Hmx: an evolutionary conserved homeobox gene family expressed in the developing nervous system in mice and Drosophila

Three homeobox genes, one from Drosophila melanogaster (Drosophila Hmx gene ) and two from mouse (murine Hmx2 and Hmx3) were isolated and the full-leng th cDNAs and corresponding genomic structures were characterized. The strik ing homeodomain similarity encoded by these three genes to previously ident ified genes in sea urchin, chick and human, as well as the recently cloned murine Hmx1 gene, and the low homology to other homeobox genes indicate tha t the Hmx genes comprise a novel gene family. The widespread existence of H mx genes in the animal kingdom suggests that this gene family is of ancient origin. Drosophila Hmx was mapped to the 90B5 region of Chromosome 3 and a t early embryonic stages is primarily expressed in distinct areas of the ne uroectoderm and subsets bf neuroblasts in the developing fly brain. Later i ts expression continues in rostral areas of the brain in a segmented patter n, suggesting a putative role in the development of the Drosophila central nervous system. During evolution, mouse Hmx2 and Hmx3 may have retained a p rimary function in central nervous system development as suggested by their expression in the postmitotic cells of the neural tube, as well as in the hypothalamus, the mesencephalon, metencephalon and discrete regions in the myelencephalon during embryogenesis. Hmx1 has diverged from other Hmx: memb ers by its expression in the dorsal root, sympathetic and vagal nerve (X) g anglia. Aside from their expression in the developing nervous system, all t hree Hmx genes display expression in sensory organ development, and in the adult uterus. Hmx2 and Hmx3 show identical expression in the otic vesicle, whereas Hmx1 is strongly expressed in the developing eye. Transgenic mouse lines were generated to examine the DNA regulatory elements controlling Hmx 2 and Hmx3. Transgenic constructs spanning more than 31 kb of genomic DNA g ave reproducible expression patterns in the developing central and peripher al nervous systems, eye, ear and other tissues, yet failed to fully recapit ulate the endogenous expression pattern of either Hmx2 or Hmx3, suggesting both the presence and absence of certain critical enhancers in the transgen es, or the requirement of proximal enhancers to work synergistically. (C) 2 000 Elsevier Science Ireland Ltd. All rights reserved.