- Open Access
The development of the adult intestinal stem cells: Insights from studies on thyroid hormone-dependent amphibian metamorphosis
© Shi et al; licensee BioMed Central Ltd. 2011
Received: 20 June 2011
Accepted: 6 September 2011
Published: 6 September 2011
Adult organ-specific stem cells are essential for organ homeostasis and repair in adult vertebrates. The intestine is one of the best-studied organs in this regard. The intestinal epithelium undergoes constant self-renewal throughout adult life across vertebrates through the proliferation and subsequent differentiation of the adult stem cells. This self-renewal system is established late during development, around birth, in mammals when endogenous thyroid hormone (T3) levels are high. Amphibian metamorphosis resembles mammalian postembryonic development around birth and is totally dependent upon the presence of high levels of T3. During this process, the tadpole intestine, predominantly a monolayer of larval epithelial cells, undergoes drastic transformation. The larval epithelial cells undergo apoptosis and concurrently, adult epithelial stem/progenitor cells develop de novo, rapidly proliferate, and then differentiate to establish a trough-crest axis of the epithelial fold, resembling the crypt-villus axis in the adult mammalian intestine. We and others have studied the T3-dependent remodeling of the intestine in Xenopus laevis. Here we will highlight some of the recent findings on the origin of the adult intestinal stem cells. We will discuss observations suggesting that liganded T3 receptor (TR) regulates cell autonomous formation of adult intestinal progenitor cells and that T3 action in the connective tissue is important for the establishment of the stem cell niche. We will further review evidence suggesting similar T3-dependent formation of adult intestinal stem cells in other vertebrates.
Organ-specific adult stem cells are essential for the development of adult organs and tissue repair and regeneration. While most vertebrates develop directly into the adult form by birth, their organ development often involves a two-step process, the formation of an immature but often functional organ during embryogenesis followed by the maturation into the adult form. This second step takes place during the so-called post-embryonic development, a period around birth in mammals such as human and mouse when plasma thyroid hormone (T3) concentrations are high . The organ-specific adult stem cells are often formed/matured during this period. One of the well-studied such organs is the intestine. The tissue responsible for the main physiological function of the intestine, the intestinal epithelium, which is responsible for the food processing and nutrient absorption, is continuously renewed throughout adult life in vertebrates. This takes place through stem cell divisions in the crypt, followed by their differentiation as the cells migrate up to and along the villus and eventual death of the differentiated cells near the tip of the villus. In adult mammals, the intestinal epithelium is replaced once every 1-6 days [2–4], and in amphibians, this occurs in 2 weeks . Such a self-renewal system has been shown to be present throughout vertebrates, from zebrafish, frogs, to human. While a number of signaling pathways have been shown to be important for intestinal development and cell renewal in the adult [4, 6], much less is known about how adult stem cells are formed during development, in part due to the difficulties to study the uterus-enclosed mammalian embryogenesis.
Intestinal remodeling during amphibian metamorphosis offers a unique opportunity to study the development of adult organ-specific stem cells in vertebrates. As during postembryonic development in mammals, T3 levels in the plasma are high during amphibian metamorphosis. In fact, T3 is both necessary and sufficient for premetamorphic tadpoles to transform into frogs [7, 8]. In premetamorphic tadpoles, there is little T3. The synthesis of endogenous T3 around stage 55 in Xenopus laevis initiates metamorphosis. The plasma T3 rises to peak levels at the climax of metamorphosis and subsequently is reduced to much lower levels by the end of metamorphosis. During metamorphosis, different organs undergo vastly different changes, including total resorption such as the tail and gills, de novo development such as the limb, and drastic remodeling such as the liver, pancreas and intestine, which involve both larval cell death and adult cell development. Despite such complex changes, all these changes are controlled by T3. An important advantage of this system is that it occurs independent of maternal influence as in the case of mammals. Furthermore, this process can be induced even in organ cultures of premetamorphic tadpoles when treated with physiological concentrations of T3 [7, 8]. This makes it easy to manipulate and study the development and regulation of the adult organ-specific stem cells.
