Homeosis refers to a class of mutations which brings about the replacement of one body part with that of another normally found elsewhere on the animal. Molecular analysis of the Drosophila homeotic regulatory genes has shown that the proteins which they encode contain a highly conserved 60 amino acid domain (the homeodomain). Homeodomain containing proteins are part of the mechanism which controls the diversity of body parts in Drosophila. The significance of the homeodomain has been highlighted by the demonstration that homeodomain proteins are found in other metazoans, including mice and humans. These observations suggests the exciting possibility that genes which control insect body plan may have partial homology to functionally related genes which control the body plans of mammals. By identifying the functional roles of these genes play in mouse development, we hope to gain insight into the basic principles which govern mammalian development. As an initial step, we have focused our efforts on the molecular biology of the murine and human Hox 1.3 homeobox gene and its encoded protein. DNA sequence analysis of Hox 1.3 cDNA and genomic clones indicates that the gene is organized into two exons and its major transcript encodes a 270 amino acid homeodomain protein. mRNA analysis shows that the gene is expressed early in embryogenesis. Hox 1.3 transcripts are also present in many adults tissues which possess different cell lineages. Immunolocalization studies detect the Hox 1.3 protein in many cell types during embryonic development, most notably in the spinal ganglia. In the adult CNS, certain subsets of fully differentiated neurons express the Hox 1.3 protein. The Purkinje neurons of the cerebellum, the pyramidal and dentate neurons of the hippocampus, and the motor neurons of the spinal cord are positive. Production of the Hox 1.3 protein in the eukaryotic Baculovirus expression system has enabled us to determine that Hox 1.3 encodes a sequence-specific DNA binding phosphoprotein. Hox 1.3 binding sites are located in many cis-regulatory elements which control both transcription and DNA replication. Analysis of the human Hox 1.3 reveals that the primary structures of this gene and its encoded protein are highly conserved. The murine and human proteins differ by only seven amino acids.
