Control of oligodendrocyte generation and proliferation by Shp2 protein tyrosine phosphatase

Glia. 2010 Sep;58(12):1407-14. doi: 10.1002/glia.21016.

Abstract

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Newborn
  • Basic Helix-Loop-Helix Transcription Factors / genetics
  • Basic Helix-Loop-Helix Transcription Factors / metabolism
  • Bromodeoxyuridine / metabolism
  • Cell Count / methods
  • Cell Differentiation / genetics
  • Cell Proliferation*
  • Central Nervous System / embryology
  • Central Nervous System / growth & development
  • Central Nervous System / metabolism
  • Central Nervous System / ultrastructure
  • Electron Microscope Tomography / methods
  • Embryo, Mammalian
  • Embryonic Stem Cells / physiology
  • Gene Expression Regulation, Developmental / genetics*
  • Mice
  • Mice, Transgenic
  • Motor Neurons / physiology
  • Motor Neurons / ultrastructure
  • Myelin Basic Protein / metabolism
  • Myelin Proteolipid Protein / metabolism
  • Nerve Tissue Proteins / metabolism
  • Oligodendrocyte Transcription Factor 2
  • Oligodendroglia / physiology*
  • Oligodendroglia / ultrastructure
  • Platelet-Derived Growth Factor / metabolism
  • Protein Tyrosine Phosphatase, Non-Receptor Type 11 / genetics
  • Protein Tyrosine Phosphatase, Non-Receptor Type 11 / metabolism*
  • Sequence Deletion / genetics
  • Signal Transduction / drug effects
  • Spinal Cord / cytology
  • Spinal Cord / embryology
  • Spinal Cord / growth & development

Substances

  • Basic Helix-Loop-Helix Transcription Factors
  • Myelin Basic Protein
  • Myelin Proteolipid Protein
  • Nerve Tissue Proteins
  • Olig1 protein, mouse
  • Olig2 protein, mouse
  • Oligodendrocyte Transcription Factor 2
  • Platelet-Derived Growth Factor
  • Plp1 protein, mouse
  • platelet-derived growth factor A
  • Protein Tyrosine Phosphatase, Non-Receptor Type 11
  • Bromodeoxyuridine