PITX2 DETERMINES LEFT-RIGHT ASYMMETRY OF INTERNAL ORGANS IN VERTEBRATES

The handedness of visceral organs is conserved among vertebrates anal is regulated by asymmetric signals relayed by molecules such as Shh, N odal and activin. The gene Pitx2 is expressed in the left lateral plat e mesoderm and, subsequently, In the left heart and gut of mouse, chic k and Xenopus embryos. Misexpression of Shh and Nodal induces Pitx2 ex pression, whereas inhibition of activin signalling blocks it. Misexpre ssion of Pitx2 alters the relative position of organs and the directio n of body rotation In chick and Xenopus embryos. Changes in Pitx2 expr ession are evident in mouse mutants with laterality defects. Thus, Pit x2 seems to serve as a critical downstream transcription target that m ediates left-right asymmetry in vertebrates.