BOC and holoprosencephaly: Cdo and Boc displayed different expression patterns during mouse embryonic development and mice with mutation of Cdo exhibited holoprosencephaly while Boc mutants showed defective commissural axon guidance26,31–33, suggesting the regulation of Hh signaling is cell context-dependent and Hh co-receptors may serve to provide tissue and context-specific “tuning” of Hh responsiveness.