Abstract
The gut endocrine gene, neurotensin (NT/N), isexpressed in a strict temporally and spatially specificpattern. Utilizing a sensitive reversetranscription-polymerase chain reaction procedure, weanalyzed foregut and midgut organs for NT/N expression,determined the earliest apparent time point that NT/N isexpressed in the gastrointestinal tract and compared thetemporal relationship of NT/N with other genes. NT/N expression was detected in thefetal and early postnatal stomach. In the small bowel,NT/N was expressed at the earliest fetal time (14 days)that the small bowel could be reliably delineated from other gut organs; in contrast, expressionof sucrase-isomaltase was only apparent at 28 days afterbirth. NT/N was expressed in the fetal (12, 14 and 16days) liver and then again on days 3 and 7 after birth; however, NT/N was detected only in thefetal (14 and 16 days) pancreas. Finally, NT/Nexpression was first detected at ~12 days gestation inthe primitive foregut and midgut, thus occurringsignificantly earlier than actual intestinalcytodifferentiation. NT/N is widely expressed in thegastrointestinal tract during fetal development,suggesting the presence of a shared ancestral stem cell;NT/N expression is then restricted to the small bowel of theadult. The determination of the cellular factorsregulating the expression of NT/N will provide a betterunderstanding of the mechanisms responsible for the strict patterning of gene expression in thegastrointestinal tract and possibly gutdifferentiation.
Similar content being viewed by others
REFERENCES
Moore KL, Persaud TVN: Thedigestivesystem. In TheDe-veloping Human: Clinically Oriented Embryology. KL Moore, TVN Persaud (eds). Philadelphia, WB Saunders, 1993, pp 237–264
Kedinger M: Growth and development of intestinal mucosa. In Medical IntelligenceUnit: Small Bowel EnterocyteCulture and Transplantation. FC Campbell (ed). Austin, RG Landes Company, 1994, pp 1–31
Dauca M, Bouziges F, Colin S, Kedinger M, Keller J-M, Schilt J, Simon-Assmann P, Haffen K: Development of thevertebrate small intestineand mechanisms of cell differentiation. Int J Dev Biol 34:205–218, 1990
Klein RM, McKenzie JC: Theroleof cell renewal in the ontogeny of theintestine. I. Cell proliferation patterns in adult, fetal and neonatal intestine. J Pediatr Gastroenterol Nutr 2:10–43, 1983
Mathan M, Moxey PC, Trier JS: Morphogenesis of fetal rat duodenal villi. Am J Anat 146:73–92, 1976
Klein RM: Small intestinal cell proliferation during development. In Human Gastrointestinal Development. ELebenthal (ed). New York, Raven Press, 1989, pp 367–392
Reinecke M: Neurotensin. Immunohistochemical localization in central and peripheral nervous system and in endocrinecells and its functional roleas neurotransmitter and endocrinehormone. Prog Histochem Cytochem 16:1–172, 1985
Andersson S, Rosell S, Hjelmquist U, Chang D, Folkers K: Inhibition of gastric and intestinal motor activity in dogs by (gln4) neurotensin. Acta Physiol Scand 100:231–235, 1977
Baca I, Feurle GE, Schwab A, Mittmann U, Knauf W, Lehnert T: Effect of neurotensin on exocrinepancreatic secretion in dogs. Digestion 23:174–183, 1982
Chung DH, Evers BM, Shimoda I, Townsend CM Jr, Rajaraman S, Thompson JC: Effect of neurotensin on gut mucosal growth in rats with jejunal and ileal Thiry-Vella fistulas. Gastroenterology 103:1254–1259, 1992
Feurle GE, Muller B, Rix E: Neurotensin induces hyperplasia of thepancreas and growth of thegastric antrum in rats. Gut 28( suppl S1):19–23, 1987
Wood JG, Hoang HD, Bussjaeger LJ, Solomon TE: Neurotensin stimulates growth of small intestinein rats. Am J Physiol 255:G813–G817, 1988
Evers BM, Ehrenfried JA, Wang X, Townsend CM Jr, Thompson JC: Temporal-specific and spatial-specific patterns of neurotensin geneexpression in thesmall bowel. Am J Physiol 267:G875–G882, 1994
Evers BM, Rajaraman S, Chung DH, Townsend CM Jr, Wang X, Graves K, Thompson JC: Differential expression of the neurotensin genein thedeveloping rat and human gastrointestinal tract. Am J Physiol 265:G482–G490, 1993
Ehrenfried JA, Zhou Z, Thompson JC, Evers BM: Expression of theneurotensin genein fetal human liver and fibrolamellar carcinoma. Ann Surg 220:484–491, 1994
