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TGFβ determines epithelial tissue spacing by regulating mesenchymal condensation.

Chan Jin Park1, Pengfei Zhang1, Carolina Trenado-Yuste1,2

  • 1Department of Chemical & Biological Engineering, Princeton University, Princeton, NJ 08544.

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|March 27, 2026
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Summary

Branch spacing in developing lungs is regulated by transforming growth factor-beta (TGFβ) signaling to the mesenchyme. This signaling drives mesenchymal cell migration, which physically separates developing epithelial branches, ensuring efficient gas exchange.

Keywords:
mechanical stressmorphogentissue morphodynamics

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Area of Science:

  • Developmental Biology
  • Cell Biology
  • Biophysics

Background:

  • Vertebrate lung development requires epithelial branches to avoid contact for efficient gas exchange.
  • Previous research suggested intrinsic epithelial growth mechanisms controlled branch spacing.
  • The physical mechanisms underlying branch spacing remained unclear.

Purpose of the Study:

  • To investigate the physical mechanisms regulating epithelial branch spacing during lung development.
  • To identify the signaling pathways involved in preventing branch contact.

Main Methods:

  • Utilized the embryonic chicken lung as a model system.
  • Analyzed cell proliferation patterns in developing lung epithelium.
  • Investigated the role of transforming growth factor-beta (TGFβ) signaling in mesenchymal cell behavior.

Main Results:

  • Branch spacing is primarily regulated by transforming growth factor-beta (TGFβ) signaling to the mesenchyme.
  • TGFβ signaling promotes directed mesenchymal cell migration, forming condensations that displace the epithelium.
  • Disruption of TGFβ signaling leads to mesenchymal condensation failure and epithelial branch contact.

Conclusions:

  • Mesenchymal cell dynamics, not epithelial self-avoidance, drive branch spacing in the developing lung.
  • TGFβ-mediated mesenchymal cell migration is crucial for establishing proper lung architecture.
  • This study reveals a novel mechanism for tissue self-organization during organogenesis.