Abstract The evolution of skin appendages has involved innovation at the levels of keratin intermediate filament proteins, which build stable cornified structures, and regulatory factors, which determine the anatomical location of skin appendages. The keratin components of nails and claws have evolved at the digit tips under the control of the transcription factor Hoxc13 in a common ancestor of tetrapods. The additional expression of hoxc13 at other skin sites allowed the evolution of hair in ma