الفهرس | Only 14 pages are availabe for public view |
Abstract Mammary gland development in the mouse is a complex process requiring co- ordinated signalling from both epithelial and stromal cells at different developmental stages. The two main phases of epithelial growth are puberty, when highly proliferative terminal end buds (TEB) drive growth of the mammary epithelial rudiment and invasion of the surrounding fat pad to form a tree like structure of ductal epithelium; and pregnancy, when the mature ductal structures undergo lateral branching, proliferation and alveologenesis. Epithelial growth is associated with changes in the extracellular matrix (ECM) around mammary epithelium that is controlled by both epithelial and stromal cells. FBLN2 was identified as a novel component of mammary gland ECM, expressed during epithelial morphogenesis. FBLN2 co- localized with versican (VCAN) and laminin in the cap cells of TEB and myoepithelial cells during very early pregnancy, and with integrin- Ü3Ý1 (ITGÜ3Ý1) exclusively in the cap cells. Mouse mammary epithelial (EpH4) cells with fbln2 knockdown (KD) cultured in 2D showed upregulation of keratin 18 (Krt18) and downregulation of Krt14 and ITGÝ1, suggesting FBLN2 affects epithelial differentiation and the surrounding collagen IV sheath formation was impaired in 3D matrigel embedded epithelial structures, suggesting FBLN2 may control BM integrity around growing epithelium |