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Mechanotransduction in collective cell migration

Nature Cell Biology volume 16, page 628 (2014) | Download Citation

The Drosophila melanogaster ovary egg chambers contain nurse cells and an oocyte surrounded by epithelial follicle cells. During oogenesis, polar cells stimulate a group of epithelial cells, termed border cells, to move between nurse cells towards the oocyte. Successful border cell migration requires E-cadherin expression in both border and nurse cells. Montell and colleagues now provide an elegant characterization of the role of E-cadherin in this process Cell 157, 1146–1159; 2014).

Using Drosophila strains with E-cadherin depleted in border, nurse or polar cells, they demonstrated that E-cadherin-based adhesions between border and nurse cells are necessary for directional migration of border cells, whereas E-cadherin depletion in polar cells disrupts border cell clusters. The authors generated transgenic flies expressing E-cadherin modified to include a Förster resonance energy transfer (FRET)-based tension sensor, to register mechanical force transduction across E-cadherin molecules. They observed a higher level of tension at the front of the border cell cluster, indicating higher adhesive strength and/or actomyosin contractility at that site. Morphodynamic profiling of protrusion and retraction behaviour of border cells expressing dominant-negative forms of PVR (PDGF- and VEGF-receptor related) and EGFR (epidermal growth factor receptor) confirmed the known role of these receptors in guiding border cells. Comparing these profiles with those from expression of dominant-negative Rac and depletion of E-cadherin indicated that PVR and EGFR stimulate Rac activity and function upstream of E-cadherin in border cell guidance. Further tension sensor experiments revealed that the guidance receptors and Rac promote tension on E-cadherin at the front of the cluster. Experiments with a Rac FRET probe and Rac photoinhibition combined with depletion of adherens junction proteins showed that E-cadherin is involved in a positive feedback amplification of Rac signalling at the front of the border cell cluster to promote forward protrusion stabilization and to allow directional migration through E-cadherin-based adhesion between border cells.

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https://doi.org/10.1038/ncb3008

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  1. Search for Alexia-Ileana Zaromytidou in:

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