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ZFIN ID: ZDB-PUB-170726-19
An Actomyosin-Arf-GEF Negative Feedback Loop for Tissue Elongation under Stress
West, J.J., Zulueta-Coarasa, T., Maier, J.A., Lee, D.M., Bruce, A.E.E., Fernandez-Gonzalez, R., Harris, T.J.C.
Date: 2017
Source: Current biology : CB   27(15): 2260-2270.e5 (Journal)
Registered Authors: Bruce, Ashley
Keywords: Arf small G protein, Drosophila, actomyosin, cytohesin, dorsal closure, epiboly, morphogenesis, negative feedback, tissue relaxation, zebrafish
MeSH Terms:
  • Animals
  • Drosophila Proteins/genetics*
  • Drosophila Proteins/metabolism
  • Drosophila melanogaster/embryology
  • Drosophila melanogaster/genetics*
  • Drosophila melanogaster/metabolism
  • Embryo, Nonmammalian/embryology
  • Embryo, Nonmammalian/metabolism
  • GTP-Binding Protein Regulators/genetics*
  • GTP-Binding Protein Regulators/metabolism
  • Guanine Nucleotide Exchange Factors/genetics*
  • Guanine Nucleotide Exchange Factors/metabolism
  • Signal Transduction*
  • Zebrafish/embryology
  • Zebrafish/genetics*
  • Zebrafish/metabolism
  • Zebrafish Proteins/genetics*
  • Zebrafish Proteins/metabolism
PubMed: 28736167 Full text @ Curr. Biol.
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.