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Rac GTPases control axon growth, guidance and branching

Nature volume 416, pages 442–447 (2002)Cite this article

Abstract

Growth, guidance and branching of axons are all essential processes for the precise wiring of the nervous system. Rho family GTPases transduce extracellular signals to regulate the actin cytoskeleton1. In particular, Rac has been implicated in axon growth and guidance2,3,4,5,6,7,8. Here we analyse the loss-of-function phenotypes of three Rac GTPases in Drosophila mushroom body neurons. We show that progressive loss of combined Rac1, Rac2 and Mtl activity leads first to defects in axon branching, then guidance, and finally growth. Expression of a Rac1 effector domain mutant that does not bind Pak rescues growth, partially rescues guidance, but does not rescue branching defects of Rac mutant neurons. Mosaic analysis reveals both cell autonomous and non-autonomous functions for Rac GTPases, the latter manifesting itself as a strong community effect in axon guidance and branching. These results demonstrate the central role of Rac GTPases in multiple aspects of axon development in vivo, and suggest that axon growth, guidance and branching could be controlled by differential activation of Rac signalling pathways.

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Figure 1: Loss-of-function mutants in Drosophila Rac1 and Rac2. a, b, Genomic organizations of the Rac2 (a) and Rac1 (b) loci. P-element positions, extent of the deletions and the genomic Rac1 rescue construct (Grac1) are shown.
Figure 2: Quantitative phenotypic analysis of Rac GTPases in MB axon branching, guidance and growth.
Figure 3: Images of wild-type and Rac mutant MB axons.
Figure 4: Effector domain mutant analysis.

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Acknowledgements

We thank the Berkeley Drosophila Genome Project for providing the P-elements, C. Goodman for the FasII antibody, and members of the Luo laboratory and M. Tessier-Lavigne for critical reading of the manuscript. J. N. was partly supported by a postdoctoral fellowship from the American Cancer Society California Division. This research was supported by grants from the National Institutes of Health to L.L., and from the Human Frontiers Science Program to L.L. and B.J.D.

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  1. Timothy Nardine and Matthew Harms: These authors contributed equally to this work

Authors and Affiliations

  1. Department of Biological Sciences, Stanford University, Stanford, 94305, California, USA

    Julian Ng, Timothy Nardine, Matthew Harms, Julia Tzu, Ann Goldstein & Liqun Luo

  2. Neurosciences Program, Stanford University, Stanford, 94305, California, USA

    Ann Goldstein & Liqun Luo

  3. Research Institute of Molecular Pathology, Dr. Bohr-Gasse 7, Vienna, A-1030, Austria

    Yan Sun, Georg Dietzl & Barry J. Dickson

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Correspondence to Liqun Luo.

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Ng, J., Nardine, T., Harms, M. et al. Rac GTPases control axon growth, guidance and branching. Nature 416, 442–447 (2002). https://doi.org/10.1038/416442a

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