TABLE 2.

Hippo signaling mediators in cardiac development and disease.

Genes	Model	Cardiac phenotypes	References
Yap, Taz	Nkx2.5Cre/+;Yapf/f	Decreased cardiomyocyte proliferation, thin ventricle wall. Embryonic death at E10.5.	Xin et al., 2011
	SM22αCre/+;Yapf/f	Ventricular hypoplasia, thin ventricle wall, VSD. Perinatal lethality.	Wang Y. et al., 2014
	Tnnt2Cre/+;Yapf/f	Hypoplastic ventricles, decreased cardiomyocyte proliferation. Embryonic death at E16.5.	von Gise et al., 2012
	α-MHCCre/+;Yapf/f orα-MHCCre/+;Yapf/+	Dilated cardiomyopathy and premature death, increased fibrosis and apoptosis; decreased proliferation, decreased cardiomyocyte proliferation and hypertrophy after MI, impaired cardiac regeneration. Attenuated cardiac hypertrophy, increased apoptosis and fibrosis after pressure overload.	Del Re et al., 2013; Xin et al., 2013; Byun et al., 2019
	α-MHCCre/+;YapS112A	Increased cardiomyocyte proliferation, thick myocardium, improved cardiac regeneration after MI.	Xin et al., 2013
	α-MyHCCre–ERT2;Yap5SA	Increased cardiomyocyte proliferation, thick ventricular wall, and small chambers, and cardiomyocyte hyperplasia. Death within 4 days after tamoxifen treatment.	Monroe et al., 2019
	β-MHCCre/+;YapS112A	Increased cardiomyocyte proliferation and thick myocardium.	Xin et al., 2011
	Tnnt2Cre/+;Rosa26fs–rtTA;TetO-YapS127A	Increased cardiomyocyte proliferation, thickened myocardium, cardiomegaly, no hypertrophy.	von Gise et al., 2012
	Tnnt2Cre/+;Yapf/S79A	Cardiac hypoplasia was similar to Yap cardiomyocyte-specific conditional knockout.	von Gise et al., 2012
	Tie2Cre/+;Yapf/f	Hypocellular endocardial cushions due to impaired EMT and reduced endocardial cell proliferation.	Zhang et al., 2014
	α-MHCCre/+;Tazf/f	No cardiac defects. It enhances cardiac phenotype (decreased proliferation, increased apoptosis, dilated cardiomyopathy, and heart failure) on a Yap null background.	Xin et al., 2013
	Sema3dGFPCre/+;Yapf/f;Tazf/f	Impaired epicardial cell proliferation, EMT and differentiation. Embryonic lethality between E11.5–12.5.	Singh et al., 2016
	Wt1CreERT2/+;Yapf/f;Tazf/f	Coronary vasculature defects due to impaired epicardial cell proliferation, EMT, and fate determination. Increased post-MI pericardial inflammation and myocardial fibrosis resulting in cardiomyopathy and death.	Singh et al., 2016; Ramjee et al., 2017
	Nfatc1IRES–Cre/+;Yapf/f;Tazf/f	Impaired myocardial growth causing early post-natal lethality.	Artap et al., 2018
Tead	Tead1–/–	Enlarged pericardial cavity, bradycardia, thin ventricular wall, reduced number of trabeculae. Embryonic lethality by E11.5.	Chen et al., 1994
	MCK-Tead1 Tg	Age-dependent cardiac dysfunction (decreased cardiac output, stroke volume, ejection fraction, and fractional shortening). Misalignment of cardiomyocytes, septal wall thickening, and fibrosis. Heart failure leading to death within 4-days after induction of pressure overload.	Tsika et al., 2010