13-P060 The role of Wnt signalling in endodermal organogenesis in zebrafish

Several signalling pathways have been implicated in early liver development and mosaic analysis has revealed an essential involvement of the lateral plate mesoderm (LPM) in this process. Consistently, a zebrafish gene, prometheus/wnt2bb, bilaterally expressed in the LPM adjacent to the forming liver, is required for liver specification. Although liver specification initially fails to occur in prt/ wnt2bb mutant embryos, a small number of endodermal cells start expressing liver-specific genes at later stages, suggesting that additional factors act in parallel in liver specification and compensate for its absence. Studies in chick have shown a complex pattern of defined Wnt gene expression domains along the intestinal anlage. Intriguingly, we find zebrafish Wnt2, closely related to Prt/ Wnt2bb, expressed in an appropriate temporal and spatial window to represent a good candidate to act in conjunction with Prt/Wnt2bb in liver formation. Therefore, we tested its involvement in this process. While Wnt2bb/Prt promotes hepatoblast specification; we observe Wnt2 function is required for subsequent hepatoblast proliferation. These findings suggest a sequential requirement of Wnt signalling in liver formation. Intriguingly, double knockdown of both Wnt ligands revealed a cooperative role in hepatoblast specification. Excitingly, this highlights the complexity of a wnt signalling network in liver/endodermal organogenesis.