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http://dx.doi.org/10.12717/DR.2019.23.4.305

Epithelial-Mesenchymal Interactions for the Development of Intestinal Villi  

Oh, Seunghoon (Dept. of Physiology, College of Medicine, Dankook University)
Yoo, Young Bok (Dept. of Anatomy, College of Medicine, Dankook University)
Publication Information
Development and Reproduction / v.23, no.4, 2019 , pp. 305-311 More about this Journal
Abstract
Small intestine has a structure called villi that increases the mucosal surface area for nutrient absorption. Intricate and tight epithelial-mesenchymal interactions are required for villi development. These interactions are regulated by signaling molecules, physical forces, and epithelial deformation. Signaling molecules include hedgehog (Hh), bone morphogenetic protein (BMP) and Wnt ligands. The Hh ligand is expressed from the epithelium and binds to the underlying mesenchymal cells, resulting in aggregation into mesenchymal clusters. The clusters express BMP and Wnt ligands to control its size and spacing between clusters. The clusters then form villi. Despite the fact that the villi formation is studied extensively, we do not have a complete understanding. In addition, the recent study shows there is a great relationship between the overexpression of the Hh signal and development of cancer in the gastrointestinal tract. Therefore, signaling between epithelial and mesenchymal cells and their physical interactions will be discussed on this review.
Keywords
Epithelial-mesenchymal interactions; Intestinal villi; Hh; BMP; Wnt; Development;
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1 Karlsson L, Lindahl P, Heath JK, Betsholtz C (2000) Abnormal gastrointestinal development in PDGF-A and PDGFR-(alpha) deficient mice implicates a novel mesenchymal structure with putative instructive properties in villus morphogenesis. Development 127:3457-3466.   DOI
2 Kolterud A, Grosse AS, Zacharias WJ, Walton KD, Kretovich KE, Madison BB, Waghray M, Ferris JE, Hu C, Merchant JL, Dlugosz AA, Kottmann AH, Gumucio DL (2009) Paracrine Hedgehog signaling in stomach and intestine: New roles for hedgehog in gastrointestinal patterning. Gastroenterology 137:618-628.   DOI
3 Korinek V, Barker N, Moerer P, Van Donselaar E, Huls G, Peters PJ, Clevers H (1998) Depletion of epithelial stem-cell compartments in the small intestine of mice lacking Tcf-4. Nat Genet 19:379-383.   DOI
4 Madison BB, Braunstein K, Kuizon E, Portman K, Qiao XT, Gumucio DL (2005) Epithelial hedgehog signals pattern the intestinal crypt-villus axis. Development 132:279-289.   DOI
5 Madison BB, McKenna LB, Dolson D, Epstein DJ, Kaestner KH (2009) FoxF1 and FoxL1 link hedgehog signaling and the control of epithelial proliferation in the developing stomach and intestine. J Biol Chem 284:5936-5944.   DOI
6 Mao J, Kim BM, Rajurkar M, Shivdasani RA, McMahon AP (2010) Hedgehog signaling controls mesenchymal growth in the developing mammalian digestive tract. Development 137:1721-1729.   DOI
7 Nigmatullina L, Norkin M, Dzama MM, Messner B, Sayols S, Soshnikova N (2017) Id2 controls specification of $Lgr5^+$ intestinal stem cell progenitors during gut development. EMBO J 36:869-885.   DOI
8 Ormestad M, Astorga J, Landgren H, Wang T, Johansson BR, Miura N, Carlsson P (2006) Foxf1 and Foxf2 control murine gut development by limiting mesenchymal Wnt signaling and promoting extracellular matrix production. Development 133:833-843.   DOI
9 Ramalho-Santos M, Melton DA, McMahon AP (2000) Hedgehog signals regulate multiple aspects of gastrointestinal development. Development 127:2763-2772.   DOI
10 Sato T, Vries RG, Snippert HJ, van de Wetering M, Barker N, Stange DE, van Es JH, Abo A, Kujala P, Peters PJ, Clevers H (2009) Single Lgr5 stem cells build crypt-villus structures in vitro without a mesenchymal niche. Nature 459:262-265.   DOI
11 Shyer AE, Tallinen T, Nerurkar NL, Wei Z, Gil ES, Kaplan DL, Tabin CJ, Mahadevan L (2013) Villification: How the gut gets its villi. Science 342:212-218.   DOI
12 Shyer AE, Huycke TR, Lee C, Mahadevan L, Tabin CJ (2015) Bending gradients: How the intestinal stem cell gets its home. Cell 161:569-580.   DOI
13 Theodosiou NA, Tabin CJ (2003) Wnt signaling during development of the gastrointestinal tract. Dev Biol 259:258-271.   DOI
