Nervous system–wide analysis of all C. elegans cadherins reveals neuron-specific functions across multiple anatomical scales

Differential expression of cell adhesion proteins is a hallmark of cell-type diversity across the animal kingdom. Gene family-wide characterization of their organismal expression and function is, however, lacking. Using genome-engineered reporter alleles, we established an atlas of expression of the entire set of 12 cadherin gene family members in the nematode Caenorhabditis elegans , revealing differential expression across neuronal classes, a dichotomy between broadly and narrowly expressed cadherins, and several context-dependent temporal transitions in expression across development. Engineered mutant null alleles of cadherins were analyzed for defects in morphology, behavior, neuronal soma positions, neurite neighborhood topology and fasciculation, and localization of synapses in many parts of the nervous system. This analysis revealed a restricted pattern of neuronal differentiation defects at discrete subsets of anatomical scales, including a novel role of cadherins in experience-dependent electrical synapse formation. In total, our analysis results in previously little explored perspectives on cadherin deployment and function.