Sizing it up: The mechanical feedback hypothesis of organ growth regulation

Buchmann, Amy; Alber, Mark; Zartman, Jeremiah J.

doi:10.1016/j.semcdb.2014.06.018

Cited by 53 publications

(50 citation statements)

References 103 publications

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“…Model parameters were calibrated using experimental data for the third instar Drosophila wing disc, which is a powerful model for studying organ formation [24,65] (Figs 4 and 5). Experimental values for similar cell lines were used to calibrate the model parameters when experimental data for Drosophila wing disc were not available.…”

Section: Resultsmentioning

confidence: 99%

Multi-scale computational study of the mechanical regulation of cell mitotic rounding in epithelia

et al. 2017

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Mitotic rounding during cell division is critical for preventing daughter cells from inheriting an abnormal number of chromosomes, a condition that occurs frequently in cancer cells. Cells must significantly expand their apical area and transition from a polygonal to circular apical shape to achieve robust mitotic rounding in epithelial tissues, which is where most cancers initiate. However, how cells mechanically regulate robust mitotic rounding within packed tissues is unknown. Here, we analyze mitotic rounding using a newly developed multi-scale subcellular element computational model that is calibrated using experimental data. Novel biologically relevant features of the model include separate representations of the sub-cellular components including the apical membrane and cytoplasm of the cell at the tissue scale level as well as detailed description of cell properties during mitotic rounding. Regression analysis of predictive model simulation results reveals the relative contributions of osmotic pressure, cell-cell adhesion and cortical stiffness to mitotic rounding. Mitotic area expansion is largely driven by regulation of cytoplasmic pressure. Surprisingly, mitotic shape roundness within physiological ranges is most sensitive to variation in cell-cell adhesivity and stiffness. An understanding of how perturbed mechanical properties impact mitotic rounding has important potential implications on, amongst others, how tumors progressively become more genetically unstable due to increased chromosomal aneuploidy and more aggressive.

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Section: Resultsmentioning

confidence: 99%

Multi-scale computational study of the mechanical regulation of cell mitotic rounding in epithelia

et al. 2017

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“…Disk size is determined by disk‐level and compartment‐specific control, and while several theories have addressed the former, how compartment‐specific control is achieved is an open question, but it cannot be achieved with many disk growth models for reasons given earlier. Extrinsic control also mediates tissue growth (Buchmann et al, ), and since Yki‐dependent growth requires dTOR activity, the extrinsic control structure may depend on a hypothetical mechanism in which dTOR affects the state of nuclear Yki (Parker & Struhl, ). Thus the dTOR and Hippo pathways may act in parallel, in that Hippo assesses local growth suitability, and dTOR ensures that organismal factors such as nutrition are sufficient to support the increased growth in the early stage of the cell cycle.…”

Section: Epilog and Future Directionsmentioning

confidence: 99%

Growth control in the Drosophila wing disk

Gou

Stotsky

Othmer

2020

WIREs Mechanisms of Disease

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The regulation of size and shape is a fundamental requirement of biological development and has been a subject of scientific study for centuries, but we still lack an understanding of how organisms know when to stop growing. Imaginal wing disks of the fruit fly Drosophila melanogaster, which are precursors of the adult wings, are an archetypal tissue for studying growth control. The growth of the disks is dependent on many inter‐ and intra‐organ factors such as morphogens, mechanical forces, nutrient levels, and hormones that influence gene expression and cell growth. Extracellular signals are transduced into gene‐control signals via complex signal transduction networks, and since cells typically receive many different signals, a mechanism for integrating the signals is needed. Our understanding of the effect of morphogens on tissue‐level growth regulation via individual pathways has increased significantly in the last half century, but our understanding of how multiple biochemical and mechanical signals are integrated to determine whether or not a cell decides to divide is still rudimentary. Numerous fundamental questions are involved in understanding the decision‐making process, and here we review the major biochemical and mechanical pathways involved in disk development with a view toward providing a basis for beginning to understand how multiple signals can be integrated at the cell level, and how this translates into growth control at the level of the imaginal disk. This article is categorized under: Analytical and Computational Methods > Computational Methods Biological Mechanisms > Cell Signaling Models of Systems Properties and Processes > Cellular Models

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“…The Drosophila wing imaginal disc has been an important model system over past decades for discovering novel biology related to a plethora of topics, including tissue growth control, pattern formation, epithelial morphogenesis, inter-cellular communication and signaling, and the biophysical interaction of cells (Buchmann et al, 2014;Garcia-Bellido, 2009;Kornberg and Guha, 2007;Restrepo et al, 2014;Worley et al, 2012). Most of this work has been carried out by dissecting, fixing and immunostaining discs from individual animals, either at different stages of development or at varying times after induction of genetic manipulations.…”

Section: Introductionmentioning

confidence: 99%

Oxygenation and adenosine deaminase support growth and proliferation of ex vivo cultured Drosophila wing imaginal discs

et al. 2017

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The Drosophila wing imaginal disc has been an important model system over past decades for discovering novel biology related to development, signaling and epithelial morphogenesis. Novel experimental approaches have been enabled using a culture setup that allows ex vivo cultures of wing discs. Current setups, however, are not able to sustain both growth and cell-cycle progression of wing discs ex vivo. We discover here a setup that requires both oxygenation of the tissue and adenosine deaminase activity in the medium, and supports both growth and proliferation of wing discs for 9 h. Nonetheless, further work will be required to extend the duration of the culturing and to enable live imaging of the cultured discs in the future.

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Sizing it up: The mechanical feedback hypothesis of organ growth regulation

Cited by 53 publications

References 103 publications

Multi-scale computational study of the mechanical regulation of cell mitotic rounding in epithelia

Multi-scale computational study of the mechanical regulation of cell mitotic rounding in epithelia

Growth control in the Drosophila wing disk

Oxygenation and adenosine deaminase support growth and proliferation of ex vivo cultured Drosophila wing imaginal discs

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