Wnt-4 is a 38 - 42 kDa member of the Wnt family of secreted glycoproteins, which act as short-range signaling molecules via Frizzled receptors and a cascade of intracellular signals in vertebrate embryogenesis. Wnt-4 has been shown to play a critical role in the development of the reproductive system and in the formation of the kidneys, adrenals, pituitary gland, and mammary tissues. In the development of the reproductive system, Wnt-4 expression is down-regulated in the developing gonad after E11.5, although it persists in the developing ovary. Targeted deletion of Wnt-4 results in masculinization of XX mice, with rudimentary development of the masculine internal (Wolffian) ducts and degeneration of the female (Mullerian) reproductive tract. In addition to its involvement in urogenital development, Wnt-4 is also expressed in the perichondrium of the long bones, and promotes osteoblast differentiation. Wnt-4 may also be associated with abnormal proliferation in human breast tissue.
In humans, mutations in Wnt-4 are the cause of SERKAL syndrome, a syndrome consisting of female to male sex reversal, renal, adrenal, and lung dysgenesis, and developmental defects. Mutations in Wnt-4 also result in Rokitansky-Kuster-Hauser syndrome, which is characterized by utero-vaginal atresia in otherwise phenotypically normal females with normal 46, XX karyotype.