Rotational motion during three-dimensional morphogenesis of mammary epithelial acini relates to laminin matrix assembly

Wang, H., Lacoche, S., Huang, L., Xue, B., Muthuswamy, S. K. (January 2013) Rotational motion during three-dimensional morphogenesis of mammary epithelial acini relates to laminin matrix assembly. Proceedings of the National Academy of Sciences of the United States of America, 110 (1). pp. 163-168. ISSN 00278424

[img]
Preview
PDF (Paper)
Muthuswamy PNAS 2013.pdf - Published Version

Download (997Kb) | Preview
URL: http://www.ncbi.nlm.nih.gov/pubmed/23248267
DOI: 10.1073/pnas.1201141110

Abstract

Our understanding of the mechanisms by which ducts and lobules develop is derived from model organisms and three-dimensional (3D) cell culture models wherein mammalian epithelial cells undergo morphogenesis to form multicellular spheres with a hollow central lumen. However, the mechanophysical properties associated with epithelial morphogenesis are poorly understood. We performed multidimensional live-cell imaging analysis to track the morphogenetic process starting from a single cell to the development of a multicellular, spherical structure composed of polarized epithelial cells surrounding a hollow lumen. We report that in addition to actively maintaining apicobasal polarity, the structures underwent rotational motions at rates of 15-20 μm/h and the structures rotated 360° every 4 h during the early phase of morphogenesis. Rotational motion was independent of the cell cycle, but was blocked by loss of the epithelial polarity proteins Scribble or Pard3, or by inhibition of dynein-based microtubule motors. Interestingly, none of the structures derived from human cancer underwent rotational motion. We found a direct relationship between rotational motion and assembly of endogenous basement membrane matrix around the 3D structures, and that structures that failed to rotate were defective in weaving exogenous laminin matrix. Dissolution of basement membrane around mature, nonrotating acini restored rotational movement and the ability to assemble exogenous laminin. Thus, coordinated rotational movement is a unique mechanophysical process observed during normal 3D morphogenesis that regulates laminin matrix assembly and is lost in cancer-derived epithelial cells.

Item Type: Paper
Subjects: organs, tissues, organelles, cell types and functions > cell types and functions > cell types
organs, tissues, organelles, cell types and functions > cell types and functions > cell types
organs, tissues, organelles, cell types and functions > cell types and functions > cell types

organs, tissues, organelles, cell types and functions > cell types and functions
organs, tissues, organelles, cell types and functions > cell types and functions > cell types > epithelial cell
organs, tissues, organelles, cell types and functions > cell types and functions > cell types > epithelial cell
organs, tissues, organelles, cell types and functions > cell types and functions > cell types > epithelial cell

organs, tissues, organelles, cell types and functions > tissues types and functions > mammary gland
organs, tissues, organelles, cell types and functions
organs, tissues, organelles, cell types and functions > tissues types and functions
CSHL Authors:
Communities: CSHL labs > Muthuswamy lab
CSHL Cancer Center Program > Signal Transduction
Depositing User: Matt Covey
Date: 2 January 2013
Date Deposited: 11 Feb 2013 19:20
Last Modified: 22 Dec 2017 17:10
PMCID: PMC3538193
Related URLs:
URI: http://repository.cshl.edu/id/eprint/27226

Actions (login required)

Administrator's edit/view item Administrator's edit/view item
CSHL HomeAbout CSHLResearchEducationNews & FeaturesCampus & Public EventsCareersGiving