Evolutionary convergence of digit loss by overlapping mechanisms in multiple species of mammals (919.6)

Since the origin of tetrapod limbs about 450 million years ago, every Class of land vertebrate ‐ reptiles, birds, amphibians, and mammals ‐ has undergone some degree of digit loss from the ancestral count of five. Even within mammals many species have independently reduced the number of digits as a locomotor adaptation. The repeated convergence on digit loss indicates it is perhaps mechanistically simple, yet little is known of the mechanisms or whether developmental constraints ensure the same mechanisms are re‐deployed in divergent species. Here we show in the three‐toed jerboa, horse, camel, and pig that the mechanisms of digit loss are varied and yet utilize recurring themes. Common characteristics of digit loss include downregulated expression of the growth factor fgf8 in the apical ectodermal ridge in the anterior and posterior limb of all species with reduced digits. We also see massively upregulated cell death in tissue that fails to become digits in the jerboa, horse, and camel. In the three‐toed jerboa, we have identified additional hindlimb specific expression differences that may be responsible for the reduction to three toes on the hindlimb while the forelimb maintains five. We see strong upregulation of bmp4 and its transcriptional target, msx2, in the hindlimb whereas the forelimb expression resembles that of the mouse. Both genes are associated with promoting cell death in mouse and chicken limbs providing a mechanistic connection that makes these two excellent candidates for investigating evolution of cis‐regulatory elements responsible for the loss of digits.