Darras Veerle M, Houbrechts Anne M, Van Herck Stijn L J
Laboratory of Comparative Endocrinology, Department of Biology, Division of Animal Physiology and Neurobiology, KU Leuven, B-3000 Leuven, Belgium.
Laboratory of Comparative Endocrinology, Department of Biology, Division of Animal Physiology and Neurobiology, KU Leuven, B-3000 Leuven, Belgium.
Biochim Biophys Acta. 2015 Feb;1849(2):130-41. doi: 10.1016/j.bbagrm.2014.05.004. Epub 2014 May 17.
Thyroid hormones (THs) play an essential role in vertebrate development, acting predominantly via nuclear TH receptors (TRs) which are ligand-dependent transcription factors. Binding of the ligand (predominantly T3) induces a switch from gene activation to gene repression or vice versa. Iodothyronine deiodinases (Ds) and TH transporters are important regulators of intracellular T3 availability and therefore contribute to the control of TR-dependent development.
The present review discusses the possible roles of Ds and TH transporters in regulating embryonic and larval (pre-juvenile) TR-dependent development in vertebrates. It focuses mainly on well-known model species for direct and indirect vertebrate development, including zebrafish, Xenopus, chicken and mouse. Data are provided on stage- and tissue/cell-specific changes in expression of Ds and TH transporters. This information is combined with functional data obtained from gain-and-loss of function studies.
Knockout/knockdown of each type of D has provided strong evidence for their implication in the control of important developmental processes and several D expression patterns and functions have been conserved throughout vertebrate evolution. Knockout/knockdown of the inactivating D3 enzyme indicates that a premature switch from unliganded to liganded TR action is often more detrimental than a delayed one. The majority of ontogenetic studies on TH transporter distribution and function have focused on brain development, showing variable impact of knockout/knockdown depending on the species. Future research in different models using conditional silencing will hopefully further improve our understanding on how TH transporters, Ds and TRs cooperate to regulate TR-mediated impact on vertebrate development. This article is part of a Special Issue entitled: Nuclear receptors in animal development.
甲状腺激素（THs）在脊椎动物发育中起关键作用，主要通过作为配体依赖性转录因子的核甲状腺激素受体（TRs）发挥作用。配体（主要是T3）的结合会诱导从基因激活到基因抑制的转变，反之亦然。碘甲状腺原氨酸脱碘酶（Ds）和甲状腺激素转运体是细胞内T3可用性的重要调节因子，因此有助于控制TR依赖性发育。
本综述讨论了Ds和甲状腺激素转运体在调节脊椎动物胚胎和幼体（幼年期前）TR依赖性发育中的可能作用。它主要关注直接和间接脊椎动物发育的著名模式物种，包括斑马鱼、非洲爪蟾、鸡和小鼠。提供了Ds和甲状腺激素转运体表达在阶段以及组织/细胞特异性变化的数据。这些信息与从功能获得和功能丧失研究中获得的功能数据相结合。
每种类型的D的敲除/敲低都为它们参与重要发育过程的控制提供了有力证据，并且几种D的表达模式和功能在整个脊椎动物进化过程中得以保留。失活的D3酶的敲除/敲低表明，从未结合配体到结合配体的TR作用的过早转变通常比延迟转变更具危害性。大多数关于甲状腺激素转运体分布和功能的个体发生学研究都集中在脑发育上，显示出敲除/敲低的影响因物种而异。未来使用条件性沉默在不同模型中的研究有望进一步增进我们对甲状腺激素转运体、Ds和TRs如何协作调节TR介导的对脊椎动物发育影响的理解。本文是名为：动物发育中的核受体的特刊的一部分。
