10779/crick.12652043.v1 Georgina C Fletcher Georgina C Fletcher Maria del Carmen Diaz De La Loza Maria del Carmen Diaz De La Loza Nerea Borreguero Muñoz Nerea Borreguero Muñoz Maxine Holder Maxine Holder Mario Aguilar Aragon Mario Aguilar Aragon Barry J Thompson Barry J Thompson Mechanical strain regulates the Hippo pathway in Drosophila The Francis Crick Institute 2020 Cell shape Drosophila Hippo pathway Mechanosensing Yorkie Animals Animals, Genetically Modified Body Patterning Cell Nucleus Drosophila Proteins Drosophila melanogaster Embryo, Nonmammalian Gene Expression Regulation, Developmental Imaginal Discs Intracellular Signaling Peptides and Proteins Mechanotransduction, Cellular Nuclear Proteins Protein Transport Protein-Serine-Threonine Kinases Signal Transduction Stress, Mechanical Trans-Activators Transcription Factors Wings, Animal Thompson FC001180 Tapon FC001175 LM-ack 06 Biological Sciences 11 Medical and Health Sciences 2020-07-15 11:21:39 Journal contribution https://crick.figshare.com/articles/journal_contribution/Mechanical_strain_regulates_the_Hippo_pathway_in_Drosophila/12652043 Animal cells are thought to sense mechanical forces via the transcriptional co-activators YAP (or YAP1) and TAZ (or WWTR1), the sole Drosophila homolog of which is named Yorkie (Yki). In mammalian cells in culture, artificial mechanical forces induce nuclear translocation of YAP and TAZ. Here, we show that physiological mechanical strain can also drive nuclear localisation of Yki and activation of Yki target genes in the Drosophila follicular epithelium. Mechanical strain activates Yki by stretching the apical domain, reducing the concentration of apical Crumbs, Expanded, Kibra and Merlin, and reducing apical Hippo kinase dimerisation. Overexpressing Hippo kinase to induce ectopic activation in the cytoplasm is sufficient to prevent Yki nuclear localisation even in flattened follicle cells. Conversely, blocking Hippo signalling in warts clones causes Yki nuclear localisation even in columnar follicle cells. We find no evidence for involvement of other pathways, such as Src42A kinase, in regulation of Yki. Finally, our results in follicle cells appear generally applicable to other tissues, as nuclear translocation of Yki is also readily detectable in other flattened epithelial cells such as the peripodial epithelium of the wing imaginal disc, where it promotes cell flattening.