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Drosophila N-cadherin mediates an attractive interaction between photoreceptor axons and their targets

Nature Neuroscience volume 8, pages 443–450 (2005)Cite this article

Abstract

Classical cadherins have been proposed to mediate interactions between pre- and postsynaptic cells that are necessary for synapse formation. We provide the first direct, genetic evidence in favor of this model by examining the role of N-cadherin in controlling the pattern of synaptic connections made by photoreceptor axons in Drosophila. N-cadherin is required in both individual photoreceptors and their target neurons for photoreceptor axon extension. Cell-by-cell reconstruction of wild-type photoreceptor axons extending within mosaic patches of mutant target cells shows that N-cadherin mediates attractive interactions between photoreceptors and their targets. This interaction is not limited to those cells that will become the synaptic partners of photoreceptors. Multiple N-cadherin isoforms are produced, but single isoforms can substitute for endogenous N-cadherin activity. We propose that N-cadherin mediates a homophilic, attractive interaction between photoreceptor growth cones and their targets that precedes synaptic partner choice.

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Figure 1: N-cadherin is the only classical cadherin involved in R-cell target selection.
Figure 2: Single-cell MARCM analysis of N-cadherin function in R cells.
Figure 3: A single N-cadherin isoform can rescue extension in all R-cell subtypes.
Figure 4: N-cadherin function is required in lamina neurons for cartridge assembly.
Figure 5: N-cadherin function is required in the target column, not the column of origin.
Figure 6: R-cell extension depends on the number of mutant lamina neurons in the target cartridge.
Figure 7: N-cadherin's role in R-cell extension is distributed among lamina neuron subtypes within the target column.

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Acknowledgements

The authors thank H.-T. Zhu and L. Luo for their generous donation of transgenes and stocks, C.-H. Lee and S.L. Zipursky for sharing reagents and for communicating results before publication, and T. Uemura for contributing his N-cadherin and E-cadherin antibodies to our work. We also thank J. Hatzidakis and B. Baker for their assistance with X-ray mutagenesis. L. Luo, J. Nelson, A. Katsov, M. Velez, K.-M. Choe, K. Clark, J. Mast and P.-L. Chen gave helpful comments on the manuscript. This work was supported, in part, by R01 EY015231-01A1 (T.R.C.). T.R.C. is a Sloan Fellow, a Searle Scholar and a recipient of a Burroughs-Wellcome Career Development Award.

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Authors and Affiliations

  1. Department of Neurobiology, 299 W. Campus Drive, Stanford University, Stanford, 94305, California, USA

    Saurabh Prakash & Thomas R Clandinin

  2. Department of Biological Sciences, University of Iowa, Iowa City, 52242, Iowa, USA

    Jason C Caldwell & Daniel F Eberl

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Correspondence to Thomas R Clandinin.

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Prakash, S., Caldwell, J., Eberl, D. et al. Drosophila N-cadherin mediates an attractive interaction between photoreceptor axons and their targets. Nat Neurosci 8, 443–450 (2005). https://doi.org/10.1038/nn1415

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