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The Hippo pathway is an important regulator of organ growth and cell fate. The major mechanism by which Hippo is known to control transcription is by dictating the nucleo-cytoplasmic shuttling rate of Yorkie, a transcription co-activator, which promotes transcription with the DNA binding protein Scalloped. The nuclear biophysical behavior of Yorkie and Scalloped, and whether this is regulated by the Hippo pathway, remains unexplored. Using multiple live-imaging modalities on Drosophila tissues, we found that Scalloped interacts with DNA on a broad range of timescales, and enrichment of Scalloped at sites of active transcription is mediated by longer DNA dwell times. Further, Yorkie increased Scalloped's DNA dwell time, whereas the repressors Nervous fingers 1 (Nerfin-1) and Tondu-domain-containing growth inhibitor (Tgi) decreased it. Therefore, the Hippo pathway influences transcription not only by controlling nuclear abundance of Yorkie but also by modifying the DNA binding kinetics of the transcription factor Scalloped. [Display omitted] • Longer DNA binding times by Scalloped are associated with enhanced transcription • Scalloped and Yorkie have different nuclear mobility and chromatin binding kinetics • Scalloped's activation/repression partners alter DNA binding time in opposing ways • Scalloped profoundly influences Yorkie's biophysical behavior and genome binding Using a range of live microscopy approaches, Manning et al. investigate how the Hippo pathway regulates transcription in vivo. The transcription factor Scalloped interacts with DNA on a broad range of timescales, and the Yorkie co-activator extends this, while the Nerfin-1 and Tgi co-repressors decrease it. [ABSTRACT FROM AUTHOR]

Organ size is controlled by numerous factors including mechanical forces, which are mediated in part by the Hippo pathway. In growing Drosophila epithelial tissues, cytoskeletal tension influences Hippo signaling by modulating the localization of key pathway proteins to different apical domains. Here, we discovered a Hippo signaling hub at basal spot junctions, which form at the basal-most point of the lateral membranes and resemble adherens junctions in protein composition. Basal spot junctions recruit the central kinase Warts via Ajuba and E-cadherin, which prevent Warts activation by segregating it from upstream Hippo pathway proteins. Basal spot junctions are prominent when tissues undergo morphogenesis and are highly sensitive to fluctuations in cytoskeletal tension. They are distinct from focal adhesions, but the latter profoundly influences basal spot junction abundance by modulating the basal-medial actomyosin network and tension experienced by spot junctions. Thus, basal spot junctions couple morphogenetic forces to Hippo pathway activity and organ growth. [Display omitted] • Discovery of a cell adhesion complex (basal spot junctions) in Drosophila epithelia • Basal spot junctions are a Hippo signaling hub in Drosophila epithelia • Basal spot junctions likely couple Hippo signaling with tissue morphogenesis and growth • Actomyosin and focal adhesions are intimately linked with basal spot junctions Kroeger et al. identify a cell-cell adhesion complex (basal spot junctions) in Drosophila epithelial tissues, which form at the basal-most region of the lateral membranes of epithelial cells. Basal spot junctions are a site of repression of the Hippo growth control pathway and likely couple tissue morphogenesis and growth. [ABSTRACT FROM AUTHOR]

Warts is the central effector kinase of the Hippo growth-control pathway. In this issue of Developmental Cell , by assessing Warts conformation in vivo, Vrabioiu and Struhl (2015) report that the Mob family protein Mats regulates Warts activity allosterically, independent of phosphorylation by Hippo. [ABSTRACT FROM AUTHOR]