Schreiber AM et al. (2005), Remodeling of the intestine during metamorphosi...

XB-ART-2252

Proc Natl Acad Sci U S A 2005 Mar 08;10210:3720-5. doi: 10.1073/pnas.0409868102.

Show Gene links Show Anatomy links

Remodeling of the intestine during metamorphosis of Xenopus laevis.

Schreiber AM , Cai L , Brown DD .

???displayArticle.abstract???
Thyroid hormone controls remodeling of the tadpole intestine during the climax of amphibian metamorphosis. In 8 days, the Xenopus laevis tadpole intestine shortens in length by 75%. Simultaneously, the longitudinal muscle fibers contract by about the same extent. The radial muscle fibers also shorten as the diameter narrows. Many radial fibers undergo programmed cell death. We conclude that muscle remodeling and contraction play key roles in the shortening process. Shortening is accompanied by a temporary "heaping" of the epithelial cells into many layers at climax. Cells that face the lumen undergo apoptosis. By the end of metamorphosis, when the epithelium is folded into crypts and villi, the epithelium is a single-cell layer once again. Throughout this remodeling, DNA replication occurs uniformly throughout the epithelium, as do changes in gene expression. The larval epithelial cells as a whole, rather than a subpopulation of stem cells, are the progenitors of the adult epithelial cells.

???displayArticle.pubmedLink??? 15738398
???displayArticle.pmcLink??? PMC553331
???displayArticle.link??? Proc Natl Acad Sci U S A

Species referenced: Xenopus laevis
Genes referenced: actl6a cdh1 fabp2 fn1 msi1 tbx2 thibz

???attribute.lit??? ???displayArticles.show???

	Fig. 1. The tadpole gut shortens dramatically during metamorphosis. The components of the gut depicted here are as follows: es, esophagus; st, stomach; du, duodenum; il, ileum; co, colon; re, rectum. The duodenum and part of the ileum comprise the intestine's outer loops that coil in a counterclockwise direction (ventral perspective). The ileum reverses direction at the switchback point (arrowhead) and coils clockwise with the colon to form the intestine's inner loops. The rectum is the final internal structure of the gut. (A) The gut of a premetamorphic NF 54 tadpole (Inset) is shown both in situ (upper) and excised and uncoiled (lower). (B) A prometamorphic NF 58 tadpole (Inset) has a much larger and longer gut than an NF 54 tadpole. (C) In a tadpole at metamorphic (NF 62) climax (Inset), the length of the gut has begun to shorten, and the number of outer and inner coils has decreased. (D) By the end of metamorphosis (NF 66) (Inset), the gut has shortened by ≈75% of its original length. (Scale bars: 2 mm.)
	Fig. 2. The intestinal epithelium thickens during metamorphic climax. Cross sections of the duodenum at different developmental stages are labeled with antibodies against proteins that are localized in the epithelium (e-cadherin, green) and mesenchyme (fibronectin, red). Nuclei are labeled with DAPI (white). (A and A′) Before metamorphosis (NF 54), the epithelium is only one to two cell layers thick. During metamorphic climax (B and B′,NF62; C and C′, NF 63), the epithelial layer becomes five to eight cell layers thick. (D and D′)At the end of climax (NF 66), the epithelium returns to one to two cell layers thick. [Scale bars: 100 μm (A–D) and 20 μm (A′–D′).] The boxed regions in A–D correspond with the magnified regions shown in A′–D′.
	Fig. 3. Three different developmental profiles of gene expression in the intestinal epithelium. Cross sections of the tadpole duodenum are shown at the following stages. (A–C) Premetamorphosis, NF 54. (A′–C′) Metamorphic climax, NF 62. (A′–C′) Postmetamorphosis, NF 66. Sections on slides were hybridized with antisense mRNA probes. (A–A′) Musashi is expressed constitutively in the epithelium before, during, and after metamorphosis. (B–B′) Intestinal fatty acid binding protein is expressed in the epithelium before metamorphosis, and the expression eclipses during climax and returns at the end of metamorphosis. (C–C′) Basic leucine zipper expression is absent before climax, is up-regulated in both the epithelium and mesenchyme during climax, and is down-regulated at the end of climax. (Scale bar:100 μm.)
	Fig. 4. Cell proliferation in the intestinal epithelium during tadpole metamorphosis. Proliferating cell nuclei were labeled with a 12-h pulse of BrdUrd injected i.p. into living tadpoles. Cryosections of the duodenum were stained with antibodies against BrdUrd (e-cadherin, green) and mesenchyme (fibronectin, red). (A) BrdUrd label is very low during premetamorphosis (NF 54); increases uniformly throughout the epithelium during metamorphic climax at stages NF 60 (B), NF 61 (C), and NF 62 (D); and continues to be widespread near the end of climax at NF 65 (E). (F) By the end of climax (NF 66), BrdUrd incorporation begins to decrease at the crest regions of the intestinal involutions. (G) Localization of BrdUrd incorporation to cells in the troughs is apparent 2 weeks after completion of metamorphosis. (Scale bar: 100 μm.)
	Fig. 5. Active caspase-3 immunoreactivity in the tadpole intestine varies with developmental stage. Intestines (duodenum) at different stages of metamorphosis were labeled in cryosections (A–C) with antibodies against active caspase-3 (green), smooth muscle (red), and nuclei counterstained with DAPI (white). (A) NF 58 tadpole. (B) Climax at NF 61. (C) The end of climax (NF 66). (Scale bar: 100 μm.)
	Fig. 6. Intestinal smooth muscle fibers shorten in response to TH treatment. Intestines were excised at 0 h (A and C) and 72 h (B and D) after treatment with 10 nM T3 and labeled in whole-mount by using antibodies against either smooth muscle actin (A and B) or e-cadherin (C and D). Longitudinal muscle fibers are oriented horizontally, and radial fibers are oriented vertically. [Scale bars: 20 μm (A and B) and 500 μm (C and D).]
	cdh1 (cadherin 1, type 1, E-cadherin (epithelial)) gene expression (green) in cross-section of Xenopus laevis gut, NF stage 66, as assayed by immunohistochemistry.

