The Power of Drosophila Genetics: The Discovery of the Hippo Pathway

The Hippo Pathway comprises a vast network of components that integrate diverse signals including mechanical cues and cell surface or cell-surface-associated molecules to define cellular outputs of growth, proliferation, cell fate, and cell survival on both the cellular and tissue level. Because of the importance of the regulators, core components, and targets of this pathway in human health and disease, individual components were often identified by efforts in mammalian models or for a role in a specific process such as stress response or cell death. However, multiple components were originally discovered in the Drosophila system, and the breakthrough of conceiving that these components worked together in a signaling pathway came from a series of Drosophila genetic screens and fundamental genetic and phenotypic characterization efforts. In this chapter, we will review the original discoveries leading to the conceptual framework of these components as a tumor suppressor network. We will review chronologically the early efforts that established our initial understanding of the core machinery that then launched the growing and vibrant field to be discussed throughout later chapters of this book.