Given the magnitude of the neuronal population and the degree of neural connectivity, the intricate nature of the human nervous system is undeniable. How do neurons reach their proper targets in a highly complex and dynamic environment? Despite their importance, only a small number of molecules have been shown to create neural circuits or specify synapse locations. My work aims to explore and clarify the mechanisms behind synapse formation and development, addressing crucial gaps in our understanding. Chapter 1 reviews our current knowledge regarding the development and wiring of the nervous system. Cell-surface receptors bind to extracellular guidance cues, directing neurons to their intended targets. These cues create intracellular signaling responses, resulting in cytoskeleton remodeling and translocation of the growth cone. The emphasis on commissural axonal guidance at the central midline and motor axon pathfinding supports later Chapters 2 and 3. Chapter 2 focuses on repulsive Netrin guidance complexes. The extracellular cue UNC-6/Netrin regulates a variety of biological functions, including axon guidance, cell morphology, axon branching, and cell adhesion, by binding to cell-surface receptors. As a result, there is a strong disease association with UNC-6/Netrins, implicated in neurological disorders as well as cancer, cardiovascular disease, and diabetes. My work characterizes the poorly understood interaction between UNC-6/Netrin and its repulsive axon guidance receptor UNC-5, elucidating the molecular mechanism of repulsive axon signaling and UNC-6/Netrin-dependent cell survival, valuable information for the design and creation of therapeutic agents to treat Netrin-associated diseases. Chapter 3 discusses the Beaten Path (Beat)-Sidestep (Side) interactome. This network of cell surface receptors is combinatorically expressed and can act as molecular identity tags on Beat-expressing motor neurons and their Side-expressing sensory neuron or muscle cell partners. Beat-Side binding influences axon growth, defasciculation, and synaptic formation. This neuronal Drosophila melanogaster protein family serves as a model to investigate the development of neuromuscular junctions and motor axon pathfinding. My work presents the first known Beat-Side complex structure, giving key structural and mechanistic details of how these proteins interact.