PT - JOURNAL ARTICLE AU - Jochen Kursawe AU - Pavel A. Brodskiy AU - Jeremiah J. Zartman AU - Ruth E. Baker AU - Alexander G. Fletcher TI - Capabilities and Limitations of Tissue Size Control Through Passive Mechanical Forces AID - 10.1101/023184 DP - 2015 Jan 01 TA - bioRxiv PG - 023184 4099 - http://biorxiv.org/content/early/2015/11/23/023184.short 4100 - http://biorxiv.org/content/early/2015/11/23/023184.full AB - 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.Author Summary Developing embryos are able to grow organs of the correct size even in the face of significant external perturbations. Such robust size control is achieved via tissue-level coordination of cell growth, proliferation, death and rearrangement, through mechanisms that are not well understood. Here, we employ computational modelling to test hypotheses of size control in the developing fruit fly. Segments in the surface tissues of the fruit fly embryo have been shown to achieve the same size even if the number of cells in each segment is perturbed genetically. We show that simple mechanical interactions between the cells of this tissue can recapitulate previously gathered data on tissue sizes and cell numbers. However, this simple model does not capture the experimentally observed spatial variation in cell death rates in this tissue, which may be explained through several adaptations to the model. These distinct adaptations may be distinguished through summary statistics of the tissue behaviour, such as statistics of cell shapes or tissue recoil after cutting. This work demonstrates how computational modelling can help investigate the complex mechanical interactions underlying tissue size and shape, which are important for understanding the underlying causes of birth defects and diseases driven by uncontrolled growth.