Proper function of the nervous system requires the precise wiring of neuronal circuitry, which is established during development via mechanisms that guide cells to establish a correct identity, direct axons to navigate to and make synaptic connections with appropriate targets, and establish and maintain the function of synaptic circuits. Dysfunction of genes implicated in one or more of these processes has been linked to human neurological disorders with behavioral and cognitive manifestations. However, our understanding of how specific gene defects affect circuitry formation, function and in turn behavior remains fragmentary.

I have used zebrafish as a genetic model system to begin to address some aspects of this central question. I performed in vivo imaging and cellular analyses of the formation of a peripheral neural circuit, synapses between motor neurons and muscle fibers, called neuromuscular junctions. I then characterized two zebrafish mutants, identified from a small-scale genetic screen for neuromuscular synaptic defects, slytherin ( srn) and xavier (xav). Analyses of srn uncovered a previously underappreciated role for protein fucosylation in several aspects of neural development. Analyses of xav suggest critical roles for mitochondria during neural development. Given that the corresponding mutations in humans result in disorders with poorly explored neural defects, the molecular and cellular characterization of these mutants may shed light on our understanding of the neural and synaptic phenotypes in human patients.