Department of Molecular Diagnostics & Endocrinology, The Core Laboratory in Medical Center of Clinical Research, State Key Laboratory of Medical Genomics, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, China.
FEBS Open Bio. 2021 May;11(5):1417-1427. doi: 10.1002/2211-5463.13150. Epub 2021 Apr 1.
Thyroid dysgenesis (TD) is a major cause of primary congenital hypothyroidism; however, the molecular mechanism underlying this process is unclear. Current knowledge regarding the morphogenesis of the thyroid gland and vascular anomalies affecting thyroid development is limited. To monitor the early stages of thyroid gland development, we generated double transgenic zebrafish embryos Tg(tg:mCherry/flk1:EGFP). We described the volume of the thyroid from 2 days postfertilization (dpf) to 5 dpf using 3D reconstruction images. We treated zebrafish embryos with the fibroblast growth factor (FGF) inhibitor PD166866 to better understand the impact of vascular defects on thyroid development and the effects of drug administration at specific time periods on different stages of thyroid development. The 3D reconstruction data revealed that the thyroid glands underwent significant transformation at critical time points. PD166866 treatment from 48 to 72 hours postfertilization (hpf) and from 72 to 96 hpf did not cause obvious reductions in thyroid volume but did result in observable abnormalities in thyroid morphology. The treatment also affected thyroid volume from 36 to 48 hpf, thus indicating that there are time-point-specific effects of drug administration during thyroid development. Three-dimensional image reconstruction provides a comprehensive picture of thyroid anatomy and can be used to complement anatomical fluorescence information. The effects of an FGF pathway inhibitor on thyroid development were determined to be time-point-dependent.
甲状腺发育不全（TD）是原发性先天性甲状腺功能减退症的主要原因；然而，这一过程的分子机制尚不清楚。目前对甲状腺发生和影响甲状腺发育的血管异常的认识有限。为了监测甲状腺发育的早期阶段，我们生成了双转基因斑马鱼胚胎 Tg(tg:mCherry/flk1:EGFP)。我们使用 3D 重建图像描述了从受精后 2 天（dpf）到 5 dpf 的甲状腺体积。我们用成纤维细胞生长因子（FGF）抑制剂 PD166866 处理斑马鱼胚胎，以更好地了解血管缺陷对甲状腺发育的影响，以及在特定时间点给药对甲状腺发育不同阶段的影响。3D 重建数据显示，甲状腺在关键时间点发生了显著的变化。PD166866 从受精后 48 小时至 72 小时（hpf）和 72 小时至 96 小时（hpf）处理并没有导致甲状腺体积明显减少，但确实导致甲状腺形态可观察到异常。该处理还影响了从 36 小时至 48 小时（hpf）的甲状腺体积，这表明在甲状腺发育过程中，药物治疗存在特定时间点的影响。三维图像重建提供了甲状腺解剖结构的全貌，可以补充解剖荧光信息。FGF 途径抑制剂对甲状腺发育的影响取决于时间点。