14 Turing AM (1952) The chemical basis of morphogenesis. Phil Trans R Soc B Biol Sci 237:37-72.
15 Van de Wetering M, Sancho E, Verweij C, De Lau W, Oving I, Hurlstone A, Van der Horn K, Batlle E, Coudreuse D, Haramis AP, Tjon-Pon-Fong M, Moerer P, van den Born M, Soete G, Pals S, Eilers M, Medema R, Clevers H (2002) The beta-catenin/TCF-4 complex imposes a crypt progenitor phenotype on colorectal cancer cells. Cell 111:241-250.   DOI
16 Walton KD, Kolterud A, Czerwinski MJ, Bell MJ, Prakash A, Kushwaha J, Grosse AS, Schnell S, Gumucio DL (2012) Hedgehog-responsive mesenchymal clusters direct patterning and emergence of intestinal villi. Proc Natl Acad Sci USA 109:15817-15822.   DOI
17 Walton KD, Whidden M, Kolterud A, Shoffner SK, Czerwinski MJ, Kushwaha J, Parmar N, Chandhrasekhar D, Freddo AM, Schnell S, Gumucio DL (2016) Villification in the mouse: BMP signals control intestinal villus patterning. Development 143:427-436.   DOI
18 Wang S, Walton KD, Gumucio DL (2019) Signals and forces shaping organogenesis of the small intestine. In: Wellik DM (ed), Organ Development. Academic Press, New York, pp 31-66.
19 Yang H, Antony PA, Wildhaber BE, Teitelbaum DH (2004) Intestinal intraepithelial lymphocyte gamma delta-T cell-derived keratinocyte growth factor modulates epithelial growth in the mouse. J Immunol 172:4151-4158.   DOI
20 Wang S, Cebrian C, Schnell S, Gumucio DL (2018) Radial WNT5A-guided post-mitotic filopodial pathfinding is critical for midgut tube elongation. Dev Cell 46:173-188.   DOI
21 Berman DM, Karhadkar SS, Maitra A, Montes de Oca R, Gerstenblith MR, Briggs K, Parker AR, Shimada Y, Eshleman JR, Watkins DN, Beachy PA (2003) Widespread requirement for Hedgehog ligand stimulation in growth of digestive tract tumours. Nature 425:846-851.   DOI
22 Breathnach AS (1978) Development and differentiation of dermal cells in man. J Invest Dermatol 71:2-8.   DOI
23 Brittan M, Wright NA (2004) The gastrointestinal stem cell. Cell Prolif 37:35-53.   DOI
24 Cheng H, Leblond CP (1974) Origin, differentiation and renewal of the four main epithelial cell types in the mouse small intestine I. Columnar cell. Am J Anat 141:461-479.   DOI
25 Chin AM, Tsai YH, Finkbeiner SR, Nagy MS, Walker EM, Ethen NJ, Williams BO, Battle MA, Spence JR (2016) A dynamic WNT/beta-CATENIN signaling environment leads to WNT-independent and WNT-dependent proliferation of embryonic intestinal progenitor cells. Stem Cell Reports 7:826-839.   DOI
26 Clarke R (1967) On the constancy of the number of villi in the duodenum of the postembryonic domestic fowl. J Embryol Exp Morphol 17:131-138.
27 de Bakker BS, de Jong KH, Hagoort J, de Bree K, Besselink CT, de Kanter FE, Veldhuis T, Bais B, Schildmeijer R, Ruijter JM, Oostra RJ, Christoffels VM, Moorman AF (2016) An interactive three-dimensional digital atlas and quantitative database of human development. Science 354:aag0053.   DOI
28 Forrester JM (1972) The number of villi in rat's jejunum and ileum: Effect of normal growth, partial enterectomy, and tube feeding. J Anat 111:283-291.
29 Freddo AM, Shoffner SK, Shao Y, Taniguchi K, Grosse AS, Guysinger MN, Wang S, Rudraraju S, Margolis B, Garikipati K, Schnell S, Gumucio DL (2016) Coordination of signaling and tissue mechanics during morphogenesis of murine intestinal villi: A role for mitotic cell rounding. Integr Biol (Camb) 8:918-928.   DOI
30 Goulet O, Ruemmele F, Lacaille F, Colomb V (2004) Irreversible intestinal failure. J Pediatr Gastroenterol Nutr 38:250-269.   DOI
31 Helander HF, Fandriks L (2014) Surface area of the digestive tract: Revisited. Scand J Gastroenterol 49:681-689.   DOI
32 Kaestner KH, Silberg DG, Traber PG, Schutz G (1997) The mesenchymal winged helix transcription factor Fkh6 is required for the control of gastrointestinal proliferation and differentiation. Genes Dev 11:1583-1595.   DOI