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Wnt-mediated axon guidance via the Drosophila Derailed receptor

Nature volume 422, pages 583–588 (2003)Cite this article

Abstract

In nervous systems with bilateral symmetry, many neurons project axons across the midline to the opposite side. In each segment of the Drosophila embryonic nervous system, axons that display this projection pattern choose one of two distinct tracts: the anterior or posterior commissure. Commissure choice is controlled by Derailed, an atypical receptor tyrosine kinase expressed on axons projecting in the anterior commissure. Here we show that Derailed keeps these axons out of the posterior commissure by acting as a receptor for Wnt5, a member of the Wnt family of secreted signalling molecules. Our results reveal an unexpected role in axon guidance for a Wnt family member, and show that the Derailed receptor is an essential component of Wnt signalling in these guidance events.

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Figure 1: Schematic diagram of the wnt5 genomic region.
Figure 2: wnt5 suppression of Drl-mediated axon switching.
Figure 3: Wnt5 CNS expression.
Figure 4: wnt5 CNS phenotypes.
Figure 5: Drl binding to Wnt5.

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Acknowledgements

We thank G. Struhl, R. Nusse, E. Wilder, B. Dickson and the Bloomington Stock Center for stocks; L. Fradkin and J. Noordermeer for the Wnt5 antibody, stocks and for sharing results prior to publication; and G. Lemke, L. Santschi and M. Boyle for discussion and critical reading of the manuscript. This work was supported by an NRSA fellowship to M.K. and grants from the NIH to R.D.M. and J.B.T. R.D.M. is a member of the Cancer Institute of New Jersey.

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  1. Molecular Neurobiology Laboratory, Salk Institute for Biological Studies, PO Box 85800, San Diego, California, 92186, USA

    Shingo Yoshikawa, Randall D. McKinnon, Michelle Kokel & John B. Thomas

  2. Departments of Surgery/Molecular Genetics Microbiology, Robert Wood Johnson Medical School, 675 Hoes Lane, Piscataway, New Jersey, 08854, USA

    Randall D. McKinnon

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Correspondence to John B. Thomas.

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Yoshikawa, S., McKinnon, R., Kokel, M. et al. Wnt-mediated axon guidance via the Drosophila Derailed receptor. Nature 422, 583–588 (2003). https://doi.org/10.1038/nature01522

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