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Defective oligodendrocyte development and severe hypomyelination in PDGF-A knockout mice
Abstract
There is a class of oligodendrocyte progenitors, called O-2A progenitors, that is characterized by expression of platelet-derived growth factor alpha-receptors (PDGFRα). It is not known whether all oligodendrocytes are derived from these PDGFRα-progenitors or whether a subset(s) of oligodendrocytes develops from a different, PDGFRα-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 PDGFRα-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 PDGFRα-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 PDGFRα-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.
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Metadata
- Authors
- Fruttiger, M., Karlsson, L., Hall, A. C., Abramsson, A., Calver, A. R., Boström, H., Willetts, K., Bertold, C.-H., Heath, J. K., Betsholtz, C., & D. Richardson, W.
- Venue
- Development
- Publisher
- The Company of Biologists
- Published
- 1999-02-01
- Volume
- 126
- Issue
- 3
- Pages
- 457-467
- ISSN
- 0950-1991 (ISSN-L)
- 1477-9129
- OpenAlex
- W2142745956
- Cited by
- 441
- References
- 57
- FWCI
- 6.13
- Type
- journal article
- Language
- en
- Open access
- closed
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