Mechanism of the regulation of Xenopus development by T3
T3 binds to T3 receptors (TRs) with high affinities. TRs are transcription factors that form heterodimers with 9-cis retinoic acid receptors (RXRs) and these dimers bind to T3 response element (TRE) in/around the promoters of T3 target genes [14–17]. For T3-inducible genes, TR/RXR functions as a repressor in the absence of T3 and as an activator in the presence of T3. TRs recruit different cofactor complexes to TREs to affect transcription [15, 18–25]. Extensive molecular and genetic studies by a number of different laboratories have shown that TR is both necessary and sufficient to mediate the metamorphic effects of T3 and that TR has dual functions during Xenopus development [26–35]. In premetamorphic Xenopus laevis tadpoles, TR recruits corepressor complexes to target genes when T3 is absent and this recruitment is important to keep the T3-inducible genes repressed, thus regulating metamorphic timing (Figure 1) [31, 36–38]. After stage 55, when endogenous T3 becomes available, corepressor complexes are released and coactivator complexes are recruited by TR, this leads to the activation of T3 target genes and metamorphosis [33, 34, 39–43].
The origin of the adult intestinal epithelial stem cells
Earlier microscopic and cytological studies of intestinal remodeling in Xenopus laevis failed to identify any adult stem cells in premetamorphic tadpoles . On the other hand, the ability to induce intestinal remodeling in intestinal organ cultures [10, 12, 13] indicates that the adult stem cells develop de novo within tadpole intestine. It is possible that non-epithelial cells may give rise to the stem cells when T3 becomes available. Alternatively, some differentiated larval epithelial cells may undergo dedifferentiation to become the stem cells during metamorphosis. This latter scenario is supported by chronological observations of intestinal metamorphosis  and the apparent presence of the proteins of the differentiated epithelial cells in proliferating adult progenitor cells [11, 45]. On the other hand, there has been no direct evidence to demonstrate the origin of the adult epithelial cells. Making use of a transgenic Xenopus line ubiquitously expressing the green fluorescent protein (GFP), we have recently carried out recombinant organ culture studies to determine the orgin of the adult intestinal epithelial stem cells .
Distinct roles of the epithelium and connective tissue in stem cell formation
Earlier organ culture studies have shown that adult epithelium formation requires the presence of the connective tissue . How the connective tissue participates in this process remains largely unknown. Given that the adult epithelial stem cells originate from the larval epithelium, it is possible that T3 induces the formation of the stem cells in a cell-autonomous manner. To investigate whether T3 signaling in the epithelium alone is sufficient for adult stem cell formation, we have carried out recombinant organ culture experiments by using premetamorphic transgenic Xenopus laevis tadpoles that express a dominant positive TR (dpTR, which is constitutively active but does not bind to T3) under the control of a heat shock inducible promoter [29, 47] (Figure 2A). Heat shock treatment of the recombinant intestinal organ cultures leads to the expression of dpTR only in the transgenic but not wild type tissues while the endogenous TR remains unliganded regardless of the treatment. When either the epithelium or the non-epithelial tissues or both were derived from the transgenic tadpoles, larval epithelial cell apoptosis could be detected after heat shock treatment for 5 days. On the other hand but expectedly, no metamorphic changes were observed after the heat shock treatment when both the epithelium and non-epithelial tissues were from the wild type animals . Thus, larval epithelial cell death can occur via two pathways: suicide cell-autonomously through T3 action in the epithelial cells versus murder through T3 action in the non-epithelial tissues, which likely involves the induction of matrix metalloproteinases such as stromelysin-3, an MMP secreted by fibroblasts that causes epithelial cell death .
Adult epithelial progenitor cells expressing Shh were also detectable after 5 days of heat shcok treatment if the recombinant was made of epithelium derived from transgenic intestine, regardless of the origin of the non-epithelial tissues . However, no such cells were present if both tissues were derived from the wild type animals or when the epithelium was from the wild type animals and the non-epithelial tissues were from the transgenic animals. Thus, TR activation in the non-epithelial tissues is not sufficient to induce the formation of the Shh+ adult progenitor cells in the epithelium, although it can induce epithelial apoptosis. The formation of the Shh+ progenitor cells appears to be cell-autonomous upon activation of TR (due to T3 binding or the expression of a constitutively active TR) in the epithelium .
