SPATIAL DIFFERENTIATION OF THE INTESTINAL EPITHELIUM - ANALYSIS OF ENTEROENDOCRINE CELLS CONTAINING IMMUNOREACTIVE SEROTONIN, SECRETIN, AND SUBSTANCE-P IN NORMAL AND TRANSGENIC MICE

The mammalian intestinal epithelium undergoes continuous and rapid renewal of its four principal terminally differentiated cell types. These cells arise from multipotent stem cells located at or near the base of the crypts of Lieberkuhn. The differentiation process is precisely organized along two spatial dimensions (axes) - from the crypt to the villus tip and from the duodenum to the colon. The enteroendocrine cell population provides a sensitive marker of the intestine's topologic differentiation. At least 15 different regionally distributed subsets have been described based on their principal neuroendocrine products. We have used immunocytochemical methods to characterize the spatial relationships of the serotonin-, secretin-, and substance P-containing enteroendocrine cell subsets in normal adult C57BL/6J x LT/Sv mice as well as in transgenic littermates that contain rat liver fatty acid-binding protein-human growth hormone fusion genes. Our results reveal precise spatial interrelationships between these populations and suggest a differentiation pathway that may involve the sequential expression of substance P, serotonin, and secretin.