Dickkopf genes are co-ordinately expressed in mesodermal lineages.
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.
Monaghan
A P
AP
Division of Molecular Biology of the Cell I, Deutsches Krebsforschungszentrum, Im Neuenheimer Feld 280, D-69120, Heidelberg, Germany.
Kioschis
P
P
Wu
W
W
Zuniga
A
A
Bock
D
D
Poustka
A
A
Delius
H
H
Niehrs
C
C
D048868:Adaptor Proteins, Signal Transducing; D000595:Amino Acid Sequence; D000818:Animals; D004475:Ectoderm / Q000378:metabolism; D004847:Epithelial Cells / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D017403:In Situ Hybridization; D036341:Intercellular Signaling Peptides and Proteins; D008648:Mesoderm / Q000378:metabolism*; D051379:Mice; D008969:Molecular Sequence Data; D011506:Proteins / Q000235:genetics* / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017386:Sequence Homology, Amino Acid; D013997:Time Factors; D014018:Tissue Distribution
D048868:Adaptor Proteins, Signal Transducing; C501127:Dkk1 protein, mouse; C405060:Dkk2 protein, mouse; C405061:Dkk3 protein, mouse; D036341:Intercellular Signaling Peptides and Proteins; D011506:Proteins