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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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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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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DOI: https://doi.org/10.1038/nn1415
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