Campinho Marco A, Saraiva João, Florindo Claudia, Power Deborah M
Comparative Endocrinology and Integrative Biology Group (M.A.C., J.S., D.M.P.), Centre of Marine Sciences, and Departamento de Ciências Biomédicas e Medicina and Centro de Biomedicina Molecular e Estrutural (C.F.), Universidade do Algarve, 8005-139 Faro, Portugal.
Mol Endocrinol. 2014 Jul;28(7):1136-49. doi: 10.1210/me.2014-1032. Epub 2014 May 30.
Teleost eggs contain an abundant store of maternal thyroid hormones (THs), and early in zebrafish embryonic development, all the genes necessary for TH signaling are expressed. Nonetheless the function of THs in embryonic development remains elusive. To test the hypothesis that THs are fundamental for zebrafish embryonic development, an monocarboxilic transporter 8 (Mct8) knockdown strategy was deployed to prevent maternal TH uptake. Absence of maternal THs did not affect early specification of the neural epithelia but profoundly modified later dorsal specification of the brain and spinal cord as well as specific neuron differentiation. Maternal THs acted upstream of pax2a, pax7, and pax8 genes but downstream of shha and fgf8a signaling. The lack of inhibitory spinal cord interneurons and increased motoneurons in the mct8 morphants is consistent with their stiff axial body and impaired mobility. The mct8 mutations are associated with X-linked mental retardation in humans, and the cellular and molecular consequences of MCT8 knockdown during embryonic development in zebrafish provides new insight into the potential role of THs in this condition.
硬骨鱼卵含有丰富的母体甲状腺激素（THs）储备，在斑马鱼胚胎发育早期，TH信号传导所需的所有基因均有表达。尽管如此，THs在胚胎发育中的功能仍不明确。为了验证THs对斑马鱼胚胎发育至关重要这一假设，采用了单羧酸转运蛋白8（Mct8）敲低策略来阻止母体TH的摄取。母体TH的缺失并不影响神经上皮的早期特化，但会显著改变后期大脑和脊髓的背侧特化以及特定神经元的分化。母体THs作用于pax2a、pax7和pax8基因的上游，但在shha和fgf8a信号传导的下游。mct8 morphants中抑制性脊髓中间神经元的缺乏和运动神经元的增加与它们僵硬的轴体和受损的运动能力一致。mct8突变与人类X连锁智力迟钝有关，斑马鱼胚胎发育过程中MCT8敲低的细胞和分子后果为THs在这种情况下的潜在作用提供了新的见解。
