During craniofacial development, the lower jaw skeleton is derived from cephalic neural crest cells that are present in the mandibular region of the first pharyngeal arch. To investigate how mandibular identity is specified,Ruest et al. analysed mandibular development in endothelin-A receptor(Ednra) null mouse embryos, which are born with severe craniofacial defects (see p. 4413). The researchers report that most of the lower jaw structures in Ednra–/– embryos are homeotically transformed into upper jaw structures, which are similar changes to those seen in mice lacking two downstream effectors of Ednra signalling – the distal-less homeobox genes Dlx5 and Dlx6. These structural changes are preceded by disrupted gene expression in the mandibular arch,except for in one region possibly involved in lower incisor development. Thus,suggest the researchers, establishing mandibular identity requires both Ednra-dependent and -independent signalling pathways.