Collective Epithelial Migration and Cell Rearrangements Drive Mammary Branching Morphogenesis

Andrew J. Ewald; Audrey Brenot; Myhanh Duong; Bianca S. Chan; Zena Werb

doi:10.1016/j.devcel.2008.03.003

Collective Epithelial Migration and Cell Rearrangements Drive Mammary Branching Morphogenesis

Andrew J. Ewald, Audrey Brenot, Myhanh Duong, Bianca S. Chan, Zena Werb

Research output: Contribution to journal › Article › peer-review

405 Scopus citations

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.

Original language	English (US)
Pages (from-to)	570-581
Number of pages	12
Journal	Developmental Cell
Volume	14
Issue number	4
DOIs	https://doi.org/10.1016/j.devcel.2008.03.003
State	Published - Apr 15 2008
Externally published	Yes

Keywords

DEVBIO

ASJC Scopus subject areas

Molecular Biology
General Biochemistry, Genetics and Molecular Biology
Developmental Biology
Cell Biology

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10.1016/j.devcel.2008.03.003

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title = "Collective Epithelial Migration and Cell Rearrangements Drive Mammary Branching Morphogenesis",

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.",

keywords = "DEVBIO",

author = "Ewald, {Andrew J.} and Audrey Brenot and Myhanh Duong and Chan, {Bianca S.} and Zena Werb",

note = "Funding Information: This study was supported by National Institutes of Health (NIH) grants to Z.W. (CA057621 and ES012801) and postdoctoral fellowships to A.J.E. (NIH National Research Service Award [HL-007731] and California Breast Cancer Research Program [11FB-0015]). We thank John Wallingford and Keith Mostov for critical comments on the manuscript; Mina Bissell, Jimmie Fata, Mark Sternlicht, Mikala Egeblad, and Joanna Phillips for stimulating discussions of the data; and Marina Burkova, Ying Yu, and Helen Capili for technical assistance. We thank Nicole Stokes and Elaine Fuchs for the K14-GFP-actin mouse line; M. Peter Marinkovich and Monique Aumailley for the laminin-332 antibodies; and George Peeters, Gary Rondeau, John Zemek, Mike Buchin, Lee Pochop, Ciprian Almonte, Bob Cowden, and Kevin Frischmann for microscopy support. ",

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AU - Ewald, Andrew J.

AU - Brenot, Audrey

AU - Duong, Myhanh

AU - Chan, Bianca S.

AU - Werb, Zena

N1 - Funding Information: This study was supported by National Institutes of Health (NIH) grants to Z.W. (CA057621 and ES012801) and postdoctoral fellowships to A.J.E. (NIH National Research Service Award [HL-007731] and California Breast Cancer Research Program [11FB-0015]). We thank John Wallingford and Keith Mostov for critical comments on the manuscript; Mina Bissell, Jimmie Fata, Mark Sternlicht, Mikala Egeblad, and Joanna Phillips for stimulating discussions of the data; and Marina Burkova, Ying Yu, and Helen Capili for technical assistance. We thank Nicole Stokes and Elaine Fuchs for the K14-GFP-actin mouse line; M. Peter Marinkovich and Monique Aumailley for the laminin-332 antibodies; and George Peeters, Gary Rondeau, John Zemek, Mike Buchin, Lee Pochop, Ciprian Almonte, Bob Cowden, and Kevin Frischmann for microscopy support.

PY - 2008/4/15

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N2 - 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.

AB - 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.

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Collective Epithelial Migration and Cell Rearrangements Drive Mammary Branching Morphogenesis

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