Roles of Hippo signaling pathway in size control of organ regeneration

Animals have an intrinsic regeneration ability for injured tissues and organs. Species that have high regeneration ability such as newts can regenerate an organ with exactly the same size and shape as those of the original one. It has been unclear how a regenerating organ grows and ceases growth at an appropriate size. Organ size control in regeneration is seen in various organs of various species that have high regeneration ability. In animal species that do not have sufficient regeneration ability, a wound heals (the injury is closed, but lost parts are not regenerated), but an organ cannot be restored to its original size. On the other hand, perturbation of regeneration sometimes results in oversized or extra structures. In this sense, organ size control plays essential roles in proper regeneration. In this article, we introduce the concept of size control in organ regeneration regulated by the Hippo signaling pathway. We focused on the transcriptional regulator Yap, which shuttles between the nuclei and cytoplasm to exert a regulatory function in a context-dependent manner. The Yap-mediated Hippo pathway is thought to sense cell density, extracellular matrix (ECM) contact and cell position and to regulate gene expression for control of organ size. This mechanism can reasonably explain size control of organ regeneration.