Dickkopf-1 related protein (DKK-1) is a member of the DKK family, which also includes DKK-2, DKK-3 and DKK-4. It was initially identified as an important embryogenic factor, especially for the development of the head. DKK-1 effects are mainly due to its role as negative regulator of Wnt signally pathway, by forming complexes with LDL-receptor-related protein 6. High expression of DKK-1 has been found during mesenchymal development, and is crucial for limbs and bones modeling, but also cardiogenesis. TNF-α plays a central role in DKK-1 induction, during arthritis, and blood levels of DKK-1 increase during multiple myeloma. DKK-1 acts also as negative regulator of neuronal survival and neural crest formation.
