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Fig. 8

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Figures for Kagermeier-Schenk et al., 2011
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Fig. 8

Waif1a Activates Noncanonical Wnt Signaling by a Dkk1-Dependent Mechanism

(A) Overexpression of zebrafish waif1a RNA (200 pg) inhibits CE movements of Xenopus Keller explants. noninj., noninjected.

(B) Fraction of elongated explants: waif1a, 200 pg; waif1c, 200 pg; dnRhoA, 50 pg; dnRac1, 50 pg; DshΔDEP, 500 pg; frizzled 7 MO, 1.6 pmol; frizzled 8 MO, 1.6 pmol; xnr3, 200 pg; lrp6, 60 pg. p < 0.05, Student′s t test. The average of three independent experiments is shown.

(C) Western blot of Xenopus embryo extracts at stage 10.5 blotted for endogenous phospho-JNK and total JNK. xwnt5a, 100 pg; xwaif1a.2, 50 pg; xdkk1, 100 pg; xwaif1a.2 MO, 1.6 pmol; xdkk1 MO, 1.6 pmol.

(D) dnRhoA (50 pg) does not, but xnr3 (200 pg) can, fully rescue zebrafish waif1a (200 pg)-induced ventralization of Xenopus embryos quantified using the DAI. p < 0.05, Student′s t test.

(E) Fraction of elongated explants. dkk1 MO low, 0.8 pmol; high, 1.6 pmol. The average of three independent experiments is shown. p < 0.05, Student′s t test.

(F) CE defects in zebrafish embryos coinjected with waif1a MO1 and dkk1 MO (52 of 61 embryos) shown by compressed myoD-positive somites (arrowheads) and widened krox20 and pax2.1-positive neural expression domains (brackets) at the 15 somite stage. waif1a MO1, 2 ng; control MO, 2 ng; dkk1 MO, 1 ng.

(G) Model of Waif1a function as modifier of Wnt signaling pathways. waif1a expression is directly regulated by β-catenin signaling during gastrulation and acts as a cell-autonomous feedback inhibitor of the pathway in Wnt-receiving cells. Waif1 interacts with LRP6 and interferes with Wnt-dependent internalization of LRP6, without affecting LRP/Frizzled interaction or LRP6 phosphorylation.

See also Figure S8.

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Reprinted from Developmental Cell, 21(6), Kagermeier-Schenk, B., Wehner, D., Ozhan-Kizil, G., Yamamoto, H., Li, J., Kirchner, K., Hoffmann, C., Stern, P., Kikuchi, A., Schambony, A., and Weidinger, G., Waif1/5T4 Inhibits Wnt/β-Catenin Signaling and Activates Noncanonical Wnt Pathways by Modifying LRP6 Subcellular Localization, 1129-43, Copyright (2011) with permission from Elsevier. Full text @ Dev. Cell