Wnt signaling and mammary stem cells

Wnt signaling is an important morphogenetic signaling pathway best known for its essential role in determining embryonic cell fates; it is often activated to re-specify fetal cells or to maintain the lineage flexibility of somatic stem cells. In this review, we consider the role of this pathway in the remarkable process of differentiation, growth and morphogenesis of the mammary gland during embryogenesis, ductal outgrowth and pregnancy. Specifically, mammary stem cells are compared with stem cells from other tissues, to identify commonalities and differences. Wnt signaling is known to be required to maintain the bipotent basal stem cell present in adult mammary ductal trees, however, the absence of this stem cell has little effect on growth or morphogenesis, and Wnt signaling is not induced during the ductal/alveolar expansion during pregnancy. The evidence for pre-determined hierarchies of mammary epithelial cells is reviewed, together with the role of signaling between mixtures of specified mammary epithelial cells in the maintenance of Wnt-dependent clonagenic stem cells. The dazzling variety of Wnt signaling components expressed by mammary epithelial cells is presented, along with some potential stromal sources of Wnt proteins that may be important starting points for the induction of plasticity in the epithelium.