Autonomous epithelial folding induced by an intracellular mechano-polarity feedback loop

PLoS Comput Biol. 2021 Dec 6;17(12):e1009614. doi: 10.1371/journal.pcbi.1009614. eCollection 2021 Dec.

Abstract

Epithelial tissues form folded structures during embryonic development and organogenesis. Whereas substantial efforts have been devoted to identifying mechanical and biochemical mechanisms that induce folding, whether and how their interplay synergistically shapes epithelial folds remains poorly understood. Here we propose a mechano-biochemical model for dorsal fold formation in the early Drosophila embryo, an epithelial folding event induced by shifts of cell polarity. Based on experimentally observed apical domain homeostasis, we couple cell mechanics to polarity and find that mechanical changes following the initial polarity shifts alter cell geometry, which in turn influences the reaction-diffusion of polarity proteins, thus forming a feedback loop between cell mechanics and polarity. This model can induce spontaneous fold formation in silico, recapitulate polarity and shape changes observed in vivo, and confer robustness to tissue shape change against small fluctuations in mechanics and polarity. These findings reveal emergent properties of a developing epithelium under control of intracellular mechano-polarity coupling.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biomechanical Phenomena / physiology*
  • Blastoderm* / cytology
  • Blastoderm* / physiology
  • Cell Polarity / physiology*
  • Drosophila / embryology
  • Embryonic Development / physiology*
  • Epithelial Cells / cytology
  • Epithelial Cells / physiology
  • Epithelium / physiology*
  • Models, Biological

Grants and funding

FLW was supported by RIKEN Special Postdoctoral Researcher Program. CWK was supported by JSPS KAKENHI Grant (JP20K15810). YCW was supported by JSPS KAKENHI Grant (JP18H02441). TS was supported by JSPS KAKENHI Grant (JP19H00996), and JST CREST Grant (JPMJCR1852). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.