Organ size control by Hippo and TOR pathways

Abstract

The determination of final organ size is a highly coordinated and complex process that relies on the precise regulation of cell number and/or cell size. Perturbation of organ size control contributes to many human diseases, including hypertrophy, degenerative diseases, and cancer. Hippo and TOR are among the key signaling pathways involved in the regulation of organ size through their respective functions in the regulation of cell number and cell size. Here, we review the general mechanisms that regulate organ growth, describe how Hippo and TOR control key aspects of growth, and discuss recent findings that highlight a possible coordination between Hippo and TOR in organ size regulation.

Figure 1. The TOR and Hippo pathways in organ size control

TOR regulates organ size by stimulating cell growth, thereby increasing cell size. Hippo controls organ size by restricting cell number via inhibition of proliferation and induction of apoptosis.

Figure 2. The Hippo pathway in Drosophila and mammals

Corresponding genes in (A) Drosophila and (B) mammals are shown. Core components, upstream regulators, and downstream targets of the Hippo pathway are labeled in blue, pink, and green boxes, respectively. See text for details.

Figure 3. The TOR pathway

Genes that activate or inhibit TOR are labeled in blue and red boxes, respectively. Downstream targets of TOR are labeled in green boxes. See text for details.