a variant of fibroblast growth factor receptor 2 (fgfr2) regulates left-right asymmetry in zebrafish基因变异的纤维母细胞生长因子受体2(fgfr2)在斑马鱼调节左右不对称.pdfVIP

A Variant of Fibroblast Growth Factor Receptor 2 (Fgfr2) Regulates Left-Right Asymmetry in Zebrafish 1 2¤ 1 3,4 1,2 Da-Wei Liu , Chia-Hao Hsu , Su-Mei Tsai , Chung-Der Hsiao , Wen-Pin Wang * 1 Institute of Medical Sciences, Tzu-Chi University, Hualien, Taiwan, 2 Department of Molecular Biology and Human Genetics, Tzu-Chi University, Hualien, Taiwan, 3 Department of Bioscience Technology, Chung Yuan Christian University, Chung-Li, Taiwan, 4 Center for Nanotechnology, Chung Yuan Christian University, Chung-Li, Taiwan Abstract Many organs in vertebrates are left-right asymmetrical located. For example, liver is at the right side and stomach is at the left side in human. Fibroblast growth factor (Fgf) signaling is important for left-right asymmetry. To investigate the roles of Fgfr2 signaling in zebrafish left-right asymmetry, we used splicing blocking morpholinos to specifically block the splicing of fgfr2b and fgfr2c variants, respectively. We found that the relative position of the liver and the pancreas were disrupted in fgfr2c morphants. Furthermore, the left-right asymmetry of the heart became random. Expression pattern of the laterality controlling genes, spaw and pitx2c, also became random in the morphants. Furthermore, lefty1 was not expressed in the posterior notochord, indicating that the molecular midline barrier had been disrupted. It was also not expressed in the brain diencephalon. Kupffer’s vesicle (KV) size became smaller in fgfr2c morphants. Furthermore, KV cilia were shorter in fgfr2c morphants. We conclude that the fgfr2c isoform plays an important role in the left-right asymmetry during zebrafish development. Citation: Liu D-W, Hsu C-H, Tsai S-M, Hsiao C-D, Wang W-P (20