Mammary epithelial tubes elongate through MAPK-dependent coordination of cell migration

Development
Robert J HuebnerAndrew J Ewald

Abstract

Mammary branching morphogenesis is regulated by receptor tyrosine kinases (RTKs). We sought to determine how these RTK signals alter proliferation and migration to accomplish tube elongation in mouse. Both behaviors occur but it has been difficult to determine their relative contribution to elongation in vivo, as mammary adipocytes scatter light and limit the depth of optical imaging. Accordingly, we utilized 3D culture to study elongation in an experimentally accessible setting. We first used antibodies to localize RTK signals and discovered that phosphorylated ERK1/2 (pERK) was spatially enriched in cells near the front of elongating ducts, whereas phosphorylated AKT was ubiquitous. We next observed a gradient of cell migration speeds from rear to front of elongating ducts, with the front characterized by both high pERK and the fastest cells. Furthermore, cells within elongating ducts oriented both their protrusions and their migration in the direction of tube elongation. By contrast, cells within the organoid body were isotropically protrusive. We next tested the requirement for proliferation and migration. Early inhibition of proliferation blocked the creation of migratory cells, whereas late inhibition of proliferation did...Continue Reading

References

Aug 1, 1995·Biochemical Society Transactions·C D Nobes, A Hall
Feb 9, 1996·Cell·D A Lauffenburger, A F Horwitz
Feb 13, 2002·American Journal of Physiology. Lung Cellular and Molecular Physiology·David E KlingJay J Schnitzer
Jan 16, 2003·Cell·Barry Lubarsky, Mark A Krasnow
Dec 6, 2003·Science·Anne J RidleyAlan Rick Horwitz
Jun 16, 2004·Developmental Biology·Tomoko Watanabe, Frank Costantini
Jul 9, 2004·Developmental Cell·Lucy Erin O'BrienKeith E Mostov
Dec 28, 2004·BMC Biotechnology·Anna-Katerina Hadjantonakis, Virginia E Papaioannou
Aug 12, 2005·Nature Reviews. Genetics·James F Crow
Oct 19, 2005·Nature Reviews. Molecular Cell Biology·Lothar Hennighausen, Gertraud W Robinson
Nov 11, 2005·Breast Cancer Research : BCR·Lindsay Hinck, Gary B Silberstein
Dec 15, 2005·Current Opinion in Cell Biology·Virginie Lecaudey, Darren Gilmour
Aug 3, 2006·Journal of Cell Science·Melinda LarsenKenneth M Yamada
Aug 19, 2006·Differentiation; Research in Biological Diversity·Mark D SternlichtZena Werb
May 15, 2007·Oncogene·A S DhillonW Kolch
Jul 3, 2007·Cell·Brendan D Manning, Lewis C Cantley
Sep 18, 2007·Genesis : the Journal of Genetics and Development·Mandar Deepak MuzumdarLiqun Luo
Jan 2, 2008·The Journal of Cell Biology·Gray W Pearson, Tony Hunter
Sep 26, 2008·Developmental Dynamics : an Official Publication of the American Association of Anatomists·Alan M CheshireDeborah J Andrew
Jan 9, 2009·PLoS Biology·Aleksandr VasilyevIain A Drummond
Sep 26, 2009·Developmental Biology·Deborah J Andrew, Andrew J Ewald
Nov 3, 2009·Cell·Lakshmi SrinivasanKlaus Rajewsky
Nov 6, 2009·Nature Reviews. Molecular Cell Biology·Markus AffolterEmmanuel Caussinus
May 27, 2010·Developmental Dynamics : an Official Publication of the American Association of Anatomists·Bilal E Kerman, Deborah J Andrew
Oct 5, 2010·Current Protocols in Molecular Biology·Arthur EdelsteinNico Stuurman
Mar 23, 2011·Annals of Medicine·Sara McNally, Finian Martin
Mar 14, 2013·Developmental Dynamics : an Official Publication of the American Association of Anatomists·Carsten Schnatwinkel, Lee Niswander

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Citations

Dec 23, 2016·The Journal of Cell Biology·Andrea Marat
Dec 30, 2016·The Journal of Cell Biology·Marina Simian, Mina J Bissell
Jan 18, 2017·Cold Spring Harbor Perspectives in Biology·Peter Friedl, Roberto Mayor
Aug 20, 2017·Journal of Cell Science·Kim-Vy Nguyen-NgocAndrew J Ewald
Oct 22, 2016·American Journal of Physiology. Lung Cellular and Molecular Physiology·Soula DanopoulosDenise Al Alam
Nov 12, 2019·Physical Biology·Anna StopkaDagmar Iber
Jan 15, 2020·Development·Shuo YangAaron N Johnson
Feb 9, 2017·The Journal of Cell Biology·Shaohe WangKenneth M Yamada
Mar 30, 2017·Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences·James W Spurlin, Celeste M Nelson
Dec 7, 2019·Development·Abhinava K MishraDenise J Montell
Apr 9, 2020·Frontiers in Cell and Developmental Biology·Jakub SumbalHan Li
Sep 22, 2020·Cellular and Molecular Bioengineering·Benjamin C Hacker, Marjan Rafat
Oct 25, 2020·Proceedings of the National Academy of Sciences of the United States of America·Nuthasuda SrijakotreChristina A Mitchell
Jan 27, 2021·Integrative Biology : Quantitative Biosciences From Nano to Macro·Emann M RabieCeleste M Nelson
Nov 20, 2020·Journal of Mammary Gland Biology and Neoplasia·Jakub SumbalZuzana Koledova
Apr 10, 2021·Journal of Mammary Gland Biology and Neoplasia·Caleb A Dawson, Jane E Visvader
Jun 15, 2021·Bio-protocol·Elsa CharifouAurélie Chiche

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