The left-right asymmetry of internal organs is established during mammalian development by a leftward fluid flow in the embryonic node cavity, expression of the secreted protein Nodal at the node, and subsequent asymmetric Nodal expression in the left lateral plate mesoderm (LPM). But, how is the Nodal signal transferred to the LPM? On , Oki and co-workers controversially propose that Nodal travels directly to the LPM from the node by interacting with sulfated glycosaminoglycans (GAGs) in the intervening basement membrane-like structure. The researchers show that externally supplied Nodal does not signal to the LPM in cultured mouse embryos, which suggests that an internal route exists for Nodal signal transfer to the LPM. They discount that Nodal signals might be indirectly relayed by showing that the Nodal co-receptor Cryptic is not needed in the node for asymmetric Nodal expression in the LPM. Finally, they show that Nodal interacts with sulfated GAGs and that inhibition of their biosynthesis prevents Nodal expression in the LPM.
