FUNCTIONAL SPECIFICITY OF HOXA-4 IN VERTEBRAL PATTERNING LIES OUTSIDEOF THE HOMEODOMAIN

The Hox family of proteins plays a central role in establishing the bo dy plan of a wide range of metazoan organisms. Each member of this fam ily of transcriptional regulators has a distinct functional specificit y, yet they bind to similar DNA target sequences through their conserv ed homeodomain. The mechanisms whereby Hox proteins achieve their dive rse specificities in vivo remain undefined. Using the opposing effects of Hoxa-4 and Hoxc-8 in vertebral patterning, we demonstrate by repla cing the homeodomain of Hoxa-4 with that of Hoxc-8 that the functional specificity of Hoxa-4 does nor track with the homeodomain. These obse rvations provide evidence that other regions of Hox proteins play an i mportant role in mediating functional specificity during mammalian emb ryogenesis.