Defective oligodendrocyte development and severe hypomyelination in PDGF-A knockout mice.
1999 (English)In: Development, ISSN 0950-1991, Vol. 126, no 3, 457-67 p.Article in journal (Refereed) Published
There is a class of oligodendrocyte progenitors, called O-2A progenitors, that is characterized by expression of platelet-derived growth factor alpha-receptors (PDGFRalpha). It is not known whether all oligodendrocytes are derived from these PDGFRalpha-progenitors or whether a subset(s) of oligodendrocytes develops from a different, PDGFR alpha-negative lineage(s). We investigated the relationship between PDGF and oligodendrogenesis by examining mice that lack either PDGF-A or PDGF-B. PDGF-A null mice had many fewer PDGFR alpha-progenitors than either wild-type or PDGF-B null mice, demonstrating that proliferation of these cells relies heavily (though not exclusively) on PDGF-AA homodimers. PDGF-A-deficient mice also had reduced numbers of oligodendrocytes and a dysmyelinating phenotype (tremor). Not all parts of the central nervous system (CNS) were equally affected in the knockout. For example, there were profound reductions in the numbers of PDGFR alpha-progenitors and oligodendrocytes in the spinal cord and cerebellum, but less severe reductions of both cell types in the medulla. This correlation suggests a close link between PDGFRalpha-progenitors and oligodendrogenesis in most or all parts of the CNS. We also provide evidence that myelin proteolipid protein (PLP/DM-20)-positive cells in the late embryonic brainstem are non-dividing cells, presumably immature oligodendrocytes, and not proliferating precursors.
Place, publisher, year, edition, pages
1999. Vol. 126, no 3, 457-67 p.
Animals, Brain/embryology, Cell Differentiation, Cell Division, Central Nervous System/*embryology, Mice, Mice; Knockout, Myelin Proteolipid Protein/physiology, Myelin Sheath/*physiology, Oligodendroglia/*physiology, Platelet-Derived Growth Factor/genetics/*physiology, Proto-Oncogene Proteins/genetics/physiology, Proto-Oncogene Proteins c-sis, Receptor; Platelet-Derived Growth Factor alpha, Receptors; Platelet-Derived Growth Factor/genetics/physiology, Research Support; Non-U.S. Gov't
IdentifiersURN: urn:nbn:se:uu:diva-73157PubMedID: 9876175OAI: oai:DiVA.org:uu-73157DiVA: diva2:101068