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Light-mediated activation reveals a key role for Rac in collective guidance of cell movement in vivo

Nature Cell Biology volume 12, pages 591–597 (2010)Cite this article

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Abstract

The small GTPase Rac induces actin polymerization, membrane ruffling and focal contact formation in cultured single cells1 but can either repress or stimulate motility in epithelial cells depending on the conditions2,3. The role of Rac in collective epithelial cell movements in vivo, which are important for both morphogenesis and metastasis4,5,6,7, is therefore difficult to predict. Recently, photoactivatable analogues of Rac (PA-Rac) have been developed, allowing rapid and reversible activation or inactivation of Rac using light8. In cultured single cells, light-activated Rac leads to focal membrane ruffling, protrusion and migration. Here we show that focal activation of Rac is also sufficient to polarize an entire group of cells in vivo, specifically the border cells of the Drosophila ovary. Moreover, activation or inactivation of Rac in one cell of the cluster caused a dramatic response in the other cells, suggesting that the cells sense direction as a group according to relative levels of Rac activity. Communication between cells of the cluster required Jun amino-terminal kinase (JNK) but not guidance receptor signalling. These studies further show that photoactivatable proteins are effective tools in vivo.

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Figure 1: Local activation of PA-Rac1 redirects an entire border cell group.
Figure 2: Forward or backward movement in response to photoactivatable Rac.
Figure 3: Responsiveness of border cells to PA-RacQ61L depends on their location within the egg chamber.
Figure 4: Local photoactivation or photoinactivation of Rac in one cell affects the morphology and behaviour of other cells in the group.
Figure 5: Rac activity pattern in migrating border cell clusters.

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Acknowledgements

This work was supported by grants GM046425 to D.J.M. and GM 057464 to K.M.H. and by the Cell Migration Consortium.

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Author notes

  1. Xiaobo Wang and Li He: These authors contributed equally.

Authors and Affiliations

  1. Department of Biological Chemistry, Center for Cell Dynamics, Johns Hopkins School of Medicine, 855 North Wolfe Street, Baltimore, 21205, MD, USA

    Xiaobo Wang, Li He & Denise J. Montell

  2. Department of Pharmacology, Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, Chapel Hill, 27599, NC, USA

    Yi I. Wu & Klaus M. Hahn

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  1. Xiaobo Wang
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Contributions

X.W. carried out the experiments documented in Figs 1, 2, 3 and Supplementary Information, Figs S1–S5. L.H. carried out the experiments shown in Figs 4, 5 and Supplementary Information, Figs S5–S7. X.W. made all of the transgenic flies and helped L.H. to collect FRET data in Fig. 5. Y.W. developed and provided the PA-Rac constructs and advised X.W. on their use. K.M.H. and D.J.M. coordinated the study. D.J.M. prepared the final version of the manuscript, based on contributions from all authors.

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Correspondence to Denise J. Montell.

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The authors declare no competing financial interests.

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Wang, X., He, L., Wu, Y. et al. Light-mediated activation reveals a key role for Rac in collective guidance of cell movement in vivo. Nat Cell Biol 12, 591–597 (2010). https://doi.org/10.1038/ncb2061

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