Pitx2 isoforms: involvement of Pitx2c but not Pitx2a or Pitx2b in vertebrate left-right asymmetry

During vertebrate left-right development the homeobox gene Pitx2 serves as a mediator between transient nodal signaling in the left lateral plate mesoderm (l-LPM) and asymmetric organ morphogenesis. Misexpression of Pitx2 in chick and frog led to alteration of organ situs. Here we report the presence of different Pitx2 isoforms in mouse and frog. Pitx2c but not Pitx2a or Pitx2b was asymmetrically expressed in the l-LPM, heart and gut, and was specifically induced by nodal in Xenopus animal cap explant cultures and whole embryos. Pitx2c induced its own transcription, suggesting a maintenance mechanism following the down-regulation of nodal in the l-LPM. Pitx2c thus represents the left-specific isoform involved in vertebrate left-right asymmetry.