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Publication : Endothelial Wnts control mammary epithelial patterning via fibroblast signaling.

First Author  Wang J Year  2021
Journal  Cell Rep Volume  34
Issue  13 Pages  108897
PubMed ID  33789106 Mgi Jnum  J:304293
Mgi Id  MGI:6694799 Doi  10.1016/j.celrep.2021.108897
Citation  Wang J, et al. (2021) Endothelial Wnts control mammary epithelial patterning via fibroblast signaling. Cell Rep 34(13):108897
abstractText  Endothelial and fibroblast niches are crucial for epithelial organs. How these heterotypic cells interact is of great interest. In this study, we reveal an axis of signaling in which fibroblasts relay Wnt signals from the endothelial niche to organize epithelial patterning. We generate an Axin2-membrane GFP (mGFP) reporter mouse and observe robust Wnt/beta-catenin signaling activities in fibroblasts surrounding the mammary epithelium. To enable cell-type-specific gene manipulation in vitro, we establish an organoid system via coculture of endothelial cells (ECs), fibroblasts, and mammary epithelial cells. Deletion of beta-catenin in fibroblasts impedes epithelium branching, and ECs are responsible for the activation of Wnt/beta-catenin signaling in fibroblasts. In vivo, EC deletion of Wntless inhibits Wnt/beta-catenin signaling activity in fibroblasts, rendering a reduction in epithelial branches. These findings highlight the significance of the endothelial niche in tissue patterning, shedding light on the interactive mechanisms in which distinct niche components orchestrate epithelial organogenesis and tissue homeostasis.
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