Expression of a homeo domain protein in noncontact-inhibited cultured cells and postmitotic neurons.

Abstract

The murine Hox 1.3 gene is one of six homeo box genes clustered on chromosome 6. Our analysis of Hox 1.3 cDNA and genomic clones indicates that the gene is organized into two exons and encodes a 270-amino-acid homeo domain protein. The predicted protein is rich in serine, glycine, and proline residues, and its homeo domain is identical to the Hox 2.1 domain. During embryogenesis, the gene is maximally expressed at midgestation but is also expressed to a lesser extent in many adult tissues possessing different cell lineages. Hox 1.3 transcripts are also present in cultured fibroblasts. The Hox 1.3 protein accumulates in the nuclei of nonconfluent cultured fibroblasts but is greatly diminished in contact-inhibited nongrowing cells. Thus, the expression of the Hox 1.3 gene correlates with growth in embryos and cultured cells. Paradoxically, it is also expressed in certain subsets of postmitotic, fully differentiated neurons, most notably the Purkinje neurons of the cerebellum, the pyramidal and dentate neurons of the hippocampus, and the motor neurons of the spinal cord. This complex pattern of expression suggests that Hox 1.3 may provide a function required by many cell types in addition to any role it may have in morphogenesis.

The mouse Hox-1.3 gene is functionally equivalent to the Drosophila Sex combs reduced gene.

“…Lai et al (1991) suggested that the HNF-3 family may maintain certain fkh functions in forming gut-related terminal embryonic structures during evolution (Lai et al 1991). Interestingly, Hox-l.3 transcripts also have been found in liver and lung (Odenwald et al 1987;Garbern et al 1989). The colocalization of Hox-l.3 and HNF-3 gene products in the same tissues may not be a coincidence.…”

“…1A). In addition, two other short regions (Odenwald et al 1987), one at the amino terminus of the proteins (the octapeptide) and the other just adjacent to the homeo domain (the pentapeptide), are also highly conserved among these proteins. However, the overall similarity of the 270-amino-acid Hox-1.3 protein to the three is low: 28% (75 amino acids) to Scr; 26% (70 amino acids) to Antp; and 24% (66 amino acids) to Deformed (Dfd).…”

“…The homeo domain is located between residues 195 and 254. The protein also contains an octapeptide (MSSYFVNS) and a pentapeptide (IYPWM) that are conserved among many vertebrate and Drosophila homeo box genes (Odenwald et al 1987}. The distribution of Hox-l.3 is progressively restricted during early mouse embryogenesis.…”

“…In mid-gestation embryos, Hox-1.3 mRNA is expressed at high levels in the mesoderm and neuroectoderm with an anterior boundary near the junction of the hindbrain and spinal cord (Dony and Gruss 1987;Fibi et al 1988). In adults, the mRNA and protein have also been detected in some tissues, including liver, lung, kidney, and central nervous system (Odenwald et al 1987;Garbem et al 1989). DNA-binding assays showed that Hox-l.3 high-affinity binding sites contain an ATTA core motif , which is also the core of Drosophila Antp class high-affinity binding sites (for review, see Scott et al 1989).…”

“…The gene was then characterized by Odenwald et al (1987) and Fibi et al (1988). It consists of two exons and one intron.…”