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Organ-Specific Requirements for Thyroid Hormone Receptor Ensure Temporal Coordination of Tissue-Specific Transformations and Completion of Xenopus Metamorphosis.

ABSTRACT: Background: Thyroid hormone (triiodothyronine [T3]) is essential for the development throughout vertebrates. Anuran metamorphosis mimics mammalian postembryonic development, a period around birth when plasma T3 level peaks and many organs/tissues mature into their adult forms. Compared with the uterus-enclosed mammalian embryos, tadpoles can be easily manipulated to study the roles of T3 and T3 receptors (TRs) in tissue remodeling and adult organ development. We and others have previously knocked out TR? or TR? in the diploid anuran Xenopus tropicalis and reported distinct effects of the two receptor knockouts on metamorphosis. However, animals lacking either TR? or TR? can complete metamorphosis and develop into reproductive adults. Methods: We have generated TR? and TR? double knockout animals and carried out molecular and morphological analyses to determine if TR is required for Xenopus development. Results: We found that the TR double knockout tadpoles do not respond to T3, supporting the view that there are no other TR genes in X. tropicalis and that TR is essential for mediating the effects of T3 in vivo. Surprisingly, the double knockout tadpoles are able to initiate metamorphosis and accomplish many metamorphic changes, such as limb development. However, all double knockout tadpoles stall and eventually die at stage 61, the climax of metamorphosis, before tail resorption takes place. Analyses of the knockout tadpoles at stage 61 revealed various developmental abnormalities, including precocious ossification and extra vertebrae. Conclusions: Our data indicate that TRs are not required for the initiation of metamorphosis but is essential for the completion of metamorphosis. Furthermore, the differential effects of TR knockout on different organs/tissues suggest tissue-specific roles for TR to control temporal coordination and progression of metamorphosis in various organs.

SUBMITTER: Shibata Y

PROVIDER: S-EPMC7047119 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature

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Organ-Specific Requirements for Thyroid Hormone Receptor Ensure Temporal Coordination of Tissue-Specific Transformations and Completion of Xenopus Metamorphosis.

Shibata Yuki Y Wen Luan L Okada Morihiro M Shi Yun-Bo YB

Thyroid : official journal of the American Thyroid Association 20200123 2

Background: Thyroid hormone (triiodothyronine [T3]) is essential for the development throughout vertebrates. Anuran metamorphosis mimics mammalian postembryonic development, a period around birth when plasma T3 level peaks and many organs/tissues mature into their adult forms. Compared with the uterus-enclosed mammalian embryos, tadpoles can be easily manipulated to study the roles of T3 and T3 receptors (TRs) in tissue remodeling and adult organ development. We and others have pre ...[more]

PMID: 31854240

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Project description:Tail resorption during anuran metamorphosis is perhaps the most dramatic tissue transformation that occurs during vertebrate development. Earlier studies in highly related anuran species Xenopus laevis and Xenopus tropicalis have shown that thyroid hormone (T3) receptor (TR) plays a necessary and sufficient role to mediate the causative effect of T3 on metamorphosis. Of the two known TR genes in vertebrates, TRα is highly expressed during both premetamorphosis and metamorphosis while TRβ expression is low in premetamorphic tadpoles but highly upregulated as a direct target gene of T3 during metamorphosis, suggesting potentially different functions during metamorphosis. Indeed, gene knockout studies have shown that knocking out TRα and TRβ has different effects on tadpole development. In particularly, homozygous TRβ knockout tadpoles become tailed frogs well after sibling wild type ones complete metamorphosis. Most noticeably, in TRβ-knockout tadpoles, an apparently normal notochord is present when the notochord in wild-type and TRα-knockout tadpoles disappears. Here, we have investigated how tail notochord resorption is regulated by TR. We show that TRβ is selectively very highly expressed in the notochord compared to TRα. We have also discovered differential regulation of several matrix metalloproteinases (MMPs), which are known to be upregulated by T3 and implicated to play a role in tissue resorption by degrading the extracellular matrix (ECM). In particular, MMP9-TH and MMP13 are extremely highly expressed in the notochord compared to the rest of the tail. In situ hybridization analyses show that these MMPs are expressed in the outer sheath cells and/or the connective tissue sheath surrounding the notochord. Our findings suggest that high levels of TRβ expression in the notochord specifically upregulate these MMPs, which in turn degrades the ECM, leading to the collapse of the notochord and its subsequent resorption during metamorphosis.

Dataset Information

Organ-Specific Requirements for Thyroid Hormone Receptor Ensure Temporal Coordination of Tissue-Specific Transformations and Completion of Xenopus Metamorphosis.

Publications

Organ-Specific Requirements for Thyroid Hormone Receptor Ensure Temporal Coordination of Tissue-Specific Transformations and Completion of <i>Xenopus</i> Metamorphosis.

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