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Sci Rep
2016 Jun 02;6:27310. doi: 10.1038/srep27310.
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Transcriptome profiles of metamorphosis in the ornamented pygmy frog Microhyla fissipes clarify the functions of thyroid hormone receptors in metamorphosis.
Zhao L, Liu L, Wang S, Wang H, Jiang J.
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Anuran metamorphosis is an excellent system in which to study postembryonic development. Studies on Xenopus (Mesobatrachia) show that thyroid hormone receptors (TRs) regulate metamorphosis in a ligand-dependent manner by coordinating the action of hundreds of genes. However, whether this mechanism is conserved among amphibians is still unknown. To understand the molecular mechanism of this universal phenomenon, we report the transcriptional profiles of the three key developmental stages in Microhyla fissipes (Neobatrachia): premetamorphosis (PM), metamorphic climax (MC) and completion of metamorphosis (CM). In total, 2,293 differentially expressed genes were identified from comparisons of transcriptomes, and these genes showed stage-specific expression patterns. Unexpectedly, we found that TRα was highly expressed in Xenopus laevis and Bufo gargarizans at premetamorphosis but showed low expression in M. fissipes. In contrast, TRβ was highly expressed during metamorphosis in M. fissipes and X. laevis. This result may imply that TRβ is essential for initiating metamorphosis, at least in M. fissipes. Thus, our work not only identifies genes that are likely to be involved in Neobatrachia metamorphosis but also clarifies the roles of unliganded TRα in regulating tadpole growth and timing of metamorphosis, which may be conserved in anurans, and the role of liganded TRβ in launching metamorphosis.
Figure 1. Samples of the three developmental stages used for gene expression profile analysis.Microhyla fissipes in the premetamorphosis (PM), metamorphic climax (MC) and completion of metamorphosis (CM) stages are presented at the left, middle and right, respectively. The scale of the animal’s body size is 1:5, and the scale bar is 1 mm.
Figure 2. Analysis of differentially expressed unigenes during Microhyla fissipes metamorphosis.Venn diagrams show the number of genes significantly (a) up-regulated and (b) down-regulated; green, blue and yellow circles represent the changes from PM to MC, MC to CM, and PM to CM, respectively. (c) Similarity of the expression profiles between genes with hierarchical clustering is shown above the heatmap. Intensity of color indicates expression levels, and the three major clusters represent the PM, MC and CM stages.
Figure 3. Expression profiles of six genes.The X axis represents the developmental stages. Lines represent the FPKM value of the transcriptome result (Y axis at right). Columns and bars represent the means and standard errors of three individual samples (Y axis at left). Each experiment was performed in triplicate.
Figure 4. GO enriched processes in three key developmental stages.The significantly overrepresented (FDR < 0.05) enrichment factors of GO biological processes of the three clusters using hierarchical clustering are shown (Table S7). Only groups containing more than five genes and having a fold enrichment factor >3 are presented.
Figure 5. Clustering profiles.Plots of SOM profiles of the reduced set with their centroids highlighted in blue. Four clusters that were further analyzed for stage-specific expression patterns are marked in black boxes. The vertical axis represents the relative gene abundance, and the horizontal axis shows the three developmental stages.
Figure 6. Expressional profiles of thyroid hormone (TH) - related genes involved in regulating metamorphosis.(a) Correlation of the expression levels of TRα, RXRα, TRβ, RXRβ and TG mRNAs with the three key developmental stages of M. fissipes. The vertical axis represents expression levels (FPKM value), and the horizontal axis represents developmental stages. (b) Expression profiles of TR genes in three key developmental stages of M. fissipes. The X axis represents the developmental stages. Lines and bars represent the means and standard errors of three individual samples (Y axis). Each experiment was performed in triplicate. (c) Comparison of the expression levels of TR genes in B. gargarizans at the PM stage. The X axis represents two TR genes. Columns and bars represent the means and standard error of three individual samples. Each experiment was performed in triplicate.
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