TRANSPLANTED OLIGODENDROCYTE PROGENITOR CELLS EXPRESSING A DOMINANT-NEGATIVE FGF RECEPTOR TRANSGENE FAIL TO MIGRATE IN-VIVO

The proliferation, migration, survival, and differentiation of oligode ndrocyte progenitor cells, precursors to myelin-forming oligodendrocyt es in the CNS, are controlled by a number of polypeptide growth factor s in vitro. The requirement and roles for individual factors in vivo, however, are primarily unknown. We have used a cell transplantation ap proach to examine the role of fibroblast growth factor (FGF) in oligod endrocyte development in vivo. A dominant-negative version of the FGF receptor-1 transgene was introduced into oligodendrocyte progenitors i n vitro, generating cells that were nonresponsive to FGF but responsiv e to other mitogens. When transplanted into the brains of neonatal rat s, mutant cells were unable to migrate and remained within the ventric les. These results suggest a role for FGF signaling in establishing a motile phenotype for oligodendrocyte progenitor cell migration in vivo and illustrate the utility of a somatic cell mutagenesis approach for the study of gene function during CNS development in vivo.