Stromal heterogeneity and fibroblast specialization during mammary gland morphogenesis

The mammary gland is a highly dynamic organ whose development depends on coordinated interactions between epithelial cells and the surrounding stroma. While fibroblasts are recognized as critical regulators of tissue morphogenesis, their diversity, regulation and specific functions during mammary gland development have been incompletely understood. Recently we identified previously unrecognized heterogeneity among mammary fibroblast populations during postnatal development. In particular, we unraveled a transient niche-forming population of specialized contractile fibroblasts (peri-TEB fibroblasts) that exclusively localize around the tips of the growing mammary epithelium and are recruited from preadipocytes in the surrounding fat pad stroma. In this talk, I will present our ongoing efforts to uncover the molecular mechanisms regulating the establishment or maintenance of these specialized fibroblasts. Our preliminary findings point to a role for WNT signaling and hormonal cues in controlling the peri-TEB fibroblast state, revealing new links between systemic developmental signals, local stromal regulation, and epithelial morphogenesis. Together, these findings provide new insight into stromal specification during organ development and may have broader implications for understanding fibroblast plasticity in breast disease and cancer.