Figure 5: Vertebrate limb evolution and distal Hox gene function. A phylogenetic tree of representative taxa and appendage skeletal patterns is shown, as well as corresponding distal Hox expression [in actinopterygians shown for Polyodon spathula (28)] and Gli3R gradient (when known). Genetically abrogating Shh signaling and reducing distal Hox function in mouse autopods (Hoxa13+/–;HoxdDel11-13/Del11-13;Gli3XtJ/XtJ) reveals ancestral skeletal characteristics shared with the pectoral fins of sharks (Chiloscyllium punctatum) and primitive ray-finned fishes (Polypterus senegalus): numerous, densely packed, and iterative elements, with a distal cartilaginous band corresponding to the distal radials of fish fins (arrows). The periodic pattern of skeletal elements evident in fins and mutant limbs strongly suggests that a self-organizing Turing-type mechanism of chondrogenesis is deeply conserved in vertebrate phylogeny. Our results further indicate that distal Hox gene dose regulates the number and spacing of skeletal elements formed, implicating distal Hox gene regulatory networks as critical drivers of the evolution of the pentadactyl limb. Figure and legend from Sheth et al 2012.