Oligodendrocytes, the specialized myelin-forming cells of the central nervous system, are produced during development by the proliferation and progressive differentiation of migratory progenitor cells. The progenitors themselves arise from germinal zones and migrate thence to populate developing white and gray matter. Although the migration of progenitor cells is crucial in the realization of myelination, little is known about he signals which stimulate, guide, or limit this process and the location of the earliest progenitors (pre-progenitors) within the CNS is not yet defined. The studies proposed in this project will exploit a new transgenic marker to approach these problems. Transgenically marked CNS tissue and cell preparations into genetically normal hosts to analyze the extent and patterns of oligodendrocyte lineage migration during development, to assess the migratory potential of identified stages in that lineage including purified differentiated oligodendrocytes, to define regions of the early developing CNS which ar capable of producing oligodendrocyte progenitors, and to isolated, identify and characterize very early, pre-progenitor cell populations. in addition, the regulation of progenitor cell migration by myelin and particular myelin-associated cell adhesion molecules will be studied using mutant and genetically manipulated mice. Restoration of oligodendrocyte populations depleted in demyelinated lesions may be essential for effective remyelination. The data generated in this project may eventually suggest strategies for enhancing this repopulation in the treatment of human demyelinating disorders such as multiple sclerosis.
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