During development, nervous system assembly is directed by a network of extracellular guidance cues that signal long- and short-range attraction and repulsion. Receptors expressed in the growth cones of axons respond to these cues, which can be secreted ligands or cell-surface proteins, leading to strengthening or reassembly of the cytoskeletal network of the growth cone. How these extracellular interactions translate into an intracellular response is yet an outstanding question in structural neurobiology, which we investigate in axonal and dendritic guidance in the developing spinal cord and olfactory system. First, the PVD neuron in Caenorhabditis elegans forms large dendritic arbors which are regulated by the quaternary Menorin complex. We demonstrate the ability to successfully purify component members from heterologous expression systems and form incomplete subcomplexes. In the mammalian spinal cord, the recently discovered NELL2-Robo3 complex has been demonstrated to mediate axon repulsion of commissural neurons during midline crossing. We present the structure of these proteins in complex and show that the EGF2-3 domains of NELL2 bind to the FN1 domain of Robo3. Mutation of the interface results in a decrease in binding affinity and a corresponding reduction in axon repulsion strength. Biophysical evidence collected using small-angle x-ray scattering (SAXS), multi-angle x-ray scattering (MALS), and analytical ultracentrifugation (AUC) suggests that Robo3 is a flexible, extended monomer in solution while NELL2 forms trimers which enhance axon repulsion. At high concentrations, NELL2-Robo3 complexes form gel-like condensates, which points to a signaling model where extended oligomers of Robo3 monomers are stabilized by NELL2 trimers. In the olfactory system, Kirrel2 and Kirrel3 regulate the coalescence of olfactory sensing neuron axons into distinct glomerular populations in the olfactory bulb. Our crystal structures reveal a mechanism of exclusive homodimer formation mediated by hydrogen bonding networks in Kirrel2 and hydrophobic interactions in Kirrel3. Furthermore, SAXS and AUC demonstrate that Kirrel2 and Kirrel3 form tip-to-tip dimers and lack additional binding sites that would enable cis-dimerization and extended oligomer formation. Ancestral sequence reconstructions of Kirrel family proteins highlight three residues that regulate the formation of homodimers through hydrophobic or hydrophilic interactions, suggesting that small changes in protein sequence were sufficient during evolution to expand the complexity of nervous system wiring. These three examples of neural wiring demonstrate the diversity of molecular interactions that mediate neurite guidance and its role in establishing complexity in the nervous system.