Periderm without IRF6: To be or not to be

Summary: Abstract Body: Epidermal morphogenesis starts with the delamination of ectoderm-derived epithelial cells from the basal layer to form a flat layer of periderm cells. Subsequent epidermal layers are formed under the periderm, which is shed right before birth after terminal differentiation is completed. Terminal epidermal differentiation is impaired in the absence of the transcription factor Interferon Regulatory Factor 6 (IRF6) as neonatal Irf6-deficient murine embryos lack the granular and cornified layers. These embryos also exhibit oral epithelium defects, with the presence of tissue-tissue fusions due to a presumptive loss of oral periderm/function. Recent examination of the literature reveals conflicting results as to whether the oral periderm is absent, or present and non-functional based on expression of periderm markers Keratin 6 and 17. In this study, we asked whether the loss of Irf6 affects the epidermal periderm. We performed systemic high magnification morphological analysis of the developing epidermis between E12.5 and E17.5 in wildtype and Irf6-null embryos. By transmission electron microscopy, we observe the presence of flat, electron-dense periderm cells in wildtype epidermis. In Irf6-null epidermis, the superficial cells are less elongated and less electron-dense. Expression of K6 and K17 starts between E12.5 and E14.5 in both wildtype and mutant epidermis (timing varies between keratins and genotype). While K6 is restricted to the periderm and K17 to the periderm early then to hair follicles by e17.5 in wildtype, their expression starts in the superficial periderm-like cells in Irf6-null embryos and then expand throughout the entire epidermis (except basal cells for K6). Similar results were observed with K4, a keratin strongly expressed in periderm cluster from scRNAseq of early mouse epidermis. These data demonstrate the presence of periderm-specific keratins in Irf6-null epidermis, suggesting that the periderm may be present after all. The function of epidermal periderm and the role of Irf6 in this function remains to be determined. Lindsey Rhea¹, Martine Dunnwald¹ 1. The University of Iowa Roy J and Lucille A Carver College of Medicine, Iowa City, IA, United States. Epidermal Structure and Barrier Function