Decision letter: A shift in anterior–posterior positional information underlies the fin-to-limb evolution

Abstract

Humans, mice, and other animals with four limbs belong to a group of land-dwelling animals known as the tetrapods. This group of animals evolved from ancient fish and one crucial adaptation to life on land involved the modification of fins to form limbs. The front pair of limbs (the ‘arms’) evolved from the ‘pectoral’ fins of the ancient fish. These fins contain numerous bones that fan out from a set of bones called the pectoral girdle. However, most of the bones nearer the front side (the thumb side in the human limb) were lost in the ancestors of tetrapods as they moved onto land. Only the bone nearest the back remained as the ‘humerus’, which forms the upper part of the limb (i.e., the upper arm of humans). In the embryos of mice and other animals, the limbs develop from structures called limb buds. For the limb to develop properly, the cells in the limb bud need to receive specific instructions that depend on their position in the bud. A protein called Gli3R provides cells with information about their position along the ‘anterior–posterior’ (or thumb-to-little finger) axis of the bud. This protein regulates several genes that are involved in limb development, and this results in different genes being expressed in cells along the anterior–posterior axis. For example, Alx4 is only expressed in a small area at the anterior end of the bud, while Hand2 expression is found in a large area towards the posterior part. Gli3R is also found in a fish called the catshark, but it is not clear how it controls the formation of fins. Onimaru et al. show that the pattern of gene expression in the catshark fin bud is different to that of the mouse limb bud. For example, Alx4 is expressed in a larger area of the fin bud that extends further towards the posterior, while Hand2 is only found in a much smaller area at the posterior end of the bud. The experiments also suggest that Gli3R is active in a much larger area of the fin bud than in the limb bud. Next, Onimaru et al. used a drug on the catshark embryos to increase the activity of another protein that can inhibit Gli3R. The fin buds of these shark had anterior shift in several gene expression domains, and the fins that formed were missing several anterior bones and had only a single bone connected to the pectoral girdle. Onimaru et al.'s findings suggest that during the evolution of the tetrapods, there may have been a shift in the anterior–posterior patterning of the fin bud to form a limb. An important area for future work will be to use genome-wide studies to study the fin/limb buds of other species.