Although much is known about possible cellular mechanisms of neurite growth in metazoans, relatively little is known about how genes and gene products are involved in this process. This proposal is designed to obtain new information about the genetic and molecular control of neurite growth patterns in the nematode worm Caenorhabditis elegans. This basic work may eventually be relevant to the study and treatment of neurological diseases which afflict humans. The major aim of this proposal is to determine the nature of the axon growth determining mechanisms in C. elegans. This will be accomplished by characterizing existing stage-specific axon growth (wiring) mutants and by isolating additional axon growth mutants using a novel technique for staining and visualizing sensory neurons in live animals. These mutants offer a unique opportunity to study the nature of stage-specific signals for axon growth in an organism with an extremely simple nervous system. Serial EM reconstructions of sensory neurons in the mutants and wild type should reveal how many of the growth determining signals are cell specific (effecting the growth of one or a few classes of neurons) and how many are global (effecting the growth of many classes of neurons). Questions about the genetic control of synaptic interactions (which have been entirely characterized in the wild type) and about the genetic specification of putative axon growth controlling cells (e.g., pioneer neurons or cells producing diffusible extracellular signals) may also be resolved by these studies. The identification of monoclonal antibodies which bind to limited classes of neurons, as proposed here, would facilitate light microscopic identification and characterization of neuronal growth mutants in this organism. Eventually, mosaic analysis will be used to determine whether the axon growth signals identified by the mutants act intrinsically (within the defective cells) or extrinsically (via extracellular signals from other cells), and to identify the cell(s) responsible for the defects seen. Ultimately, techniques of molecular genetics will be used to characterize the genes and gene products of central importance to axon growth and guidance in this model metazoan organism.
