KU Leuven, Laboratory of Comparative Endocrinology, Department of Biology, B-3000, Leuven, Belgium.
KU Leuven, Laboratory of Comparative Endocrinology, Department of Biology, B-3000, Leuven, Belgium.
Mol Cell Endocrinol. 2017 Dec 25;459:71-78. doi: 10.1016/j.mce.2017.01.045. Epub 2017 Jan 31.
Thyroid hormones (THs) are important mediators of vertebrate central nervous system (CNS) development, thereby regulating the expression of a wide variety of genes by binding to nuclear TH receptors. TH transporters and deiodinases are both needed to ensure appropriate intracellular TH availability, but the precise function of each of these regulators and their coaction during brain development is only partially understood. Rodent knockout models already provided some crucial insights, but their in utero development severely hampers research regarding the role of TH regulators during early embryonic stages. The establishment of novel gain- and loss-of-function techniques has boosted the position of externally developing non-mammalian vertebrates as research models in developmental endocrinology. Here, we elaborate on the chicken as a model organism to elucidate the function of TH regulators during embryonic CNS development. The fast-developing, relatively big and accessible embryo allows easy experimental manipulation, especially at early stages of brain development. Recent data on the characterisation and spatiotemporal expression pattern of different TH regulators in embryonic chicken CNS have provided the necessary background to dissect the function of each of them in more detail. We highlight some recent advances and important strategies to investigate the role of TH transporters and deiodinases in various CNS structures like the brain barriers, the cerebellum, the retina and the hypothalamus. Exploiting the advantages of this non-classical model can greatly contribute to complete our understanding of the regulation of TH bioavailability throughout embryonic CNS development.
甲状腺激素（THs）是脊椎动物中枢神经系统（CNS）发育的重要介质，通过与核 TH 受体结合来调节广泛的基因表达。TH 转运蛋白和脱碘酶对于确保适当的细胞内 TH 可用性都是必需的，但这些调节剂的每个功能及其在大脑发育过程中的共同作用仅部分被理解。啮齿动物敲除模型已经提供了一些关键的见解，但它们的胚胎内发育严重阻碍了关于 TH 调节剂在早期胚胎阶段的作用的研究。新型的增益和损耗功能技术的建立提高了外部发育的非哺乳动物脊椎动物在发育内分泌学中的研究模型地位。在这里，我们详细阐述了鸡作为一种模型生物，以阐明 TH 调节剂在胚胎 CNS 发育过程中的功能。快速发育、相对较大且易于接近的胚胎允许进行容易的实验操作，特别是在大脑发育的早期阶段。最近关于不同 TH 调节剂在胚胎鸡 CNS 中的特征和时空表达模式的数据为详细剖析它们各自的功能提供了必要的背景。我们强调了一些最近的进展和重要策略，以研究 TH 转运蛋白和脱碘酶在各种 CNS 结构（如脑屏障、小脑、视网膜和下丘脑）中的作用。利用这个非经典模型的优势可以极大地促进我们对整个胚胎 CNS 发育过程中 TH 生物利用度的调节的理解。
