The vertebrate hindbrain is divided into serially homologous segments, the rhombomeres (r). Pbx and Hox proteins are hypothesized to form heterodimeric, DNA binding transcription complexes which specify rhombomere identities. Here, we show that eliminating zebrafish Lzr/Pbx4 and Pbx2 function prevents hindbrain segmentation and causes a wholesale anterior homeotic transformation of r2-r6, to r1 identity. We demonstrate that Pbx proteins interact with Hox paralog group 1 proteins to specify segment identities broadly within the hindbrain, and that this process involves the Pbx:Hox-1-dependent induction of Fgf signals in r4. We propose that in the absence of Pbx function, r2-r6 acquire a homogeneous ground state identity, that of r1, and that Pbx proteins, functioning primarily with their Hox partners, function to modify this ground state identity during normal hindbrain development.

Individual vertebrate Hox genes specify aspects of segment identity along the anterior-posterior axis. The exquisite in vivo specificity of Hox proteins is thought to result from their interactions with members of the Pbx/Exd family of homeodomain proteins. Here, we report the identification and cloning of a zebrafish gene, lazarus, which is required globally for segmental patterning in the hindbrain and anterior trunk. We show that lazarus is a novel pbx gene and provide evidence that it is the primary pbx gene required for the functions of multiple hox genes during zebrafish development. lazarus plays a critical role in orchestrating the corresponding segmentation of the hindbrain and the pharyngeal arches, a key step in the development of the vertebrate body plan.