Interplay of cell shape and division orientation promotes robust morphogenesis of developing epithelia

Fengzhu Xiong, Wenzhe Ma, Tom W. Hiscock, Kishore R. Mosaliganti, Andrea R. Tentner, Kenneth A. Brakke, Nicolas Rannou, Arnaud Gelas, Lydie Souhait, Ian A. Swinburne, Nikolaus D. Obholzer, Sean G. Megason*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

81 Citations (Scopus)


Epithelial cells acquire functionally important shapes (e.g., squamous, cuboidal, columnar) during development. Here, we combine theory, quantitative imaging, and perturbations to analyze how tissue geometry, cell divisions, and mechanics interact to shape the presumptive enveloping layer (pre-EVL) on the zebrafish embryonic surface. We find that, under geometrical constraints, pre-EVL flattening is regulated by surface cell number changes following differentially oriented cell divisions. The division pattern is, in turn, determined by the cell shape distribution, which forms under geometrical constraints by cell-cell mechanical coupling. An integrated mathematical model of this shape-division feedback loop recapitulates empirical observations. Surprisingly, the model predicts that cell shape is robust to changes of tissue surface area, cell volume, and cell number, which we confirm in vivo. Further simulations and perturbations suggest the parameter linking cell shape and division orientation contributes to epithelial diversity. Together, our work identifies an evolvable design logic that enables robust cell-level regulation of tissue-level development.

Original languageEnglish
Pages (from-to)415-427
Number of pages13
Issue number2
Publication statusPublished - 9 Oct 2014

Bibliographical note

Acknowledgments: We thank D. D’India for fish care. H. Otsuna, M. Wuhr, J. Zhang, K. Ishihara, M. Yajima, C. Heisenberg, P. Keller, N. Papalopulu, T. Mitchison, M. Kirschner, R. Ward, and the S.G.M. laboratory members for reagents, communications, and comments. This work is supported by NIH grants HG004071, DC010791, and GM026875. I.A.S. acknowledges NIH fellowship 5F32HL097599, a Hearing Health Foundation Emerging Research Grant, and a Novartis Fellowship in Systems Biology. F.X. is also supported by the graduate program of Biological Sciences in Dental Medicine at Harvard University.


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