Cell type specificity of Hippo-YAP signaling in cardiac development and disease

The Hippo-YAP pathway is an evolutionarily conserved signaling module that regulates cell survival, proliferation, and differentiation to control organ size. Recent work has demonstrated critical roles for Hippo-YAP signaling in cardiac development and disease, including its ability to modulate both pathological and regenerative responses in the heart. Therefore, targeting the Hippo-YAP pathway for therapeutic benefit has gained attention and holds substantial promise for improving outcomes in patients with heart disease. Importantly, however, much of our understanding of cardiac Hippo-YAP signaling is based on studies in cardiomyocytes, and far less is known in other cell types in the heart. This review will focus primarily on the role of Hippo-YAP signaling in cardiomyocytes, cardiac fibroblasts, and macrophages, and explore how cell type-specific functions can impact heart development, as well as injury responses that can drive divergent outcomes in heart disease.