Abstract

What precursor cells are the source of the macroglia generated during postnatal development? In order to answer this question, we studied the expression of glial specific antigens in proliferating neuroglia in postnatal rodent brain and optic nerve. Immunocytochemistry using antibodies to oligodendrocyte (OL) specific markers (sulfatide and galactocerebroside) and an astrocyte (AS) specific marker (glial fibrillary acidic protein) was combined with thymidine autoradiography. During the first week of postnatal development when most ASs are being generated, one third to one half of the proliferating cells in the optic system are positive for glial fibrillary acidic protein after a 1 h injection of thymidine (Skoff, Dev. Biol., 139:149-168, 1990). During the second postnatal week when OLs are being generated, 30 to 100% of the proliferating cells in presumptive white matter tracts are sulfatide positive and at least 10% are galactocerebroside positive. This finding demonstrates that ASs and OLs divide during postnatal development. These results confirm previous electron microscopic autoradiographic studies showing that the vast majority of proliferating cells in postnatal rat optic nerve have the morphologic characteristics of differentiating ASs or OLs (Skoff, J. Comp. Neurol., 169:291-312, 1976). Since proliferating ASs (astroblasts) and OLs (oligodendroblasts) constitute the majority of the dividing cells at the time that ASs and OLs are being generated, these glioblasts must be the major source for the macroglia generated postnatally. The findings strongly suggest that separate lineages exist for ASs and OLs during postnatal development. There is no compelling in vivo evidence for a bipotential progenitor cell that generates the majority of OLs and certain ASs in postnatal rodent brain. There may, of course, be distinct lineages for the subtypes of ASs and possibly even for subtypes of OLs. We review the concepts of commitment and plasticity and apply these terms to glial differentiation. In situ, the presence of oligodendroblasts and astroblasts demonstrates the COMMITMENT of proliferating cells to a specific glial lineage during normal development. Culture conditions may provide an environment that permits proliferating glial cells to vacillate in their selection of a specific lineage. This situation demonstrates developmental PLASTICITY and the ability of glia to adapt to an altered environment. Whether committed glial cells in situ can be induced to switch their lineage when normal CNS conditions are altered is an intriguing question that remains to be answered.

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