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Int J Mol Sci 2022 Jan 22;233:. doi: 10.3390/ijms23031223.
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Thyroid Hormone Receptor α Controls the Hind Limb Metamorphosis by Regulating Cell Proliferation and Wnt Signaling Pathways in Xenopus tropicalis.

Tanizaki Y , Shibata Y , Zhang H , Shi YB .

Thyroid hormone (T3) receptors (TRs) mediate T3 effects on vertebrate development. We have studied Xenopus tropicalis metamorphosis as a model for postembryonic human development and demonstrated that TRα knockout induces precocious hind limb development. To reveal the molecular pathways regulated by TRα during limb development, we performed chromatin immunoprecipitation- and RNA-sequencing on the hind limb of premetamorphic wild type and TRα knockout tadpoles, and identified over 700 TR-bound genes upregulated by T3 treatment in wild type but not TRα knockout tadpoles. Interestingly, most of these genes were expressed at higher levels in the hind limb of premetamorphic TRα knockout tadpoles than stage-matched wild-type tadpoles, suggesting their derepression upon TRα knockout. Bioinformatic analyses revealed that these genes were highly enriched with cell cycle and Wingless/Integrated (Wnt) signaling-related genes. Furthermore, cell cycle and Wnt signaling pathways were also highly enriched among genes bound by TR in wild type but not TRα knockout hind limb. These findings suggest that direct binding of TRα to target genes related to cell cycle and Wnt pathways is important for limb development: first preventing precocious hind limb formation by repressing these pathways as unliganded TR before metamorphosis and later promoting hind limb development during metamorphosis by mediating T3 activation of these pathways.

PubMed ID: 35163147
Article link: Int J Mol Sci
Grant support: [+]

Species referenced: Xenopus tropicalis
Genes referenced: klf9 tecta.2 thibz thrb
GO keywords: metamorphosis [+]

Disease Ontology terms: neurodevelopmental disorder with hypotonia, stereotypic hand movements, and impaired language
GEO Series: GSE193363: NCBI
GSE193364: NCBI

Article Images: [+] show captions
References [+] :
Brown, Thyroid hormone controls multiple independent programs required for limb development in Xenopus laevis metamorphosis. 2005, Pubmed, Xenbase