Left-right (LR) axis establishment during embryogenesis underlies the asymmetric body plan of adult animals, for example, the siting of the heart on the left side of the human body. On p. 4847, Bunney et al. report that the signalling molecule 14-3-3E is involved very early in LR patterning in Xenopus laevis. The researchers show that the treatment of newly fertilised eggs with Fusiococcin-A, a fungal toxin that interacts with 14-3-3 proteins, randomised on which side of the body the heart, gut and gall bladder developed in the embryos, as did the blockade of 14-3-3 function with a phosphopeptide containing a 14-3-3 interaction motif and the overexpression of 14-3-3E. Their demonstration that 14-3-3E is asymmetrically localised at the first cell division of fertilised Xenopus eggs identifies the earliest LR asymmetric molecular localisation in any species to date.