DISTRIBUTION AND DIFFERENTIATION OF A2B5(-CORD() GLIAL PRECURSORS IN THE DEVELOPING RAT SPINAL)

In many regions of the rat central nervous system, oligodendrocytes de velop from migratory A2B5(+) precursor cells. In the rat spinal cord, during early embryonic development the capacity for oligodendrogenesis appears to be restricted to ventral regions of the spinal cord, while cultures of postnatal rat spinal cord contain a distinct population o f A2B5 + astrocyte precursors. To determine if, as in other regions of the CNS, spinal cord A2B5(+) cells give rise directly to oligodendroc ytes and astrocytes, the initial distribution, and subsequent dispersi on, proliferation, and differentiation of spinal cord A2B5(+) cells ha ve been examined in both explant and dissociated cell cultures. Spinal cord oligodendrocytes develop from A2B5(+) cells. At E14, A2B5(+) cel ls are restricted to ventral regions of the spinal cord and as develop ment proceeds they become more uniformly distributed throughout the sp inal cord. In explant cultures, greater than 95% of the explants that contain oligodendrocytes also contain A2B5(+) cells and a proportion o f mature oligodendrocytes retain detectable A2B5 immunoreactivity brie fly on their surface. The maturation of spinal cord oligodendrocyte pr ecursors occurs in a number of distinct stages characterized by the ex pression of O4 immunoreactivity, which first appears at E16, and GC im munoreactivity, which first appears at E18. As spinal cord oligodendro cyte precursors acquire O4 immunoreactivity they appear to lose the ab ility to proliferate in response to PDGF but retain the ability to pro liferate in response to bFGF, suggesting that the control of prolifera tion of oligodendrocyte precursors is, in part, dependent on their mat urational state. In the presence of high serum, spinal cord A2B5(+) ce lls fail to develop in isolated E14 dorsal spinal cord cultures, while in ventral cultures they subsequently differentiate into A2B5(+) astr ocytes suggesting that A2B5(+) astrocyte precursors are also initially ventrally located. Unlike oligodendrocyte differentiation, however, t he differentiation of spinal cord A2B5(+) cells into astrocytes is del ayed in early embryonic-derived cultures compared to those from older animals. These observations suggest that local influences may regulate the timing of spinal cord A2B5(+) astrocyte development, but not spin al cord oligodendrocyte development. (C) 1994 Wiley-Liss, Inc.