Michael D. Gershon, M.D.
Professor and Chairman
Organization and development of the enteric nervous system
Our research is focused on the enteric nervous system (ENS), the intrinsic innervation of the bowel. This is the only part of the peripheral nervous system that is capable of mediating reflex behavior in the absence of input from the brain or spinal cord. Our goals are to understand the organization of the two neural plexuses that comprise the ENS, and to determine how enteric microcircuits and the activity of individual neurons within these circuits control the primitive motile, secretory, and absorptive behaviors of the gut. We have devised novel techniques to study enteric microcircuits. In addition to electrophysiology, these include optical imaging techniques with probes that permit neuronal activity to be assessed and neuronal connections to be identified. We also study the cellular biology and function of serotonin in initiating enteric reflexes and signaling to the brain. These studies include the analysis of the behavior of the gut in transgenic mice that lack individual subtypes of serotonin receptor and/or the transporter molecule that is primarily responsible for the inactivation of serotonin within the bowel.
In additon to studies of the adult ENS, we are investigating its development. The ENS is known to be derived from precursors that migrate to the gut from the neural crest. We are currently identifying the molecular signals (guidance molecules and growth factors) utilized by to migrate correctly from their neural crest origin to their final destinations in the bowel, to stop migrating when they reach these destinations, and what microenvironmental cues help to influence the phenotypic expression of neural and glial precursors within the ENS. This work involves tissue and organ culture, the construction of chick-quail interspecies chimeras, and work on the molecular basis of a defect in a mutant strain of mouse that causes a segment of bowel not to be colonized by crest-derived precursors.
Selected publicationsChalazonitis, A., Pham, T.D., Rothman, T.P., DiStefano, P.S., Bothwell, M., Blair-Flynn, J., Tessarollo, L., and Gershon, M.D. 2001. Neurotrophin-3 is required for the survival/differentiation of subsets of developing enteric neurons. J.Neurosci., 21(15) 5620-5636.
Pothos EN, Larsen KE, Krantz DE, Liu Y, Haycock JW, Setlik W, Gershon MD, Edwards RH, Sulzer D. 2000. Synaptic vesicle transporter expression regulates vesicle phenotype and quantal size. J Neurosci.. 20(19):7297-306.
Pan H, Gershon MD. 2000. Activation of intrinsic afferent pathways in submucosal ganglia of the guinea pig small intestine. J Neurosci. 20(9):3295-309.
Wu JJ, Rothman TP, Gershon MD. 2000. Development of the interstitial cell of Cajal: origin, kit dependence and neuronal and nonneuronal sources of kit ligand. J Neurosci Res. 59(3):384-401.
Liu K, Hsiung S, Adlersberg M, Sacktor T, Gershon MD, Tamir H. 2000. Ca(2+)-evoked serotonin secretion by parafollicular cells: roles in signal transduction of phosphatidylinositol 3'-kinase, and the gamma and zeta isoforms of protein kinase C. J Neurosci. 20(4):1365-73.