Nodal and its feedback inhibitor Lefty instruct left-right (LR) asymmetry in vertebrates, but what controls the spatial distribution of these ligands in the embryo? On , Lindsay Marjoram and Christopher Wright address this question by expressing functional epitope-tagged Nodal and Lefty from grafts implanted into tailbud Xenopus embryos. Both ligands move long distances along the extracellular matrix (ECM), they report, with Lefty moving faster than Nodal. Moreover, sulphated proteoglycans in the ECM seem to facilitate Nodal movement. Thus, the researchers propose, Nodal autoregulation aided by rapid ligand transport underlies the anteriorward shift of Nodal expression along the left lateral plate mesoderm (LPM), with higher levels of chondroitin-sulphate proteoglycan in more mature anterior regions providing directional transport cues. Finally, they report, Lefty moves from the left to the right LPM, a result that strengthens LR patterning models that involve active blocking of right-sided Nodal expression. Future molecular studies into how Nodal and Lefty interact with sulphated proteoglycan-rich ECM should provide additional insights into the establishment of LR asymmetry.
