In vivo imaging of mammary epithelial cell dynamics in response to lineage-biased Wnt/β-catenin activation

Real-time, in vivo imaging provides an essential window into the spatiotemporal cellular and molecular events contributing to tissue development and pathology. By coupling longitudinal intravital imaging with genetic lineage tracing, here we captured the earliest cellular events underlying the impact of active Wnt/β-catenin signaling on the organization and differentiation of the mammary epithelium. This enabled us to interrogate how Wnt/β-catenin regulates the dynamics of distinct subpopulations of mammary epithelial cells in vivo and in real time. We show that β-catenin stabilization, when targeted to either of the mammary luminal or basal epithelial lineages, invariably leads to cellular rearrangements that precipitate the formation of hyperplastic lesions that undergo squamous transdifferentiation. These results enhance our understanding of the earliest stages of hyperplastic lesion formation in vivo , and reveal that in mammary neoplastic development, β-catenin activation dictates a hair-follicle/epidermal differentiation program independently of the targeted cell of origin.