Shimozono, S. et al. Nature 496, 363–366 (2013).

Early embryos owe much of their patterning to morphogens: signaling molecules with a graded distribution that direct cells to assume different identities according to molecule concentration. Retinoic acid, a morphogen that patterns posterior tissues in chordates, is believed to act by forming diffusion gradients, but scientists have been able to infer its distribution only indirectly. Shimozono et al. enable a more direct look by engineering three genetically encoded probes for retinoic acid. The probes consist of retinoic acid–receptor ligand-binding domains of different affinities flanked by cyan fluorescent protein and yellow fluorescent protein, which produce a Förster resonance energy transfer signal in the presence of the ligand. Imaging and perturbation studies confirmed a disputed two-tailed linear gradient of retinoic acid in the early zebrafish embryo hindbrain.