Rauskolb, C. | Search bioRxiv

bioRxiv2025

Regulation of Hippo signaling by Atrophin in the developing Drosophila wing

Organ development is directed through integration of signaling networks and their transcriptional programs. We have investigated connections between Hippo signaling and the transcriptional co-repressor Atrophin. We find that Atrophin modulates Hippo signaling outputs in the developing Drosophila wing and does so in distinct ways in different regions. Near the dorsal-ventral boundary, loss of Atrophin leads to upregulation of targets of the Hippo pathway transcription factor Yorkie. This is explained by impairment of Notch signaling, and consequent downregulation of Vestigial, which normally competes with Yorkie for binding to Scalloped. In proximal regions of the wing disc, loss of Atrophin leads to downregulation of Yorkie activity. This is explained by downregulation of Dachs, as Dachs inhibits Warts, the central kinase controlling Yorkie activity. Downregulation of Dachs is explained by modulation of its upstream regulators Dachsous and Four-jointed, which is explained in turn by our discovery that Atrophin interacts genetically and physically with Vestigial and competes with Scalloped for Vestigial binding. These studies define new roles for Atrophin and enhance our understanding of the interplay of transcriptional activators and repressors that modulate Hippo signaling to shape wing development.

developmental biology↗

bioRxiv2022

Analysis of the Drosophila Ajuba LIM protein defines functions for distinct LIM domains

The Ajuba LIM protein Jub mediates regulation of Hippo signaling by cytoskeletal tension through interaction with the kinase Warts, and also participates in feedback regulation of junctional tension through regulation of the cytohesin Steppke. To investigate how Jub interacts with and regulates its distinct partners, we investigated the ability of Jub proteins missing different combinations of its three LIM domains to rescue jub phenotypes and to interact with -catenin, Warts and Steppke. Multiple regions of Jub contribute to its ability to bind -catenin and to localize to adherens junctions in Drosophila wing imaginal discs. Co-immunoprecipitation experiments in cultured cells identified a specific requirement for LIM2 for binding to Warts. However, in vivo, both LIM1 and LIM2, but not LIM3, were required for regulation of wing growth, Yorkie activity, and Warts localization. Conversely, LIM2 and LIM3, but not LIM1, were required for regulation of cell shape and Steppke localization in vivo, and for maximal Steppke binding in co-immunoprecipitation experiments. These observations identify distinct functions for the different LIM domains of Jub.

cell biology↗