The role of fibroblast growth factor receptor 2 in liver specification and left-right asymmetry

• Main Authors: Chia-Hao Hsu, 許家豪
• Other Authors: Wen-Pin Wang
• Format: Others
• Language: en_US
• Published: 2008
• Online Access: http://ndltd.ncl.edu.tw/handle/t9rr2j

碩士 === 慈濟大學 === 分子生物及細胞生物研究所 === 96 === Fibroblast growth factor (Fgf) signaling had been identified as the critical signaling in the liver specification process by hsp70:dnFgfr1-EGFP transgene zebrafish. However, the critical Fgf ligands and receptors in the processing had not been identified. Previously, we had identified Fgfr2 as the major Fgf receptor in the endoderm at 24 hpf. In the study, we investigated that the role of Fgfr2 receptor in liver development. We found that the FoxA3 signaling were reduced in liver but not pancreas at 48 hpf in the Fgfr2 morphants (R2 morphants). The liver specification marker, Hhex, was also reduced or absent in R2 morphants. These results indicted that Fgfr2 played an important role in liver specification. Besides, the candidate Fgf ligands in liver specification had been identified by RT-PCR and WISH. We screened all zebrafish Fgfs in the development stages. The genes which expressed in the critical period were selected to perform WISH. So far, we identified that the Fgf24 is expressed in the liver forming region at 24 hpf. Unexpectedly, we found that the LR asymmetry was disrupted in Fgfr2 morphants. Therefore, the issue of Fgfr2 in LR asymmetry regulation was also investigated in this study. The visceral orangs and heart were randomized in Fgfr2 morphants. In the molecular level, Spaw, lefty1 and 2 were also randomized in morphants. However, the notochord structure, the cilia morphology and gene exression around KV showed no difference between WT and morphants. Further examine the gene expression in KV, the dnah9 expression was reduced in morphant but not WT. So fgfr2 may affect the left-right asymmetry at early stage to regulate gene expression in KV. All together, we conclude that fgfr2 signaling pathway is important in the liver specification and asymmetry regulation.