EGFR and hair shaft differentiation

EGFR signaling controls skin development and homeostasis in mice and humans and its deficiency causes severe skin inflammation, which might affect epidermal stem cell behaviour. Here, we describe the inflammation-independent effects of EGFR-deficiency during skin morphogenesis and in adult HFSCs. Expression and alternative splicing analysis of RNAseq data from interfollicular epidermis and outer root sheath indicate that EGFR controls genes involved in epidermal differentiation, but also in centrosome function, DNA damage, cell cycle and apoptosis. Genetic experiments employing p53-deletion in EGFR–deficient epidermis reveal that EGFR signalling exhibits p53-dependent functions in proliferative epidermal compartments, as well as p53–independent functions in differentiated hair shaft keratinocytes. Loss of EGFR leads to absence of Lef1 protein specifically in the innermost epithelial hair layers, resulting in disorganization of medulla cells. Thus, our results uncover important spatial and temporal features of cell-autonomous EGFR functions in the epidermis.