Genetic Regulation of Shox2 on Sinoatrial Node Development and Pacemaker Cell Fate

Abstract: The sinoatrial node controls heart rate， which is the primary pacemaker for the generation and conduction of electrocardiosignals in the cardiac conduction system. Defect of this structure will lead to various types of cardiac arrhythmias. Shox2 (short stature homeobox 2)， a member of the homeobox gene family， is critical for the development of sinoatrial node and its normal biological function. Mutations of Shox2 can lead to sinus node hypoplasia in mice， which contribute to the symptoms of severe sinus bradycardia and cardiac arrhythmia. The mutations in mice and human Shox2 are also closely related to atrial fibrillation. In addition， Shox2 regulates a genetic network through the repression of Nkx2.5(NK2 homeobox 5) to maintain the pacemaker cell fate in sinoatrial node and thus plays key roles in pacemaker cells differentiation. This review summarizes the regulation mechanism of Shox2 in sinoatrial node development and pacemaker cell fate， further explores the causes of atrial fibrillation， and provides a theoretical basis for biological pacemaker therapies.

CSTR: 32200.14.cjcb.2019.03.0022