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Volume 17, Number 23, Issue of December 1, 1997 pp. 9122-9132

Transplanted Oligodendrocyte Progenitor Cells Expressing a Dominant-Negative FGF Receptor Transgene Fail to Migrate In Vivo

Received July 1, 1997; revised Aug. 29, 1997; accepted Sept. 16, 1997.

Donna J. Osterhout¹, Sylvie Ebner¹, Jingsong Xu², David M. Ornitz², George A. Zazanis¹, and Randall D. McKinnon¹

¹ Division of Neurosurgery, Department of Surgery, University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School, Piscataway, New Jersey 08854, and ² Department of Molecular Biology and Pharmacology, Washington University Medical School, St. Louis, Missouri 63110

The proliferation, migration, survival, and differentiation of oligodendrocyte progenitor cells, precursors to myelin-forming oligodendrocytes in the CNS, are controlled by a number of polypeptide growth factors in vitro. The requirement and roles for individual factors in vivo, however, are primarily unknown. We have used a cell transplantation approach to examine the role of fibroblast growth factor (FGF) in oligodendrocyte development in vivo. A dominant-negative version of the FGF receptor-1 transgene was introduced into oligodendrocyte progenitors in vitro, generating cells that were nonresponsive to FGF but responsive to other mitogens. When transplanted into the brains of neonatal rats, mutant cells were unable to migrate and remained within the ventricles. 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.

Key words: CNS development; myelin; oligodendrocyte; O-2A progenitor; transplantation; migration; fibroblast growth factor receptor; dominant-negative

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