Proliferation-driven mechanical compression induces signalling centre formation during mammalian organ development

Publikation: Beitrag in FachzeitschriftForschungsartikelBeigetragenBegutachtung

Beitragende

  • Neha Pincha Shroff - , University of California at San Francisco (Gemeinsame:r Erstautor:in)
  • Pengfei Xu - , University of California at San Francisco (Gemeinsame:r Erstautor:in)
  • Sangwoo Kim - , University of California at Santa Barbara, École Polytechnique Fédérale de Lausanne (Autor:in)
  • Elijah R. Shelton - , University of California at Santa Barbara (Autor:in)
  • Ben J. Gross - , University of California at Santa Barbara (Autor:in)
  • Yucen Liu - , University of California at Santa Barbara (Autor:in)
  • Carlos O. Gomez - , University of California at Santa Barbara (Autor:in)
  • Qianlin Ye - , University of California at Los Angeles (Autor:in)
  • Tingsheng Yu Drennon - , University of California at San Francisco (Autor:in)
  • Jimmy K. Hu - , University of California at Los Angeles (Autor:in)
  • Jeremy B.A. Green - , King's College London (KCL) (Autor:in)
  • Otger Campàs - , Professur für Dynamik von Geweben (CMCB), Exzellenzcluster PoL: Physik des Lebens, University of California at Santa Barbara, Max Planck Institute of Molecular Cell Biology and Genetics, Zentrum für Systembiologie Dresden (CSBD) (Autor:in)
  • Ophir D. Klein - , University of California at San Francisco, Cedars-Sinai Medical Center (Autor:in)

Abstract

Localized sources of morphogens, called signalling centres, play a fundamental role in coordinating tissue growth and cell fate specification during organogenesis. However, how these signalling centres are established in tissues during embryonic development is still unclear. Here we show that the main signalling centre orchestrating development of rodent incisors, the enamel knot (EK), is specified by a cell proliferation-driven buildup in compressive stresses (mechanical pressure) in the tissue. Direct mechanical measurements indicate that the stresses generated by cell proliferation are resisted by the surrounding tissue, creating a circular pattern of mechanical anisotropy with a region of high compressive stress at its centre that becomes the EK. Pharmacological inhibition of proliferation reduces stresses and suppresses EK formation, and application of external pressure in proliferation-inhibited conditions rescues the formation of the EK. Mechanical information is relayed intracellularly through YAP protein localization, which is cytoplasmic in the region of compressive stress that establishes the EK and nuclear in the stretched anisotropic cells that resist the pressure buildup around the EK. Together, our data identify a new role for proliferation-driven mechanical compression in the specification of a model signalling centre during mammalian organ development.

Details

OriginalspracheEnglisch
Seiten (von - bis)519–529
Seitenumfang11
FachzeitschriftNature cell biology
Jahrgang26
Ausgabenummer4
PublikationsstatusVeröffentlicht - 3 Apr. 2024
Peer-Review-StatusJa

Schlagworte

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