Large scale transgenic and cluster deletion analysis of the HoxD complex separate an ancestral regulatory module from evolutionary innovations

The ancestral role of the Hox gene family is specifying morphogenetic diffe rences along the main body axis. In vertebrates, HoxD genes were also co-op ted along with the emergence of novel structures such as limbs and genitali a. We propose that these functional recruitments relied on the appearance, or implementation, of regulatory sequences outside of the complex. Whereas transgenic human and murine HOXD clusters could function during axial patte rning, in mice they were not expressed outside the trunk. Accordingly, dele tion of the entire cluster abolished axial expression, whereas recently acq uired regulatory controls were preserved.