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.