Abstract
Integral analysis of the development of the epithelium, mesenchyme, and smooth muscle cell (SMC) layers, i.e., the inner circular (IC) and outer longitudinal layers, as well as their relation with the mesentery is necessary to understand macroscopic gut development. We here focused on the proximal duodenum with the characteristic “C”-shaped loop and analyzed the duodenum down to the duodenojejunal flexure in C57BL/6J mouse embryos at embryonic days (E) 13.5, 15.5, and 17.5 by histomorphometric analysis. We examined the angle of the axis of the epithelial lumen, which was oval at E13.5 against the mesentery, along with the epithelial cell nuclear shape, the adjacent mesenchymal cell density in relation to the epithelial lumen axis, and the development of SMC layers. The luminal axis of the oval epithelial lumen at E13.5 rotated clockwise against the mesentery in the proximal duodenum. The shape of epithelial nuclei was longer and thinner at the long axis but shorter and broader at the short axis, whereas mesenchymal density was significantly lower in the area on the luminal long axis than that on the short axis. The number of SMC layers in the IC at E13.5, E15.5, and E17.5 showed a regional difference in relation to the mesentery, but no regional difference along the long axis of the duodenum. These findings suggest that epithelial lumen winding against the mesentery and the corresponding changes in the epithelial cell shape and surrounding mesenchymal density may be involved in the formation of the “C” loop of the proximal duodenum.
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References
Chevalier NR, De Witte TM, Cornelissen AJM, Dufour S, Proux-Gillardeaux V, Asnacios A (2018) Mechanical tension drives elongational growth of the embryonic gut. Sci Rep 8:5995
Davis NM, Kurpios NA, Sun X, Gros J, Martin JF, Tabin CJ (2008) The chirality of gut rotation derives from left-right asymmetric changes in the architecture of the dorsal mesentery. Dev Cell 15:134–145
Getachew D, Kaneda R, Saeki Y, Matsumoto A, Otani H (2020) Morphologic changes in the cytoskeleton and adhesion apparatus during the conversion from pseudostratified single columnar to stratified squamous epithelium in the developing mouse esophagus. Congenit Anom (Kyoto). https://doi.org/10.1111/cga.12389
Jahan E, Rafiq AM, Matsumoto A, Jahan N, Otani H (2020) Development of the smooth muscle layer in the ileum of mouse embryos. Anat Sci Int. https://doi.org/10.1007/s12565-020-00565-9
Jayewickreme CD, Shivdasani RA (2015) Control of stomach smooth muscle development and intestinal rotation by transcription factor BARX1. Dev Biol 405:21–32
Kaneda R, Saeki Y, Getachew D, Matsumoto A, Furuya M, Ogawa N, Motoya T, Rafiq AM, Jahan E, Udagawa J, Hashimoto R, Otani H (2018) Interkinetic nuclear migration in the tracheal and esophageal epithelia of the mouse embryo: Possible implications for tracheo-esophageal anomalies. Congenit Anom (Kyoto) 58:62–70
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
Kishimoto K, Tamura M, Nishita M, Minami Y, Yamaoka A, Abe T, Shigeta M, Morimoto M (2018) Synchronized mesenchymal cell polarization and differentiation shape the formation of the murine trachea and esophagus. Nat Commun 9:2816
Kluth D, Jaeschke-Melli S, Fiegel H (2003) The embryology of gut rotation. Semin Pediatr Surg 12:275–279
Kurpios NA, Iba EM, Davis NM, Lui W, Katz T, Martin JF, Izpis A, Belmonte JC, Tabin CJ (2008) The direction of gut looping is established by changes in the extracellular matrix and in cell:cell adhesion. Proc Natl Acad Sci USA 105:8499–8506
Le Guen L, Marchal S, Faure S, De Santa BP (2015) Mesenchymal-epithelial interactions during digestive tract development and epithelial stem cell regeneration. Cell Mol Life Sci 72:3883–3896
Matsumoto A, Hashimoto K, Yoshioka T, Otani H (2002) Occlusion and subsequent re-canalization in early duodenal development of human embryos: integrated organogenesis and histogenesis through a possible epithelial-mesenchymal interaction. Anat Embryol (Berl) 205:53–65
McHugh KM (1995) Molecular analysis of smooth muscle development in the mouse. Dev Dyn 204:278–290
Nitta T, Ogawa N, Getachew D, Matsumoto A, Udagawa J, Otani H (2017) Spatiotemporal difference in the mode of interkinetic nuclear migration in the mouse embryonic intestinal epithelium. Shimane J Med Sci 33:85
Onouchi S, Ichii O, Otsuka S, Hashimoto Y, Kon Y (2013) Analysis of duodenojejunal flexure formation in mice: implications for understanding the genetic basis for gastrointestinal morphology in mammals. J Anat 223:385–398
Onouchi S, Ichii O, Otsuka-Kanazawa S, Kon Y (2015) Asymmetric morphology of the cells comprising the inner and outer bending sides of the murine duodenojejunal flexure. Cell Tissue Res 360:273–285
Otani H, Udagawa J, Naito K (2016) Statistical analyses in trials for the comprehensive understanding of organogenesis and histogenesis in humans and mice. J Biochem 159:553–561
Savin T, Kurpios NA, Shyer AE, Florescu P, Liang H, Mahadevan L, Tabin CJ (2011) On the growth and form of the gut. Nature 476:57–62
Sbarbati R (1982) Morphogenesis of the intestinal villi of the mouse embryo: chance and spatial necessity. J Anat 135:477–499
Soffers JHM, Hikspoors JPJM, Mekonen HK, Koehler SE, Lamers WH (2015) The growth pattern of the human intestine and its mesentery. BMC Dev Biol 15:31–31
Ueda Y, Yamada S, Uwabe C, Kose K, Takakuwa T (2016) Intestinal rotation and physiological umbilical herniation during the embryonic period. Anat Rec (Hoboken) 299:197–206
Walton KD, Freddo AM, Wang S, Gumucio DL (2016a) Generation of intestinal surface: an absorbing tale. Development 143:2261–2272
Walton KD, Whidden M, Kolterud Å, Shoffner SK, Czerwinski MJ, Kushwaha J, Parmar N, Chandhrasekhar D, Freddo AM, Schnell S, Gumucio DL (2016b) Villification in the mouse: Bmp signals control intestinal villus patterning. Development 143:427–436
Yamada M, Udagawa J, Matsumoto A, Hashimoto R, Hatta T, Nishita M, Minami Y, Otani H (2010) Ror2 is required for midgut elongation during mouse development. Dev Dyn 239:941–953
Yamada M, Udagawa J, Hashimoto R, Matsumoto A, Hatta T, Otani H (2013) Interkinetic nuclear migration during early development of midgut and ureteric epithelia. Anat Sci Int 88:31–37
Young HM (2008) On the outside looking in: longitudinal muscle development in the gut. Neurogastroenterol Motil 20:431–433
Acknowledgements
The authors are very grateful to Ms. Y. Takeda for her tireless help in sectioning the tissue. This work was supported by MEXT KAKENHI Grant number 23112006.
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Jahan, N., Jahan, E., Rafiq, A.M. et al. Histomorphometric analysis of the epithelial lumen, mesenchyme, smooth muscle cell layers, and mesentery of the mouse developing duodenum in relation with the macroscopic morphogenesis. Anat Sci Int 96, 450–460 (2021). https://doi.org/10.1007/s12565-021-00611-0
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DOI: https://doi.org/10.1007/s12565-021-00611-0