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J Neurosci. 2016 Dec 7;36(49):12351-12367.

Gpr126/Adgrg6 Has Schwann Cell Autonomous and Nonautonomous Functions in Peripheral Nerve Injury and Repair.

Author information

1
Department of Developmental Biology.
2
Department of Neuroscience, and.
3
Institute of Molecular Health Sciences, Department of Biology, Swiss Federal Institute of Technology, Zurich, ETH Zurich, CH-8093 Zurich, Switzerland, and.
4
Division of Newborn Medicine, Department of Medicine, Boston Children's Hospital and Harvard Medical School, Boston, Massachusetts 02115.
5
Hope Center for Neurological Disorders, Washington University School of Medicine, St. Louis, Missouri 63110.
6
Department of Developmental Biology, monkk@wustl.edu.

Abstract

Schwann cells (SCs) are essential for proper peripheral nerve development and repair, although the mechanisms regulating these processes are incompletely understood. We previously showed that the adhesion G protein-coupled receptor Gpr126/Adgrg6 is essential for SC development and myelination. Interestingly, the expression of Gpr126 is maintained in adult SCs, suggestive of a function in the mature nerve. We therefore investigated the role of Gpr126 in nerve repair by studying an inducible SC-specific Gpr126 knock-out mouse model. Here, we show that remyelination is severely delayed after nerve-crush injury. Moreover, we also observe noncell-autonomous defects in macrophage recruitment and axon regeneration in injured nerves following loss of Gpr126 in SCs. This work demonstrates that Gpr126 has critical SC-autonomous and SC-nonautonomous functions in remyelination and peripheral nerve repair.

SIGNIFICANCE STATEMENT:

Lack of robust remyelination represents one of the major barriers to recovery of neurological functions in disease or following injury in many disorders of the nervous system. Here we show that the adhesion class G protein-coupled receptor (GPCR) Gpr126/Adgrg6 is required for remyelination, macrophage recruitment, and axon regeneration following nerve injury. At least 30% of all approved drugs target GPCRs; thus, Gpr126 represents an attractive potential target to stimulate repair in myelin disease or following nerve injury.

KEYWORDS:

Gpr126; Schwann cell; adhesion GPCR; nerve injury; remyelination

PMID:
27927955
PMCID:
PMC5148226
DOI:
10.1523/JNEUROSCI.3854-15.2016
[Indexed for MEDLINE]
Free PMC Article

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