The lefty-related factor Xatv acts as a feedback inhibitor of Nodal signaling in mesoderm induction and L-R axis development in Xenopus

In mouse, lefty genes play critical roles in the left-right (LR) axis deter mination pathway, Here, we characterize the Xenopus lefty-related factor an tivin (Xatv), Xatv expression is first observed in the marginal zone early during gastrulation, later becoming restricted to axial tissues. During tai lbud stages, axial expression resolves to the neural tube floorplate, hypoc hord, and (transiently) the notochord anlage, and is joined by dynamic expr ession in the left lateral plate mesoderm (LPM) and left dorsal endoderm, An emerging paradigm in embryonic patterning is that secreted antagonists r egulate the activity of intercellular signaling factors, thereby modulating cell fate specification. Xatv, expression is rapidly induced by dorsoanter ior-type mesoderm inducers such as activin or Xnr2. Xatv is not an inducer itself, but antagonizes both Xnr2 and activin, Together with its expression pattern, this suggests that Xatv functions during gastrulation in a negati ve feedback loop with Xnrs to affect the amount and/or character of mesoder m induced, Our data also provide insights into the way that lefty/nodal sig nals interact in the initiation of differential L-R morphogenesis. Right-si ded misexpression of Xnr1 (endogenously expressed in the left LPM) induces bilateral Xatv expression Left-sided Xatv overexpression suppresses Xnr1/XP itx2 expression in the left LPM, and leads to severely disturbed visceral a symmetry, suggesting that active 'left' signals are critical for L-R axis d etermination in frog embryos. We propose that the induction of lefty/Xatv i n the left LPM by nodal/Xnr1 provides an efficient self-regulating mechanis m to downregulate nodal/Xnr1 expression and ensure a transient 'left' signa l within the embryo.