Mechanical feedback defines organizing centers to drive digit emergence
Research output: Contribution to journal › Research article › Contributed › peer-review
Contributors
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 language | English |
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Pages (from-to) | 854-866.e6 |
Journal | Developmental cell |
Volume | 57 |
Issue number | 7 |
Publication status | Published - 11 Apr 2022 |
Peer-reviewed | Yes |
External IDs
PubMed | 35413235 |
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Keywords
ASJC Scopus subject areas
Keywords
- chondrogenesis, digit, limb development, mechanical feedback, mechanobiology, organizing centers, phalanx-forming region/digit crescent, self-organization, tissue mechanics