Molecular Evolution of Vertebrate Cornification
Attila Sachslehner, Department of Dermatology, Medical University of Vienna, Vienna, Austria
July 10, 2025 | 15h00 | Hybrid Seminar (Zoom Link: https://videoconf-colibri.zoom.us/j/97813420256)
The evolution of cornified skin and its appendages, such as claws and hair, were major steps in the diversifying evolution of terrestrial vertebrates. Their development is a dynamic process which depends on several biochemical mechanisms such as Hoxc13 depending regulation of skin appendages and the process of transglutamination. Hoxc13 is a transcription factor which controls the development of hair and nails in mammals. The main components of hair are known as hair keratins. We identified hair keratins in the claw bearing frog Xenopus tropicalis. Hair keratins and hoxc13 are co-expressed in the claw epithelium, and Hoxc13 binding sites were identified in the hair keratin promoters of X. tropicalis. To test the function of Hoxc13, CRISPR/Cas9 genome editing was used to generate Hoxc13 deficient frogs, which lack cornified claws. Our results suggest that Hoxc13-controlled expression of specific keratins on toe tips evolved in basal tetrapods. Transglutaminases (TGMs) cross-link structural proteins during cornification. We determined the catalogue of TGMs in chordates via comparative genomics and phylogeny. Our data suggest that TGM1 is the phylogenetically oldest epithelial TGM. Gene duplications led to an increasing number TGM genes in the lineage leading to terrestrial vertebrates of which many show epithelium associated expression. We identified two previously uncharacterized proteins, TGM9 and TGM10. TGM10 is exclusively found in primary aquatic vertebrates, and its function is currently unknown. TGM9 is expressed in the epithelial egg tooth of birds. The corresponding gene is conserved in crocodilians, turtles and the platypus, which develop a cornified egg tooth. In mammals, in particular, TGM3 and TGM6 contribute to the growth of hair and both genes were lost in hair less whales. This study suggests that the gain and loss of TGM genes was associated with the evolution of cornified skin appendages in vertebrates.
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