Piezo regulates epithelial topology and promotes precision in organ size control
Mayesha Sahir Mim,
Nilay Kumar,
Megan Levis,
Maria F. Unger,
Gabriel Miranda,
David Gazzo,
Trent Robinett,
Jeremiah J. Zartman
Affiliations
Mayesha Sahir Mim
Department of Chemical and Biomolecular Engineering, University of Notre Dame, Notre Dame, IN 46556, USA; Bioengineering Graduate Program, University of Notre Dame, Notre Dame, IN 46556, USA
Nilay Kumar
Department of Chemical and Biomolecular Engineering, University of Notre Dame, Notre Dame, IN 46556, USA
Megan Levis
Department of Chemical and Biomolecular Engineering, University of Notre Dame, Notre Dame, IN 46556, USA; Bioengineering Graduate Program, University of Notre Dame, Notre Dame, IN 46556, USA
Maria F. Unger
Department of Chemical and Biomolecular Engineering, University of Notre Dame, Notre Dame, IN 46556, USA
Gabriel Miranda
Department of Chemical and Biomolecular Engineering, University of Notre Dame, Notre Dame, IN 46556, USA
David Gazzo
Department of Chemical and Biomolecular Engineering, University of Notre Dame, Notre Dame, IN 46556, USA; Bioengineering Graduate Program, University of Notre Dame, Notre Dame, IN 46556, USA
Trent Robinett
Department of Chemical and Biomolecular Engineering, University of Notre Dame, Notre Dame, IN 46556, USA
Jeremiah J. Zartman
Department of Chemical and Biomolecular Engineering, University of Notre Dame, Notre Dame, IN 46556, USA; Bioengineering Graduate Program, University of Notre Dame, Notre Dame, IN 46556, USA; Department of Biological Sciences, University of Notre Dame, Notre Dame, IN 46556, USA; Corresponding author
Summary: Mechanosensitive Piezo channels regulate cell division, cell extrusion, and cell death. However, systems-level functions of Piezo in regulating organogenesis remain poorly understood. Here, we demonstrate that Piezo controls epithelial cell topology to ensure precise organ growth by integrating live-imaging experiments with pharmacological and genetic perturbations and computational modeling. Notably, the knockout or knockdown of Piezo increases bilateral asymmetry in wing size. Piezo’s multifaceted functions can be deconstructed as either autonomous or non-autonomous based on a comparison between tissue-compartment-level perturbations or between genetic perturbation populations at the whole-tissue level. A computational model that posits cell proliferation and apoptosis regulation through modulation of the cutoff tension required for Piezo channel activation explains key cell and tissue phenotypes arising from perturbations of Piezo expression levels. Our findings demonstrate that Piezo promotes robustness in regulating epithelial topology and is necessary for precise organ size control.
