Collective epithelial migration and cell rearrangements drive mammary branching morphogenesis.
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, suggesting common mechanisms of epithelial growth.
Ewald
Andrew J
AJ
Department of Anatomy and Program in Cell Biology, University of California, San Francisco, San Francisco, CA 94143, USA. andrew.ewald@ucsf.edu
Brenot
Audrey
A
Duong
Myhanh
M
Chan
Bianca S
BS
Werb
Zena
Z
D000199:Actins / Q000378:metabolism; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D002465:Cell Movement / Q000502:physiology*; D016764:Cell Polarity; D049109:Cell Proliferation; D022081:Cell Surface Extensions / Q000378:metabolism / Q000648:ultrastructure; D002478:Cells, Cultured; D018450:Disease Progression; D004791:Enzyme Inhibitors / Q000378:metabolism; D004847:Epithelial Cells / Q000166:cytology / Q000502:physiology*; D004848:Epithelium / Q000033:anatomy & histology / Q000502:physiology; D005260:Female; D008321:Mammary Glands, Animal / Q000166:cytology / Q000254:growth & development; D015674:Mammary Neoplasms, Animal / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008822:Mice, Transgenic; D009024:Morphogenesis / Q000502:physiology*; D009219:Myosin-Light-Chain Kinase / Q000037:antagonists & inhibitors / Q000378:metabolism; D009940:Organoids / Q000166:cytology / Q000502:physiology; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D020830:rac1 GTP-Binding Protein / Q000037:antagonists & inhibitors / Q000378:metabolism; D054460:rho-Associated Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism
D000199:Actins; D015415:Biomarkers; D004791:Enzyme Inhibitors; D011993:Recombinant Fusion Proteins; D054460:rho-Associated Kinases; D009219:Myosin-Light-Chain Kinase; D020830:rac1 GTP-Binding Protein