Nature Neuroscience5, 1147 - 1154 (2002)
Published online: 15 October 2002; | doi:10.1038/nn956
Shared receptors in axon guidance: SAX-3/Robo signals via UNC-34/Enabled and a Netrin-independent UNC-40/DCC function
Timothy W. Yu1, Joe C. Hao1, 2, Wendell Lim3, Marc Tessier-Lavigne2
& Cornelia I. Bargmann1
1
Howard Hughes Medical Institute, Program in Neuroscience, Department of Anatomy and of Biochemistry and Biophysics, The University of California, San Francisco, California 94143, USA
2
Present address: Department of Biological Sciences, Howard Hughes Medical Institute, 371 Serra Hall, Stanford University, Stanford, California 94305, USA
3
Department of Molecular and Cellular Pharmacology, The University of California, San Francisco, California 94143, USA
Correspondence should be addressed to Cornelia I. Bargmann cori@itsa.ucsf.edu
The C. elegans SAX-3/Robo receptor acts in anterior−posterior, dorsal−ventral and midline guidance decisions. Here we show that SAX-3 signaling involves the C. elegans Enabled protein UNC-34 and an unexpected Netrin-independent function of the Netrin receptor UNC-40/DCC. Genetic interactions with gain- and loss-of-function mutations suggest that unc-34 and unc-40 act together with sax-3 in several guidance decisions, but the C. elegans Netrin gene unc-6 does not act in the same genetic pathways. Within the migrating axon, sax-3, unc-34 and unc-40 all act cell-autonomously. Our results support a role for UNC-34/Enabled proteins in SAX-3-mediated repulsion, and show that UNC-40/DCC can potentiate SAX-3/Robo signaling via a mechanism that may involve direct binding of the two guidance receptors. A combinatorial logic dictates alternative functions for UNC-40/DCC, which can act in attraction to UNC-6/Netrin, repulsion from Netrin (with UNC-5), or repulsion from Slit (with SAX-3).
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