TY - JOUR
T1 - Collective Epithelial Migration and Cell Rearrangements Drive Mammary Branching Morphogenesis
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
Y1 - 2008/4/15
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.
KW - DEVBIO
UR - http://www.scopus.com/inward/record.url?scp=41649121862&partnerID=8YFLogxK
U2 - 10.1016/j.devcel.2008.03.003
DO - 10.1016/j.devcel.2008.03.003
M3 - Article
C2 - 18410732
AN - SCOPUS:41649121862
SN - 1534-5807
VL - 14
SP - 570
EP - 581
JO - Developmental cell
JF - Developmental cell
IS - 4
ER -