Functional specificity of the Hoxa13 homeobox

To better define Abd-B type homeodomain function, to test models that predi ct functional equivalence of all Hox genes and to initiate a search for the downstream targets of Hoxa13, we have performed a homeobox swap by replaci ng 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-t ype function in the development of the kidneys, axial skeleton and mate rep roductive tract, consistent with functional equivalence models. In the limb s and female reproductive tract, however, the A1113hd allele appeared to as sume dominant Hoxa13 function. The uterus, in particular, showed a striking homeotic transformation towards cervix/ vagina, where Hoxa13 is normally e xpressed. Gene chips were used to create a molecular portrait of this tissu e conversion and revealed over 100 diagnostic gene expression changes. This work identifies candidate downstream targets of the Hoxa13 gene and demons trates that even contiguous Abd-B homeoboxes have functional specificity.