The Hippo pathway coactivator Yorkie can reprogram cell fates and create compartment-boundary-like interactions at clone margins.

Abstract

During development, tissue-specific patterns of gene expression are established by transcription factors and then stably maintained via epigenetic mechanisms. Cancer cells often express genes that are inappropriate for that tissue or developmental stage. Here, we show that high activity levels of Yki, the Hippo pathway coactivator that causes overgrowth in <i>Drosophila</i> imaginal discs, can also disrupt cell fates by altering expression of selector genes like <i>engrailed</i> (<i>en</i>) and <i>Ultrabithorax</i> (<i>Ubx</i>). Posterior clones expressing activated Yki can down-regulate <i>en</i> and express an anterior selector gene, <i>cubitus interruptus</i> (<i>ci</i>). The microRNA <i>bantam</i> and the chromatin regulator Taranis both function downstream of Yki in promoting <i>ci</i> expression. The boundary between Yki-expressing posterior clones and surrounding wild-type cells acquires properties reminiscent of the anteroposterior compartment boundary; Hedgehog signaling pathway activation results in production of Dpp. Thus, at least in principle, heterotypic interactions between Yki-expressing cells and their neighbors could activate boundary-specific signaling mechanisms.