Not Too Large and Not Too Small–Just the Right Size: A Hippo-Sized Heart

Abstract

### Hippo Pathway Inhibits Wnt Signaling to Restrain Cardiomyocyte Proliferation and Heart Size Heallen et al Science . 2011;332:458–461. Hippo signaling is an important regulator of organ size by balancing both cell proliferation and apoptosis. In cardiac development, Wnt signaling has been shown to be an important mediator of early cardiomyocyte proliferation and differentiation. Recent studies have now shown that the Hippo pathway negatively regulates heart size through recruitment of the coactivator Yap to the Wnt transcriptional effector β-catenin to balance the level of cardiomyocyte proliferation.1 How organs obtain the correct size during development is one of the least understood processes during development. The coordination of the proper level of cell proliferation as well as differentiation and maturation is regulated by multiple developmental pathways, but few have been specifically implicated in controlling organ size. Heart function is quite sensitive to the effects of cardiac organ size, especially during development. A heart that is too small can lead to cardiac insufficiency and developmental demise. In contrast, in the adult, pathological cardiac hypertrophy, which can cause an enlarged heart, can result in decreased cardiac function and severe heart disease. Thus, during development, regulation of cardiac size can have an important impact on cardiovascular function. The Hippo pathway was originally shown to regulate organ size in Drosophila imaginal disc development.2,3 In vertebrates, the function of the Hippo pathway is less understood, but several orthologues of the Drosophila Hippo genes Mst1 and Mst2, which are serine/threonine kinases, have been identified as well as …