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Rac function and regulation during Drosophila development

Abstract

Rac GTPases regulate the actin cytoskeleton to control changes in cell shape1,2. To date, the analysis of Rac function during development has relied heavily on the use of dominant mutant isoforms. Here, we use loss-of-function mutations to show that the three Drosophila Rac genes, Rac1, Rac2 and Mtl, have overlapping functions in the control of epithelial morphogenesis, myoblast fusion, and axon growth and guidance. They are not required for the establishment of planar cell polarity, as had been suggested on the basis of studies using dominant mutant isoforms3,4. The guanine nucleotide exchange factor, Trio, is essential for Rac function in axon growth and guidance, but not for epithelial morphogenesis or myoblast fusion. Different Rac activators thus act in different developmental processes. The specific cellular response to Rac activation may be determined more by the upstream activator than the specific Rac protein involved.

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Figure 1: Rac GTPases are required for dorsal closure and myoblast fusion, but not for planar cell polarity.
Figure 2: Axon growth and guidance defects in Rac mutant embryos.
Figure 3: Photoreceptor axon projections in Rac mutants.
Figure 4: Rac1 and Rac2 suppress a trio gain-of-function phenotype.

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Acknowledgements

We thank H. Halbritter for scanning electron microscopy; P. Rørth for generating and providing the EP0855 line; T. Newsome for the initial characterization of trio mutant embryos; and J. Knoblich, K. Nasmyth and members of the Dickson laboratory for comments on the manuscript. This research was supported by funding from Boehringer Ingelheim GmbH (B.J.D.), and grants from the National Institutes of Health (L.L.) and the Human Frontiers of Science Program (B.J.D. and L.L.).

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Correspondence to Barry J. Dickson.

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Hakeda-Suzuki, S., Ng, J., Tzu, J. et al. Rac function and regulation during Drosophila development. Nature 416, 438–442 (2002). https://doi.org/10.1038/416438a

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