Essential function of Wnt-4 in mammary gland development downstream of progesterone signaling

Female reproductive hormones control mammary gland morphogenesis,In the abs ence of the progesterone receptor (PR) from the mammary epithelium, ductal side-branching fails to occur. We can overcome this defect by ectopic expre ssion of the protooncogene Wnt-1. Transplantation of mammary epithelia from Wnt-4(-)/(-) mice shows that Wnt-4 has an essential role in side-branching early in pregnancy. PR and Wnt-4 mRNAs colocalize to the luminal compartme nt of the ductal epithelium. Progesterone induces Wnt-4 in mammary epitheli al cells and is required for increased Wnt-4 expression during pregnancy. T hus, Wnt signaling is essential in mediating progesterone function during m ammary gland morphogenesis.