Introduction: The Hippo pathway is a highly conserved signalling pathway that regulates many developmental processes, including tissue growth, proliferation and differentiation. Deregulation of Hippo signalling has been identified in a wide range of cancers. In Drosophila, Hippo signalling converges on the activity of the transcriptional coactivator Yorkie (YAP and TAZ in mammals), which drives a diverse transcriptional output. The core kinases of the Hippo pathway are understood to inhibit the activity of Yorkie by restricting its access to the nucleus through phosphorylation; however, the temporal and spatial scale of Yorkie regulation and how this impacts on normal growth is not well understood.
Methods: We are using a combination of ex vivo imaging of developing larval epithelia and fixed tissue imaging to gain insight in to the mechanisms by which Yorkie is regulated over time throughout different tissue compartments, with the aim of uncovering novel regulatory mechanisms. These are then further investigated using RNA interference and studies of mutant tissue to test for potential involvement of various signalling pathways and cellular processes in the regulation of Yorkie activity.
Results: We have developed a detailed picture of Yorkie levels and localisation throughout larval development and show a specific role for Yorkie in development of the dorsal-ventral boundary of the wing. This has provided potential insights into novel mechanisms of Yorkie regulation, which are under further investigation.
Significance: These studies highlight potentially novel mechanisms of Hippo pathway regulation, and provide new settings for addressing the ways in which other developmental pathways affect Hippo pathway function to ensure normal organ growth.