Defective oligodendrocyte development and severe hypomyelination in PDGF-A knockout mice.
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.
Fruttiger
M
M
MRC Laboratory for Molecular Cell Biology and Department of Biology, University College London, Gower Street, London WC1E 6BT, UK.
Karlsson
L
L
Hall
A C
AC
Abramsson
A
A
Calver
A R
AR
Boström
H
H
Willetts
K
K
Bertold
C H
CH
Heath
J K
JK
Betsholtz
C
C
Richardson
W D
WD
D000818:Animals; D001921:Brain / Q000196:embryology; D002454:Cell Differentiation; D002455:Cell Division; D002490:Central Nervous System / Q000196:embryology*; D051379:Mice; D018345:Mice, Knockout; D018991:Myelin Proteolipid Protein / Q000502:physiology; D009186:Myelin Sheath / Q000502:physiology*; D009836:Oligodendroglia / Q000502:physiology*; D010982:Platelet-Derived Growth Factor / Q000235:genetics / Q000502:physiology*; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000502:physiology; D020574:Proto-Oncogene Proteins c-sis; D020796:Receptor, Platelet-Derived Growth Factor alpha; D017479:Receptors, Platelet-Derived Growth Factor / Q000235:genetics / Q000502:physiology
D018991:Myelin Proteolipid Protein; D010982:Platelet-Derived Growth Factor; D011518:Proto-Oncogene Proteins; D020574:Proto-Oncogene Proteins c-sis; C075278:platelet-derived growth factor A; D020796:Receptor, Platelet-Derived Growth Factor alpha; D017479:Receptors, Platelet-Derived Growth Factor