Pairing morphology with gene expression in thyroid hormone-induced intestinal remodeling and identification of a core set of TH-induced genes across tadpole tissues

Abstract

Thyroid hormone (T3) plays a central role in vertebrate post-embryonic development, and amphibian metamorphosis provides a unique opportunity to examine T3-dependent developmental changes. To establish a molecular framework for understanding T3-induced morphological change, we identified a set of gene expression profiles controlled by T3 in the intestine via microarray analysis. Samples were obtained from premetamorphic Xenopus laevis tadpole intestines after 0, 1, 3, and 6 days of T3 treatment, which induces successive cell death and proliferation essential for intestinal remodeling. Using a set of 21,807 60-mer oligonucleotide probes representing >98% of the Unigene clusters, we found that 1997 genes were differentially regulated by 1.5-fold or more during this remodeling process and were clustered into four temporal expression profiles; transiently up- or downregulated and late up- or downregulated. Gene Ontology categories most significantly associated with these clusters were proteolysis, cell cycle, development and transcription, and electron transport and metabolism, respectively. These categories are common with those found for T3-regulated genes from brain, limb, and tail, although more than 70% of T3-regulated genes are tissue-specific, likely due to the fact that not all genes are annotated into GO categories and that GO categories common to different organs also contain genes regulated by T3 tissue specifically. Finally, a core set of upregulated genes, most previously unknown to be T3-regulated, were identified and enriched in genes involved in transcription and cell signaling.