The fax-1 nuclear hormone receptor regulates axon pathfinding and neurotransmitter expression

Specification of neuron identity requires the activation of a number of discrete developmental programs. Among these is pathway selection by growth cones: in order for a neuron's growth cone to respond appropriately to guidance cues presented by other cells or the extracellular matrix, the neuron must express genes to mediate the response. The fax-1 gene of C. elegans is required for pathfinding of axons that extend along the ventral nerve cord. We show that fax-1 is also required for pathfinding of axons in the nerve ring, the largest nerve bundle in the nematode, and for normal expression of FMRFamide-like neurotransmitters in the AVK interneurons. The fax-1 gene encodes a member of the superfamily of nuclear hormone receptors and has a DNA-binding domain related to the human PNR and Drosophila Tailless proteins. We observe fax-1 expression in embryonic neurons, including the AVK interneurons, just prior to axon extension, but after neurogenesis. These data suggest that fax-1 coordinately regulates the transcription of genes that function in the selection of axon pathways, neurotransmitter expression and, perhaps, other aspects of the specification of neuron identity.