Fig. 7

Lrp6 Is Required to Mediate the Roles of EpCAM and Wnt2bb in Hepatic Development(A–G) At 102 hpf, liver phenotypes in hi2151 mutants (B, 61/84) or wnt2bb morphants (D, 90/104) are rescued by lrp6 mRNA (C, 70/103; and E, 26/38), whereas reduced liver size in lrp6 morphants (F, 101/137) cannot be rescued by epcam mRNA (G, 78/102) as shown under the Tg(lfabp:GFP) background.(H–U) Expressions of hhex (H–N) at 28 hpf and cp (O–U) at 52 hpf in the hepatic endoderm.(V) A model of determinations of cell type and position of hepatic development. Presence of EpCAM in the endoderm and Wnt2bb at a specific anterior-posterior position in the LPM determine the cell type and the position of liver, respectively. They cooperatively activate Wnt2bb signaling in the hepatic endoderm. L, hepatic endoderm.(W) In nonendodermal cells around Wnt2bb, EpCAM is absent. Lrp6 forms an inhibitory ternary complex with Kremen1 and Dkk2. Thus, Lrp6 is removed from the cell surface and Wnt2bb signaling is not licensed.(X) In hepatic endodermal cells, EpCAM directly binds to Kremen1, which disrupts the Dkk2-Kremen1 interaction. This stabilizes Lrp6 on the endodermal cell surface and allows formation of active Lrp6-signalosomes, licenses, and cooperatively activates Wnt2bb signaling for hepatic development.See also Figures S1, S7, and Table S1.