21-P043 Fibroblast growth factor (Fgf) signaling regulates left–right asymmetry and intestinal cell differentiation in zebrafish

Previously, we identified Fgfr2 as the major Fgf receptor in liver specification. Expression of Hhex in the liver was reduced in Fgfr2 morphants. Unexpectedly, we found the relative position of the liver and pancreas were disrupted. In addition to visceral organs, we found the heart was randomized in Fgfr2 morphants. Expression patterns of genes controlling laterality including Spaw, lefty1 and 2 were also randomized. Despite of these findings, Kupffer’s vesicle (KV) formed normally. We suggest that Fgfr2 may affect the left–right asymmetry at early stage to influence gene expression. In addition to LR asymmetry, abnormal differentiation of goblet cells was observed in Fgfr2 morphants. But the detailed mechanism remains to be elucidated. We found Fgf10, a ligand for Fgfr2b, was expressed in the intestine. Differentiation of goblet cells was affected in the Fgf10 mutant dae. However, the phenotypes were not that severe compared to Fgfr2 morphants. It raised the possibility that other Fgfs are involved in controlling the process. After screening for Fgf ligands, we analyzed the differentiation of goblet cell in Fgf24 morphants. The number of goblet cells was reduced. We concluded that Fgf signaling could regulate the differentiation in zebrafish. In dae mutant fish intestine, we found DeltaD-expressing cells were increased. We also found when inactivating Notch signaling in mib mutant fish or Su(H) morphants, the differentiation of goblet cells was severely impaired. These data indicated that Notch pathway might be disrupted in dae and therefore the goblet cell differentiation was inhibited.