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

• Published in: Current biology Vol. 27; no. 15; pp. 2260 - 2270.e5
• Main Authors: West, Junior J., Zulueta-Coarasa, Teresa, Maier, Janna A., Lee, Donghoon M., Bruce, Ashley E.E., Fernandez-Gonzalez, Rodrigo, Harris, Tony J.C.
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 07.08.2017
• Subjects: actomyosin; Animals; Arf small G protein; cytohesin; dorsal closure; Drosophila; Drosophila melanogaster - embryology; Drosophila melanogaster - genetics; Drosophila melanogaster - metabolism; Drosophila Proteins - genetics; Drosophila Proteins - metabolism; Embryo, Nonmammalian - embryology; Embryo, Nonmammalian - metabolism; epiboly; GTP-Binding Protein Regulators - genetics; GTP-Binding Protein Regulators - metabolism; Guanine Nucleotide Exchange Factors - genetics; Guanine Nucleotide Exchange Factors - metabolism; morphogenesis; negative feedback; Signal Transduction; tissue relaxation; zebrafish; Zebrafish - embryology; Zebrafish - genetics; Zebrafish - metabolism; Zebrafish Proteins - genetics; Zebrafish Proteins - metabolism; cytohesin; epiboly; morphogenesis; actomyosin; Drosophila; dorsal closure; zebrafish; negative feedback; Arf small G protein; tissue relaxation
• ISSN: 0960-9822; 1879-0445
• DOI: 10.1016/j.cub.2017.06.038

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. [Display omitted] •The Arf-GEF Steppke relaxes tissue tension to allow stretching by a pulling force•Steppke antagonizes the assembly of actomyosin cables at cell-cell junctions•Actomyosin networks recruit Steppke for local negative feedback•Cytohesin family Arf-GEFs promote tissue spreading in both flies and fish West et al. report a molecular mechanism that relaxes epithelial tissues for uniform stretching by a pulling force. The Arf-GEF Steppke is recruited to cell-cell junctions by actomyosin. Arf-GEF activity inhibits these contractile junctional networks to reduce tissue tension and allow stretching in both Drosophila and zebrafish embryos.