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 axes(1,2). In humans, altered left-right development results in severe cardiovascular and visceral abnormalities in individuals and in conjoined twins(3,4). Although zygotically transcribed genes that are asymmetrically expressed have been identified(5-8), the mechanism by which left-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 dorsoanterior development(10), initiates left-right axis formation. Altered 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 nodal-related molecular marker for left-right developments, Furthermore, the orientation of the left-right asis in conjoined twins is dependent upon which cell-signalling molecule initiated twin formation and on whether the secondary axis is on the left or right side of the primary embryonic axis, implicating a molecular pathway leading to the formation of conjoined twins.