Glial and Neuronal Protein Tyrosine Phosphatase Alpha (PTPα) Regulate Oligodendrocyte Differentiation and Myelination

  • Yuda Shih
  • Philip T. T. Ly
  • Jing Wang
  • Catherine J. Pallen
Article

Abstract

CNS myelination defects occur in mice deficient in receptor-like protein tyrosine phosphatase alpha (PTPα). Here, we investigated the role of PTPα in oligodendrocyte differentiation and myelination using cells and tissues from wild-type (WT) and PTPα knockout (KO) mice. PTPα promoted the timely differentiation of neural stem cell-derived oligodendrocyte progenitor cells (OPCs). Compared to WT OPCs, KO OPC cultures had more NG2+ progenitors, fewer myelin basic protein (MBP)+ oligodendrocytes, and reduced morphological complexity. In longer co-cultures with WT neurons, more KO than WT OPCs remained NG2+ and while equivalent MBP+ populations of WT and KO cells formed, the reduced area occupied by the MBP+ KO cells suggested that their morphological maturation was impeded. These defects were associated with reduced myelin formation in KO OPC/WT neuron co-cultures. Myelin formation was also impaired when WT OPCs were co-cultured with KO neurons, revealing a novel role for neuronal PTPα in myelination. Canonical Wnt/β-catenin signaling is an important regulator of OPC differentiation and myelination. Wnt signaling activity was not dysregulated in OPCs lacking PTPα, but suppression of Wnt signaling by the small molecule XAV939 remediated defects in KO oligodendrocyte differentiation and enhanced myelin formation by KO oligodendrocytes. However, the myelin segments that formed were significantly shorter than those produced by WT oligodendrocytes, raising the possibility of a role for glial PTPα in myelin extension distinct from its pro-differentiating actions. Altogether, this study reveals PTPα as a molecular coordinator of oligodendroglial and neuronal signals that controls multiple aspects of oligodendrocyte development and myelination.

Keywords

Protein tyrosine phosphatase alpha Oligodendrocyte maturation Myelination Remediation 

Supplementary material

12031_2017_941_MOESM1_ESM.pdf (98 kb)
ESM 1(PDF 97 kb)

Copyright information

© Springer Science+Business Media, LLC 2017

Authors and Affiliations

  • Yuda Shih
    • 1
    • 2
    • 3
  • Philip T. T. Ly
    • 4
    • 2
    • 3
  • Jing Wang
    • 4
    • 3
  • Catherine J. Pallen
    • 1
    • 4
    • 2
    • 3
  1. 1.Department of Pathology and Laboratory MedicineUniversity of British ColumbiaVancouverCanada
  2. 2.International Collaboration on Repair DiscoveriesUniversity of British ColumbiaVancouverCanada
  3. 3.BC Children’s Hospital Research InstituteUniversity of British ColumbiaVancouverCanada
  4. 4.Department of PediatricsUniversity of British ColumbiaVancouverCanada

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