Transsynaptic interactions between IgSF proteins DIP-α and Dpr10 are required for motor neuron targeting specificity
The Drosophila larval neuromuscular system provides an ideal context in which to study synaptic partner choice, because it contains a small number of pre- and postsynaptic cells connected in an invariant pattern. The discovery of interactions between two subfamilies of IgSF cell surface proteins, the Dprs and the DIPs, provided new candidates for cellular labels controlling synaptic specificity. Here we show that DIP-α is expressed by two identified motor neurons, while its binding partner Dpr10 is expressed by postsynaptic muscle targets. Removal of either DIP-α or Dpr10 results in loss of specific axonal branches and NMJs formed by one motor neuron, MNISN-1s, while other branches of the MNISN-1s axon develop normally. The temporal and spatial expression pattern of dpr10 correlates with muscle innervation by MNISN-1s during embryonic development. We propose a model whereby DIP-α and Dpr10 on opposing synaptic partners interact with each other to generate proper motor neuron connectivity.
© 2019, Ashley et al. This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited. Received: October 9, 2018; Accepted: January 31, 2019; Accepted Manuscript published: February 4, 2019. We thank Larry Zipursky for sharing unpublished dpr10 and DIP-α CRISPR and UAS transgenic lines and Hugo Bellen for dpr6-T2A-GAL4, dpr10-T2A-GAL4, and DIP-α-T2A-GAL4. Transgenic UAS-dpr10-RNAi stock was obtained from the Vienna Drosophila Resource Center (VDRC, www.vdrc.at). Stocks obtained from the Bloomington Drosophila Stock Center (NIH P40OD018537) were used in this study. The monoclonal antibodies, 4F3, 1D4 developed by Goodman, C. (University of California, Berkeley) were obtained from the Developmental Studies Hybridoma Bank, created by the NICHD of the NIH and maintained at The University of Iowa, Department of Biology, Iowa City, IA 52242. We thank Ellie Heckscher, Maria Plutarco, Larry Zipursky, Richard Mann, and Lalanti Venkatasubramanian for helpful discussions and comments. This work was supported by National Institutes of Health Grants K01 NS102342 (to RAC), R01 NS096509 (to KZ), R01 NS097161 (subcontract to KZ from Engin Özkan), and T32 GM007183 (to ML-R), and funding from the University of Chicago BSD Office of Diversity and Inclusion (to RAC) and the Grossman Institute for Neuroscience, Quantitative Biology and Human Behavior (to RAC). The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication. The authors declare no competing interests. Data availability: All data generated or analysed during this study are included in the manuscript and supporting files.
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