The Hippo pathway effectors YAP and TAZ are known to respond to mechanical forces, translocating to the nucleus to activate target genes in cultured mammalian cells. However, the physiological relevance of this response and the molecular factors that trigger it are poorly understood. Now, Barry Thompson and colleagues report that Yorkie (Yki), the sole Drosophila homolog of YAP and TAZ, senses mechanical forces in Drosophila ovarian follicles via the canonical Hippo pathway. They first reveal that Yki activity increases as follicle cells flatten to form so-called stretch cells; by contrast, Yki activity is repressed in cells that remain columnar. Using a Yki:GFP knock-in line, the authors show that Yki localises to the nucleus in stretch cells, while remaining cytoplasmic in columnar cells. They further demonstrate that upstream Hippo pathway regulators are apically localised in columnar cells but become diluted across the apical surface of stretch cells. Accordingly, a Hippo kinase dimerisation sensor is shown to be active at the apical domain of columnar, but not stretch, cells. Finally, the authors report that Yki nuclear translocation occurs in other flattened epithelial cells, such as those of the wing imaginal disc. Based on their findings, the authors propose that apical domain stretching during development dilutes Hippo pathway components, leading to reduced Hippo kinase dimerisation and hence an increase in Yki activity within stretched cells.
