Click here to close
Hello! We notice that you are using Internet Explorer, which is not supported by Xenbase and may cause the site to display incorrectly.
We suggest using a current version of Chrome,
FireFox, or Safari.
???displayArticle.abstract???
At metamorphosis the Xenopus laevis tadpoleexocrine pancreas remodels in two stages. At the climax of metamorphosis thyroid hormone (TH) induces dedifferentiation of the entire exocrine pancreas to a progenitor state. The organ shrinks to 20% of its size, and approximately 40% of its cells die. The acinar cells lose their zymogen granules and approximately 75% of their RNA. The mRNAs that encode exocrine-specific proteins (including the transcription factor Ptf1a) undergo almost complete extinction at climax, whereas PDX-1, Notch-1, and Hes-1, genes implicated in differentiation of the progenitor cells, are activated. At the end of spontaneous metamorphosis when the endogenous TH has reached a low level, the pancreas begins to redifferentiate. Exogenous TH induces the dedifferentiation phase but not the redifferentation phase. The tadpolepancreas lacks the mature ductal system that is found in adult vertebrate pancreases, including the frog. Exocrine pancreases of transgenic tadpoles expressing a dominant negative form of the TH receptor controlled by the elastase promoter are resistant to TH. They do not shrink when subjected to TH. Their acinar cells do not dedifferentiate at climax, nor do they down-regulate exocrine-specific genes or activate Notch-1 and Hes-1. Even 2 months after metamorphosis these frogs have not developed a mature ductal system and the acinar cells are abnormally arranged. The TH-dependent dedifferentiation of the tadpole acinar cells at climax is a necessary step in the formation of a mature frog pancreas.
Fig. 2. Change in gene expression in the exocrine pancreas during metamorphosis. (A–D and I–L) In situ hybridization with amylase (A–D) and Ptf1a (I–L) probes. Every mRNA encoding a “terminally differentiated†exocrine protein that we have tested is extinguished at metamorphic climax (NF62) to the same extent as these 2 mRNAs (see discussion). (E–H) Although amylase mRNA is extinguished at climax, amylase protein was still detected by immunohistochemistry, confirming the dedifferentiation stages of previously differentiated exocrine cells. (Scale bar: 40 μm.)
Fig. 3. Change in gene expression in the exocrine pancreas during metamorphosis. (A–C) In situ hybridization with PDX-1 probes. PDX-1 is expressed exclusively in islet cells in the tadpole (A) and frog pancreases (C), and at climax expression is extended to the dedifferentiated exocrine cells (B). (D–I) Notch-1 (D–F) and Hes-1 (G–I) genes are activated at climax, although low level of expression of Notch-1 and Hes-1 has been observed at premetamorphic and adult frogs. (Scale bar: 40 μm.)
Fig. 7. Schematic representation of morphological and gene expression changes in the exocrine pancreas during X. laevis metamorphosis. The adult frog pancreas has all of the types of ducts that have been described for adult vertebrates. Tadpoles lack the intercalated ducts. At the climax of metamorphosis, TH induces dedifferentiation of the exocrine pancreas to a progenitor state that has extinguished the mRNAs encoding terminally differentiated proteins (represented by amylase). PDX-1, Notch-1, and Hes-1 are up-regulated. Late in climaxPtf1a is reactivated followed by the differentiation of acinar and duct cells. Abbreviations: ac-acinar; ld-lobular duct, icd-intercalated duct. Figure is not drawn to scale.
Afelik,
Combined ectopic expression of Pdx1 and Ptf1a/p48 results in the stable conversion of posterior endoderm into endocrine and exocrine pancreatic tissue.
2006, Pubmed,
Xenbase
Afelik,
Combined ectopic expression of Pdx1 and Ptf1a/p48 results in the stable conversion of posterior endoderm into endocrine and exocrine pancreatic tissue.
2006,
Pubmed
,
Xenbase Apelqvist,
Notch signalling controls pancreatic cell differentiation.
1999,
Pubmed
,
Xenbase Beck,
Gut specific expression using mammalian promoters in transgenic Xenopus laevis.
1999,
Pubmed
,
Xenbase Berry,
The expression pattern of thyroid hormone response genes in the tadpole tail identifies multiple resorption programs.
1998,
Pubmed
,
Xenbase Bollin,
Anuran pancreas development during thyroxine-induced metamorphosis of Rana catesbeiana: RNA metabolism during the regressive phase of pancreas development.
1973,
Pubmed Brown,
Thyroid hormone controls multiple independent programs required for limb development in Xenopus laevis metamorphosis.
2005,
Pubmed
,
Xenbase Cai,
Expression of type II iodothyronine deiodinase marks the time that a tissue responds to thyroid hormone-induced metamorphosis in Xenopus laevis.
