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Updated: Jan 10, 2026

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Probing the Roles of Physical Forces in Early Chick Embryonic Morphogenesis
Published on: June 5, 2018
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Convergent flow-mediated mesenchymal force drives embryonic foregut constriction and splitting
Rui Yan1, Ludwig A Hoffmann2, Panagiotis Oikonomou3
1Department of Genetics, Blavatnik Institute, Harvard Medical School, Boston, MA, USA.
Nature Communications
|November 27, 2025
Summary
Mesenchymal cells drive epithelial tube splitting during embryonic development through a compressive force. This process, crucial for forming diverse animal structures, can be influenced by signals like Sonic hedgehog (SHH).
Area of Science:
- Developmental biology
- Biophysics
- Morphogenesis
Background:
- Epithelial sheet transformation into 3D structures is key for animal form diversity.
- Epithelial folding mechanisms are known, but tube splitting remains poorly understood.
- Epithelial splitting involves extreme folding and topological transitions.
Purpose of the Study:
- Investigate the biomechanical basis of epithelial tube splitting.
- Utilize the conserved tracheal-esophageal separation (TES) event in tetrapod embryogenesis as a model.
- Identify forces and signaling pathways governing epithelial splitting.
Main Methods:
- Studied tracheal-esophageal separation (TES) in embryonic development.
- Analyzed the role of surrounding mesenchyme and cell migration.
- Investigated the function of Sonic hedgehog (SHH) signaling.
- Used external pressure application to rescue defects.
Main Results:
- Identified a conserved compressive force from surrounding mesenchyme driving epithelial constriction and splitting.
- Convergent flow of mesenchymal cells towards the epithelium mediates this force.
- SHH signaling attracts mesenchymal cells to the epithelium.
- Mesenchyme removal, inhibited cell migration, or loss of SHH signaling disrupt TES.
- External pressure can rescue the abrogation of TES.
Conclusions:
- Unveiled the biomechanical basis of epithelial tube splitting.
- Mesenchymal compressive forces, guided by SHH, are essential for TES.
- Findings suggest potential mesenchymal origins for tracheal-esophageal birth defects.
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