Our research is directed toward discovering the molecular mechanisms that control development of the enteric nervous system (ENS). The ENS is a complex network of neurons and glia within the wall of the gut. This neuronal network controls intestinal motility, responds to sensory stimuli from the gut, and regulates mucosal secretion and blood flow. The cells that give rise to the ENS originate in the vagal and sacral neural crest. These pluripotent cells migrate into the gut starting at E9 in the mouse, and have reached the distal gut by E14. As the neural crest cells migrate, they also actively proliferate to form enough cells to populate the ENS. Enteric neural crest precursors give rise to both enteric neurons and glia. Once committed to the neuronal lineage, these cells differentiate into a wide variety of neuronal subtypes that are required to act in a coordinated fashion to control intestinal function. While much has been learned over the past few years about the molecular machinery that controls ENS morphogenesis, many aspects of the development of the ENS are not yet understood. The laboratory has three primary areas of focus in model systems. First, we are using mutant mouse models to understand the role of Ret signaling in ENS development. Second, we are exploring the effect of retinoids (biologically active forms of Vitamin A) on ENS development. Finally, we are using a variety of molecular and genetic approaches to identify novel genes that control specific aspects of enteric neural crest development.
These ongoing studies in model systems have led to new ideas about the pathogenesis of human intestinal motility disorders like Hirschsprung disease and other neural crest associated disorders. We are particularly intesested in identifying environmental risk factors for human birth defects so that the occurrence of these disorders can be reduced. We focus on the role of maternal health, medications, and nutrition as modulators for neural crest associated birth defects. For this reason we are now pursuing human translational research studies.
Robert O. Heuckeroth M.D., Ph.D.
660 S. Euclid Avenue
Campus Box 8208
St. Louis, MO 63110