A novel activity of the Dickkopf-1 amino terminal domain promotes axial and heart development independently of canonical Wnt inhibition.

ABSTRACT: The secreted Dickkopf-1 (Dkk1) protein mediates numerous cell fate decisions and morphogenetic processes. Its carboxyl terminal cysteine-rich region (termed C1) binds LRP5/6 and inhibits canonical Wnt signaling. Paradoxically, the isolated C1 domain of Dkk1 as well as Wnt antagonists that act by sequestering Wnts, such as Frz-B, WIF-1 and Crescent, are poor mimics of the inductive and patterning activities of Dkk1 critical for heart and axial development. To understand the basis for the unique properties of Dkk1, we investigated the function of its amino terminal cysteine-rich region (N1). N1 does not bind LRP or Kremen nor inhibit Wnt signaling and has had no known function. We show that it can synergize with BMP antagonism to induce prechordal and axial mesoderm when expressed as an inde

SUBMITTER: Korol O 

PROVIDER: S-EPMC3038239 | biostudies-literature | 2008 Dec

REPOSITORIES: biostudies-literature