lazarus Is a Novel pbx Gene that Globally Mediates hox Gene Function in Zebrafish

Abstract

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.

HOXB4 homeodomain protein is expressed in developing epidermis and skin disorders and modulates keratinocyte proliferation

“…In the current study, much of the HOXB4 is nuclear in both the developing and adult epidermis, particularly in hyperproliferative conditions. Our finding of substantial nuclear HOXB4 expression is consistent with both biochemical data (Chang et al, 1995;Shen et al, 1996), gene transfection studies , and transgenic animal studies (Gould et al, 1997;Popperl et al, 2000) that indicate that HOXB4 forms biologically active DNA binding complexes with PBX proteins.…”

Constructing the hindbrain: Insights from the zebrafish

“…Although lzr/pbx4 mRNA is expressed ubiquitously, Pbx protein accumulates at higher levels posterior to the r1/2 boundary ( Fig. 8A; Pöpperl et al, 2000). The r1/2 boundary is also the anterior limit of both meis and hox expression within the hindbrain (Fig.…”

“…The vertebrate Pbx and Meis genes encode divergent homeodomain-containing proteins of the TALE (three amino acid Loop extension) class, which are essential DNA binding partners for the Hox proteins (reviewed by Mann and Affolter, 1998). Two zebrafish pbx genes and five zebrafish meis genes are expressed in the presumptive hindbrain during the period when Hox genes are specifying segment identity (Pöpperl et al, 2000;Vlachakis et al, 2000;Waskiewicz et al, 2001;Zerucha and Prince, 2001). Eliminating the zygotic function of one of these, Pbx4, as occurs in the lazarus (lzr)/pbx4 mutant, mimics the phenotypes associated with loss of several different Hox genes in the mouse (Pöpperl et al, 2000;K.L.…”

“…For example, in lzr/pbx4 mutants the motor neurons of the seventh cranial nerve do not migrate posteriorly from r4 (a phenotype identical to that of both hoxb1 mutant mice and zebrafish embryos injected with a hoxb1a morpholino oligonucleotide); and motor neurons of the fifth cranial nerve project aberrantly into the second pharyngeal arch (identical to the hoxa2 mutant mouse). Direct evidence that lzr/pbx4 is indeed broadly required for Hox protein function in zebrafish is the observation that lzr/pbx4 function is required for the gain-of-function phenotypes associated with hoxb1a, hoxb1b, hoxa2b, and hoxb2a overexpression (Pöpperl et al, 2000;K.L. Cooper, V.E.…”

Turning heads: Development of vertebrate branchiomotor neurons

“…Multiple genes encoding this class of Hox-binding transcriptional cofactors have been identified in mouse and zebrafish (Popperl et al, 2000;Waskiewicz et al, 2002). Zebrafish pbx genes are expressed in broad overlapping domains, and pbx2 and pbx4 are expressed sufficiently early to play direct roles in generating rhombomere identities (Waskiewicz et al, 2002).…”