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 Lieberkühn. 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.
Department of Pathology, Washington University School of Medicine, Saint Louis, MO 63110.
K A
KA
Roth
J I
JI
Gordon
D000818:Animals; D002352:Carrier Proteins / Q000032:analysis / Q000235:genetics; D004847:Epithelial Cells; D000071438:Fatty Acid-Binding Protein 7; D050556:Fatty Acid-Binding Proteins; D005455:Fluorescent Antibody Technique; D013006:Growth Hormone / Q000032:analysis / Q000235:genetics; D006801:Humans; D007421:Intestine, Small / Q000033:anatomy & histology* / Q000166:cytology; D008099:Liver / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL / Q000378:metabolism; D008822:Mice, Transgenic / Q000378:metabolism*; D008871:Microvilli / Q000648:ultrastructure; D009130:Muscle, Smooth / Q000033:anatomy & histology / Q000166:cytology; D009363:Neoplasm Proteins; D009419:Nerve Tissue Proteins; D051381:Rats; D011993:Recombinant Fusion Proteins / Q000032:analysis; D012633:Secretin / Q000032:analysis*; D012701:Serotonin / Q000032:analysis*; D013373:Substance P / Q000032:analysis*; D025521:Tumor Suppressor Proteins
D002352:Carrier Proteins; C107608:FABP7 protein, human; C082667:Fabp5 protein, mouse; C086936:Fabp7 protein, mouse; C490174:Fabp7 protein, rat; D000071438:Fatty Acid-Binding Protein 7; D050556:Fatty Acid-Binding Proteins; D009363:Neoplasm Proteins; D009419:Nerve Tissue Proteins; D011993:Recombinant Fusion Proteins; D025521:Tumor Suppressor Proteins; D012633:Secretin; D012701:Serotonin; D013373:Substance P; D013006:Growth Hormone