Abstract
In the Xenopus laevis intestine during metamorphosis, stem cells appear and generate the adult epithelium analogous to the mammalian one. We have previously shown that connective tissue cells surrounding the epithelium are essential for the stem cell development. To clarify whether such cells correspond to mammalian Foxl1-expressing mesenchymal cells, which have recently been shown to be a critical component of intestinal stem cell niche, we here examined the expression profile of Foxl1 in the X. laevis intestine by using RT-PCR and immunohistochemistry. Foxl1 expression was transiently upregulated only in connective tissue cells during the early period of metamorphic climax and was the highest just beneath the proliferating stem/progenitor cells. In addition, electron microscopic analysis showed that these subepithelial cells are ultrastructurally identified as telocytes like the mammalian Foxl1-expressing cells. Furthermore, we experimentally showed that Foxl1 expression is indirectly upregulated by thyroid hormone (TH) through Shh signaling and that TH organ-autonomously induces the Foxl1-expressing cells concomitantly with appearance of the stem cells in the tadpole intestine in vitro. The present results suggest that intestinal niche cells expressing Foxl1 are evolutionally conserved among terrestrial vertebrates and can be induced by TH/Shh signaling during amphibian metamorphosis for stem cell development.
Highlights
In the Xenopus laevis intestine during metamorphosis, stem cells appear and generate the adult epithelium analogous to the mammalian one
Our results indicate that Foxl[1] is expressed in the connective tissue cells surrounding the adult epithelial primordia and that its expression is indirectly upregulated by thyroid hormone (TH) through sonic hedgehog (Shh) signaling
To study the temporal gene regulation of Foxl[1] during intestinal remodeling, we first carried out real-time RT-PCR using total RNA extracted from the X. laevis small intestine at various metamorphic stages (Fig. 1)
Summary
In the Xenopus laevis intestine during metamorphosis, stem cells appear and generate the adult epithelium analogous to the mammalian one. Our previous in situ hybridization (ISH) analyses of TH response genes indicated that the connective tissue cells close to the adult epithelial primordia highly express several signaling genes such as bone morphogenetic protein (BMP) 420, patched 1 (Ptc1), Gli[121] and CD4422 These results strongly suggest that the connective tissue cells surrounding the adult epithelial primordia play important roles in the stem cell development as a niche component. It is not yet known whether these cells express Foxl[1] just like the mammalian subepithelial Foxl1-expressing cells, and if so, what signals upregulate Foxl[1] expression in the amphibian remodeling intestine. The amphibian Foxl1-expressing cells share common molecular and morphological characteristics with the mammalian ones, suggesting their evolutionally conserved roles as the intestinal stem cell niche
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