Organization of mouse Iroquois homeobox genes in two clusters suggests a conserved regulation and function in vertebrate development

Iroquois proteins comprise a conserved family of homeodomain-containing tra nscription factors involved in patterning and regionalization of embryonic tissues in both vertebrates and invertebrates. Earlier studies identified f our murine Iroquois (Irx) genes. Here we report the isolation of two additi onal members of the murine gene family, Irx5 and Irx6. Phylogenetic analysi s of the Irx gene family revealed distinct clades for Fly and vertebrate ge nes, and vertebrate members themselves were classified into three pairs of cognate genes. Mapping of the murine Irx genes identified two gene clusters located on mouse chromosomes 8 and 13, respectively. Each gene cluster is represented by three Im genes whose relative positions within both clusters are strictly conserved. Combined results from phylogenetic, linkage, and p hysical mapping studies provide evidence for the evolution of two Irx gene clusters by duplication of a larger chromosomal region and dispersion to tw o chromosomal locations. The maintenance of two cognate Irx gene clusters d uring vertebrate evolution suggests that their genomic organization is impo rtant for the regulation, expression, and function of Irx genes during embr yonic development.