Hippo signaling and organ size control

Hippo signaling is a growth control pathway first described in Drosophila and more recently studied in mammals. At the core of the Drosophila Hippo signaling pathway is a cascade composed of the Hippo and warts serine threonine kinases whose function in the context of Hippo signaling is to restrict the activity of the transcriptional coactivator yorkie by phosphorylation and cytoplasmic retention. In mammals, a similar cascade is present with the mst1 and mst2 kinases serving the function of Hippo and the lats1 and lats2 kinases functioning as orthologs of warts. Mammals also have two yorkie-related genes, yap and taz. Emerging evidence suggests that a common theme of Hippo signaling in epithelial tissues is to regulate growth, either in a homeostatic or developmental framework, or in pathological situations such as cancer. Much initial and recent attention has focused on Hippo signaling in the context of organ size control. Indeed, how final organ size is achieved during animal development and how it is maintained in adults is a long standing and fundamental problem. In this chapter, basic concepts of organ size determination and the relationship between progenitor, stem cells, and regulation of organ size, both during development and in adult tissue homeostasis are reviewed in the context of Hippo signaling.