ABSTRACT
Mammalian skin, including human and mouse skin, does not regenerate completely after injury; it is repaired, leaving a scar. However, it is known that skin wounds up to a certain stage of embryonic development can regenerate. The mechanism behind the transition from regeneration to scar formation is not fully understood. Panniculus carnosus muscle (PCM) is present beneath the dermal fat layer and is a very important tissue for wound contraction. In rodents, PCM is present throughout the body. In humans, on the other hand, it disappears and becomes a shallow fascia on the trunk. Fetal cutaneous wounds, including PCM made until embryonic day 13 (E13), regenerate completely, but not beyond E14. We visualized the previously uncharacterized development of PCM in the fetus and investigated the temporal and spatial changes in PCM at different developmental stages, ranging from full regeneration to non-regeneration. Furthermore, we report that E13 epidermal closure occurs through actin cables, which are bundles of actomyosin formed at wound margins. The wound healing process of PCM suggests that actin cables may also be associated with PCM. Our findings reveal that PCM regenerates through a similar mechanism.
ABSTRACT
Up to a certain developmental stage, a fetus can completely regenerate wounds in the skin. To clarify the mechanism of fetal skin regeneration, identifying when the skin switches from fetal-type wound regeneration to adult-type wound repair is necessary. We hypothesized that this switch occurs at several time points and that complete skin regeneration requires epidermal-dermal interactions and the formation of actin cables. We compared normal skin and wound morphology at each developmental stage. We examined two parameters: epidermal texture and dermal structure. We found that the three-dimensional structure of the skin was completely regenerated in full-thickness skin incisions made before embryonic day (E) 13. However, the skin texture did not regenerate in wounds made after E14. We also found that the dermal structure regenerates up to E16, but wounds created after E17 heal as scars with dermal fibrosis. By controlling the activity of AMP-activated protein kinase and altering actin cable formation, we could regulate scar formation in utero. These findings may contribute to therapies that allow complete skin regeneration without scarring.
