PATTERNING THE HEARTS LEFT-RIGHT AXIS - FROM ZEBRAFISH TO MAN

Normal left-right asymmetry is highly conserved among vertebrates. Err ors in the proper patterning of this axis are believed to lead to cong enital anomalies of the heart and abdominal viscera, often with profou nd clinical consequences. We review briefly the nature of potential si gnals and signaling sources that lead to the break in left-right symme try. The evidence suggests that left-right reversal, or homogenization , of these signals may lead to different consequences, and we explain some malpositions and malalignments of the atria, ventricles, and/or o utflow tract thai are seen in a variety of congenital cardiac diseases . We speculate that there are units of organ assembly responsive to la terality signals, and these units may be driven independently. One cru cial source of signals appears to be the notochord and floorplate. in order io examine the clinical relationship of these midline structures to putative disorders of laterality, we review all patients with dist urbances of normal laterality seen at the Massachusetts General past 2 0 years. We find a significant association between laterality defects and anomalies of the spine and other midline structures. (C) 1998 Wile y-Liss, Inc.