Piezo ensures robust tissue size regulation by balancing proliferation, cell size, anisotropy and cell death
Authors: Nilay Kumar; Megan Levis; Mayesha Sahir Mim; Maria Unger; Jeremiah J. Zartman
Affiliation: University of Notre Dame
Keywords: g. wing disc; j. other signaling pathways
Mechanisms ensuring robustness in organ size regulation are critical for proper development. In epithelial tissues, mechanosensitive Piezo channels are critical for maintaining homeostasis through regulations of cell division and apoptosis. Stretch activation of Piezo triggers cell proliferation. It has been hypothesized that calcium spiking from Piezo activates ERK signaling and induces a G2-to-M transition during cell division. However, the tissue-level mechanistic and functional roles of Piezo during development remain unknown. Here, we have combined pharmacological and genetic approaches to study Piezo’s roles in regulating the development of the Drosophila wing imaginal disc, an excellent model organism for epithelial organ development. We investigated the combined outcomes on tissue size, shape and mechanical properties. We found that Piezo overexpression increases the relative concentration levels of cytoskeletal integrin and non-muscle myosin-II leading to increased tissue curvature. Both genetic overexpression and pharmacological activation of Piezo increased proliferation and apoptosis in the tissue. Surprisingly, calcium signaling activity was blocked when Peizo was either overexpressed or knocked down but was increased with acute pharmacological activation. We hypothesize that this loss of calcium activity is due to desensitization of the Piezo channel. Further, knockdown of Piezo increased the numbers of cell neighbors, increased cell area, and decreased cell anisotropy. Piezo overexpression slightly increased the number of cell neighbors and cell area. This highlights the critical role of Piezo in regulating overcrowding within the epithelia during organ growth. In sum, these results support Piezo as a key regulator of epithelial homeostasis through a feedback mechanism that regulates the balance of forces within the epithelium. The outcomes of this feedback loop contribute to the robustness of organ size regulation.