Ya Fang, Jia-Ping Wan, Zheng Wang, Shi-Yang Song, Cao-Xu Zhang, Liu Yang, Qian-Yue Zhang, Chen-Yan Yan, Feng-Yao Wu, Sang-Yu Lu, Feng Sun, Bing Han, Shuang-Xia Zhao, Mei Dong, Huai-Dong Song
The mechanisms of bifurcation, a key step in thyroid development, are largely unknown. Here we find three zebrafish lines from a forward genetic screening with similar thyroid dysgenesis phenotypes and identify a stop-gain mutation in hgfa and two missense mutations in met by positional cloning from these zebrafish lines. The elongation of the thyroid primordium along the pharyngeal midline was dramatically disrupted in these zebrafish lines carrying a mutation in hgfa or met. Further studies show that MAPK inhibitor U0126 could mimic thyroid dysgenesis in zebrafish, and the phenotypes are rescued by overexpression of constitutively active MEK or Snail, downstream molecules of the HGF/Met pathway, in thyrocytes...
April 11, 2024: Nature Communications