Role for keratins 6 and 17 during wound closure in embryonic mouse skin.

Injury to adult skin triggers a response designed to restore its vital barrier function. A conserved aspect of this response is a rapid switch in gene expression whereby the type II keratin 6 (K6) and type I keratins 16 and 17 (K16, K17) are induced in epithelial cells at the wound edge. This induction occurs at the expense of the keratins normally expressed during terminal differentiation and correlates with the activation of epithelial cells at the wound edge, ahead of their migration into the wound site. Here, we show that the capacity to enact this switch is already acquired in E11.5 stage mouse embryos. Such early timing is well ahead of the onset of differentiation-specific gene expression (approximately E13.5) and the acquisition of barrier formation by developing epidermis (approximately E16.5). Induction of K6, K16, and K17 correlates with changes in the morphology of epithelial cells at the wound edge. The closure of embryonic wounds is significantly delayed in K17 null embryos, but not embryos null for K6. These observations significantly extend the correlation between K6, K16, and K17 expression and epithelial wound closure, and provide direct evidence that expression of these keratins, K17 in particular, is important for the timeliness of this process.