Gpr126 is essential for peripheral nerve development and myelination in mammals

Kelly Monk, Kazuo Oshima, Simone Jörs, Stefan Heller, William S. Talbot

Research output: Contribution to journalArticle

113 Citations (Scopus)

Abstract

In peripheral nerves, Schwann cells form the myelin sheath that insulates axons and allows rapid propagation of action potentials. Although a number of regulators of Schwann cell development are known, the signaling pathways that control myelination are incompletely understood. In this study, we show that Gpr126 is essential for myelination and other aspects of peripheral nerve development in mammals. A mutation in Gpr126 causes a severe congenital hypomyelinating peripheral neuropathy in mice, and expression of differentiated Schwann cell markers, including Pou3f1, Egr2, myelin protein zero and myelin basic protein, is reduced. Ultrastructural studies of Gpr126-/- mice showed that axonal sorting by Schwann cells is delayed, Remak bundles (non-myelinating Schwann cells associated with small caliber axons) are not observed, and Schwann cells are ultimately arrested at the promyelinating stage. Additionally, ectopic perineurial fibroblasts form aberrant fascicles throughout the endoneurium of the mutant sciatic nerve. This analysis shows that Gpr126 is required for Schwann cell myelination in mammals, and defines new roles for Gpr126 in axonal sorting, formation of mature non-myelinating Schwann cells and organization of the perineurium.

Original languageEnglish (US)
Pages (from-to)2673-2680
Number of pages8
JournalDevelopment
Volume138
Issue number13
DOIs
StatePublished - Jul 1 2011
Externally publishedYes

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Schwann Cells
Peripheral Nerves
Mammals
Axons
Myelin P0 Protein
Myelin Basic Protein
Peripheral Nervous System Diseases
Sciatic Nerve
Myelin Sheath
Action Potentials
Fibroblasts
Neurons
Mutation

Keywords

  • Gpr126
  • Mouse
  • Myelin
  • Schwann cell

ASJC Scopus subject areas

  • Molecular Biology
  • Developmental Biology

Cite this

Gpr126 is essential for peripheral nerve development and myelination in mammals. / Monk, Kelly; Oshima, Kazuo; Jörs, Simone; Heller, Stefan; Talbot, William S.

In: Development, Vol. 138, No. 13, 01.07.2011, p. 2673-2680.

Research output: Contribution to journalArticle

Monk, K, Oshima, K, Jörs, S, Heller, S & Talbot, WS 2011, 'Gpr126 is essential for peripheral nerve development and myelination in mammals', Development, vol. 138, no. 13, pp. 2673-2680. https://doi.org/10.1242/dev.062224
Monk, Kelly ; Oshima, Kazuo ; Jörs, Simone ; Heller, Stefan ; Talbot, William S. / Gpr126 is essential for peripheral nerve development and myelination in mammals. In: Development. 2011 ; Vol. 138, No. 13. pp. 2673-2680.
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