Abstract
Calcitonin receptor-immunoreactivity (CTR-ir) was found in enteric neurons of the mouse gastrointestinal tract from embryonic day 13.5 (E13.5) to post-natal day 28 (P28). CTR-ir occurred in cell bodies in ganglia of the myenteric plexus extending from the esophagus to the colon and in nerve cells of the submucosal ganglia of the small and large intestines. CTR-ir was also found in vagal nerve trunks and mesenteric nerves. Counts in the ileal myenteric plexus revealed CTR-ir in 80% of neurons. CTR-ir was clearly evident in the cell bodies of enteric neurons by E15.5. The immunoreactivity reached maximum intensity between P1.5 and P12 but was weaker at P18 and barely detectable at P28. The receptor was detected in nerve processes in the intestine for only a brief period around E17.5, when it was present in one to two axonal processes per villus in the small intestine. In late gestation and soon after birth, CTR-ir was also evident in the mucosal epithelium. The perinatal expression of CTR within the ENS suggests that the calcitonin/CTR system may have a role in the maturation of enteric neurons. Signals may reach enteric neurons in milk, which contains high levels of calcitonin.
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Anderson RB, Stewart AL, Young HM (2006) Phenotypes of neural-crest-derived cells in vagal and sacral pathways. Cell Tissue Res 323:11–25
Becskei C, Riediger T, Zünd D, Wookey P, Lutz TA (2004) Immunohistochemical mapping of calcitonin receptors in the adult rat brain. Brain Res 1030:221–233
Burns AJ, Roberts RR, Bornstein JC, Young HM (2009) Development of the enteric nervous system and its role in intestinal motility during fetal and early postnatal stages. Semin Pediatr Surg 18:196–205
Dacquin R, Davey RA, Laplace C, Levasseur R, Morris HA, Goldring SR, Gebre-Medhin S, Galson DL, Zajac JD, Karsenty G (2004) Amylin inhibits bone resorption while the calcitonin receptor controls bone formation in vivo. J Cell Biol 164:509–514
Fairman CL, Clagett Dame M, Lennon VA, Epstein ML (1995) Appearance of neurons in the developing chick gut. Dev Dyn 204:192–201
Findlay DM (2006) Regulation of cell growth mediated by the calcitonin receptor. Cell Mol Biol 52:3–8
Fukada S-I, Uezumi A, Ikemoto M, Masuda S, Segawa M, Tanimura N, Yamamoto H, Miyagoe-Suzuki Y, Takeda S (2007) Molecular signature of quiescent satellite cells in adult skeletal muscle. Stem Cells 25:2448–2459
Gershon MD (2010) Developmental determinants of the independence and complexity of the enteric nervous system. Trends Neurosci 33:446–456
Gnocchi VF, White RB, Ono Y, Ellis JA, Zammit PS (2009) Further Characterisation of the molecular signature of quiescent and activated mouse muscle satellite cells. PLoS One 4:e5205
Hao MM, Young HM (2009) Development of enteric neuron diversity. J Cell Mol Med 13:1193–1210
Hao MM, Moore RE, Roberts RR, Nguyen T, Furness JB, Anderson RB, Young HM (2010) The role of neural activity in the migration and differentiation of enteric neuron precursors. Neurogastroenterol Motil 22:e127–e137
Ismail PM, DeMayo FJ, Amato P, Lydon JP (2004) Progesterone induction of calcitonin expression in the murine mammary gland. J Endocrinol 180:287–295
Jagger C, Gallagher A, Chambers T, Pondel M (1999) The porcine calcitonin receptor promoter directs expression of a linked reporter gene in a tissue and developmental specific manner in transgenic mice. Endocrinology 140:492–499
Jagger C, Chambers T, Pondel M (2000) Transgenic mice reveal novel sites of calcitonin receptor gene expression during development. Biochem Biophys Res Commun 274:124–129
Katafuchi T, Kikumoto K, Hamano K, Kangawa K, Matsuo H, Minamino N (2003) Calcitonin receptor-stimulating peptide, a new member of the calcitonin gene-related peptide family. J Biol Chem 278:12046–12054
Kumar S, Zhu L-J, Polihronis M, Cameron ST, Baird DT, Schatz F, Dua A, Ying Y-K, Bagchi MK, Bagchi IC (1998) Progesterone induces calcitonin gene expression in human endometrium within the putative window of implantation. J Clin Endocrinol Metab 83:4443–4450
Pácha J (2000) Development of intestinal transport function in mammals. Physiol Rev 80:1633–1667
Tikellis C, Xuereb L, Casley D, Brasier G, Cooper ME, Wookey PJ (2003) Calcitonin receptor isoforms expressed in the developing rat kidney. Kidney Int 63:416–426
Tolcos M, Tikellis C, Rees S, Cooper M, Wookey P (2003) Ontogeny of calcitonin receptor mRNA and protein in the developing central nervous system of the rat. J Comp Neurol 456:29–38
Tverberg LA, Gustavson MF, Scott TL, Arzumanova IV, Provost ER, Yan AW, Rawie SA (2000) Induction of calcitonin and calcitonin receptor expression in rat mammary tissue during pregnancy. Endocrinology 141:3696–3702
Werner S, Widström A-M, Wahlberg V, Winberg J (1982) Immunoreactive calcitonin in maternal milk and serum in relation to prolactin and neurotensin. Early Hum Dev 6:77–82
Woodrow JP, Sharpe CJ, Fudge NJ, Hoff AO, Gagel RF, Kovacs CS (2006) Calcitonin plays a critical role in regulating skeletal mineral metabolism during lactation. Endocrinol 147:4010–4012
Wookey PJ (2009) A review of calcitonin receptor expression in embryonic, foetal and adult tissues, with an hypothesis on the connection between expression during foetal development and disease. Open Zool J 2:53–61
Wookey PJ, Zulli A, Buxton BF, Hare DL (2008) Calcitonin receptor immunoreactivity associated with specific cell types in diseased radial and internal mammary arteries. Histopathology 52:605–612
Wookey PJ, Zulli A, Hare DL (2009) The elevated expression of calcitonin receptor by cells recruited into the endothelial layer and neo-intima of atherosclerotic plaque. Histochem Cell Biol 132:181–189
Zhu L-J, Cullinan-Bove K, Polihronis M, Bagchi MK, Bagchi IC (1998) Calcitonin is a progesterone-regulated marker that forecasts the receptive state of endometrium during implantation. Endocrinology 138:3923–3924
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This work was supported by a grant from the National Health and Medical Research Council of Australia (grant number 566696).
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Wookey, P.J., Turner, K. & Furness, J.B. Transient expression of the calcitonin receptor by enteric neurons of the embryonic and early post-natal mouse. Cell Tissue Res 347, 311–317 (2012). https://doi.org/10.1007/s00441-011-1303-6
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DOI: https://doi.org/10.1007/s00441-011-1303-6