Defective oligodendrocyte development and severe hypomyelination in PDGF-A knockout mice
| Autor: | Alexandra Abramsson, Marcus Fruttiger, Christer Betsholtz, L. Karlsson, Karen Willetts, William D. Richardson, Andrew R. Calver, Claes Henric Bertold, John K. Heath, Anita C. Hall, Hans Boström |
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| Rok vydání: | 1999 |
| Předmět: |
Central Nervous System
Receptor Platelet-Derived Growth Factor alpha Cellular differentiation Central nervous system Subventricular zone Biology Myelin Mice Proto-Oncogene Proteins medicine Animals Receptors Platelet-Derived Growth Factor Myelin Proteolipid Protein Molecular Biology Myelin Sheath Mice Knockout Platelet-Derived Growth Factor Brain Cell Differentiation Proto-Oncogene Proteins c-sis Embryonic stem cell Oligodendrocyte Myelin proteolipid protein Cell biology Oligodendroglia medicine.anatomical_structure Immunology Knockout mouse Cell Division Developmental Biology |
| Zdroj: | Europe PubMed Central |
| ISSN: | 0950-1991 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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