McArdle Laboratory for Cancer Research, University of Wisconsin-Madison School of Medicine and Public Health, Madison, WI, United States.
Vitam Horm. 2021;116:21-50. doi: 10.1016/bs.vh.2021.02.001. Epub 2021 Mar 10.
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.
Wnt 信号通路是一种重要的形态发生信号通路，其在决定胚胎细胞命运方面的作用最为重要；它通常被激活以重新指定胎儿细胞或维持体干细胞的谱系灵活性。在这篇综述中，我们考虑了该途径在胚胎发生、导管生长和妊娠期间乳腺分化、生长和形态发生过程中的作用。具体来说，将乳腺干细胞与来自其他组织的干细胞进行比较，以确定其共性和差异。Wnt 信号通路被认为是维持成年乳腺导管树中存在的双潜能基底干细胞所必需的，然而，这种干细胞的缺失对生长或形态发生几乎没有影响，并且在妊娠期间导管/肺泡扩张期间不会诱导 Wnt 信号通路。我们回顾了乳腺上皮细胞预先确定的等级结构的证据，以及特定乳腺上皮细胞混合物之间信号转导在维持 Wnt 依赖性克隆性干细胞中的作用。我们介绍了乳腺上皮细胞表达的各种 Wnt 信号通路成分，以及一些潜在的 Wnt 蛋白的基质来源，它们可能是诱导上皮可塑性的重要起点。
