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Wound healing recapitulates morphogenesis in Drosophila embryos

Nature Cell Biology volume 4, pages 907–912 (2002)Cite this article

Abstract

The capacity to repair a wound is a fundamental survival mechanism that is activated at any site of damage throughout embryonic and adult life1. To study the cell biology and genetics of this process, we have developed a wounding model in Drosophila melanogaster embryos that allows live imaging of rearrangements and changes in cell shape, and of the cytoskeletal machinery that draws closed an in vivo wound. Using embryos expressing green fluorescent protein (GFP) fusion proteins, we show that two cytoskeletal-dependent elements — an actin cable and dynamic filopodial/lamellipodial protrusions — are expressed by epithelial cells at the wound edge and are pivotal for repair. Modulating the activities of the small GTPases Rho and Cdc42 demonstrates that these actin-dependent elements have differing cellular functions, but that either alone can drive wound closure. The actin cable operates as a 'purse-string' to draw the hole closed, whereas filopodia are essential for the final 'knitting' together of epithelial cells at the end of repair. Our data suggest a more complex model for epithelial repair than previously envisaged and highlight remarkable similarities with the well-characterized morphogenetic movement of dorsal closure in Drosophila.

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Figure 1: Changes in cell shape and rearrangements during wound closure.
Figure 2: The cytoskeletal machinery of wound closure.
Figure 3: Filopodial interactions during repair.
Figure 4: Analysis of wound repair in Rho mutant embryos.
Figure 5: Analysis of repair in dominant-negative Cdc42-expressing wounds.

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Acknowledgements

We thank all in the Martin lab for constant encouragement and support, K. Barrett and K. Nikolaidou for helpful discussions, M. Turmaine for help with electron microscopy and A. Martinez-Arias for continued enthusiasm and advice. The GFP fusion fly stocks were generously supplied by H. Oda (GFP–actin and α-catenin) and R. Karess (GFP–sqh). The anti-Rho1 antiserum was kindly provided by C. Magie and S. Parkhurst. Thanks also to the Bloomington Stock Center, D. Strutt, B. Dickson and N. Harden for other fly stocks. This work is funded by the Medical Research Council, The Wellcome Trust, The Royal Society and a Pfizer UK studentship to W.W.

Author information

Author notes

  1. Antonio Jacinto

    Present address: Instituto Gulbenkian de Ciência, Rua da Quinta Grande, 6, 2780-156, Oeiras, Portugal

  2. Richard Grose

    Present address: Cancer Research UK, Lincolns Inn Fields, London, WC2 3PX, UK

Authors and Affiliations

  1. Department of Anatomy and Developmental Biology, University College London, Gower Street, London, WC1E 6BT, UK

    William Wood, Antonio Jacinto, Richard Grose, Sarah Woolner & Paul Martin

  2. Department of Physiology, University College London, Gower Street, London, WC1E 6BT, UK

    Jonathan Gale

  3. Department of Human Anatomy and Genetics, University of Oxford, South Parks Rd, Oxford, OX1 3QX, UK

    Clive Wilson

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Corresponding author

Correspondence to Paul Martin.

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The authors declare no competing financial interests.

Supplementary information

Movie 1

Movie 1 shows the final hour of epithelial repair in a wild type embryo expressing GFP-actin. (MOV 2762 kb)

Movie 2

Movie 2 illustrates repair of a mechanically-created incisional wound made to an embryo expressing GFP-actin. (MOV 2163 kb)

Movie 3

Movie 3 reveals actin dynamics during wound closure in a Rho mutant embryo expressing GFP-actin. (MOV 2270 kb)

Movie 4

Movie 4 shows a direct comparison of wild type (right) and Rho mutant (left) wound closure in embryos expressing GFP-actin. (MOV 4667 kb)

Movie 5

Movie 5 is a direct comparison of wild type (right) and Cdc42N17-expressing (left) wounds. (MOV 3257 kb)

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Legends to movies (PDF 12 kb)

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Wood, W., Jacinto, A., Grose, R. et al. Wound healing recapitulates morphogenesis in Drosophila embryos. Nat Cell Biol 4, 907–912 (2002). https://doi.org/10.1038/ncb875

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