Abstract
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.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Actins / metabolism
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Animals
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Biomarkers / metabolism
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Cell Movement / physiology*
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Cell Polarity
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Cell Proliferation
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Cell Surface Extensions / metabolism
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Cell Surface Extensions / ultrastructure
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Cells, Cultured
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Disease Progression
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Enzyme Inhibitors / metabolism
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Epithelial Cells / cytology
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Epithelial Cells / physiology*
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Epithelium / anatomy & histology
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Epithelium / physiology
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Female
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Mammary Glands, Animal* / cytology
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Mammary Glands, Animal* / growth & development
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Mammary Neoplasms, Animal / metabolism
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Mammary Neoplasms, Animal / pathology
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Mice
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Mice, Transgenic
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Morphogenesis / physiology*
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Myosin-Light-Chain Kinase / antagonists & inhibitors
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Myosin-Light-Chain Kinase / metabolism
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Organoids / cytology
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Organoids / physiology
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Recombinant Fusion Proteins / genetics
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Recombinant Fusion Proteins / metabolism
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Signal Transduction / physiology
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rac1 GTP-Binding Protein / antagonists & inhibitors
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rac1 GTP-Binding Protein / metabolism
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rho-Associated Kinases / antagonists & inhibitors
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rho-Associated Kinases / metabolism
Substances
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Actins
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Biomarkers
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Enzyme Inhibitors
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Recombinant Fusion Proteins
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rho-Associated Kinases
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Myosin-Light-Chain Kinase
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rac1 GTP-Binding Protein