LAUSR

Tetrapods are characterized by the presence of digits at the distal end of their limbs, which have emerged during the transition from fins to limbs. While variations in digit number are observed in extant tetrapods, most have five digits per limb and divergence from this pentadactyl ground state is always a reduction in digit number. Paleontological data revealed that stem‐group tetrapods were polydactylous indicating that the evolution from fish fin to modern tetrapod limbs involved two major transitions; the emergence of digits and the shift from polydactyly to pentadactyly. The absence of living polydactyl tetrapod species is a major limitation in assessing the foundation of the pentadactyl constraint. Nonetheless, several genes having the capacity of modulating digit number have been identified and studying their functional and regulatory phylogeny will likely be critical in our comprehension of the emergence of the pentadactyl state. In this review, we provide an overview of the data obtained from mouse genetics that uncovered the role of Hox genes in controlling digit number and discuss regulatory changes that could have been implicated in the emergence of the pentadactyl ground state.