Morvan Dubois Ghislaine, Sebillot Anthony, Kuiper George G J M, Verhoelst Carla H J, Darras Veerle M, Visser Theo J, Demeneix Barbara A
Department of Regulations, Development, and Molecular Diversity, Muséum National d'Histoire Naturelle, 75231 Paris Cedex 05, France.
Endocrinology. 2006 Oct;147(10):4941-9. doi: 10.1210/en.2006-0609. Epub 2006 Jul 6.
Thyroid hormones orchestrate amphibian metamorphosis. The type 2 and type 3 deiodinases make vital contributions to this process by controlling levels of the thyroid hormones T(4) and T(3) available to different tissues. Because the tadpole thyroid gland is not functional until stage NF44, it has been widely assumed that thyroid signaling is absent during amphibian early development, thyroid hormone only becoming a major regulator during premetamorphic stages. Similarly, in mammals, thyroid function is known to be essential to neuronal development, especially during the perinatal stages, but again little is known about early stages of development. Here we demonstrate that key elements of thyroid hormone signaling are present during early development of Xenopus. In particular, we find functional thyroid hormone-activating deiodinases and significant levels of their substrates, T(4) and T(3), during early embryogenesis. Furthermore, we have further characterized a recently identified deiodinase in amphibians, homologous to mammalian type 1 deiodinase (D1). This enzyme is expressed in marked, spatially defined patterns during embryogenesis. The patterns of expression of type 1 deiodinase are distinct from those of type 2 and type 3 deiodinases. Deiodinase expression is found in neurogenic areas from stage NF30 onward, both in the central and peripheral nervous systems. We conclude that both activating and inactivating deiodinases show dynamic patterns of expression during early embryogenesis in amphibians, particularly in neurogenic areas. These findings suggest that thyroid hormone signaling is a key component of early neuronal development in vertebrates.
甲状腺激素调控两栖动物的变态发育。2型和3型脱碘酶通过控制不同组织可利用的甲状腺激素T4和T3水平,对这一过程做出了至关重要的贡献。由于蝌蚪的甲状腺直到NF44期才开始发挥功能,人们普遍认为两栖动物早期发育过程中不存在甲状腺信号传导,甲状腺激素仅在变态前阶段才成为主要调节因子。同样,在哺乳动物中,已知甲状腺功能对神经元发育至关重要,尤其是在围产期阶段,但对发育早期阶段的了解同样很少。在此,我们证明非洲爪蟾早期发育过程中存在甲状腺激素信号传导的关键元件。具体而言,我们在早期胚胎发育过程中发现了具有功能的甲状腺激素激活脱碘酶及其底物T4和T3的显著水平。此外,我们进一步对两栖动物中最近鉴定出的一种与哺乳动物1型脱碘酶(D1)同源的脱碘酶进行了表征。该酶在胚胎发育过程中以明显的、空间限定的模式表达。1型脱碘酶的表达模式与2型和3型脱碘酶不同。从NF30期开始,在中枢和外周神经系统的神经发生区域均发现了脱碘酶的表达。我们得出结论,激活型和失活型脱碘酶在两栖动物早期胚胎发育过程中均呈现动态表达模式,尤其是在神经发生区域。这些发现表明甲状腺激素信号传导是脊椎动物早期神经元发育的关键组成部分。