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Dickkopf-1 (dkk-1) is member of a novel family of secreted proteins and functions in head induction during Xenopus embryogenesis, acting as a potent inhibitor of Wnt signalling. Here we report: (1) the isolation of two additional 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 and spatially regulated. They define overlapping deep domains in mesenchymal lineages suggesting a co-ordinated mode of action. All dkks show distinct and elevated expression patterns in tissues that mediate epithelial- mesenchyme transformations suggesting that they may participate in heart, tooth, hair and whisker follicle, limb and bone induction. In the limb buds expression 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 Xenopus dkk-1 and chicken dkk-3 shows evolutionarily conserved expression patterns. Our observations indicate that dkk genes constitute a new family of secreted proteins that may mediate inductive interactions between epithelial and mesenchymal cells.
Fig. 9. Expression of Xenopus dkk-1 and chicken dkk-3.
Expression of Xenopus dkk-1 (A-C) and chicken dkk-3 (D-F) was analyzed by whole mount in situ hybridisation.
(A) dkk-1 expression in early tailbud (stage 26). Dorsal view with anterior to the left. Inset shows transverse vibratome section at the level indicated by the dashed line. Expression occurs in cranial nerves (cn), eye (ey), forming somites (fs), otic vesicle (ov), proctodeum (pr). Three stripes of expression running along the dorsal trunk correspond to cells of the dorsal neural tube (dn) and cells at boundary of dorsal somite and neural tube (ds). (B, C) dkk-1 expression in tailbud (stage 32). Expression occurs in cranial nerves (cn), dorsal eye (de), dorsal otic vesicle (do), fin mesenchyme (fm), forming somites (fs) pituitary (pi), proctodeum (pr) as well as an unidentified population of cells around the pronephros that may represent pigment cells by location and shape. Transverse section at hindbrain level shows expression in archenteron roof (C). (D) Chicken embryos at stage 8 (four somites), (E) stage 15 (about 24 somites), (F) stage 21 (3.5 days, 45 somites), dorsal view. Inset: 1-2 mm thick transverse slice of spinal cord taken at hindlimb level.
ao, area opaca;
pm, pre-somitic mesoderm;
rp, roof plate;
dkk1 (dickkopf WNT signaling pathway inhibitor 1) gene expression in Xenopus laevis embryo, assayed via in situ hybridization, NF stage 26, dorsal view, anterior left. Inset is a transverse section at the level indicated.
Key: ey = eye, ov= otic vesicle; dn= dorsal neural tube/roof plate; cn = cranial nerves; ds= cells at boundary of dorsal somite and neural tube; fs is rostral somite; pr= proctodeum.
dkk1 (dickkopf WNT signaling pathway inhibitor 1) gene expression in Xenopus laevis embryo, assayed via in situ hybridization, NF stage 32, lateral view, anterior left, dorsal up.