When the expression of two stem cell markers of the adult mammalian intestine, Musashi-1 (Msi-1) and Akt [49–51], were analyzed after 5 days of heat shock treatment, they were detected in the Shh+ cells when both of the epithelium and non-epithelial tissues used to make the recombinant intestine were derived from dpTR-transgenic tadpole intestine (Figure 2B). Upon prolonged culturing (5 days of heat shock treatment followed by 2 days of culture without heat shock treatment), such organ cultures formed adult epithelium expressing IFABP, a marker for the absorptive epithelium (Figure 2B). On the other hand, if only the epithelium was derived from the transgenic tadpoles, the Shh+ progenitor cells produced after heat shock treatment failed to express either of the stem cell markers and failed to develop into differentiated adult epithelium expressing IFABP (Figure 2B). These results indicate that while the adult progenitor/stem cells can be induced by T3 in the larval epithelium, liganded TR-mediated gene expression in the surrounding tissues other than the epithelium is required for them to develop into adult stem cells, suggesting that T3 activation of the non-epithelial tissues, most likely the underlying connective tissue is required for the establishment of the stem cell niche in the amphibian intestine during metamorphosis. Consistently, an earlier transgenic study where a dominant negative TR was expressed under the control of epithelial-, fibroblast-, and muscle-specific gene promoters showed that while mutant TR expression in different tissues caused distinct phenotypes in the postmetamorphic intestine, its expression in either the epithelium and fibroblasts led to abnormal epithelia and mesenchyme development , supporting our conclusion that TR activation in both the epithelium and connective tissue is important for adult epithelium development.
A role of the TR-coactivator protein arginine methyltransferase 1 (PRMT1) in stem cell formation during metamorphosis by T3
Evolutionary conservation in adult intestinal stem cell development
Organ-specific adult stem cells play an essential role in organ homeostasis and tissue repair and regeneration. Understanding the mechanisms of their development is undoubtedly important for the generation and utilization of such cells for tissue replacement therapies and prevention of stem cell-related diseases. The uterus-enclosed development of mammalian embryos has hindered the study of the development of adult organ-specific stem cells in mammals. On the other hand, the conservation of the organ function and development makes it possible to use non-mammalian models for such purpose. The intestine is such an organ that is structurally and physiologically conserved across vertebrate species. Using Xenopus laevis metamorphosis as a model, we and others have shown that the adult intestinal stem cells develop de novo and are distinct molecularly from the larval cells. It is interesting to note that larval epithelial cells in premetamorphic tadpole intestines are mitotically active, even though they are differentiated and serve the physiological function of the intestinal epithelium . Thus, to develop into stem cells, the larval epithelial cells merely need to repress the expression of the genes associated with differentiated cells and escape the T3-induced apoptotic fate that most other epithelial cells have. Intestinal organ culture studies suggest that T3 induces the epithelium to undergo cell-autonomous formation of adult progenitor cells and also induces the non-epithelial tissues, most likely the connective tissue, to form or contribute to the establishment of the adult stem cell niche. It is possible that some of the larval epithelial cells, in the context of the stem cell niche formed with the participation of the T3-activated connective tissue, adopt the pathway of stem cell development during metamorphosis. The vast majority of the larval epithelial cells undergo apoptosis due to the lack of the proper stem cell niche environment even though they also lose the expression of at least some differentiation markers such as IFABP. The studies with PRMT1 have not only revealed an important role of this TR-coactivator in adult stem cell development/proliferation but also provided further evidence that adult stem cell development utilize conserved mechanisms across vertebrates.
This research was supported in part by the Intramural Research Program of NICHD, NIH and the JSPS Grants-in-Aid for Scientific Research (C) (Grant number 20570060 to A. I.-O.).
