The transcription factor Pitx2 mediates situs-specific morphogenesis in response to left-right asymmetric signals.

Abstract

The mechanism by which asymmetric signals induce left-right-specific morphogenesis has been elusive. Pitx2 encodes a transcription factor expressed throughout the left lateral plate mesoderm and subsequently on the left side of asymmetric organs such as the heart and gut during organogenesis in the chick embryo. Pitx2 is induced by the asymmetric signals encoded by Nodal and Sonic hedgehog, and its expression is blocked by prior treatment with an antibody against Sonic hedgehog. Misexpression of Pitx2 on the right side of the embryo is sufficient to produce reversed heart looping and heart isomerisms, reversed body rotation, and reversed gut situs.