References [+] :

Amano, Metamorphosis-associated and region-specific expression of calbindin gene in the posterior intestinal epithelium of Xenopus laevis larva. 1998, Pubmed, Xenbase

Amano, Metamorphosis-associated and region-specific expression of calbindin gene in the posterior intestinal epithelium of Xenopus laevis larva. 1998, Pubmed , Xenbase
BONNEVILLE, FINE STRUCTURAL CHANGES IN THE INTESTINAL EPITHELIUM OF THE BULLFROG DURING METAMORPHOSIS. 1963, Pubmed
Berry, The expression pattern of thyroid hormone response genes in the tadpole tail identifies multiple resorption programs. 1998, Pubmed , Xenbase
Berry, The expression pattern of thyroid hormone response genes in remodeling tadpole tissues defines distinct growth and resorption gene expression programs. 1998, Pubmed , Xenbase
Bonneville, Brush border development in the intestinal absorptive cells of Xenopus during metamorphosis. 1970, Pubmed , Xenbase
Das, Multiple thyroid hormone-induced muscle growth and death programs during metamorphosis in Xenopus laevis. 2002, Pubmed , Xenbase
Elinson, Novel structural elements identified during tail resorption in Xenopus laevis metamorphosis: lessons from tailed frogs. 1999, Pubmed , Xenbase
Ikuzawa, Stomach remodeling-associated changes of H+/K+-ATPase beta subunit expression in Xenopus laevis and H+/K+-ATPase-dependent acid secretion in tadpole stomach. 2004, Pubmed , Xenbase
Ishizuya-Oka, Thyroid hormone-upregulated expression of Musashi-1 is specific for progenitor cells of the adult epithelium during amphibian gastrointestinal remodeling. 2003, Pubmed , Xenbase
Ishizuya-Oka, Apoptosis and cell proliferation in the Xenopus small intestine during metamorphosis. 1996, Pubmed , Xenbase
Ishizuya-Oka, Temporal and spatial regulation of a putative transcriptional repressor implicates it as playing a role in thyroid hormone-dependent organ transformation. 1997, Pubmed , Xenbase
Ishizuya-Oka, Anteroposterior gradient of epithelial transformation during amphibian intestinal remodeling: immunohistochemical detection of intestinal fatty acid-binding protein. 1997, Pubmed , Xenbase
Marsh-Armstrong, Thyroid hormone controls the development of connections between the spinal cord and limbs during Xenopus laevis metamorphosis. 2004, Pubmed , Xenbase
Marshall, Cell specialization in the epithelium of the small intestine of feeding Xenopus laevis tadpoles. 1978, Pubmed , Xenbase
Nakamura, Musashi, a neural RNA-binding protein required for Drosophila adult external sensory organ development. 1994, Pubmed
Pretty, Metamorphic shortening of the alimentary tract in anuran larvae (Rana catesbeiana). 1995, Pubmed
Schreiber, Diverse developmental programs of Xenopus laevis metamorphosis are inhibited by a dominant negative thyroid hormone receptor. 2001, Pubmed , Xenbase
Schreiber, Tadpole skin dies autonomously in response to thyroid hormone at metamorphosis. 2003, Pubmed , Xenbase
Shi, The earliest changes in gene expression in tadpole intestine induced by thyroid hormone. 1993, Pubmed , Xenbase
Shi, Thyroid hormone-dependent regulation of the intestinal fatty acid-binding protein gene during amphibian metamorphosis. 1994, Pubmed , Xenbase