TEAD1 is crucial for developmental myelination, Remak bundles, and functional regeneration of peripheral nerves

  1. Matthew Grove
  2. Hyukmin Kim
  3. Shuhuan Pang
  4. Jose Paz Amaya
  5. Guoqing Hu
  6. Jiliang Zhou
  7. Michel A Lemay
  8. Young-Jin Son  Is a corresponding author
  1. Temple University, United States
  2. 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

  1. Matthew Grove

    Department of Neural Sciences, Temple University, Philadelphia, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Hyukmin Kim

    Department of Neural Sciences, Temple University, Philadelphia, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-3270-4681
  3. Shuhuan Pang

    Department of Neural Sciences, Temple University, Philadelphia, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Jose Paz Amaya

    Department of Bioengineering, Temple University, Philadelphia, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Guoqing Hu

    Department of Pharmacology and Toxicology, Augusta University, Augusta, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. Jiliang Zhou

    Department of Pharmacology and Toxicology, Augusta University, Augusta, United States
    Competing interests
    The authors declare that no competing interests exist.
  7. Michel A Lemay

    Department of Bioengineering, Temple University, Philadelphia, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-5636-0297
  8. Young-Jin Son

    Department of Neural Sciences, Temple University, Philadelphia, United States
    For correspondence
    yson@temple.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-5725-9775

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.

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.

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.

Metrics

  • 693
    views
  • 128
    downloads
  • 6
    citations

Views, downloads and citations are aggregated across all versions of this paper published by eLife.

Download links

A two-part list of links to download the article, or parts of the article, in various formats.

Downloads (link to download the article as PDF)

Open citations (links to open the citations from this article in various online reference manager services)

Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)

  1. Matthew Grove
  2. Hyukmin Kim
  3. Shuhuan Pang
  4. Jose Paz Amaya
  5. Guoqing Hu
  6. Jiliang Zhou
  7. Michel A Lemay
  8. Young-Jin Son
(2024)
TEAD1 is crucial for developmental myelination, Remak bundles, and functional regeneration of peripheral nerves
eLife 13:e87394.
https://doi.org/10.7554/eLife.87394

Share this article

https://doi.org/10.7554/eLife.87394

Further reading

    1. Cell Biology
    2. Neuroscience
    Vibhavari Aysha Bansal, Jia Min Tan ... Toh Hean Ch'ng
    Research Article

    The emergence of Aβ pathology is one of the hallmarks of Alzheimer’s disease (AD), but the mechanisms and impact of Aβ in progression of the disease is unclear. The nuclear pore complex (NPC) is a multi-protein assembly in mammalian cells that regulates movement of macromolecules across the nuclear envelope; its function is shown to undergo age-dependent decline during normal aging and is also impaired in multiple neurodegenerative disorders. Yet not much is known about the impact of Aβ on NPC function in neurons. Here, we examined NPC and nucleoporin (NUP) distribution and nucleocytoplasmic transport using a mouse model of AD (AppNL-G-F/NL-G-F) that expresses Aβ in young animals. Our studies revealed that a time-dependent accumulation of intracellular Aβ corresponded with a reduction of NPCs and NUPs in the nuclear envelope which resulted in the degradation of the permeability barrier and inefficient segregation of nucleocytoplasmic proteins, and active transport. As a result of the NPC dysfunction App KI neurons become more vulnerable to inflammation-induced necroptosis – a programmed cell death pathway where the core components are activated via phosphorylation through nucleocytoplasmic shutting. Collectively, our data implicates Aβ in progressive impairment of nuclear pore function and further confirms that the protein complex is vulnerable to disruption in various neurodegenerative diseases and is a potential therapeutic target.

    1. Neuroscience
    Matthew R Kleinman, David J Foster
    Research Article

    Sequenced reactivations of hippocampal neurons called replays, concomitant with sharp-wave ripples in the local field potential, are critical for the consolidation of episodic memory, but whether replays depend on the brain’s reward or novelty signals is unknown. Here, we combined chemogenetic silencing of dopamine neurons in ventral tegmental area (VTA) and simultaneous electrophysiological recordings in dorsal hippocampal CA1, in freely behaving male rats experiencing changes to reward magnitude and environmental novelty. Surprisingly, VTA silencing did not prevent ripple increases where reward was increased, but caused dramatic, aberrant ripple increases where reward was unchanged. These increases were associated with increased reverse-ordered replays. On familiar tracks this effect disappeared, and ripples tracked reward prediction error (RPE), indicating that non-VTA reward signals were sufficient to direct replay. Our results reveal a novel dependence of hippocampal replay on dopamine, and a role for a VTA-independent RPE signal that is reliable only in familiar environments.