title: Capabilities and Limitations of Tissue Size Control through Passive Mechanical Forces.
abstract: Embryogenesis is an extraordinarily robust process, exhibiting the ability to control tissue size and repair patterning defects in the face of environmental and genetic perturbations. The size and shape of a developing tissue is a function of the number and size of its constituent cells as well as their geometric packing. How these cellular properties are coordinated at the tissue level to ensure developmental robustness remains a mystery; understanding this process requires studying multiple concurrent processes that make up morphogenesis, including the spatial patterning of cell fates and apoptosis, as well as cell intercalations. In this work, we develop a computational model that aims to understand aspects of the robust pattern repair mechanisms of the Drosophila embryonic epidermal tissues. Size control in this system has previously been shown to rely on the regulation of apoptosis rather than proliferation; however, to date little work has been done to understand the role of cellular mechanics in this process. We employ a vertex model of an embryonic segment to test hypotheses about the emergence of this size control. Comparing the model to previously published data across wild type and genetic perturbations, we show that passive mechanical forces suffice to explain the observed size control in the posterior (P) compartment of a segment. However, observed asymmetries in cell death frequencies across the segment are demonstrated to require patterning of cellular properties in the model. Finally, we show that distinct forms of mechanical regulation in the model may be distinguished by differences in cell shapes in the P compartment, as quantified through experimentally accessible summary statistics, as well as by the tissue recoil after laser ablation experiments.
authors.affiliation: Mathematical Institute, University of Oxford, Oxford, United Kingdom.
authors.forename: Jochen
authors.initials: J
authors.lastname: Kursawe
authors.affiliation: Department of Chemical and Biomolecular Engineering, University of Notre Dame, Notre Dame, Indiana, United States of America.
authors.forename: Pavel A
authors.initials: PA
authors.lastname: Brodskiy
authors.affiliation: Department of Chemical and Biomolecular Engineering, University of Notre Dame, Notre Dame, Indiana, United States of America.
authors.forename: Jeremiah J
authors.initials: JJ
authors.lastname: Zartman
authors.affiliation: Mathematical Institute, University of Oxford, Oxford, United Kingdom.
authors.forename: Ruth E
authors.initials: RE
authors.lastname: Baker
authors.affiliation: Mathematical Institute, University of Oxford, Oxford, United Kingdom.|School of Mathematics and Statistics, University of Sheffield, Sheffield, United Kingdom.
authors.forename: Alexander G
authors.initials: AG
authors.lastname: Fletcher
mesh_terms: D000818:Animals; D001696:Biomechanical Phenomena / Q000502:physiology*; D016923:Cell Death; D049109:Cell Proliferation / Q000502:physiology*; D048430:Cell Shape / Q000502:physiology*; D019295:Computational Biology; D004330:Drosophila / Q000166:cytology / Q000196:embryology; D047108:Embryonic Development / Q000502:physiology*; D008954:Models, Biological