Epithelial and non-epithelial play opposing roles to regulate proliferation and morphogenesis of the mouse mammary gland.

Patched 1 () has epithelial, stromal and systemic roles in murine mammary gland organogenesis, yet specific functions remain undefined. -recombinase-mediated ablation in mammary epithelium increased proliferation and branching, but did not phenocopy transgenic expression of activated smoothened (). The epithelium showed no evidence of canonical hedgehog signaling, and hyperproliferation was not blocked by smoothened (SMO) inhibition, suggesting a non-canonical function of PTCH1. Consistent with this possibility, nuclear localization of cyclin B1 was increased. In non-epithelial cells, heterozygous mediated ablation increased proliferation and branching, with dysplastic terminal end buds (TEB) and ducts. By contrast, homozygous ablation decreased proliferation and branching, producing stunted ducts filled with luminal cells showing altered ovarian hormone receptor expression. Whole-gland transplantation into wild-type hosts or estrogen/progesterone treatment rescued outgrowth and hormone receptor expression, but not the histological changes. Bone marrow transplantation failed to rescue outgrowth. Ducts of mice were similar to ducts, but outgrowths were not stunted, suggesting that the histology might be mediated by in the local stroma, with systemic required for ductal outgrowth and proper hormone receptor expression in the mammary epithelium.