Defective oligodendrocyte development and severe hypomyelination in PDGF-Aknockout mice

There is a class of oligodendrocyte progenitors, called O-2A progenitors, t hat is characterized by expression of platelet-derived growth factor alpha- receptors (PDGFR alpha), It is not known whether all oligodendrocytes are d erived from these PDGFR alpha-progenitors or whether a subset(s) of oligode ndrocytes develops from a different, PDGFR alpha-negative lineage(s), We in vestigated the relationship between PDGF and oligodendrogenesis by examinin g mice that lack either PDGF-A or PDGF-B, PDGF-A null mice had many fewer P DGFR alpha-progenitors than either wild-type or PDGF-B null mice, demonstra ting that proliferation of these cells relies heavily (though not exclusive ly) on PDGF-AA homodimers. PDGF-A-deficient mice also had reduced numbers o f oligodendrocytes and a dysmyelinating phenotype (tremor), Not all parts o f the central nervous system (CNS) were equally affected in the knockout. F or example, there were profound reductions in the numbers of PDGFR alpha-pr ogenitors and oligodendrocytes in the spinal cord and cerebellum, but less severe reductions of both cell types in the medulla, This correlation sugge sts a close link between PDGFR alpha-progenitors and oligodendrogenesis in most or all parts of the CNS, We also provide evidence that myelin proteoli pid protein (PLP/DM-20)-positive cells in the late embryonic brainstem are non-dividing cells, presumably immature oligodendrocytes, and not prolifera ting precursors.