Polarity, cell division, and out-of-equilibrium dynamics control the growth of epithelial structures

Benedetta Cerruti, Alberto Puliafito, Annette M. Shewan, Wei Yu, Alexander N. Combes, Melissa H. Little, Federica Chianale, Luca Primo, Guido Serini, Keith E. Mostov, Antonio Celani, Andrea Gamba

Research output: Contribution to journalArticle

Abstract

The growth of a well-formed epithelial structure is governed by mechanical constraints, cellular apicobasal polarity, and spatially controlled cell division. Here we compared the predictions of a mathematical model of epithelial growth with the morphological analysis of 3D epithelial structures. In both in vitro cyst models and in developing epithelial structures in vivo, epithelial growth could take place close to or far from mechanical equilibrium, and was determined by the hierarchy of time-scales of cell division, cell-cell rearrangements, and lumen dynamics. Equilibrium properties could be inferred by the analysis of cell-cell contact topologies, and the nonequilibrium phenotype was altered by inhibiting ROCK activity. The occurrence of an aberrant multilumen phenotype was linked to fast nonequilibrium growth, even when geometric control of cell division was correctly enforced. We predicted and verified experimentally that slowing down cell division partially rescued a multilumen phenotype induced by altered polarity. These results improve our understanding of the development of epithelial organs and, ultimately, of carcinogenesis.

Original languageEnglish
Pages (from-to)359-372
Number of pages14
JournalJournal of Cell Biology
Volume203
Issue number2
DOIs
Publication statusPublished - Oct 28 2013

ASJC Scopus subject areas

  • Cell Biology

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    Cerruti, B., Puliafito, A., Shewan, A. M., Yu, W., Combes, A. N., Little, M. H., Chianale, F., Primo, L., Serini, G., Mostov, K. E., Celani, A., & Gamba, A. (2013). Polarity, cell division, and out-of-equilibrium dynamics control the growth of epithelial structures. Journal of Cell Biology, 203(2), 359-372. https://doi.org/10.1083/jcb.201305044