XB-ART-1028Dev Growth Differ December 1, 2005; 47 (9): 601-7.
Molecular mechanisms for thyroid hormone-induced remodeling in the amphibian digestive tract: a model for studying organ regeneration.
During amphibian metamorphosis the digestive tract is extensively remodeled under the control of epithelial-connective tissue interactions. At the cellular level, larval epithelial cells undergo apoptosis, while a small number of stem cells appear, actively proliferate, and then differentiate to form adult epithelium that is analogous to its mammalian counterpart. Therefore the amphibian digestive tract is a unique model system for the study of postembryonic organ regeneration. As amphibian intestinal remodeling can be triggered by thyroid hormone (TH), the molecular mechanisms involved can be studied from the perspective of examining the expression cascade of TH response genes. A number of these genes have been isolated from the intestine of Xenopus laevis. Recent progress in the functional analysis of this cascade has shed light on key molecules in intestinal remodeling such as matrix metalloproteinase-11, sonic hedgehog, and bone morphogenetic protein-4. These genes are also thought to play key roles in organogenesis and/or homeostasis in both chick and mammalian digestive tract, suggesting the existence of conserved mechanisms underlying such events in terrestrial vertebrates. In this article, we review our recent findings in this field, focusing on the development of adult epithelium in the X. laevis intestine.
PubMed ID: 16316405
Article link: Dev Growth Differ
Species referenced: Xenopus
Genes referenced: bmp1 bmp4 mmp11 msi1 shh
Article Images: [+] show captions
|Fig. 1. Remodeling of the Xenopus digestive tract during metamorphosis. The larval intestine before metamorphosis is long and structurally simple, having a single fold, the typhlosole, whereas the adult intestine after metamorphosis is shorter and more complex, with numerous intestinal folds. The simple columnar epithelium of the adult intestine undergoes cell renewal along the trough–crest axis of the fold.|
|Fig. 2. Development of adult intestinal epithelium during Xenopus metamorphosis. (A,B) Primordia of the adult intestinal epithelium (arrowheads) appear as islets between the larval epithelium (le) and the connective tissue (ct). They are stained deep red with methyl green-pyronin Y (A) and express high levels of Msi-1 mRNA (B). (C) Primordia of the adult epithelium (ae) invaginate into the connective tissue by active cell proliferation. Arrows indicate mitotic cells. HE staining. (D) Connective tissue cells around the growing primordia express BMP-4 mRNA with a gradient toward the primordia. (E) Adult epithelium, stained red with methyl green-pyronin Y, differentiates into single columnar epithelium as intestinal folds (if) form. m, muscles. Bars, 20 μm.|
|Fig. 3. Epithelial–connective tissue interfaces in the Xenopus intestine. (A) In a wild type tadpole before metamorphosis, the basal lamina (bl) remains thin and continuous. (B) In a wild type tadpole at the start of metamorphic climax, the basal lamina suddenly becomes thick and then amorphous. Through the modified basal lamina, cell contacts between the adult epithelial primordia (ae) and fibroblasts (f) possessing well-developed rough endoplasmic reticulum (rer) occur frequently (inset; arrowhead). (C) In a transgenic premetamorphic tadpole overexpressing ST3, the basal lamina becomes amorphous or disappears. Cell contacts (arrowhead) through the modified basal lamina occur frequently, and appear similar to those occurring in wild tadpoles during metamorphosis. Bars, 1 μm.|
|Fig. 4. Schematic drawing showing potential roles for thyroid hormone response genes in Xenopus intestinal remodeling. Thyroid hormone (TH) directly upregulates expression of ST3 and Tolloid/BMP-1 in fibroblasts and that of Shh in epithelium. ST3 affects both larval epithelial apoptosis and the invasion of adult epithelial primordia into the connective tissue by modifying epithelial cell–extracellular matrix interactions. Shh promotes cell proliferation in the connective tissue and induces expression of BMP-4 in subepithelial fibroblasts, which in turn affects differentiation of the adult epithelium.|