Dickkopf genes are co-ordinately expressed in mesodermal lineages

Dickkopf-1 (dkk-1) is member of a novel family of secreted proteins and fun ctions in head induction during Xenopus embryogenesis, acting as a potent i nhibitor of Wnt signalling. Here we report: (1) the isolation of two additi onal murine members of the dkk family, dkk-2 and dkk-3; and (2) analysis of adult and embryonic gene expression of mouse dkk-1,-2, and -3, Xenopus dkk -1 as well as chicken dkk-3. Comparative developmental analyses of the dkk- 1, dkk-2 and dkk-3 in mice indicate that these genes are both temporally an d spatially regulated. They define overlapping deep domains in mesenchymal lineages suggesting a co-ordinated mode of action. All dkks show distinct a nd elevated expression patterns in tissues that mediate epithelial-mesenchy me transformations suggesting that they may participate in heart, tooth, ha ir and whisker follicle, limb and bone induction. In the limb buds expressi on of these genes are found in regions of programmed cell death. In a given organ, dkk-1 tends to be the earliest member expressed. Comparison with Xe nopus dkk-1 and chicken dkk-3 shows evolutionarily conserved expression pat terns. Our observations indicate that dkk genes constitute a new family of secreted proteins that may mediate inductive interactions between epithelia l and mesenchymal cells. (C) 1999 Elsevier Science Ireland Ltd. All rights reserved.