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Although a number of genes that are involved in the establishment of left-right asymmetry have been identified, earlier events in the molecular pathway developing left-right asymmetry remain to be elucidated. Here we present evidence suggesting that the transforming growth factor-beta family member derrière is involved in the development of left-right asymmetry in Xenopus embryos. Ectopic expression of derrière on the right side can fully invert cardiac and visceral left-right orientation and nodal expression, and expression of a dominant-negative form of derrière on the left side can partially randomize the left-right orientation and nodal expression. Moreover, while expression of the dominant-negative derrière does not inhibit the activity of Vg1 directly, it can rescue the altered left-right orientation induced by Vg1. Vg1 can induce derrière in animal cap explants. These results suggest that derrière is involved in earlier molecular pathways developing the left-right asymmetry.
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