Evolution uncovered: The key genetic event that changed fins to limbs and gave rise to early tetrapods

Scientists from the Tokyo Institute of Technology believe they have made a breakthrough in the quest to find out how fish fins evolved into limbs. A study of catsharks has revealed how alterations in the expression and function of certain genes in limb buds underlie the evolution of fish fins to limbs, something that has long puzzled the scientific community.

(a) Skeletal pattern. In a catshark fin, three basal bones are connected to the pectoral girdle, whereas in a mouse limb, a single basal bone is connected to the body trunk. (b) Expression patterns of genes involved in anterior-posterior patterning of fins/limbs. The balance of anterior field (Alx4, Pax9-positive region) and posterior field (Hand2-positive field) shifted in between a catshark pectoral fin and a mouse forelimb.

A key regulator protein controlling the balance of the limb buds of tetrapods is called Gli3. This protein is expressed in the anterior part of limb buds, and regulates the expression of a number of genes providing cells with information about their position.

To determine whether shifts in the balance of anterior and posterior field occurred during fin-to-limb evolution, scientists carefully compared the expression, function and regulation of genes involved in anterior-posterior patterning in pectoral fins of catsharks, with those of mice. They found that, in pectoral fin of catshark embryos, Gli3 expression was intensified posteriorly, and the balance of the anterior and posterior fields was shifted . This indicates that a major genetic shift (posteriorisation) occurred as tetrapods evolved.

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A gradual shift of the balance of anterior (green) and posterior (blue) field might have led to the evolution from fins into limbs.

Furthermore, they found that the catshark genome lacked a sequence found in mice and other tetrapods, which is responsible for preventing Gli3 expression in the posterior part of tetrapod limb buds. As a known repressor, the restriction of Gli3 to the anterior may result in the loss of skeletal structure in this domain.

 These results suggest that one of the key genetic events during the fin-to-limb evolution was a shift of the balance of the anterior and posterior fields (a “posteriorisation”) and loss of anterior skeletal elements. Further research involving genome-wide studies, particularly into the role of Gli3, will help explore these results more fully, although the study so far has been hugely successful.

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