Control of oligodendrocyte generation and proliferation by Shp2 protein tyrosine phosphatase.
Extracellular signals play essential roles in controlling the proliferation and differentiation of oligodendrocyte progenitor cells in the developing central nervous system. However, the intracellular pathways that transduce these extrinsic signals remain to be elucidated. In this study, we showed that conditional ablation of the nonreceptor tyrosine phosphatase Shp2 in Olig1-expressing oligodendrocyte lineage resulted in dramatic reduction in the generation and proliferation of oligodendrocyte progenitor cells in the spinal cord. Maturation and myelination of oligodendrocytes were also compromised in the Shp2 mutants. The deficits in oligodendrocyte development in Shp2 mutants nearly phenocopied those observed in PDGF-A mutants, suggesting that Shp2 is a crucial component in transducing PDGF-A signals in the control of oligodendrocyte proliferation and maturation.
Zhu
Ying
Y
Department of Anatomical Sciences and Neurobiology, University of Louisville School of Medicine, Louisville, Kentucky, USA.
Park
Jinsil
J
Hu
Xuemei
X
Zheng
Kang
K
Li
Hong
H
Cao
Qilin
Q
Feng
Gen-Sheng
GS
Qiu
Mengsheng
M
D000818:Animals; D000831:Animals, Newborn; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000378:metabolism; D001973:Bromodeoxyuridine / Q000378:metabolism; D002452:Cell Count / Q000379:methods; D002454:Cell Differentiation / Q000235:genetics; D049109:Cell Proliferation; D002490:Central Nervous System / Q000196:embryology / Q000254:growth & development / Q000378:metabolism / Q000648:ultrastructure; D055032:Electron Microscope Tomography / Q000379:methods; D004622:Embryo, Mammalian; D053595:Embryonic Stem Cells / Q000502:physiology; D018507:Gene Expression Regulation, Developmental / Q000235:genetics*; D051379:Mice; D008822:Mice, Transgenic; D009046:Motor Neurons / Q000502:physiology / Q000648:ultrastructure; D004676:Myelin Basic Protein / Q000378:metabolism; D018991:Myelin Proteolipid Protein / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000378:metabolism; D000076104:Oligodendrocyte Transcription Factor 2; D009836:Oligodendroglia / Q000502:physiology* / Q000648:ultrastructure; D010982:Platelet-Derived Growth Factor / Q000378:metabolism; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11 / Q000235:genetics / Q000378:metabolism*; D017384:Sequence Deletion / Q000235:genetics; D015398:Signal Transduction / Q000187:drug effects; D013116:Spinal Cord / Q000166:cytology / Q000196:embryology / Q000254:growth & development
D051792:Basic Helix-Loop-Helix Proteins; D001973:Bromodeoxyuridine; D004676:Myelin Basic Protein; D018991:Myelin Proteolipid Protein; D009419:Nerve Tissue Proteins; D000076104:Oligodendrocyte Transcription Factor 2; D010982:Platelet-Derived Growth Factor; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11; C494786:Olig1 protein, mouse; C512773:Olig2 protein, mouse; C047516:Plp1 protein, mouse; C075278:platelet-derived growth factor A