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Mechanisms of epithelial fusion and repair

Abstract

One of the principal functions of any epithelium in the embryonic or adult organism is to act as a self-sealing barrier layer. From the earliest stages of development, embryonic epithelia are required to close naturally occurring holes and to fuse wherever two free edges are brought together, and at the simplest level that is precisely what the epidermis must do to repair itself wherever it is damaged. Parallels can be drawn between the artificially triggered epithelial movements of wound repair and the naturally occurring epithelial movements that shape the embryo during morphogenesis. Recent in vitro and in vivo wound-healing studies and analysis of paradigm morphogenetic movements in genetically tractable embryos, like those of Drosophila and Caenorhabditis elegans, have begun to identify both the signals that initiate these movements and the cytoskeletal machinery that drives motility. We are also gaining insight into the nature of the brakes and stop signals, and the mechanisms by which the confronting epithelial sheets knit together to form a seam.

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Figure 1: Lamellipodial crawling versus purse-string closure of an epithelial wound.
Figure 2: Cell-shape changes and shuffling occurring during repair of an epithelial tissue culture wound.
Figure 3: Parallels between wound repair and morphogenetic movements.
Figure 4: Filopodial priming as part of the epithelial adhesion machinery.
Figure 5: Filopodia may act as 'sensors' for leading-edge epithelial cells, as they do in axonal growth cones.
Figure 6: Keratin 6 is expressed by wound-edge keratinocytes and at sites of fetal epithelial fusion.

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Acknowledgements

The work in our laboratories is funded by the MRC, Wellcome Trust and Pfizer UK (P.M.) and the Wellcome Trust (A.M.-A.). We thank R. Grose for advice regarding knockout mice studies and we thank W. Wood for all his support.

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Correspondence to Paul Martin.

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Jacinto, A., Martinez-Arias, A. & Martin, P. Mechanisms of epithelial fusion and repair. Nat Cell Biol 3, E117–E123 (2001). https://doi.org/10.1038/35074643

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