Dickkopf-like 1-a protein unique to mammals that is associated both with formation of trophoblast stem cells and with spermatogenesis

Dickkopf-like 1 (Dkkl1) is related to a group of secreted proteins that are antagonists of Wingless (Wnt) signal transduction pathways. The Dkkl1 gene is found only in mammals, where it is closely linked to the transcription factor Tead2; both genes are among the first to be expressed at the beginning of mouse development. In cells derived frompreimplantation embryos, the Dkkl1 gene is selectively expressed in trophoblast stem cells and repressed in embryonic stem cells. Thus, Dkkl1 appears to be required in the placental lineage, where it appears in the trophectoderm and eventually in the trophoblast giant cells that are involved in implantation, but is toxic to the embryonic lineage. In adult mammals, Dkkl1 is expressed predominantly (although not exclusively) during the formation of the male germ cells, where it eventually localizes to the acrosome of mature sperm. Following capacitation, some of the Dkkl1 protein migrates to the surface of the sperm, where it may be involved in fertilization. Thus, Dkkl1 is involved in two seemingly unrelated functions: the production of sperm, and the production of trophectoderm cells and their derivatives.