Dickkopf-1 is a member of a new family of secreted proteins and functions in head induction

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Abstract

The Spemann organizer in amphibian embryos is a tissue with potent head-inducing activity, the molecular nature of which is unresolved. Here we describe dickkopf-1 (dkk-1), which encodes Dkk-1, a secreted inducer of Spemann's organizer in Xenopus and a member of a new protein family. Injections of mRNA and antibody indicate that dkk-1 is sufficient and necessary to cause head induction. dkk-1 is a potent antagonist of Wnt signalling, suggesting that dkk genes encode a family of secreted Wnt inhibitors.

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Figure 1: Dkk-1 is secreted and is a member of a new protein family.
Figure 2: Expression of dkk-1 in Xenopus and mouse.
Figure 3: Head induction by dkk-1.
Figure 4: Molecular markers induced by dkk-1.
Figure 5: dkk-1 inhibits Wnt signalling.
Figure 6: dkk-1 is required for head formation.

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Acknowledgements

We thank D. Bock, R. Dosch, V. Gawantka, R. Nitsch and N. Pollet for in situ hybridizations; P. Kioschis and N. Pollet for help with DNA sequence analysis; I. Schuster for histology; U.Hebling for assistance with sequencing work; S. Cohen for critically reading the manuscript; and B.Ferreiro, H. Herrmann, D. Kimelman, P. Lemaire, R. Moon, C. Otto, S. Sokol and M. Ueno for providing materials. This work was supported in part by the Deutsche Forschungsgemeinschaft.

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Correspondence to Christof Niehrs.

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