Thyroid hormone-induced expression of a bZip-containing transcription factor activates epithelial cell proliferation during Xenopus larval-to-adult intestinal remodeling

Abstract

In the intestine during amphibian metamorphosis, stem cells appear, actively proliferate, and differentiate into an adult epithelium analogous to the mammalian counterpart. To clarify the molecular mechanisms regulating this process, we focused on a bZip-containing transcription factor (TH/bZip). We previously isolated TH/bZip from the Xenopus intestine as one of the candidate genes involved in adult epithelial development. Northern blot and in situ hybridization analyses showed that the transient and region-dependent expression of TH/bZip mRNA correlates well with the growth of adult epithelial primordia originating from the stem cells throughout the Xenopus intestine. To investigate its role in the adult epithelial development, we established an in vitro gene transfer system by using electroporation and organ culture techniques, and we overexpressed TH/bZip in the epithelium of Xenopus tadpole intestines. In the presence of thyroid hormone (TH) where the adult epithelial primordia appeared after 3 days of cultivation, overexpression of TH/bZip significantly increased their proliferating activity. On the other hand, in the absence of TH where the epithelium remained as larval-type without any metamorphic changes, ectopic expression of TH/bZip significantly increased the proliferating activity of the larval epithelium but had no effects on its differentiated state. These results indicate that TH/bZip functions as a growth activator during amphibian intestinal remodeling, although TH/bZip expression in the epithelium alone is not sufficient for inducing the stem cells.