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PreprintCC BY-NC-NDbioRxiv

Epidermal cells sculpt sensory nerve endings through actomyosin contractility

  1. 1Duke University

Abstract

Peripheral sensory neurons innervate the skin to detect mechanical, thermal, and noxious stimuli. Within the epidermis, nerve fibers terminate beneath tight junctions, shielding them from environmental exposure. Although epidermal differentiation coordinates tight junction assembly, its role in organizing nerve terminals is poorly understood. Here, we show that activation of Notch, a master regulator of epidermal differentiation, caused near-complete loss of epidermal innervation. This was largely the result of increased contractility rather than impaired differentiation. Inducing epidermal contractility was sufficient to deplete nerve fibers with striking spatial precision, and restoring normal contractility reversed this effect. Actomyosin contractility is highest in the granular layers of the epidermis, where tight junctions form and nerve fibers terminate. Ablation of nonmuscle myosin II allowed nerve fibers to extend beyond their normal termination zone and caused touch hypersensitivity. Together, these findings demonstrate that epidermal contractility positions sensory nerve endings through spatially controlled pruning and defines a mechanical boundary established by epidermal cells that restricts neuronal outgrowth.

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BibTeX
@misc{lee2026epidermal,
  title = {{Epidermal cells sculpt sensory nerve endings through actomyosin contractility}},
  author = {M. Lee and J. Underwood and J. Xu and R.-R. Ji and T. Lechler},
  howpublished = {bioRxiv},
  year = {2026},
  month = aug,
  doi = {10.64898/2026.08.28.747813},
  url = {https://www.biorxiv.org/content/10.64898/2026.08.28.747813v1},
  note = {CC BY-NC-ND},
}
RIS
TY  - UNPB
TI  - Epidermal cells sculpt sensory nerve endings through actomyosin contractility
AU  - M. Lee
AU  - J. Underwood
AU  - J. Xu
AU  - R.-R. Ji
AU  - T. Lechler
PY  - 2026
DA  - 2026/08/28
PB  - bioRxiv
DO  - 10.64898/2026.08.28.747813
UR  - https://www.biorxiv.org/content/10.64898/2026.08.28.747813v1
AB  - Peripheral sensory neurons innervate the skin to detect mechanical, thermal, and noxious stimuli. Within the epidermis, nerve fibers terminate beneath tight junctions, shielding them from environmental exposure. Although epidermal differentiation coordinates tight junction assembly, its role in organizing nerve terminals is poorly understood. Here, we show that activation of Notch, a master regulator of epidermal differentiation, caused near-complete loss of epidermal innervation. This was largely the result of increased contractility rather than impaired differentiation. Inducing epidermal contractility was sufficient to deplete nerve fibers with striking spatial precision, and restoring normal contractility reversed this effect. Actomyosin contractility is highest in the granular layers of the epidermis, where tight junctions form and nerve fibers terminate. Ablation of nonmuscle myosin II allowed nerve fibers to extend beyond their normal termination zone and caused touch hypersensitivity. Together, these findings demonstrate that epidermal contractility positions sensory nerve endings through spatially controlled pruning and defines a mechanical boundary established by epidermal cells that restricts neuronal outgrowth.
ER  -