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Defective oligodendrocyte development and severe hypomyelination in PDGF-A knockout mice.

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Author

  • M. Fruttiger
  • L. Karlsson
  • A. C. Hall
  • A. Abramsson
  • A. R. Calver
  • Hans Ehrencrona
  • K. Willetts
  • C. H. Bertold
  • J. K. Heath
  • C. Betsholtz
  • W. D. Richardson
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Summary, in English

There is a class of oligodendrocyte progenitors, called O-2A progenitors, that is characterized by expression of platelet-derived growth factor &agr;-receptors (PDGFR(&agr;)). 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.

Publishing year

1999

Language

English

Pages

457-467

Publication/Series

Development: For advances in developmental biology and stem cells

Volume

126

Issue

3

Document type

Journal article

Publisher

The Company of Biologists Ltd

Topic

  • Developmental Biology

Keywords

  • Proto-Oncogene Proteins
  • Platelet-Derived Growth Factor
  • Oligodendroglia
  • Myelin Sheath
  • Myelin Proteolipid Protein
  • Knockout
  • Mice
  • Central Nervous System
  • Cell Division
  • Cell Differentiation
  • Animals
  • Brain
  • Proto-Oncogene Proteins c-sis
  • Receptor
  • Platelet-Derived Growth Factor alpha
  • Receptors

Status

Published

ISBN/ISSN/Other

  • ISSN: 1477-9129