YAP and TAZ regulate remyelination in the central nervous system

Author:

Hong Jiayue1,Kirkland Julia M.1,Acheta Jenica1,Marziali Leandro N.2,Beck Brianna1,Jeanette Haley1,Bhatia Urja1,Davis Grace1,Herron Jacob1,Roué Clémence1,Abi‐Ghanem Charly1,Feltri M. Laura23ORCID,Zuloaga Kristen L.1ORCID,Bechler Marie E.4ORCID,Poitelon Yannick1ORCID,Belin Sophie1ORCID

Affiliation:

1. Department of Neuroscience and Experimental Therapeutics Albany Medical College Albany New York USA

2. Department of Biochemistry, Department of Neurology Institute for Myelin and Glia Exploration, Jacobs School of Medicine and Biomedical Sciences, State University of New York at Buffalo Buffalo New York USA

3. Department of Medical Biotechnology and Translational Medicine Università degli Studi di Milano Milan Italy

4. Department of Cell and Developmental Biology, and Department of Neuroscience and Physiology State University of New York Upstate Medical University Syracuse New York USA

Abstract

AbstractMyelinating cells are sensitive to mechanical stimuli from their extracellular matrix. Ablation of YAP and TAZ mechanotransducers in Schwann cells abolishes the axon–Schwann cell recognition, myelination, and remyelination in the peripheral nervous system. It was unknown if YAP and TAZ are also required for myelination and remyelination in the central nervous system. Here we define the importance of oligodendrocyte (OL) YAP and TAZ in vivo, by specific deletion in oligodendroglial cells in adult OLs during myelin repair. Blocking YAP and TAZ expression in OL lineage cells did not affect animal viability or any major defects on OL maturation and myelination. However, using a mouse model of demyelination/remyelination, we demonstrate that YAP and TAZ modulate the capacity of OLs to remyelinate axons, particularly during the early stage of the repair process, when OL proliferation is most important. These results indicate that YAP and TAZ signaling is necessary for effective remyelination of the mouse brain.

Funder

National Institute of Neurological Disorders and Stroke

National Multiple Sclerosis Society

Publisher

Wiley

Subject

Cellular and Molecular Neuroscience,Neurology

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