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Dickkopf genes are co-ordinately expressed in mesodermal lineages
A P Monaghan1, P Kioschis, W Wu
1Division of Molecular Biology of the Cell I, Deutsches Krebsforschungszentrum, Im Neuenheimer Feld 280, D-69120, Heidelberg, Germany.
Mechanisms of Development
|September 24, 1999
Summary
Dickkopf (DKK) genes, including newly identified DKK-2 and DKK-3, are secreted proteins involved in embryonic development. Their conserved expression patterns suggest roles in epithelial-mesenchymal interactions during organ formation.
Area of Science:
- Developmental Biology
- Molecular Biology
- Genetics
Background:
- Dickkopf-1 (DKK-1) is a secreted protein crucial for head induction in Xenopus embryogenesis.
- DKK-1 acts as a potent inhibitor of the Wnt signaling pathway.
- The DKK family comprises novel secreted proteins with significant roles in developmental processes.
Purpose of the Study:
- To isolate and characterize additional murine members of the DKK family, specifically DKK-2 and DKK-3.
- To analyze the gene expression patterns of mouse DKK-1, DKK-2, and DKK-3 during embryonic and adult stages.
- To compare the expression patterns of DKK genes across different species, including Xenopus and chicken, to understand evolutionary conservation.
Main Methods:
- Isolation of new murine DKK family members.
- Gene expression analysis using adult and embryonic tissues from mice, Xenopus, and chicken.
- Comparative developmental expression profiling.
Main Results:
- Two additional murine DKK family members, DKK-2 and DKK-3, were isolated.
- Mouse DKK-1, DKK-2, and DKK-3 genes exhibit temporally and spatially regulated expression during development.
- Overlapping expression domains in mesenchymal lineages suggest coordinated action, particularly in tissues undergoing epithelial-mesenchymal transformations (e.g., heart, tooth, limb, bone).
- Expression was also noted in regions of programmed cell death within limb buds.
- DKK-1 tends to be the earliest expressed member within a given organ.
- Conserved expression patterns were observed between mouse, Xenopus DKK-1, and chicken DKK-3.
Conclusions:
- The DKK gene family consists of secreted proteins involved in mediating inductive interactions between epithelial and mesenchymal cells.
- These genes play significant roles in various developmental processes, including organogenesis and tissue patterning.
- Evolutionary conservation of DKK gene expression highlights their fundamental importance in vertebrate development.