal contacts, In contrast, aligned astrocytes showed striking arrang ements of actin stress fibres. These results establish glial cells as potentially the most topographically sensitive cell types within the c entral nervous system. Furthermore, the topographical pattern inducing maximal alignment of oligodendrocyte lineage cells corresponds to the diameters of single axons within the 7 day optic nerve, Thus the migr ation of oligodendrocyte-type 2 astrocyte progenitors and axonal enshe athment by oligodendrocytes may be guided by axonal topography within the developing nerve.