Thyroid hormone-upregulated expression of Musashi-1 is specific for progenitor cells of the adult epithelium during amphibian gastrointestinal remodeling

Abstract

In the amphibian gastrointestine during metamorphosis, the primary (larval) epithelium undergoes apoptosis. By contrast, a small number of undifferentiated cells including stem cells actively proliferate and differentiate into the secondary (adult) epithelium that resembles the mammalian counterpart. In the present study, to clarify whether Musashi-1 (Msi-1), an RNA-binding protein, serves as a marker for progenitor cells of the adult epithelium, we chronologically examined Msi-1 expression in the Xenopus laevis gastrointestine by using in situ hybridization and immunohistochemistry. Similar expression profiles of Msi-1 were observed at both mRNA and protein levels. In both the small intestine and the stomach, the transient expression of Msi-1 during metamorphosis spatio-temporally correlated well with active proliferation of the progenitor cells including stem cells of the adult epithelium but did not with apoptosis of the larval epithelium. As the adult progenitor cells differentiated into organ-specific epithelial cells after active proliferation, Msi-1 expression was rapidly downregulated. Therefore, Msi-1 is useful to identify the adult progenitor cells that actively proliferate before final differentiation in the amphibian gastrointestine. Furthermore, our culture experiments have shown that thyroid hormone (TH) organ-autonomously induces Msi-1 expression only in the adult progenitor cells of the X. laevis intestine in vitro as in vivo. However, TH could not induce Msi-1 expression in the intestinal epithelium separated from the connective tissue, where the adult epithelium never developed. These results suggest that Msi-1 expression is upregulated by TH in the adult progenitor cells under the control of the connective tissue and plays important roles in their maintenance and/or active proliferation during amphibian gastrointestinal remodeling.