Molecular evolution of skin appendages

The evolution of cornified skin appendages, such as claws and hair, was critical for the evolution of land-dwelling vertebrates. Hair, which is the best characterized type of skin appendage, depends on its main protein components, the hair keratins, and on Hoxc13, a regulator of keratin gene expression. The molecular control of other skin appendages and their evolutionary relationships are not well understood. The aim of the present project is to gain insights into the evolutionary origin of the genetic program which controls the growth and protein composition of cornified skin appendages. We hypothesize that hair keratin-like proteins and their regulation by Hoxc13 have originated already during the water-to-land transition of early tetrapods. Accordingly, they are predicted to play critical roles not only in hair but also in cornified skin appendages of amphibians. To test these hypotheses, we will determine the protein composition of claws and the effect of Hoxc13 deletion in a model species, the western clawed frog. The genetic control of claws will be compared among representative species from all main clades of tetrapods. This project will inform about key steps in the evolution of cornified skin appendages in terrestrial vertebrates.

Skin appendages, such as hair, feathers and scales, are important for the life of mammals, birds and reptiles. It has remained largely unknown how these skin structures have appeared and changed during the evolution of land-dwelling vertebrates. The main skin appendages of humans and other mammals are hair fibers, which consist of so-called hair keratins and grow under the control of the regulatory protein Hoxc13. Hair keratins and Hoxc13 are also important for the growth of human nails. This research project showed that proteins closely related to hair keratins exist in frogs and other amphibians. Hair keratin-like proteins build the claws of Xenopus frogs, also known as clawed frogs, and similar proteins protect the toe tips of salamanders. Like mammalian hair keratins, the related proteins of amphibians depend on Hoxc13. Accordingly, the suppression of Hoxc13 converted clawed frogs into clawless frogs. These results indicate that amphibians and mammals have inherited Hoxc13-dependent keratins for claws and nails from a common ancestor that lived around 350 million years ago. Interestingly, amphibians develop various types of small skin appendages that also depend on hair keratin-like proteins, suggesting that they have evolved in parallel to hair in mammals. Further studies of this project identified keratinized teeth of jawless vertebrates as the evolutionarily oldest hard skin appendages. In summary, the results of this project provide important insights into the evolution of skin appendages of vertebrates.