LINKAGE OF CARDIAC LEFT-RIGHT ASYMMETRY AND DORSAL-ANTERIOR DEVELOPMENT IN XENOPUS

The left-right body axis is defined relative to the dorsal-ventral and anterior-posterior body axes. Since left-right asymmetries are not ra ndomly oriented with respect to dorsal-ventral and anterior-posterior spatial patterns, it is possible that a common mechanism determines al l three axes in a coordinate manner. Two approaches were undertaken to determine whether alteration in dorsal-anterior development perturbs the left-right orientation of heart looping. Treatments known to decre ase dorsal-anterior development in Xenopus laevis, UV irradiation duri ng the first cell cycle or Xwnt-8 DNA injections into dorsal blastomer es, caused an increase in cardiac left-right reversals. The frequency of left-right reversal was correlated with the severity of dorsal-ante rior perturbation and with the extent of anterior notochord regression . Injection of Xwnt-8 DNA into dorsal midline cells resulted in decrea sed dorsal-anterior development and a correlated increase in cardiac l eft-right reversals. In contrast, injection of Xwnt-8 DNA into cardiac progenitor blastomeres did not result in left-right reversals, and do rsal-anterior development and notochord formation were normal. Disrupt ing development of dorsal-anterior cells, including cells that give ri se to the Organizer region and the notochord, results in the randomiza tion of cardiac left-right asymmetry. These results suggest dorsal-ant erior development and the regulation of left-right orientation are lin ked.