Characterization of a murine homeo box gene, Hox-2.6, related to the Drosophila Deformed gene.

Abstract

The Hox-2 locus on chromosome 11 represents one of the major clusters of homeo-box-containing genes in the mouse. We have identified two new members (Hox-2.6 and Hox-2. 7), which form part of this cluster of seven linked genes, and it appears that the Hoxo2 locus is related by duplication and divergence to at least one other mouse homeo box cluster, Hox-1. The Hox-2.6 gene encodes a predicted protein of 250 amino acids, which displays extensive similarity in multiple regions to certain mouse, human, Xenopus, and zebra fish homeo domain proteins. The Drosophila Deformed (Dfd) gene also shares these same regions of similarity, and based on this sequence conservation, we suggest that Hox-2.6 forms part of a vertebrate 'Dfd-like' family. Hox-2.6 is expressed in fetal and adult tissues and is modulated during the differentiation of F9 teratocarcinoma stem cells.In situ hybridization analysis of mouse embryos shows that the Hox-2.6 is expressed in ectodermal derivatives:spinal cord, hindbrain, dorsal root ganglia, and the Xth cranial ganglia. In the central nervous system, expression is observed in the most posterior parts of the spinal cord, with the anterior limit residing in a region of the hindbrain and no expression in the mid-or forebrain. In mesodermal structures, Hox-2.6 is expressed in the kidney, the mesenchyme of the stomach and lung, and the longitudinal muscle layer of the gut. Expression has not been observed in derivatives of embryonic endoderm. The patterns of Hox-2.6 expression in both mesoderm and ectoderm are spatially restricted and may reflect a role for the gene in the response to or establishment of positional cues in the embryo.

Zyxin and cCRP: two interactive LIM domain proteins associated with the cytoskeleton.

“…Several other cytoskeletal proteins including vinculin (Coutu and Craig, 1988;Price et al, 1989), ezrin (Gould et al, 1989;Turunen et al, 1989), and radixin (Funayama et al, 1991), exhibit small clusters of contiguous proline residues, but the overall proline content of zyxin is much higher than in these proteins. Homology searches with the zyxin protein sequence have revealed that a number of DNA tumor virus-encoded proteins (for example, Cheung, 1989;Baer et ai., 1984) and a presumed transcription factor, the hox 2.6 protein (Graham et al, 1988), display regions of proline-rich sequence reminiscent of the proline arrays found in zyxin; however, no functional relationship between zyxin and these proteins has yet been defined.…”

ANA, a novel member of Tob/BTG1 family, is expressed in the ventricular zone of the developing central nervous system

“…Sonic hedgehog (Shh) and members of the transforming growth factor-b (TGF-b) family in¯uence ventral and dorsal features of the development in the caudal neural tube, and recombinant Shh induces¯oor plate cells and motor neurons in neural plate explants (McKay, 1997;Roelink et al, 1995;Marti et al, 1995). In addition to extracellular signals, several region-and cell-typespeci®c transcription factors are involved in neural development: the products of the Hox, Pax and POU genes are involved in the de®nition of speci®c regions along the rostro-caudal axis of the developing nervous system (Kessel and Gruss, 1990;Graham et al, 1991), and basic helix ± loop ± helix (bHLH) transcription factors are implicated in the neural commitment and di erentiation (Lee, 1997). Then a question arises: how are the extracellular signals transmitted to the nucleus in the cells?…”

The structural and functional organization of the murine HOX gene family resembles that of Drosophila homeotic genes.

“…Based on protein sequence similarity, these genes can be grouped into subfamilies which are represented once in each cluster. Since each subfamily member is found in the same relative position within each cluster (Hart et al, 1987;Duboule et al, 1989;Graham et al, 1988), the HOX-1, -2, -3 and -5 complexes are likely to be the result of largescale duplication events daring evolution.…”