Fat and Dachsous Signaling—Controlling Growth Requires Both Competition and Cooperation

The Hippo signaling pathway plays a key role in organ size control in normal development and tumorigenesis. While many components of this pathway are well understood, its upstream regulation remains unclear. Among the most enigmatic upstream regulators are the protocadherins Dachsous and Fat. These transmembrane proteins regulate a growth-promoting complex composed of the atypical myosin Dachs, the adaptor protein Dlish, and the palmitoyltransferase Approximated (together termed the core complex). We propose that by default the core complex promotes growth and that Dachsous and Fat, which previously have been thought to act antagonistically, can also function synergistically to repress core complex function and therefore restrict growth. Understanding the molecular mechanisms underlying Dachsous-Fat signaling offers insight into how multicellular organisms precisely control organ size.