YAP and TAZ control peripheral myelination and the expression of laminin receptors in Schwann cells

Nat Neurosci. 2016 Jul;19(7):879-87. doi: 10.1038/nn.4316. Epub 2016 Jun 6.

Abstract

Myelination is essential for nervous system function. Schwann cells interact with neurons and the basal lamina to myelinate axons using known receptors, signals and transcription factors. In contrast, the transcriptional control of axonal sorting and the role of mechanotransduction in myelination are largely unknown. Yap and Taz are effectors of the Hippo pathway that integrate chemical and mechanical signals in cells. We describe a previously unknown role for the Hippo pathway in myelination. Using conditional mutagenesis in mice, we show that Taz is required in Schwann cells for radial sorting and myelination and that Yap is redundant with Taz. Yap and Taz are activated in Schwann cells by mechanical stimuli and regulate Schwann cell proliferation and transcription of basal lamina receptor genes, both necessary for radial sorting of axons and subsequent myelination. These data link transcriptional effectors of the Hippo pathway and of mechanotransduction to myelin formation in Schwann cells.

MeSH terms

  • Adaptor Proteins, Signal Transducing / metabolism*
  • Animals
  • Axons / physiology
  • Axons / ultrastructure
  • Cell Cycle Proteins
  • Cell Movement / physiology*
  • Cell Proliferation / physiology*
  • Cells, Cultured
  • Mechanotransduction, Cellular / physiology
  • Mice, Inbred C57BL
  • Myelin Sheath / metabolism*
  • Neurogenesis / physiology
  • Phosphoproteins / metabolism*
  • Receptors, Laminin / metabolism
  • Schwann Cells / cytology
  • Schwann Cells / metabolism*
  • Transcription Factors / metabolism*

Substances

  • Adaptor Proteins, Signal Transducing
  • Cell Cycle Proteins
  • Phosphoproteins
  • Receptors, Laminin
  • Taz protein, mouse
  • Transcription Factors
  • Yap1 protein, mouse