Postmitotic oligodendrocytes generated during postnatal cerebral development are derived from proliferation of immature oligodendrocytes

Abstract

The phenotype of proliferating glia is examined during postnatal rodent development by combining immunocytochemistry (ICC) with 3H-thymidine autoradiography (ARG) to identify cells in the S phase of the cell cycle. Antibodies (ABs) which are specific for cells in the oligodendrocyte (OL) lineage were utilized, with emphasis placed upon the proliferation of OLs as it remains unclear whether this cell type divides in situ. The results show that proliferating cells stain with ABs which are specific for OLs and myelin glycolipids. The proliferating OLs (oligodendroblasts), although they do not appear to have formed myelin sheaths, have quite elaborate and distinctive morphologies. These oligodendroblasts give rise to very long, thin processes which in turn have additional branches. Their cytoarchitecture corresponds closely to cells described as oligodendroblasts with electron microscopy and whose processes often appear to be in the initial phase of myelination (Skoff et al: J. Comp. Neurol. 169:291-312, 1976a). These proliferating OLs are still quite immature because the expression of myelin specific proteins is only occasionally observed in 3H-thymidine labeled cells. The phenotype of the oligodendroblasts is quite different from that of proliferating astrocytes (astroblasts). As shown in previous studies (Skoff; Dev. Biol. 139:149-163, 1990), the astroblasts, which are identified by the presence of glial fibrillary acidic protein (GFAP), usually have thick, stubby processes, and both their nucleus and cytoplasm are larger and of lighter density than those found in oligodendroblasts. In early myelinating regions of the cerebrum, glycolipid positive cells account for the majority of the 3H-thymidine labeled cells. This data, when combined with the quantification of proliferating astrocytes (ASs) from previous immunocytochemical and electron microscopic studies, indicate that oligodendroblasts and astroblasts constitute the vast majority of the proliferating glia in the brain and in optic nerve at times when ASs and OLs are being generated. In normal postnatal cerebral development, the immature ASs and OLs which proliferate are the direct, immediate precursors for most postmitotic ASs and OLs.