The enteric nervous system controls motility. Enteric neurons produce a variety of neurotransmitters and form a neuronal network in the gut. The long-term objective of this research is to elucidate the mechanisms which regulate the development of these neuronal transmitter phenotypes and the formation of the enteric neuronal circuitry. Evidence indicates that the environment in general and the gut in particular can influence the expression of peptide transmitter phenotypes. The goal of this research is to find the components in the gut environment that are instructive to the neural crest cells which are the precursors of enteric neurons. Previous work from Dr. Epstein's laboratory has indicated that instruction is best observed in intact gut. Studies will be carried out to describe systematically the formation of enteric ganglia and the differentiation of enteric neurons in order to pinpoint conditions critical to these processes. Immunostaining and radioautography will be used to characterize the phenotypes and birthdates of cells in ganglia from intact gut. Studies will also be carried out to determine the number, location, and phenotypes of the descendants of single neural crest cells injected into pieces of isolated chick gut grown on chorioallantoic membrane of chick hosts. These cells and their descendants will be detected by either quail-specific antisera or by the presence of a histochemical marker for beta-galactosidase. Quail cells will have been previously transfected with a retro- virus carrying the beta-galactosidase gene. The single cell experiments will indicate if patterns of expression can be detected in cells placed in the intact gut environment. The knowledge obtained will be useful in designing future experiments to elucidate the mechanisms which regulate the phenotypic expression. Basic information about the development and organization of the enteric neuronal circuitry will help in understanding the reasons for defects in gut motility as manifested by conditions such as pseudo-obstruction.
