biostudies-literatureZheng MNHLBI NIH HHS1694-1711https://www.ebi.ac.uk/biostudies/studies/S-EPMC9897204biostudies-literatureUnknown146(22)<h4>Background</h4>The sinoatrial node (SAN) functions as the pacemaker of the heart, initiating rhythmic heartbeats. Despite its importance, the SAN is one of the most poorly understood cardiac entities because of its small size and complex composition and function. The Hippo signaling pathway is a molecular signaling pathway fundamental to heart development and regeneration. Although abnormalities of the Hippo pathway are associated with cardiac arrhythmias in human patients, the role of this pathway in the SAN is unknown.<h4>Methods</h4>We investigated key regulators of the Hippo pathway in SAN pacemaker cells by conditionally inactivating the Hippo signaling kinases <i>Lats1</i> and <i>Lats2</i> using the tamoxifen-inducible, cardiac conduction system-specific Cre driver <i>Hcn4<sup>CrCirculationHippo-Yap Signaling Maintains Sinoatrial Node Homeostasis.PMC9897204R01 HL147108R01 HL163277R56 HL142704R01 HL142704R01 HL136389T32 HL007676Christoffels VMLi RGNguyen BHWang JSong JLi MZhao XLi NLi XTang LErhardt SZheng MChen WEvans SMfalseHippo-Yap Signaling Maintains Sinoatrial Node Homeostasis.<h4>Background</h4>The sinoatrial node (SAN) functions as the pacemaker of the heart, initiating rhythmic heartbeats. Despite its importance, the SAN is one of the most poorly understood cardiac entities because of its small size and complex composition and function. The Hippo signaling pathway is a molecular signaling pathway fundamental to heart development and regeneration. Although abnormalities of the Hippo pathway are associated with cardiac arrhythmias in human patients, the role of this pathway in the SAN is unknown.<h4>Methods</h4>We investigated key regulators of the Hippo pathway in SAN pacemaker cells by conditionally inactivating the Hippo signaling kinases <i>Lats1</i> and <i>Lats2</i> using the tamoxifen-inducible, cardiac conduction system-specific Cre driver <i>Hcn4<sup>Cr2022-01-01T00:00:00Z2022 Nov2025-04-04T03:01:02.042Z2025-02-19T04:43:50.563ZS-EPMC98972043631752910.1161/circulationaha.121.05877710.1161/CIRCULATIONAHA.121.058777