Mechanical feedback defines organizing centers to drive digit emergence

Publikation: Beitrag in FachzeitschriftForschungsartikelBeigetragenBegutachtung

Beitragende

  • Carolina Parada - , Institut Pasteur Paris, Centre national de la recherche scientifique (CNRS) (Autor:in)
  • Samhita P. Banavar - , University of California at Santa Barbara (Autor:in)
  • Parisa Khalilian - , Institut Pasteur Paris, Centre national de la recherche scientifique (CNRS) (Autor:in)
  • Stephane Rigaud - , Institut Pasteur Paris (Autor:in)
  • Arthur Michaut - , Institut Pasteur Paris, Centre national de la recherche scientifique (CNRS) (Autor:in)
  • Yucen Liu - , University of California at Santa Barbara (Autor:in)
  • Dennis Manjaly Joshy - , University of California at Santa Barbara (Autor:in)
  • Otger Campàs - , Professur für Dynamik von Geweben, Exzellenzcluster PoL: Physik des Lebens, University of California at Santa Barbara (Autor:in)
  • Jerome Gros - , Institut Pasteur Paris, Centre national de la recherche scientifique (CNRS) (Autor:in)

Abstract

During embryonic development, digits gradually emerge in a periodic pattern. Although genetic evidence indicates that digit formation results from a self-organizing process, the underlying mechanisms are still unclear. Here, we find that convergent-extension tissue flows driven by active stresses underlie digit formation. These active stresses simultaneously shape cartilage condensations and lead to the emergence of a compressive stress region that promotes high activin/p-SMAD/SOX9 expression, thereby defining digit-organizing centers via a mechanical feedback. In Wnt5a mutants, such mechanical feedback is disrupted due to the loss of active stresses, organizing centers do not emerge, and digit formation is precluded. Thus, digit emergence does not result solely from molecular interactions, as was previously thought, but requires a mechanical feedback that ensures continuous coupling between phalanx specification and elongation. Our work, which links mechanical and molecular signals, provides a mechanistic context for the emergence of organizing centers that may underlie various developmental processes.

Details

OriginalspracheEnglisch
Seiten (von - bis)854-866.e6
FachzeitschriftDevelopmental cell
Jahrgang57
Ausgabenummer7
PublikationsstatusVeröffentlicht - 11 Apr. 2022
Peer-Review-StatusJa

Externe IDs

PubMed 35413235

Schlagworte

Schlagwörter

  • chondrogenesis, digit, limb development, mechanical feedback, mechanobiology, organizing centers, phalanx-forming region/digit crescent, self-organization, tissue mechanics