Control of Synaptic Connectivity by a Network of Drosophila IgSF Cell Surface Proteins

We have defined a network of interacting Drosophila cell surface proteins in which a 21-member IgSF subfamily, the Dprs, binds to a nine-member subfamily, the DIPs. The structural basis of the Dpr-DIP interaction code appears to be dictated by shape complementarity within the Dpr-DIP binding interface. Each of the six dpr and DIP genes examined here is expressed by a unique subset of larval and pupal neurons. In the neuromuscular system, interactions between Dpr11 and DIP-γ affect presynaptic terminal development, trophic factor responses, and neurotransmission. In the visual system, dpr11 is selectively expressed by R7 photoreceptors that use Rh4 opsin (yR7s). Their primary synaptic targets, Dm8 amacrine neurons, express DIP-γ. In dpr11 or DIP-γ mutants, yR7 terminals extend beyond their normal termination zones in layer M6 of the medulla. DIP-γ is also required for Dm8 survival or differentiation. Our findings suggest that Dpr-DIP interactions are important determinants of synaptic connectivity. [Display omitted] •Twenty-one Dpr and nine DIP surface proteins form a complex interaction network in Drosophila•Dprs and DIPs interact via a hydrophobic interface between their first Ig domains•Each Dpr and DIP is expressed by a unique small subset of larval and pupal neurons•Loss of Dpr-DIP interactions affects synaptic connectivity in the brain A network of 30 interacting cell surface proteins in Drosophila called Dprs and DIPs are expressed on subsets of larval and pupal neurons. The complexes they form resemble neural and immune cell adhesion complexes, and their interactions are required for normal formation of synaptic connections between a photoreceptor and a brain interneuron.