Contributions of 5'HoxA/D regulation to actinodin evolution and the fin-to-limb transition

The evolution of tetrapod limbs from paired fish fins comprised major changes to the appendicular dermal and endochondral skeleton. Fish fin rays were lost, and the endochondral bone was modified and elaborated to form three distinct segments common to all tetrapod limbs: the stylopod, the zeugopod and the autopod. Identifying the molecular mechanisms that contributed to these morphological changes presents a unique insight into our own evolutionary history. This review first summarizes previously identified cis-acting regulatory elements for the 5'HoxA/D genes and actinodin1 that were tested using transgenic swap experiments between fish and tetrapods. Conserved regulatory networks provide evidence for a deep homology between distal fin structures and the autopod, while diverging regulatory strategies highlight potential molecular mechanisms that contributed to the fin-to-limb transition. Next, we summarize studies that performed functional analysis to recapitulate fish-tetrapod diverging regulatory strategies and then discuss their potential morphological consequences during limb evolution. Finally, we also discuss here some of the advantages and disadvantages of using zebrafish to study molecular and morphological changes during the fin-to-limb transition.