WNT7A
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Protein Wnt-7a is a protein that in humans is encoded by the WNT7A gene.
Function
The WNT gene family consists of structurally related genes that encode secreted signaling proteins. These proteins have been implicated in oncogenesis and in several developmental processes, including regulation of cell fate and patterning during embryogenesis. This gene is a member of the WNT gene family. It encodes a protein showing 99% amino acid identity to the mouse Wnt7A protein. This gene not only guides the development of the anterior-posterior axis in the female reproductive tract but also plays a critical role in uterine smooth muscle pattering and maintenance of adult uterine function. It is also responsive to changes in the levels of sex steroid hormone in the female reproductive tract. Decreased expression of this gene in human uterine leiomyoma is found to be inversely associated with the expression of estrogen receptor alpha.
Santos syndrome
Santos syndrome is characterized by short stature, fibular agenesis or hypoplasia, clubfeet with oligodactyly, acromial dimples, limited forearm/hand range of motion, and severe nail hypoplasia or anonychia. It is caused by a homozygous mutation in the WNT7A gene, leading to a phenotype similar to Fuhrmann syndrome but with preaxial polydactyly and less severe limb defects. The inheritance pattern is autosomal dominant with incomplete penetrance. This mutation has a recent origin (73 years) and is located inside a Native-american homozygous haplotype. It was discovered by Silvana Santos, a Brazilian researcher who won the 100 Woman BBC prize in 2024.
Knockout and Functional Evidence
The signaling molecule Wnt7-a is expressed within the female embryo, controlling the proper establishment of the uterus and the anterior-posterior axis within the female reproductive tract. Prenatal knockout of the Wnt7-a gene disrupts the early stages of the female reproductive tract, resulting in the lack of a comprehensive analysis of the gene’s role in development. However, a conditional knockout of the gene after birth, provided greater insight into the role of the gene in terms of uterine development. Initial appearance between the control mice and mutant mice appear similar, as both models presented with a vagina, cervix, oviduct, and ovary. In postnatal development, the Wnt7-a-null mice failed to develop endometrial glands and lacked the expression of genes Foxa2, Hoxa10, Hoxa11, Msx1, and Wnt16. The lack of endometrial glands within the mice resulted in infertility, as blastocyst failed to implant in the immature uterus. Loss of Wnt7-a during prenatal development results in absence of normal female anatomy and infertility while loss of Wnt7-a during postnatal development results in the presence of normal female anatomy and infertility.