- Tata JR: Gene expression during metamorphosis: an ideal model for post-embryonic development. Bioessays. 1993, 15 (4): 239-248. 10.1002/bies.950150404View ArticlePubMedGoogle Scholar
- MacDonald WC, Trier JS, Everett NB: Cell proliferation and migration in the stomach, duodenum, and rectum of man: Radioautographic studies. Gastroenterology. 1964, 46: 405-417.PubMedGoogle Scholar
- Toner PG, Carr KE, Wyburn GM: The Digestive System: An Ultrastructural Atlas and Review. 1971, London: Butterworth.Google Scholar
- van der Flier LG, Clevers H: Stem Cells, Self-Renewal, and Differentiation in the Intestinal Epithelium. Annu Rev Physiol. 2009, 71: 241-260. 10.1146/annurev.physiol.010908.163145View ArticlePubMedGoogle Scholar
- McAvoy JW, Dixon KE: Cell proliferation and renewal in the small intestinal epithelium of metamorphosing and adult Xenopus laevis. J Exp Zool. 1977, 202: 129-138. 10.1002/jez.1402020115View ArticleGoogle Scholar
- Sancho E, Eduard Batlle E, Clevers H: Signaling pathways in intestinal development and cancer. Annu Rev Cell DevBiol. 2004, 20: 695-723. 10.1146/annurev.cellbio.20.010403.092805View ArticleGoogle Scholar
- Gilbert LI, Tata JR, Atkinson BG: Metamorphosis: Post-embryonic reprogramming of gene expression in amphibian and insect cells. 1996, New York: Academic Press.Google Scholar
- Shi Y-B: Amphibian Metamorphosis: From morphology to molecular biology. 1999, New York: John Wiley & Sons, Inc.Google Scholar
- Shi Y-B, Ishizuya-Oka A: Biphasic intestinal development in amphibians: Embryogensis and remodeling during metamorphosis. Current Topics in Develop Biol. 1996, 32: 205-235.View ArticleGoogle Scholar
- Ishizuya-Oka A, Hasebe T, Buchholz DR, Kajita M, Fu L, Shi YB: Origin of the adult intestinal stem cells induced by thyroid hormone in Xenopus laevis. Faseb J. 2009, 23: 2568-2575. 10.1096/fj.08-128124PubMed CentralView ArticlePubMedGoogle Scholar
- Schreiber AM, Cai L, Brown DD: Remodeling of the intestine during metamorphosis of Xenopus laevis. Proc Natl Acad Sci USA. 2005, 102 (10): 3720-3725. 10.1073/pnas.0409868102PubMed CentralView ArticlePubMedGoogle Scholar
- Ishizuya-Oka A, Shimozawa A: Induction of metamorphosis by thyroid hormone in anuran small intestine cultured organotypically in vitro. In Vitro Cell Dev Biol. 1991, 27A (11): 853-857.View ArticlePubMedGoogle Scholar
- Ishizuya-Oka A, Ueda S, Damjanovski S, Li Q, Liang VC, Shi Y-B: Anteroposterior gradient of epithelial transformation during amphibian intestinal remodeling: immunohistochemical detection of intestinal fatty acid-binding protein. Dev Biol. 1997, 192 (1): 149-161. 10.1006/dbio.1997.8749View ArticlePubMedGoogle Scholar
- Lazar MA: Thyroid hormone receptors: multiple forms, multiple possibilities. Endocr Rev. 1993, 14 (2): 184-193.PubMedGoogle Scholar
- Yen PM: Physiological and molecular basis of thyroid hormone action. Physiol Rev. 2001, 81 (3): 1097-1142.PubMedGoogle Scholar
- Mangelsdorf DJ, Thummel C, Beato M, Herrlich P, Schutz G, Umesono K: The nuclear receptor superfamily: the second decade. Cell. 1995, 83 (6): 835-839. 10.1016/0092-8674(95)90199-XView ArticlePubMedGoogle Scholar
- Tsai MJ, O'Malley BW: Molecular mechanisms of action of steroid/thyroid receptor superfamily members. Ann Rev Biochem. 1994, 63: 451-486. 10.1146/annurev.bi.63.070194.002315View ArticlePubMedGoogle Scholar
- Ito M, Roeder RG: The TRAP/SMCC/Mediator complex and thyroid hormone receptor function. Trends Endocrinol Metab. 2001, 12 (3): 127-134. 10.1016/S1043-2760(00)00355-6View ArticlePubMedGoogle Scholar
