DKK1

Function

This gene encodes a protein that is a member of the dickkopf family. It is a secreted protein with two cysteine rich regions and is involved in embryonic development through its inhibition of the Wnt signaling pathway. Dickkopf WNT signaling pathway inhibitor 1 (Dkk1) is a protein-coding gene that acts from the anterior visceral endoderm. The dickkopf protein encoded by DKK1 is an antagonistic inhibitor of the WNT signaling pathway that acts by isolating the LRP6 co-receptor so that it cannot aid in activating the WNT signaling pathway. DKK1 was also demonstrated to antagonize the Wnt/β-catenin pathway via a reduction in β-catenin and an increase in OCT4 expression. This inhibition plays a key role in heart, head and forelimb development during anterior morphogenesis of the embryo.

Interactions

DKK1 has been shown to interact with LRP6.

Clinical significance

Elevated levels of DKK1 in bone marrow, plasma and peripheral blood is associated with the presence of osteolytic bone lesions in patients with multiple myeloma.

Animal studies

Scientists have created a DKK1 knockout model in mice that revealed the effects of this gene. All mice that were homozygous for the DKK1 knockout were dead at birth due to defects in the cranium and structures formed by the neural crest, such as failed development of eyes, olfactory placodes, frontonasal mass and mandibular processes, as well as incomplete development of the forebrain and midbrain and fusion of the digits of the forelimb. This evidence supports the idea that inhibition of the Wnt signaling pathway by DKK1 is crucial to proper cranial development.

DKK1 is one of the most upregulated genes in androgen-potentiated balding, with DKK-1 messenger RNA upregulated a few hours after DHT treatment of hair follicles at the dermal papilla in vitro. Neutralizing body against DKK-1 reversed DHT effects on outer root sheath keratinocytes. DKK-1 expression is attenuated by L-threonate in vitro, with the latter a metabolite of ascorbate.