2004,
Pubmed
,
Xenbase Cockell,
Identification of a cell-specific DNA-binding activity that interacts with a transcriptional activator of genes expressed in the acinar pancreas.
1989,
Pubmed Das,
Multiple thyroid hormone-induced muscle growth and death programs during metamorphosis in Xenopus laevis.
2002,
Pubmed
,
Xenbase Egerbacher,
Morphology of the pancreatic duct system in mammals.
,
Pubmed Esni,
Notch inhibits Ptf1 function and acinar cell differentiation in developing mouse and zebrafish pancreas.
2004,
Pubmed Ghosh,
Interactions between hairy/enhancer of split-related proteins and the pancreatic transcription factor Ptf1-p48 modulate function of the PTF1 transcriptional complex.
2006,
Pubmed Guz,
Expression of murine STF-1, a putative insulin gene transcription factor, in beta cells of pancreas, duodenal epithelium and pancreatic exocrine and endocrine progenitors during ontogeny.
1995,
Pubmed
,
Xenbase Habener,
Minireview: transcriptional regulation in pancreatic development.
2005,
Pubmed Habener,
A newly discovered role of transcription factors involved in pancreas development and the pathogenesis of diabetes mellitus.
1998,
Pubmed Hald,
Activated Notch1 prevents differentiation of pancreatic acinar cells and attenuate endocrine development.
2003,
Pubmed Horb,
Expression of amylase and other pancreatic genes in Xenopus.
2002,
Pubmed
,
Xenbase Huang,
Metamorphosis is inhibited in transgenic Xenopus laevis tadpoles that overexpress type III deiodinase.
1999,
Pubmed
,
Xenbase Jarikji,
Differential ability of Ptf1a and Ptf1a-VP16 to convert stomach, duodenum and liver to pancreas.
2007,
Pubmed
,
Xenbase Jensen,
Control of endodermal endocrine development by Hes-1.
2000,
Pubmed Jensen,
Recapitulation of elements of embryonic development in adult mouse pancreatic regeneration.
2005,
Pubmed Kroll,
Transgenic Xenopus embryos from sperm nuclear transplantations reveal FGF signaling requirements during gastrulation.
1996,
Pubmed
,
Xenbase Kruse,
An endocrine-specific element is an integral component of an exocrine-specific pancreatic enhancer.
1993,
Pubmed Lardon,
Metaplasia in the pancreas.
2005,
Pubmed Leone,
Ultrastructural analysis of some functional aspects of Xenopus laevis pancreas during development and metamorphosis.
1976,
Pubmed
,
Xenbase Lin,
Differential requirement for ptf1a in endocrine and exocrine lineages of developing zebrafish pancreas.
2004,
Pubmed Löhr,
Immortalized bovine pancreatic duct cells become tumorigenic after transfection with mutant k-ras.
2001,
Pubmed Marsh-Armstrong,
Thyroid hormone controls the development of connections between the spinal cord and limbs during Xenopus laevis metamorphosis.
2004,
Pubmed
,
Xenbase Means,
Pancreatic epithelial plasticity mediated by acinar cell transdifferentiation and generation of nestin-positive intermediates.
2005,
Pubmed Milano,
Morphogenesis of the pancreas of Bufo bufo during metamorphosis.
1995,
Pubmed Murtaugh,
Notch signaling controls multiple steps of pancreatic differentiation.
2003,
Pubmed Rooman,
Expression of the Notch signaling pathway and effect on exocrine cell proliferation in adult rat pancreas.
2006,
Pubmed Sawey,
Matrix metalloproteinase 7 controls pancreatic acinar cell transdifferentiation by activating the Notch signaling pathway.
2007,
Pubmed Schreiber,
Remodeling of the intestine during metamorphosis of Xenopus laevis.
2005,
Pubmed
,
Xenbase Schreiber,
Diverse developmental programs of Xenopus laevis metamorphosis are inhibited by a dominant negative thyroid hormone receptor.
2001,
Pubmed
,
Xenbase Shi,
Developmental and thyroid hormone-dependent regulation of pancreatic genes in Xenopus laevis.
1990,
Pubmed
,
Xenbase Smolich,
Characterization of Xenopus laevis gamma-crystallin-encoding genes.
1993,
Pubmed
,
Xenbase Strobel,
Beta cell transdifferentiation does not contribute to preneoplastic/metaplastic ductal lesions of the pancreas by genetic lineage tracing in vivo.
2007,
Pubmed Tezel,
REG I as a marker for human pancreatic acinoductular cells.
2004,
Pubmed Wang,
Duct- to islet-cell differentiation and islet growth in the pancreas of duct-ligated adult rats.
1995,
Pubmed