- Rachez C, Freedman LP: Mechanisms of gene regulation by vitamin D(3) receptor: a network of coactivator interactions. Gene. 2000, 246 (1-2): 9-21. 10.1016/S0378-1119(00)00052-4View ArticlePubMedGoogle Scholar
- Zhang J, Lazar MA: The mechanism of action of thyroid hormones. Annu Rev Physiol. 2000, 62: 439-466. 10.1146/annurev.physiol.62.1.439View ArticlePubMedGoogle Scholar
- Burke LJ, Baniahmad A: Co-repressors 2000. FASEB J. 2000, 14 (13): 1876-1888. 10.1096/fj.99-0943revView ArticlePubMedGoogle Scholar
- Jepsen K, Rosenfeld MG: Biological roles and mechanistic actions of co-repressor complexes. J Cell Sci. 2002, 115 (Pt 4): 689-698.PubMedGoogle Scholar
- Jones PL, Shi Y-B: N-CoR-HDAC corepressor complexes: Roles in transcriptional regulation by nuclear hormone receptors. Current Topics in Microbiology and Immunology: Protein Complexes that Modify Chromatin. Edited by: Workman JL. Berlin: Springer-Verlag; 2003, 274: 237-268.View ArticleGoogle Scholar
- Rachez C, Freedman LP: Mediator complexes and transcription. Curr Opin Cell Biol. 2001, 13 (3): 274-280. 10.1016/S0955-0674(00)00209-XView ArticlePubMedGoogle Scholar
- Hu X, Lazar MA: Transcriptional Repression by Nuclear Hormone Receptors. TEM. 2000, 11 (1): 6-10.PubMedGoogle Scholar
- Schreiber AM, Das B, Huang H, Marsh-Armstrong N, Brown DD: Diverse developmental programs of Xenopus laevis metamorphosis are inhibited by a dominant negative thyroid hormone receptor. PNAS. 2001, 98: 10739-10744. 10.1073/pnas.191361698PubMed CentralView ArticlePubMedGoogle Scholar
- Brown DD, Cai L: Amphibian metamorphosis. Dev Biol. 2007, 306 (1): 20-33. 10.1016/j.ydbio.2007.03.021PubMed CentralView ArticlePubMedGoogle Scholar
- Buchholz DR, Hsia VS-C, Fu L, Shi Y-B: A dominant negative thyroid hormone receptor blocks amphibian metamorphosis by retaining corepressors at target genes. Mol Cell Biol. 2003, 23: 6750-6758. 10.1128/MCB.23.19.6750-6758.2003PubMed CentralView ArticlePubMedGoogle Scholar
- Buchholz DR, Tomita A, Fu L, Paul BD, Shi Y-B: Transgenic analysis reveals that thyroid hormone receptor is sufficient to mediate the thyroid hormone signal in frog metamorphosis. Mol Cell Biol. 2004, 24: 9026-9037. 10.1128/MCB.24.20.9026-9037.2004PubMed CentralView ArticlePubMedGoogle Scholar
- Buchholz DR, Paul BD, Fu L, Shi YB: Molecular and developmental analyses of thyroid hormone receptor function in Xenopus laevis, the African clawed frog. Gen Comp Endocrinol. 2006, 145 (1): 1-19. 10.1016/j.ygcen.2005.07.009View ArticlePubMedGoogle Scholar
- Shi Y-B: Dual functions of thyroid hormone receptors in vertebrate development: the roles of histone-modifying cofactor complexes. Thyroid. 2009, 19: 987-999. 10.1089/thy.2009.0041PubMed CentralView ArticlePubMedGoogle Scholar
- Nakajima K, Yaoita Y: Dual mechanisms governing muscle cell death in tadpole tail during amphibian metamorphosis. Dev Dyn. 2003, 227: 246-255. 10.1002/dvdy.10300View ArticlePubMedGoogle Scholar
- Denver RJ, Hu F, Scanlan TS, Furlow JD: Thyroid hormone receptor subtype specificity for hormone-dependent neurogenesis in Xenopus laevis. Dev Biol. 2009, 326 (1): 155-168. 10.1016/j.ydbio.2008.11.005View ArticlePubMedGoogle Scholar
- Bagamasbad P, Howdeshell KL, Sachs LM, Demeneix BA, Denver RJ: A role for basic transcription element-binding protein 1 (BTEB1) in the autoinduction of thyroid hormone receptor beta. J Biol Chem. 2008, 283: 2275-2285.View ArticlePubMedGoogle Scholar
- Schreiber AM, Mukhi S, Brown DD: Cell-cell interactions during remodeling of the intestine at metamorphosis in Xenopus laevis. Dev Biol. 2009, 331 (1): 89-98. 10.1016/j.ydbio.2009.04.033PubMed CentralView ArticlePubMedGoogle Scholar
