Regulation of adult intestinal epithelial stem cell development by thyroid hormone during Xenopus laevis metamorphosis

Abstract

During amphibian metamorphosis, most or all of the larval intestinal epithelial cells undergo apoptosis. In contrast, stem cells of yet-unknown origin actively proliferate and, under the influence of the connective tissue, differentiate into the adult epithelium analogous to the mammalian counterpart. Thus, amphibian intestinal remodeling is useful for studying the stem cell niche, the clarification of which is urgently needed for regenerative therapies. This review highlights the molecular aspects of the niche using the Xenopus laevis intestine as a model. Because amphibian metamorphosis is completely controlled by thyroid hormone (TH), the analysis of TH response genes serves as a powerful means for clarifying its molecular mechanisms. Although functional analysis of the genes is still on the way, recent progresses in organ culture and transgenic studies have gradually uncovered important roles of cell-cell and cell-extracellular matrix interactions through stromelysin-3 and sonic hedgehog/bone morphogenetic protein-4 signaling pathway in the epithelial stem cell development. Developmental Dynamics 236:3358 -3368, 2007.

Novel Functions of Protein Arginine Methyltransferase 1 in Thyroid Hormone Receptor-Mediated Transcription and in the Regulation of Metamorphic Rate in Xenopus laevis

“…Like other metamorphic processes, all of these changes are completely controlled by T3. The molecular transformations during intestinal remodeling in X. laevis have been extensively characterized and documented (15,32,71), making the Xenopus intestine a powerful model to study the molecular mechanism of TR-mediated transcription in vivo. Thus, we analyzed the expression of PRMT1 mRNA and protein by quantitative real-time reverse transcription-PCR (qRT-PCR) and Western blotting, respectively.…”

Thyroid hormone-regulated expression of nuclear lamins correlates with dedifferentiation of intestinal epithelial cells during Xenopus laevis metamorphosis

“…The adult progenitor cells during X. laevis intestinal remodeling include the stem cells and their descendent proliferating cells. However, both cell types are morphologically indistinguishable and cannot be distinguished by MG-PY staining nor by immunohistochemistry for any stem cell marker such as Musashi-1, which are also expressed in both the stem cells and their descendent cells in the mammalian intestine (Ishizuya-Oka and Shi 2007;Ishizuya-Oka et al 2001). In the present study, interestingly, the expression level of LA was different in different adult progenitor cells even in the same islet.…”

“…That is, the adult epithelium is continuously renewed from stem cells localized in the troughs of the intestinal folds. These chronological observations indicate that the adult progenitor cells detected at stage 60 include the stem cells analogous to the mammalian ones (Ishizuya-Oka and Shi 2007). Thus, the X. laevis intestinal remodeling provides us a unique model for the study of postembryonic stem cell development conserved between amphibian and mammals.…”

“…Since all of the larval epithelial cells are morphologically and immunohistochemically differentiated in the X. laevis intestine until stage 59 (Ishizuya-Oka and Shi 2007;Marshall and Dixon 1978), this provides experimental evidence that some of the differentiated larval epithelial cells dedifferentiate into the adult stem cells. Although there is increasing evidence that larval cells dedifferentiate into stem cells in other X. laevis remodeling organs (Mukhi et al 2008), the mechanisms underlying dedifferentiation are poorly understood.…”

Identification and gastrointestinal expression of Xenopus laevis FoxF2

“…From a molecular perspective, the expression of FoxF2 in the mesenchyme of Xenopus laevis appears very similar to BMP-4 and BMP-1 expression (Ishizuya-Oka and Shi, 2007). During embryonic development, BMP-4 is known to be upstream of FoxF1 both in vascular and visceral mesoderm development (Astorga and Carlsson, 2007, Ormestad et al, 2006, Tseng et al, 2004.…”