Hormone-Responsive BMP Signaling Expands Myoepithelial Cell Lineages and Prevents Alveolar Precocity in Mammary Gland

• DOI: 10.3389/fcell.2021.691050
• Publication Date: 2021-07-15T12:46:31Z
• Authors: Chunlei Shao; Pengbo Lou; Ruiqi Liu; Xueyun Bi; Guilin Li; Xu Yang; Xiaole Sheng; Jiuzhi Xu; Cong Lv; Zhengquan Yu
• Keywords: Conditional gene knockout

Myoepithelial and luminal cells synergistically expand in the mammary gland during pregnancy, this process is precisely governed by hormone-related signaling pathways. The bone morphogenetic protein (BMP) pathway now known to play crucial roles all organ systems. However, functions of BMP remain unclear. Here, we found that BMPR1a upregulated hormone-induced Sp1 at pregnancy. Using a doxycycline (Dox)-inducible conditional knockout mouse model, demonstrated loss myoepithelium results compromised myoepithelial integrity, reduced stem precocious alveolar differentiation Mechanistically, regulates expression p63 Slug, two key regulators maintenance, through pSmad1/5-Smad4 complexes, consequently activate P-cadherin Furthermore, observed upregulation secreted Spp1 could account for layer, suggesting defective basal-to-luminal paracrine mechanism. Collectively, these findings identify novel role maintaining identity suppressing formation.