- Tomita A, Buchholz DR, Shi Y-B: Recruitment of N-CoR/SMRT-TBLR1 corepressor complex by unliganded thyroid hormone receptor for gene repression during frog development. Mol Cell Biol. 2004, 24: 3337-3346. 10.1128/MCB.24.8.3337-3346.2004PubMed CentralView ArticlePubMedGoogle Scholar
- Sachs LM, Jones PL, Havis E, Rouse N, Demeneix BA, Shi Y-B: N-CoR recruitment by unliganded thyroid hormone receptor in gene repression during Xenopus laevis development. Mol Cell Biol. 2002, 22: 8527-8538. 10.1128/MCB.22.24.8527-8538.2002PubMed CentralView ArticlePubMedGoogle Scholar
- Sato Y, Buchholz DR, Paul BD, Shi Y-B: A role of unliganded thyroid hormone receptor in postembryonic development in Xenopus laevis. Mechanisms of Development. 2007, 124: 476-488. 10.1016/j.mod.2007.03.006PubMed CentralView ArticlePubMedGoogle Scholar
- Matsuda H, Paul BD, Choi CY, Hasebe T, Shi Y-B: Novel functions of protein arginine methyltransferase 1 in thyroid hormone receptor-mediated transcription and in the regulation of metamorphic rate in Xenopus laevis. Mol Cell Biol. 2009, 29: 745-757. 10.1128/MCB.00827-08PubMed CentralView ArticlePubMedGoogle Scholar
- Paul BD, Buchholz DR, Fu L, Shi Y-B: Tissue- and gene-specific recruitment of steroid receptor coactivator-3 by thyroid hormone receptor during development. J Biol Chem. 2005, 280: 27165-27172. 10.1074/jbc.M503999200View ArticlePubMedGoogle Scholar
- Paul BD, Fu L, Buchholz DR, Shi Y-B: Coactivator recruitment is essential for liganded thyroid hormone receptor to initiate amphibian metamorphosis. Mol Cell Biol. 2005, 25: 5712-5724. 10.1128/MCB.25.13.5712-5724.2005PubMed CentralView ArticlePubMedGoogle Scholar
- Paul BD, Buchholz DR, Fu L, Shi Y-B: SRC-p300 coactivator complex is required for thyroid hormone induced amphibian metamorphosis/. J Biol Chem. 2007, 282: 7472-7481.View ArticlePubMedGoogle Scholar
- Havis E, Sachs LM, Demeneix BA: Metamorphic T3-response genes have specific co-regulator requirements. EMBO Reports. 2003, 4: 883-888. 10.1038/sj.embor.embor908PubMed CentralView ArticlePubMedGoogle Scholar
- Marshall JA, Dixon KE: Cell proliferation in the intestinal epithelium of Xenopus laevis tadpoles. J Exp Zool. 1978, 203: 31-40. 10.1002/jez.1402030104View ArticleGoogle Scholar
- Amano T, Noro N, Kawabata H, Kobayashi Y, Yoshizato K: Metamorphosis-associated and region-specific expression of calbindin gene in the posterior intestinal epithelium of Xenopus laevis larva. Dev Growth Differ. 1998, 40: 177-188. 10.1046/j.1440-169X.1998.00007.xView ArticlePubMedGoogle Scholar
- Ishizuya-Oka A, Shimozawa A: Connective tissue is involved in adult epithelial development of the small intestine during anuran metamorphosis in vitro. Roux's Arch Dev Biol. 1992, 201: 322-329. 10.1007/BF00592113View ArticleGoogle Scholar
- Hasebe T, Buchholz DR, Shi YB, Ishizuya-Oka A: Epithelial-connective tissue interactions induced by thyroid hormone receptor are essential for adult stem cell development in the Xenopus laevis intestine. Stem Cells. 2011, 29 (1): 154-161. 10.1002/stem.560PubMed CentralView ArticlePubMedGoogle Scholar
- Fu L, Ishizuya-Oka A, Buchholz DR, Amano T, Matsuda H, Shi YB: A causative role of stromelysin-3 in extracellular matrix remodeling and epithelial apoptosis during intestinal metamorphosis in Xenopus laevis. J Biol Chem. 2005, 280 (30): 27856-27865. 10.1074/jbc.M413275200View ArticlePubMedGoogle Scholar
- Hasebe T, Kajita M, Shi YB, Ishizuya-Oka A: Thyroid hormone-up-regulated hedgehog interacting protein is involved in larval-to-adult intestinal remodeling by regulating sonic hedgehog signaling pathway in Xenopus laevis. Dev Dyn. 2008, 237 (10): 3006-3015. 10.1002/dvdy.21698PubMed CentralView ArticlePubMedGoogle Scholar
