An Actomyosin-Arf-GEF Negative Feedback Loop for Tissue Elongation under Stress

Junior J. West, Teresa Zulueta-Coarasa, Janna A. Maier, Donghoon M. Lee, Ashley E.E. Bruce, Rodrigo Fernandez-Gonzalez, Tony J.C. Harris

Research output: Contribution to journalArticlepeer-review

27 Scopus citations


In response to a pulling force, a material can elongate, hold fast, or fracture. During animal development, multi-cellular contraction of one region often stretches neighboring tissue. Such local contraction occurs by induced actomyosin activity, but molecular mechanisms are unknown for regulating the physical properties of connected tissue for elongation under stress. We show that cytohesins, and their Arf small G protein guanine nucleotide exchange activity, are required for tissues to elongate under stress during both Drosophila dorsal closure (DC) and zebrafish epiboly. In Drosophila, protein localization, laser ablation, and genetic interaction studies indicate that the cytohesin Steppke reduces tissue tension by inhibiting actomyosin activity at adherens junctions. Without Steppke, embryogenesis fails, with epidermal distortions and tears resulting from myosin misregulation. Remarkably, actomyosin network assembly is necessary and sufficient for local Steppke accumulation, where live imaging shows Steppke recruitment within minutes. This rapid negative feedback loop provides a molecular mechanism for attenuating the main tension generator of animal tissues. Such attenuation relaxes tissues and allows orderly elongation under stress.

Original languageEnglish (US)
Pages (from-to)2260-2270.e5
JournalCurrent Biology
Issue number15
StatePublished - Aug 7 2017
Externally publishedYes


  • actomyosin
  • Arf small G protein
  • cytohesin
  • dorsal closure
  • Drosophila
  • epiboly
  • morphogenesis
  • negative feedback
  • tissue relaxation
  • zebrafish

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)


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