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

Content Provider	PubMed Central
Author	Wang, Hui Sam, Lacoche Huang, Ling Xue, Bin Muthuswamy, Senthil K.
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.
Related Links	http://dx.doi.org/10.1073/pnas.1201141110
Ending Page	168
Page Count	6
Starting Page	163
File Format	PDF
ISSN	10916490
e-ISSN	10916490
Journal	Proceedings of the National Academy of Sciences of the United States of America
Issue Number	1
Volume Number	110
Language	English
Publisher	National Academy of Sciences
Publisher Date	2013-01-02
Access Restriction	Open
Rights Holder	National Academy of Sciences
Subject Keyword	Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Multidisciplinary

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