Tissue-Specific Upregulation of MDS/EVI Gene Transcripts in the Intestine by Thyroid Hormone during Xenopus Metamorphosis

Thomas C Miller,Atsuko Ishizuya-Oka,Guihong Sun,Takashi Hasebe,Yun-Bo Shi,Biswajit Das,Liezhen Fu,Rachel A Heimeier,Michelina Plateroti

doi:10.1371/journal.pone.0055585

Abstract

BackgroundIntestinal remodeling during amphibian metamorphosis resembles the maturation of the adult intestine during mammalian postembryonic development when the adult epithelial self-renewing system is established under the influence of high concentrations of plasma thyroid hormone (T3). This process involves de novo formation and subsequent proliferation and differentiation of the adult stem cells.Methodology/Principal FindingsThe T3-dependence of the formation of adult intestinal stem cell during Xenopus laevis metamorphosis offers a unique opportunity to identify genes likely important for adult organ-specific stem cell development. We have cloned and characterized the ectopic viral integration site 1 (EVI) and its variant myelodysplastic syndrome 1 (MDS)/EVI generated via transcription from the upstream MDS promoter and alternative splicing. EVI and MDS/EVI have been implicated in a number of cancers including breast, leukemia, ovarian, and intestinal cancers. We show that EVI and MDS/EVI transcripts are upregulated by T3 in the epithelium but not the rest of the intestine in Xenopus laevis when adult stem cells are forming in the epithelium.Conclusions/SignificanceOur results suggest that EVI and MDS/EVI are likely involved in the development and/or proliferation of newly forming adult intestinal epithelial cells.

Highlights

Amphibian metamorphosis resembles the postembryonic development around birth in mammals with both processes taking place when plasma thyroid hormone (T3) concentrations are high [1,2,3]
Xenopus and human myelodysplastic syndrome 1 (MDS)/ectopic viral integration site 1 (EVI) are highly conserved In an effort to identify genes that are involved in the formation of adult intestinal stem cells during metamorphosis, we carried out a microarray analysis of genes regulated in the epithelium (Ep) or the rest of the intestine during X. laevis metamorphosis
We failed to identify the equivalent of the 3rd exon of human MDS gene, we did obtained a version of the MDS transcript that extended past the end of exon 2 and was homologous to the intron region immediately after exon 2 of the MDS gene in X. tropicalis, suggesting that it likely represents a splicing intermediate

Summary

Introduction

Amphibian metamorphosis resembles the postembryonic development around birth in mammals with both processes taking place when plasma thyroid hormone (T3) concentrations are high [1,2,3] Both metamorphosis and mammalian postembryonic development involve the formation/maturation of adult organs and the establishment of the adult stem cell systems critical for tissue renewal and replacement in the adult. Intestinal remodeling during amphibian metamorphosis resembles the maturation of the adult intestine during mammalian postembryonic development when the adult epithelial self-renewing system is established under the influence of high concentrations of plasma thyroid hormone (T3) This process involves de novo formation and subsequent proliferation and differentiation of the adult stem cells

Methods

Results

Conclusion