Mechanical feedback defines organizing centers to drive digit emergence

Research output: Contribution to journalResearch articleContributedpeer-review

Contributors

  • Carolina Parada - , Institut Pasteur Paris, French National Centre for Scientific Research (CNRS) (Author)
  • Samhita P. Banavar - , University of California at Santa Barbara (Author)
  • Parisa Khalilian - , Institut Pasteur Paris, French National Centre for Scientific Research (CNRS) (Author)
  • Stephane Rigaud - , Institut Pasteur Paris (Author)
  • Arthur Michaut - , Institut Pasteur Paris, French National Centre for Scientific Research (CNRS) (Author)
  • Yucen Liu - , University of California at Santa Barbara (Author)
  • Dennis Manjaly Joshy - , University of California at Santa Barbara (Author)
  • Otger Campàs - , Chair of Tissue Dynamics, Clusters of Excellence PoL: Physics of Life, University of California at Santa Barbara (Author)
  • Jerome Gros - , Institut Pasteur Paris, French National Centre for Scientific Research (CNRS) (Author)

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

Original languageEnglish
Pages (from-to)854-866.e6
JournalDevelopmental cell
Volume57
Issue number7
Publication statusPublished - 11 Apr 2022
Peer-reviewedYes

External IDs

PubMed 35413235

Keywords

Keywords

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