Regulation of midline development by antagonism of lefty and nodal signaling

The embryonic midline is crucial for the development of embryonic pattern i ncluding bilateral symmetry and left-right asymmetry. In zebrafish, lefty1 (lft1) and lefty2 (lft2) have distinct midline expression domains along the anteroposterior axis that overlap with the expression patterns of the noda l-related genes cyclops and squint. Altered expression patterns of lft1 and lft2 in zebrafish mutants that affect midline development suggests differe nt upstream pathways regulate each expression domain. Ectopic expression an alysis demonstrates that a balance of lefty and cyclops signaling is requir ed for normal mesendoderm patterning and goosecoid, no tail and pitx2 expre ssion. In late somite-stage embryos, lft1 and lft2 are expressed asymmetric ally in the left diencephalon and left lateral plate respectively, suggesti ng an additional role in laterality development. A model is proposed by whi ch the vertebrate midline, and thus bilateral symmetry, is established and maintained by antagonistic interactions among co-expressed members of the l efty and nodal subfamilies of TGF-beta signaling molecules.