Functional Homology in Teleost and Mammalian Epidermal Morphogenesis

Abstract

The epidermis is a stratified epithelium that makes up the outermost component of the skin. During embryogenesis, this portion of the skin undergoes a complex series of transformations to reach a mature state and provide a protective barrier. By understanding these molecular mechanisms, valuable knowledge of the molecular pathogenesis of diseases of the skin such as squamous cell carcinoma can be gained. Genes such as Irf6, 14-3-3σ, Chuk/Ikkα, and Ovol1 have been identified as key players in the proliferation-differentiation switch of epidermal structures in mammals, where knockout mice exhibit phenotypes involving hyperproliferative epidermal cells. Mice are costly, and relatively complicated, vertebrate models compared to zebrafish. For this reason, the degree of functional homology between mice and zebrafish was examined in this study to determine if zebrafish are appropriate models for this system. The zebrafish maternal-effect mutant poky has a similar phenotype to the previously described knockout mice, exhibiting a hyperproliferative epidermal layer called the enveloping layer (EVL) as well as a delay in epiboly. The poky gene has been identified as the zebrafish homolog of chuk/ikkα. It was hypothesized that the gene regulators of mammalian epidermal morphogenesis would be functionally conserved in zebrafish. If these players are conserved, zebrafish could provide a more cost-effective model system for studying epidermal morphogenesis. Results of this study suggest that previously described molecular regulators of the cell cycle and terminal differentiation in mice are not functionally conserved in zebrafish. Therefore, zebrafish would not provide a suitable model for the study of the molecular regulation of human skin development and diseased states such as squamous cell carcinoma. However, there is a fair amount of previous research that should be considered describing EVL involvement of genes such as irf6, chuk/ikkα, and 14-3-3ι/ywhai.