English: Fish and tetrapod HoxA and HoxD clusters are regulated by 3′ and 5′ regulatory landscapes, represented here as triangles due to their correspondence to topological domains.[1][2] Enhancer (indicated with colored shapes) interactions within these domains (indicated by arrows) occur with the neighboring parts of the Hox clusters, resulting in a regulatory partition between 3′ and 5′ parts of the clusters. In fishes, this mechanism may be used for patterning the fin proximal (red) to distal (orange) (P-D) polarity, through the potential function of these two landscapes in slightly different fin domains. Variation in the regulatory balance between these 3′ and 5′ landscapes through the acquisition of novel enhancers potentially explains interspecies differences in P-D fin morphology, as for instance between zebrafish and species such as coelacanth, which possesses a more elaborate fin skeleton. Although these regulatory landscapes may underlie the P-D patterning of fin skeletons, they both elicit a proximal response when assessed in transgenic mice, and hence the fish 5′ landscape is indicated as “proximal” (orange). In tetrapods, the 5′ domain (blue) has acquired new enhancers or modified existing ones, thereby evolving a novel, more distal autopodial identity, perhaps as a response to preexisting signals emanating from the apical ectoderm.