Pitx2 expression defines a left cardiac lineage of cells: Evidence for atrial and ventricular molecular isomerism in the iv/iv mice

The homeobox gene Pitx2 has been characterized as a mediator of left-right signaling in heart, gut, and lung morphogenesis. However, the relationship between the developmental role of Pitx2 and its expression pattern at the o rgan level has not been explored. In this study we focus on the role of Pit x2 in heart morphogenesis. Chicken Pitx2 transcripts are present in the lef t portion of the cardiac crescent and in the left side of the heart tube. T hrough looping Pitx2 is present in the left atrium, in the ventral portion of the ventricles and in the left-ventral part of the outflow tract. Mouse Pitx2 shows a similar developmental profile of expression. To test whether Pitx2 represents a lineage marker we have tagged the left portion of the ch icken cardiac tube with fluorescent DiD. Labeled cells were found at HH16 i n the left atrium and in the ventral region of the ventricles and the outfl ow tract. In the iv/iv mouse model of cardiac heterotaxia Pitx2 was abnorma lly expressed in the atrial and in the ventricular chambers. Furthermore, a ltered Pitx2 expression correlated with the occurrence of DORV. Our data re veal the existence of molecular isomerism not only in the atrial, but also in the ventricular compartment of the heart. (C) 2001 Academic Press.