Hedgehog (Hh) signalling gradients control many developmental processes and are influenced by numerous positive and negative regulators. The transmembrane protein Brother of Cdo (Boc) has been implicated in Sonic hedgehog (Shh)-mediated commissural axon guidance in the CNS, but how Boc affects the cellular Hh response in vivo is unclear. Here, Rolf Karlstrom and colleagues reveal that Boc is cell-autonomously required for Hh-mediated ventral CNS patterning in zebrafish (see p. 75). The umleitung (uml) zebrafish mutant is characterised by defects in retinotectal projections. The researchers show first that uml encodes Boc. Then, by analysing the phenotypes of uml mutants, they show that Boc is a positive regulator of Hh signalling in the spinal cord, hypothalamus, pituitary, somites and upper jaw, but that Boc might be a negative regulator of Hh signalling in the lower jaw. Overall, these results reveal a role for Boc in ventral CNS cells that receive high levels of Hh, and uncover novel roles for Boc in vertebrate development.