THE BHLH FACTORS, DHAND AND EHAND, SPECIFY PULMONARY AND SYSTEMIC CARDIAC VENTRICLES INDEPENDENT OF LEFT-RIGHT SIDEDNESS

dHAND and eHAND are basic helix-loop-helix transcription factors that play critical roles in cardiac development. The HAND genes have a comp lementary left-right cardiac asymmetry of expression with dHAND predom inantly on the right side and eHAND on the left side of the looped hea rt tube. Here we show that although eHAND is asymmetrically expressed along the anterior-posterior and dorsal-ventral embryonic axes, it is symmetrically expressed along the left-right axis at early stages of e mbryonic and cardiac development. After cardiac looping, dHAND and eHA ND are expressed in the right (pulmonary) and left (systemic) ventricl es, respectively. The left-right (LR) sidedness of dHAND and eHAND exp ression is demonstrated to be anatomically reversed in situs inversus (inv/inv) mouse embryos; however, dHAND expression persists in the pul monary ventricle and eHAND in the systemic ventricle regardless of ana tomic position, indicating chamber specificity of expression. Previous ly we showed that dHAND-null mice fail to form a right-sided pulmonary ventricle. Here mice homozygous for the dHAND and inv mutations are d emonstrated to have only a right-sided ventricle which is morphologica lly a left (systemic) ventricle. These data suggest that the HAND gene s are involved in development of segments of the heart tube which give rise to specific chambers of the heart during cardiogenesis, rather t han controlling the direction of cardiac looping by interpreting the c ascade of LR embryonic signals. (C) 1998 Academic Press.