title: Differential growth triggers mechanical feedback that elevates Hippo signaling.
abstract: Mechanical stress can influence cell proliferation in vitro, but whether it makes a significant contribution to growth control in vivo, and how it is modulated and experienced by cells within developing tissues, has remained unclear. Here we report that differential growth reduces cytoskeletal tension along cell junctions within faster-growing cells. We propose a theoretical model to explain the observed reduction of tension within faster-growing clones, supporting it by computer simulations based on a generalized vertex model. This reduced tension modulates a biomechanical Hippo pathway, decreasing recruitment of Ajuba LIM protein and the Hippo pathway kinase Warts, and decreasing the activity of the growth-promoting transcription factor Yorkie. These observations provide a specific mechanism for a mechanical feedback that contributes to evenly distributed growth, and we show that genetically suppressing mechanical feedback alters patterns of cell proliferation in the developingDrosophilawing. By providing experimental support for the induction of mechanical stress by differential growth, and a molecular mechanism linking this stress to the regulation of growth in developing organs, our results confirm and extend the mechanical feedback hypothesis.
authors: Howard Hughes Medical Institute, Waksman Institute and Department of Molecular Biology and Biochemistry, Rutgers University, Piscataway, NJ 08854.
authors: Yuanwang
authors: Y
authors: Pan
authors: Kavli Institute of Theoretical Physics, University of California, Santa Barbara, CA 93101.
authors: Idse
authors: I
authors: Heemskerk
authors: Howard Hughes Medical Institute, Waksman Institute and Department of Molecular Biology and Biochemistry, Rutgers University, Piscataway, NJ 08854.
authors: Consuelo
authors: C
authors: Ibar
authors: Kavli Institute of Theoretical Physics, University of California, Santa Barbara, CA 93101 shraiman@kitp.ucsb.edu irvine@waksman.rutgers.edu.
authors: Boris I
authors: BI
authors: Shraiman
authors: Howard Hughes Medical Institute, Waksman Institute and Department of Molecular Biology and Biochemistry, Rutgers University, Piscataway, NJ 08854; shraiman@kitp.ucsb.edu irvine@waksman.rutgers.edu.
authors: Kenneth D
authors: KD
authors: Irvine
keywords: Ajuba; Drosophila development; Hippo; cytoskeleton; tissue mechanics