The emergence of multicellular organisms coincided with the expansion of families of cell adhesion proteins and other cell surface molecules that mediate intercellular communication. Among the most remarkable outcomes of the transition to multicellularity was the development of specialized biological structures, such as complex nervous systems. In animals, neural circuits coordinate many critical functions, from sensory perception and processing to endocrine homeostasis, motor functions, and behavior. Given the nervous system's integrative role in nearly all vital aspects of organisms' function, understanding its development and function in health and disease is paramount. Research over the past few decades strongly suggests that the assembly of intricate and stereotyped nervous systems is guided by Cell Surface Proteins (CSPs) acting as identity markers for individual neuronal cells and cells interacting directly with the nervous system. However, we still do not fully understand the molecular principles for how the complexity and accuracy of neural circuits architecture is achieved. To gain deeper insight into the mechanisms for how cell surface proteins and their interactions contribute to neural circuit assembly, we focused on studying aspects of the biology of Dprs and DIPs – two interacting families of neural wiring receptors that mediate connectivity in various parts of the fruit fly nervous system. Dprs and DIPs are cell adhesion molecules that lack intracellular regions that could serve as signaling motifs. Our research revealed that many of these proteins are tethered to the plasma membrane by GPI anchors, precluding their direct signaling into the cell's interior and suggesting the need for co-receptors' action for synapse assembly and function. We also investigated the interplay of Dprs and DIPs with the BMP pathway, discovering that they directly interact with soluble antagonists of BMP signaling, which can have consequences for synapse growth at the fly neuromuscular junction. Additionally, we studied the role of cDIP, a soluble protein that binds to many Dprs and DIPs. We determined that cDIP can disrupt Dpr-DIP-mediated cell adhesion, which suggests its potential function as a negative regulator of synapse formation. The work presented here provides new insights into Dpr/DIP signaling mechanisms and regulation of the Dpr-DIP interactome. One of the major obstacles to a complete understanding of nervous system wiring processes is the gaps in relevant Protein-Protein Interaction (PPI) maps. Many molecules implicated in nervous system development and function remain orphan. To add to the knowledge of current PPI networks, we conducted the most comprehensive to-date interaction screen of extracellular molecules of C. elegans, a key model organism for studying neurodevelopment. We revealed 159 novel PPIs, uncovering new binding partners for the worm's Dpr and DIP proteins, ZIG-8 and RIG-5, and previously unknown connections between canonical axon guidance molecules. We also discovered soluble high-affinity binders for the worm's insulins and new ligands for conserved RTK receptors, including the worm's FGFR homolog. The findings open new avenues for studying nervous system wiring and other aspects of C. elegans biology.