The epidermal circadian clock integrates and subverts brain signals to guarantee skin homeostasis

Thomas Mortimer*, Valentina M. Zinna, Muge Atalay, Carmelo Laudanna, Oleg Deryagin, Guillem Posas, Jacob G. Smith, Elisa García-Lara, Mireia Vaca-Dempere, Leonardo Vinícius Monteiro de Assis, Isabel Heyde, Kevin B. Koronowski, Paul Petrus, Carolina M. Greco, Stephen Forrow, Henrik Oster, Paolo Sassone-Corsi, Patrick Simon Welz*, Pura Muñoz-Cánoves*, Salvador Aznar Benitah*

*Korrespondierende/r Autor/-in für diese Arbeit

Abstract

In mammals, the circadian clock network drives daily rhythms of tissue-specific homeostasis. To dissect daily inter-tissue communication, we constructed a mouse minimal clock network comprising only two nodes: the peripheral epidermal clock and the central brain clock. By transcriptomic and functional characterization of this isolated connection, we identified a gatekeeping function of the peripheral tissue clock with respect to systemic inputs. The epidermal clock concurrently integrates and subverts brain signals to ensure timely execution of epidermal daily physiology. Timely cell-cycle termination in the epidermal stem cell compartment depends upon incorporation of clock-driven signals originating from the brain. In contrast, the epidermal clock corrects or outcompetes potentially disruptive feeding-related signals to ensure the optimal timing of DNA replication. Together, we present an approach for cataloging the systemic dependencies of daily temporal organization in a tissue and identify an essential gate-keeping function of peripheral circadian clocks that guarantees tissue homeostasis.

OriginalspracheEnglisch
ZeitschriftCell Stem Cell
Jahrgang31
Ausgabenummer6
Seiten (von - bis)834-849.e4
ISSN1934-5909
DOIs
PublikationsstatusVeröffentlicht - 06.06.2024

Strategische Forschungsbereiche und Zentren

  • Forschungsschwerpunkt: Gehirn, Hormone, Verhalten - Center for Brain, Behavior and Metabolism (CBBM)

DFG-Fachsystematik

  • 2.23-04 Kognitive, systemische und Verhaltensneurobiologie
  • 2.23-01 Entwicklungsneurobiologie
  • 2.22-17 Endokrinologie, Diabetologie, Metabolismus

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