Collective Epithelial Migration and Cell Rearrangements Drive Mammary Branching Morphogenesis

• Published in: Developmental cell 2008-04, Vol.14 (4), p.570-581
• Main Authors: Ewald, Andrew J., Brenot, Audrey, Duong, Myhanh, Chan, Bianca S., Werb, Zena
• Format: Article
• Language: English
• Subjects: Actins - metabolism; Animals; Biological and medical sciences; Biomarkers - metabolism; Cell differentiation, maturation, development, hematopoiesis; Cell Movement - physiology; Cell physiology; Cell Polarity; Cell Proliferation; Cell Surface Extensions - metabolism; Cell Surface Extensions - ultrastructure; Cells, Cultured; DEVBIO; Disease Progression; Enzyme Inhibitors - metabolism; Epithelial Cells - cytology; Epithelial Cells - physiology; Epithelium - anatomy & histology; Epithelium - physiology; Female; Fundamental and applied biological sciences. Psychology; Mammary Glands, Animal - cytology; Mammary Glands, Animal - growth & development; Mammary Neoplasms, Animal - metabolism; Mammary Neoplasms, Animal - pathology; Mice; Mice, Transgenic; Molecular and cellular biology; Morphogenesis - physiology; Myosin-Light-Chain Kinase - antagonists & inhibitors; Myosin-Light-Chain Kinase - metabolism; Organoids - cytology; Organoids - physiology; rac1 GTP-Binding Protein - antagonists & inhibitors; rac1 GTP-Binding Protein - metabolism; Recombinant Fusion Proteins - genetics; Recombinant Fusion Proteins - metabolism; rho-Associated Kinases - antagonists & inhibitors; rho-Associated Kinases - metabolism; Signal Transduction - physiology
• ISSN: 1534-5807; 1878-1551
• DOI: 10.1016/j.devcel.2008.03.003

Epithelial organs are built through the movement of groups of interconnected cells. We observed cells in elongating mammary ducts reorganize into a multilayered epithelium, migrate collectively, and rearrange dynamically, all without forming leading cellular extensions. Duct initiation required proliferation, Rac, and myosin light-chain kinase, whereas repolarization to a bilayer depended on Rho kinase. We observed that branching morphogenesis results from the active motility of both luminal and myoepithelial cells. Luminal epithelial cells advanced collectively, whereas myoepithelial cells appeared to restrain elongating ducts. Significantly, we observed that normal epithelium and neoplastic hyperplasias are organized similarly during morphogenesis, suggesting common mechanisms of epithelial growth.