title: Interplay of cell shape and division orientation promotes robust morphogenesis of developing epithelia.
abstract: 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.
authors.affiliation: Department of Systems Biology, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Fengzhu
authors.initials: F
authors.lastname: Xiong
authors.affiliation: Department of Systems Biology, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Wenzhe
authors.initials: W
authors.lastname: Ma
authors.affiliation: Department of Systems Biology, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Tom W
authors.initials: TW
authors.lastname: Hiscock
authors.affiliation: Department of Systems Biology, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Kishore R
authors.initials: KR
authors.lastname: Mosaliganti
authors.affiliation: Department of Systems Biology, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Andrea R
authors.initials: AR
authors.lastname: Tentner
authors.affiliation: Mathematics Department, Susquehanna University, Selinsgrove, PA 17870, USA.
authors.forename: Kenneth A
authors.initials: KA
authors.lastname: Brakke
authors.affiliation: Department of Systems Biology, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Rannou
authors.affiliation: Department of Systems Biology, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Arnaud
authors.initials: A
authors.lastname: Gelas
authors.affiliation: Department of Systems Biology, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Lydie
authors.initials: L
authors.lastname: Souhait
authors.affiliation: Department of Systems Biology, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Ian A
authors.initials: IA
authors.lastname: Swinburne
authors.affiliation: Department of Systems Biology, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Nikolaus D
authors.initials: ND
authors.lastname: Obholzer
authors.affiliation: Department of Systems Biology, Harvard Medical School, Boston, MA 02115, USA. Electronic address: megason@hms.harvard.edu.
authors.forename: Sean G
authors.initials: SG
authors.lastname: Megason
mesh_terms: D000818:Animals; D001696:Biomechanical Phenomena; D002452:Cell Count; D002455:Cell Division; D048430:Cell Shape; D004625:Embryo, Nonmammalian / Q000166:cytology; D004847:Epithelial Cells / Q000166:cytology*; D008954:Models, Biological; D009024:Morphogenesis; D015027:Zebrafish / Q000196:embryology*