Hox genes and kidney patterning.

Abstract

Hox gene activity is essential for proper organization or pattern of the vertebrate body plan and is necessary for organogenesis. Sequence conservation within this family of genes is high yet they are involved in very diverse developmental processes. How this family functions in these processes is a challenging question, but is important for the understanding of renal organogenesis. Multiple Hox genes are expressed in the kidney and mutation in at least one group of paralogous genes results in severe renal defects. Recent studies in mice with targeted Hox gene mutations and in kidney cell lines demonstrate that these genes have evolved to control tissue specific functions through their ability to regulate the expression of renal morphogens. The studies also demonstrate that Hox gene activity is not only restricted by the domain of expression but also by the specificity of the DNA binding homeodomain. Interestingly, these conserved homeodomains are not wholly interchangeable for normal renal organogenesis while they do appear to be interchangeable for axial skeleton development. It is clear that Hox genes regulate important interactions between the ureteric bud and metanephric mesenchyme. Nevertheless, much work remains to define the expression patterns of multiple Hox genes during kidney development, to better determine the functional relationships of the encoded proteins, and to identify additional Hox downstream targets.