title: Developmental stage and time dictate the fate of Wnt/β-catenin-responsive stem cells in the mammary gland.
abstract: The mammary epithelium undergoes extensive growth and remodeling during pregnancy, suggesting a role for stem cells. Yet their origin, identity, and behavior in the intact tissue remain unknown. Using an Axin2(CreERT2) allele, we labeled and traced Wnt/β-catenin-responsive cells throughout mammary gland development. This reveals a switch in Wnt/β-catenin signaling around birth and shows that, depending on the developmental stage, Axin2(+) cells contribute differently to basal and luminal epithelial cell lineages of the mammary epithelium. Moreover, an important difference exists between the developmental potential tested in transplantation assays and that displayed by the same cell population in situ. Finally, Axin2(+) cells in the adult build alveolar structures during multiple pregnancies, demonstrating the existence of a Wnt/β-catenin-responsive adult stem cell. Our study uncovers dynamic changes in Wnt/β-catenin signaling in the mammary epithelium and offers insights into the developmental fate of mammary gland stem and progenitor cells.
authors.affiliation: Department of Developmental Biology and Howard Hughes Medical Institute, Stanford University, Stanford, CA 94305, USA. r.v.amerongen@nki.nl
authors.forename: Renée
authors.initials: R
authors.lastname: van Amerongen
authors.forename: Angela N
authors.initials: AN
authors.lastname: Bowman
authors.forename: Roel
authors.initials: R
authors.lastname: Nusse
mesh_terms: D000818:Animals; D060466:Axin Protein / Q000378:metabolism; D019070:Cell Lineage; D049109:Cell Proliferation; D002999:Clone Cells; D004622:Embryo, Mammalian / Q000166:cytology / Q000378:metabolism; D004848:Epithelium / Q000254:growth & development / Q000378:metabolism; D005260:Female; D008321:Mammary Glands, Animal / Q000166:cytology* / Q000196:embryology / Q000254:growth & development*; D051379:Mice; D039902:Multipotent Stem Cells / Q000166:cytology / Q000378:metabolism; D011247:Pregnancy; D012741:Sexual Maturation; D033581:Stem Cell Transplantation; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism; D013997:Time Factors; D060449:Wnt Signaling Pathway
chemical_list: D060466:Axin Protein; C111729:Axin2 protein, mouse