Developmental and thyroid hormone-dependent regulation of pancreatic genes in Xenopus laevis.

Brown

2009

Developmental Biology

Amphibian metamorphosis is accompanied by extensive intestinal remodeling. This process, mediated by thyroid hormone (TH) and its nuclear receptors, affects every cell type. Gut remodeling in Xenopus laevis involves epithelial and mesenchymal proliferation, smooth muscle thickening, neuronal aggregation, formation of intestinal folds, and shortening of its length by 75%. Transgenic tadpoles expressing a dominant negative TH receptor (TRDN) controlled by epilthelial-, fibroblast-, and muscle-specific gene promoters were studied. TRDN expression in the epithelium caused abnormal development of virtually all cell types, with froglet guts displaying reduced intestinal folds, thin muscle and mesenchyme, absence of neurons, and reduced cell proliferation. TRDN expression in fibroblasts caused abnormal epithelia and mesenchyme development, and expression in muscle produced fewer enteric neurons and a reduced inter-muscular space. Gut shortening was inhibited only when TRDN was expressed in fibroblasts. Gut remodeling results from both cell-autonomous and cell-cell interactions.

Section: Discussionmentioning

confidence: 99%

Cell–cell interactions during remodeling of the intestine at metamorphosis in Xenopus laevis

Schreiber

Brown

2009

Developmental Biology

“…The size of the pancreas steadily increases as the tadpole grows up to the climax of metamorphosis, and then at this stage the pancreas loses Ϸ80% of its volume (9). This pancreatic ''regression'' at climax is marked by histolysis and cell death (2, 10, 11) and also down-regulation (''extinction'') of exocrine-specific mRNAs and their proteins (11,12).We report here that the regression of the tadpole exocrine pancreas involves a TH-controlled dedifferentiation of the acinar cells to a progenitor state. These cells then redifferentiate in the frog to form a typical vertebrate pancreas.…”

mentioning

confidence: 88%

mentioning

confidence: 99%

Remodeling the exocrine pancreas at metamorphosis in Xenopus laevis

Proc. Natl. Acad. Sci. U.S.A.

Mao

Brown

2008

At metamorphosis the Xenopus laevis tadpole exocrine 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 Ϸ40% of its cells die. The acinar cells lose their zymogen granules and Ϸ75% of their RNA. The mRNAs that encode exocrinespecific 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 tadpole pancreas 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.dedifferentiation ͉ thyroid hormone ͉ Thyroid hormone receptor dominant negative ͉ gene expression T he concentration of thyroid hormone (TH) controls amphibian metamorphosis. The TH level increases steadily in tadpoles as they proceed to metamorphosis and then decreases to a base line level after metamorphic climax (1). Metamorphosis in Xenopus laevis involves the remodeling of various organs including skin, brain, intestine, liver, and pancreas (2). Adding TH to the rearing water induces organ remodeling, and antithyroid chemicals like methimazole or perchlorate prevent remodeling. The essential role of thyroid receptors (TRs) has been demonstrated for diverse metamorphic programs by the inhibitory properties of a dominant negative form of the TR (TRDN) on the metamorphosis of various cell types and organs (3-7).The tadpole exocrine pancreas consists of acinar cells with well developed zymogen granules. Exocrine-specific proteins have been detected as early as stage NF41 (8). The size of the pancreas steadily increases as the tadpole grows up to the climax of metamorphosis, and then at this stage the pancreas loses Ϸ80% of its volume (9). This pancreatic ''regression'' at climax is marked by histolysis and cell death (2, 10, 11) and also down-regulation (''extinction'') of exocrine-specific mRNAs and their proteins (11,12).We report here that the regression of the tadpole exocrine pancreas involves a TH-controlled dedifferentiation of the acinar cells to a progenitor state. These cells then redifferentiate in...

“…We have observed that at metamorphosis, remodeling begins with the dedifferentiation of the entire exocrine pancreas followed by a redifferentiation phase in the growing frog (Mukhi et al, 2008). One of the first changes in the tadpole exocrine pancreas at metamorphosis in response to the increase in thyroid hormone (TH) is the steady decline of mRNAs that encode the terminally differentiated enzymes (Shi and Brown, 1990; Mukhi et al, 2008). The levels of these mRNAs begin dropping at prometamorphosis (NF56), until they are almost totally absent by the middle of the metamorphic climax (NF62) (Figs.…”

Section: Pancreas Development During Metamorphosis (After Nf55)mentioning

confidence: 99%

Xenopus pancreas development

Pearl

Bilogan

et al. 2009

Developmental Dynamics

Understanding how the pancreas develops is vital to finding new treatments for a range of pancreatic diseases, including diabetes and pancreatic cancer. Xenopus is a relatively new model organism for the elucidation of pancreas development, and has already made contributions to the field. Recent studies have shown benefits of using Xenopus for understanding both early patterning and lineage specification aspects of pancreas organogenesis. This review focuses specifically on Xenopus pancreas development, and covers events from the end of gastrulation, when regional specification of the endoderm is occurring, right through metamorphosis, when the mature pancreas is fully formed. We have attempted to cover pancreas development in Xenopus comprehensively enough to assist newcomers to the field and also to enable those studying pancreas development in other model organisms to better place the results from Xenopus research into the context of the field in general and their studies specifically.