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

Abstract

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.

Molecular and genetic studies suggest that thyroid hormone receptor is both necessary and sufficient to mediate the developmental effects of thyroid hormone

“…The same conclusion was also reached in several labs in subsequent studies, where a dominant negative TR was overexpressed by using in vivo transfection or transgenesis with ubiquitous and tissue-specific promoters (Fig. 3) (Buchholz et al, 2003; Das et al, 2002; Nakajima and Yaoita, 2003; Schreiber and Brown, 2003; Schreiber et al, 2009). These in vivo studies also showed that the expression of the dominant negative TR inhibited TH-induced transcription of target genes.…”

Transdifferentiation of tadpole pancreatic acinar cells to duct cells mediated by Notch and stromelysin-3

“…ST3 is a direct response gene of TH in tail fibroblasts (Wang and Brown, 1993) and in the tadpole intestinal mesenchyme (Shi and Brown, 1993). A TH-responsive promoter in the X. laevis genome has been identified next to the ST3 gene (Li et al, 1998) and confirmed by transgenic experiments (Schreiber et al, 2009). ST3 is dramatically and rapidly up regulated by TH in the tadpole exocrine pancreas (Fig.1).…”

“…ST3 is so dramatically up regulated by TH during metamorphosis that it has been a prime suspect in the massive apoptosis and remodeling that occurs (reviewed by Mathew et al, 2010). The direct response nature of the ST3 gene was confirmed by identifying a thyroid response element near the first ST3 exon (Li et al, 1998) that responds to TH by up regulating GFP in transgenic X. laevis (Schreiber et al, 2009). ST3 has been implicated in the remodeling of the intestine at the climax of metamorphosis (Ishizuya-Oka et al, 2000).…”

Adult-type myogenesis of the frog Xenopus laevis specifically suppressed by notochord cells but promoted by spinal cord cells in vitro

“…One is the deletion of larval organs such as tadpole tail (Kerr et al 1974), the second is the formation of new organs such as fore-and hindlimbs (Muntz 1975), and the third is the larval-to-adult conversion of organs such as dorsal muscles (Nishikawa and Hayashi 1994;Shimizu-Nishikawa et al 2002) and intestinal epithelium (Ishizuya-Oka and Ueda 1996;Ishizuya-Oka et al 2001). These events are triggered by the action of thyroid hormone, triiodothyronine (T 3 ; Das et al 2009;Mukhi et al 2010) and modulated by cell-to-cell (Schreiber et al 2009) and cell-to-extracellular matrix interactions (Ishizuya-Oka et al 2000). Amphibian metamorphosis thus serves as an attractive system for studying organ remodeling during development.…”