Homeobox transcription factor Pitx2: The rise of an asymmetry gene in cardiogenesis and arrhythmogenesis

Abstract The homeobox transcription factor Pitx2 displays a highly specific expression pattern during embryogenesis. Gain and loss of function experiments have unraveled its pivotal role in left–right signaling. Conditional deletion in mice has demonstrated a complex and intricate role for Pitx2 in distinct aspects of cardiac development and more recently a link to atrial fibrillation has been proposed based on genome-wide association studies. In this review we will revise the role of Pitx2 in the developing heart, starting from the early events of left–right determination followed by its role in cardiac morphogenesis and ending with its role in cardiac arrhythmogenesis.