ORGANIZER INDUCTION DETERMINES LEFT-RIGHT ASYMMETRY IN XENOPUS

Vertebrates appear bilaterally symmetrical but have considerable left- right (LR) asymmetry in the anatomy and placement of internal organs s uch as the heart. Although a number of asymmetrically expressed genes are known to affect LR patterning, both the initial source of asymmetr y and the mechanism that correctly orients the LR axis remain controve rsial. In this study, we show that the induction of dorsal organizing centers in the embryo can orient ER asymmetry. Ectopic organizing cent ers were induced by microinjection of mRNA encoding a variety of body asis duplicating proteins, including members of the Wnt signal transdu ction pathway. The ectopic and primary body axes farm side-by-side con joined twins, with the secondary ads developing as either the left or right sibling. In all cases, correct LR asymmetry was observed In the left twin, regardless of whether it was derived from the primary axis or induced de novo by injection of Xwnt-8, beta-catenin, or Siamois mR NA, In contrast, the right twin was generally unbiased, regardless of the origin of the left body axis, as seen in many instances of experim entally induced and spontaneous conjoined twins. An unanticipated exce ption was that right twins induced by beta-catenin and Siamois, two do wnstream effecters of Wnt signaling, exhibited predominately normal he art looping, even when they formed the right twin. Taken together, the se results indicate that LR asymmetry is locally oriented as a consequ ence of Wnt signaling through beta-catenin and Siamois. We discuss the possibility that signal upstream of beta-catenin and Siamois might be required in order for a right sibling to be randomized. (C) 1997 Acad emic Press.