Evers BM, Rajaraman S, Chung DH, Townsend CM Jr, Wang X, Graves K, Thompson JC: Developmental expression of the neurotensin genein therat liver. Ann Surg 218:183–188, 1993
Blackburn AM, Bryant MG, Adrian TE, Bloom SR: Pancreatic tumors produceneurotensin. J Clin Endocrinol Metab 52:820–822, 1981
Carraway RE, Mitra SP, Feurle GE, Hacki WH: Presenceof neurotensin and neuromedin-N within a common precursor from a human pancreatic neuroendocrinetumor. J Clin Endocrinol Metab 66:1323–1328, 1988
Theodorsson-Norheim E, Oè berg K, Rosell S, Bostroè m H: Neurotensinlikeimmunoreactivity in plasma and tumor tissue from patients with endocrinetumors of thepancreas and gut. Gastroenterology 85:881–889, 1983
Gittes GK, Rutter WJ: Onset of cell-specific geneexpression in thedeveloping mousepancreas. Proc Natl Acad Sci USA 89:1128–1132, 1992
Chomczynski P, Sacchi N: Single-step method of RNA isolation by acid guanidinium thiocyanate–phenol–chloroform extraction. Anal Biochem 162:156–159, 1987
Mehra M: RNA isolation from cells and tissues. In A Laboratory Guideto RNA: Isolation, Analysis, and Synthesis. PA Krieg (ed). New York, Wiley-Liss, 1996, pp 1–20
Henning SJ: Ontogeny of enzymes in thesmall intestine. Annu Rev Physiol 47:231–245, 1985
Nanthakumar NN, Henning SJ: Ontogeny of sucrase– isomaltasegeneexpression in rat intestine: Responsiveness to glucocorticoids. Am J Physiol 264:G306–G311, 1993
Traber PG: Regulation of sucrase-isomaltasegeneexpression along thecrypt–villus axis of rat small intestine. Biochem Biophys Res Commun 173:765–773, 1990
Iwai K, Ishikura H, Inoue T, Yoshiki T: A caseof AFP-positive pancreas papi llary carcinoma suggestiveof a primitive endoderm phenotype. Acta Pathol Jpn 43:434–439, 1993
Shinagawa T, Tadokoro M, Maeyama S, Maeda C, Yamaguchi S, Morohoshi T, Ishikawa E: Alpha fetoprotein-producing acinar cell carcinoma of thepancreas showing multiplelines of differentiation. Virchows Arch 426:419–423, 1995
Panduro A, Shalaby F, Shafritz DA: Changing pattern of transcriptional and posttranscriptional control of liver-specific geneexpression during rat development. Genes Dev 1:1172–1182, 1987
Sigal SH, Brill S, Fiorino AS, Reid LM: Theliver as a stem cell and lineagesystem. Am J Physiol 263:G139–G148, 1992
Carraway RE, Mitra SP, Evers BM, Townsend CM Jr: BON cells display theintestinal pattern of neurotensin/neuromedin N precursor processing. Regul Pept 53:17–29, 1994
Tateishi K, Funakoshi A, Kitayama N, Matsuoka Y: Secretion of neurotensin from a human pancreatic islet cell carcinoma cell line(QGP-1N). Regul Pept 49:119–123, 1993
Le Douarin NB: On theorigin of pancreatic endocrinecells. Cell 53:169–171, 1988
Evers BM, Wang X, Zhou Z, Townsend CM Jr, McNeil GP, Dobner PR: Characterization of promoter elements required for cell-specific expression of theneurotensin/neuromedin N genein a human endocrinecell line. Mol Cell Biol 15:3870–3881, 1995
Simon TC, Gordon JI: Intestinal epithelial cell differentiation: New insights from mice,flies and nematodes. Curr Opin Genet Dev 5:577–586, 1995
Traber PG, Silberg DG: Intestine-specific genetranscription. Annu Rev Physiol 58:275–297, 1996
Kafri T, Ariel M, Brandeis M, Shemer R, Urven L, McCarrey J, Cedar H, Razin A: Developmental pattern of gene-specific DNA methylation in themouseembryo and germ line. Genes Dev 6:705–714, 1992
Tate PH, Bird AP: Effects of DNA methylation on DNAbinding proteins and geneexpression. Curr Opin Genet Dev 3:226–231, 1993
Dong Z, Wang X, Zhao Q, Townsend CM Jr, Evers BM: DNA methylation contributes to expression of thehuman neurotensin/ neuromedin N gene. Am J Physiol 274:G535–G543, 1998
Cheng H, Le Blond CP: Origin, differentiation and renewal of thefour main epithelial cell types in themousesmall intestine. V. Unitarian theory of theorigin of thefour epithelial cell types. Am J Anat 141:537–561, 1974
Rights and permissions
About this article
Cite this article
Wang, XM., Evers, B.M. Characterization of Early Developmental Pattern of Expression of Neurotensin/Neuromedin N Gene in Foregut and Midgut. Dig Dis Sci 44, 33–40 (1999). https://doi.org/10.1023/A:1026637730050
Issue Date:
DOI: https://doi.org/10.1023/A:1026637730050