Functional specificity of the Hoxa13 homeobox.
To better define Abd-B type homeodomain function, to test models that predict functional equivalence of all Hox genes and to initiate a search for the downstream targets of Hoxa13, we have performed a homeobox swap by replacing the homeobox of the Hoxa11 gene with that of the Hoxa13 gene. The Hoxa11 and Hoxa13 genes are contiguous Abd-B type genes located at the 5' end of the HoxA cluster. The modified Hoxa11 allele (A11(13hd)) showed near wild-type function in the development of the kidneys, axial skeleton and male reproductive tract, consistent with functional equivalence models. In the limbs and female reproductive tract, however, the A11(13hd) allele appeared to assume dominant Hoxa13 function. The uterus, in particular, showed a striking homeotic transformation towards cervix/vagina, where Hoxa13 is normally expressed. Gene chips were used to create a molecular portrait of this tissue conversion and revealed over 100 diagnostic gene expression changes. This work identifies candidate downstream targets of the Hoxa13 gene and demonstrates that even contiguous Abd-B homeoboxes have functional specificity.
Zhao
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Division of Developmental Biology, Children's Hospital Medical Center, Cincinnati, OH 45224, USA.
Potter
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D000483:Alleles; D000595:Amino Acid Sequence; D000818:Animals; D015139:Blotting, Southern; D001846:Bone Development; D001842:Bone and Bones / Q000196:embryology; D002584:Cervix Uteri / Q000196:embryology; D005260:Female; D006412:Hematopoietic Stem Cells / Q000166:cytology; D018398:Homeodomain Proteins / Q000378:metabolism*; D017403:In Situ Hybridization; D007668:Kidney / Q000196:embryology; D008297:Male; D051379:Mice; D008817:Mice, Mutant Strains; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D009154:Mutation; D020411:Oligonucleotide Array Sequence Analysis; D010641:Phenotype; D014599:Uterus / Q000196:embryology; D014621:Vagina / Q000196:embryology
D018398:Homeodomain Proteins; C099959:homeobox protein HOXA13