Department of Biomedical Molecular Biology, Ghent University, 9000, Ghent, Belgium.
Department of Biomolecular Medicine, Ghent University and Center for Medical Genetics, Ghent University Hospital, 9000, Ghent, Belgium.
Nat Commun. 2024 Mar 18;15(1):2328. doi: 10.1038/s41467-024-46373-x.
Cornified skin appendages, such as hair and nails, are major evolutionary innovations of terrestrial vertebrates. Human hair and nails consist largely of special intermediate filament proteins, known as hair keratins, which are expressed under the control of the transcription factor Hoxc13. Here, we show that the cornified claws of Xenopus frogs contain homologs of hair keratins and the genes encoding these keratins are flanked by promoters in which binding sites of Hoxc13 are conserved. Furthermore, these keratins and Hoxc13 are co-expressed in the claw-forming epithelium of frog toe tips. Upon deletion of hoxc13, the expression of hair keratin homologs is abolished and the development of cornified claws is abrogated in X. tropicalis. These results indicate that Hoxc13-dependent expression of hair keratin homologs evolved already in stem tetrapods, presumably as a mechanism for protecting toe tips, and that this ancestral genetic program was coopted to the growth of hair in mammals.
角化皮肤附属物，如毛发和指甲，是陆生脊椎动物的主要进化创新。人类的毛发和指甲主要由特殊的中间丝蛋白组成，称为毛发角蛋白，这些蛋白受转录因子 Hoxc13 的控制表达。在这里，我们发现非洲爪蟾的角化爪含有角蛋白的同源物，并且编码这些角蛋白的基因侧翼是 Hoxc13 结合位点保守的启动子。此外，这些角蛋白和 Hoxc13 在蛙趾尖端的爪形成上皮细胞中共同表达。当 hoxc13 缺失时，毛发角蛋白同源物的表达被废除，非洲爪蟾的角化爪发育被阻断。这些结果表明，依赖于 Hoxc13 的毛发角蛋白同源物的表达在四足动物的祖先中就已经进化，可能是保护趾尖的一种机制，而这个古老的遗传程序被用于哺乳动物毛发的生长。
