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Published 24 December 2001. doi:10.1083/jcb.200110077
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© The Rockefeller University Press, 0021-9525/2001/12/1117 $5.00
The Journal of Cell Biology, Volume 155, Number 7, December 24, 2001 1117-1122

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 A novel Dbl family RhoGEF promotes Rho-dependent axon attraction to the central nervous system midline in Drosophila and overcomes Robo repulsion

Greg J. Bashaw1,2, Hailan Hu2, Catherine D. Nobes3 and Corey S. Goodman2

1 Department of Neuroscience, University of Pennsylvania, Philadelphia, PA 19104
2 Howard Hughes Medical Institute, Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720
3 MRC Laboratory for Molecular Cell Biology, University College London, Gower Street, London WC1E 6BT, UK

Address correspondence to Greg J. Bashaw, Department of Neuroscience, University of Pennsylvania, Philadelphia, PA 19104. Tel.: (215) 898-0829. Fax: (215) 573-7601. E-mail: gbashaw{at}mail.med.upenn.edu

The key role of the Rho family GTPases Rac, Rho, and CDC42 in regulating the actin cytoskeleton is well established (Hall, A. 1998. Science. 279:509–514). Increasing evidence suggests that the Rho GTPases and their upstream positive regulators, guanine nucleotide exchange factors (GEFs), also play important roles in the control of growth cone guidance in the developing nervous system (Luo, L. 2000. Nat. Rev. Neurosci. 1:173–180; Dickson, B.J. 2001. Curr. Opin. Neurobiol. 11:103–110). Here, we present the identification and molecular characterization of a novel Dbl family Rho GEF, GEF64C, that promotes axon attraction to the central nervous system midline in the embryonic Drosophila nervous system. In sensitized genetic backgrounds, loss of GEF64C function causes a phenotype where too few axons cross the midline. In contrast, ectopic expression of GEF64C throughout the nervous system results in a phenotype in which far too many axons cross the midline, a phenotype reminiscent of loss of function mutations in the Roundabout (Robo) repulsive guidance receptor. Genetic analysis indicates that GEF64C expression can in fact overcome Robo repulsion. Surprisingly, evidence from genetic, biochemical, and cell culture experiments suggests that the promotion of axon attraction by GEF64C is dependent on the activation of Rho, but not Rac or Cdc42.

Key Words: axon guidance; attraction; repulsion; Rho; GEF


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