Mutations in the Caenorhabditis elegans unc–4 gene alter the synaptic input to ventral cord motor neurons

Abstract

IDENTIFICATION of the genes orchestrating neurogenesis would greatly enhance our understanding of this process. Genes have been identified that specify neuron type (for examplecut¹ and numb² inDrosophila andmec-3 in Caenorhabditis elegans³) and process guidance (for example,unc-5,unc-6 andunc-40 inC. elegans⁴and thefas-1 gene of Drosophila⁵). We sought genes defining synaptic specificity by identifying mutations that alter synaptic connectivity in the motor circuitry in the nematodeC.elegans. We used electron microscopy of serial sections⁶ to recon-struct the ventral nerve-cords of uncoordinated (unc) mutants^7,8 that have distinctive locomotory choreographies. Here we describe the phenotype of mutations in theunc-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.