- Ishizuya-Oka A, Ueda S, Inokuchi T, Amano T, Damjanovski S, Stolow M: Thyroid hormone-induced expression of Sonic hedgehog correlates with adult epithelial development during remodeling of the Xenopus stomach and intestine. Differentiation. 2001, 69: 27-37. 10.1046/j.1432-0436.2001.690103.xView ArticlePubMedGoogle Scholar
- Ishizuya-Oka A, Shimizu K, Sakakibara S, Okano H, Ueda S: Thyroid hormone-upregulated expression of Musashi-1 is specific for progenitor cells of the adult epithelium during amphibian gastrointestinal remodeling. J Cell Sci. 2003, 116 (Pt 15): 3157-3164.View ArticlePubMedGoogle Scholar
- Sun G, Hasebe T, Fujimoto K, Lu R, Fu L, Matsuda H: Spatio-temporal expression profile of stem cell-associated gene LGR5 in the intestine during thyroid hormone-dependent metamorphosis in Xenopus laevis. PLoS One. 2010, 5 (10): e13605. 10.1371/journal.pone.0013605PubMed CentralView ArticlePubMedGoogle Scholar
- Matsuda H, Shi YB: An essential and evolutionarily conserved role of protein arginine methyltransferase 1 for adult intestinal stem cells during postembryonic development. Stem Cells. 2010, 28 (11): 2073-2083. 10.1002/stem.529PubMed CentralView ArticlePubMedGoogle Scholar
- Plateroti M, Gauthier K, Domon-Dell C, Freund JN, Samarut J, Chassande O: Functional interference between thyroid hormone receptor alpha (TRalpha) and natural truncated TRDeltaalpha isoforms in the control of intestine development. Mol Cell Biol. 2001, 21 (14): 4761-4772. 10.1128/MCB.21.14.4761-4772.2001PubMed CentralView ArticlePubMedGoogle Scholar
- Flamant F, Poguet AL, Plateroti M, Chassande O, Gauthier K, Streichenberger N: Congenital hypothyroid Pax8(-/-) mutant mice can be rescued by inactivating the TRalpha gene. Mol Endocrinol. 2002, 16 (1): 24-32. 10.1210/me.16.1.24PubMedGoogle Scholar
- Kress E, Rezza A, Nadjar J, Samarut J, Plateroti M: The frizzled-related sFRP2 gene is a target of thyroid hormone receptor alpha1 and activates beta-catenin signaling in mouse intestine. J Biol Chem. 2009, 284 (2): 1234-1241.View ArticlePubMedGoogle Scholar
- Plateroti M, Chassande O, Fraichard A, Gauthier K, Freund JN, Samarut J: Involvement of T3Ralpha- and beta-receptor subtypes in mediation of T3 functions during postnatal murine intestinal development. Gastroenterology. 1999, 116 (6): 1367-1378. 10.1016/S0016-5085(99)70501-9View ArticlePubMedGoogle Scholar
- Plateroti M, Kress E, Mori JI, Samarut J: Thyroid hormone receptor alpha1 directly controls transcription of the beta-catenin gene in intestinal epithelial cells. Mol Cell Biol. 2006, 26 (8): 3204-3214. 10.1128/MCB.26.8.3204-3214.2006PubMed CentralView ArticlePubMedGoogle Scholar
- Brown DD: The role of thyroid hormone in zebrafish and axoloft development. Proc Natl Acad Sci USA. 1997, 94: 13011-13016. 10.1073/pnas.94.24.13011PubMed CentralView ArticlePubMedGoogle Scholar
- Friedrichsen S, Christ S, Heuer H, Schäfer MKH, Mansouri A, Bauer K: Regulation of iodothyronine deiodinases in the Pax8-/- mouse model of congenital hypothyroidism. Endocrinology. 2003, 144: 777-784. 10.1210/en.2002-220715View ArticlePubMedGoogle Scholar
- Fu L, Buchholz D, Shi YB: Novel double promoter approach for identification of transgenic animals: A tool for in vivo analysis of gene function and development of gene-based therapies. Mol Reprod Dev. 2002, 62 (4): 470-476. 10.1002/mrd.10137View ArticlePubMedGoogle Scholar
This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.