INITIATION OF VERTEBRATE LEFT-RIGHT AXIS FORMATION BY MATERNAL VG1

IN the development of the three-dimensional vertebrate body plant the left-right axis is linked to the dorsoventral and anterioposterior axe s(1,2). In humans, altered left-right development results in severe ca rdiovascular and visceral abnormalities in individuals and in conjoine d twins(3,4). Although zygotically transcribed genes that are asymmetr ically expressed have been identified(5-8), the mechanism by which lef t-right asymmetries are established during embryogenesis is unknown(9) . Here we show that the Xenopus maternal gene Vg1, a member of the TGF -beta family of cell-signalling molecules which are implicated in dors oanterior development(10), initiates left-right axis formation. Altere d expression of Vg1 on the right side of 16-cell embryos or disruption of endogenous Vg1 signalling on the left side randomizes cardiac and visceral left-right orientation and alters expression of Xnr-1, a noda l-related molecular marker for left-right developments, Furthermore, t he orientation of the left-right asis in conjoined twins is dependent upon which cell-signalling molecule initiated twin formation and on wh ether the secondary axis is on the left or right side of the primary e mbryonic axis, implicating a molecular pathway leading to the formatio n of conjoined twins.