MUTATIONS IN THE CAENORHABDITIS-ELEGANS UNC-4 GENE ALTER THE SYNAPTIC INPUT TO VENTRAL CORD MOTOR NEURONS

IDENTIFICATION of the genes orchestrating neurogenesis would greatly enhance our understanding of this process. Genes have been identified that specify neuron type (for example cut 1 and numb 2 in Drosophila and mec-3 in Caenorhabditis elegans 3) and process guidance (for example, unc-5, unc-6 and unc-40 in C. elegans 4 and the fas-1 gene of Drosophila 5). We sought genes defining synaptic specificity by identifying mutations that alter synaptic connectivity in the motor circuitry in the nematode C. elegans. We used electron microscopy of serial sections 6 to reconstruct the ventral nerve-cords of uncoordinated (unc) mutants 7,8 that have distinctive locomotory choreographies. Here we describe the phenotype of mutations in the unc-4 gene in which a locomotory defect is correlated with specific changes in synaptic input to a subset of the excitatory VA motor neurons, normally used in reverse locomotion. The circuitry alterations do not arise because of the inaccessibility of the appropriate synaptic partners, but are a consequence of changes in synaptic specificity. The VA motor neurons with altered synaptic inputs are all lineal sisters of VB motor neurons; the VA motor neurons without VB sisters have essentially the same synaptic inputs as in wild-type animals. The normal function of the wild-type allele of unc-4 may thus be to invoke the appropriate synaptic specificities to VA motor neurons produced in particular developmental contexts.