TEAD1 is crucial for developmental myelination, Remak bundles, and functional regeneration of peripheral nerves
- Temple University, United States
- Augusta University, United States
Abstract
Previously we showed that the hippo pathway transcriptional effectors, YAP and TAZ, are essential for Schwann cells (SCs) to develop, maintain and regenerate myelin (Grove et al., 2017; Grove, Lee, Zhao, & Son, 2020). Although TEAD1 has been implicated as a partner transcription factor, the mechanisms by which it mediates YAP/TAZ regulation of SC myelination are unclear. Here, using conditional and inducible knockout mice, we show that TEAD1 is crucial for SCs to develop and regenerate myelin. It promotes myelination by both positively and negatively regulating SC proliferation, enabling Krox20/Egr2 to upregulate myelin proteins, and upregulating the cholesterol biosynthetic enzymes FDPS and IDI1. We also show stage-dependent redundancy of TEAD1 and that non-myelinating SCs have a unique requirement for TEAD1 to enwrap nociceptive axons in Remak bundles. Our findings establish TEAD1 as a major partner of YAP/TAZ in developmental myelination and functional nerve regeneration and as a novel transcription factor regulating Remak bundle integrity.
Data availability
All data generated or analysed during this study are included in the manuscript and supporting file; Source Data files have been provided for all the figures.
Article and author information
Author details
Funding
National Institute of Neurological Disorders and Stroke (NS105796)
- Young-Jin Son
Shriners Hospitals for Children (84050)
- Young-Jin Son
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Klaus-Armin Nave, Max Planck Institute for Multidisciplinary Sciences, Germany
Ethics
Animal experimentation: All surgical procedures and animal maintenance complied with the National Institute of Health guidelines regarding the care and use of experimental animals and were approved by the Institutional Animal Care and Use Committee (Protocol# 4920) of Temple University, Philadelphia, PA, USA.
Version history
- Preprint posted: February 28, 2023 (view preprint)
- Received: March 15, 2023
- Accepted: March 6, 2024
- Accepted Manuscript published: March 8, 2024 (version 1)
- Version of Record published: March 22, 2024 (version 2)
Copyright
© 2024, Grove et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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TEAD1 is crucial for developmental myelination, Remak bundles, and functional regeneration of peripheral nerves
eLife 13:e87394.
https://doi.org/10.7554/eLife.87394
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