Skin regeneration of amphibians: A novel model for skin regeneration as adults

Abstract

Adult mammals do not regenerate the dermis of the skin but form a scar after a deep skin injury. Since a scar causes serious medical problems, skin regeneration, instead of formation of a scar, has been strongly desired from a clinical point of view. Recent studies have suggested multiple origins of myofibroblasts, which are scar-forming cells in skin wound healing of mammals. While amphibians have skin structures that are basically common to mammals as tetrapods, both urodele and anuran amphibians regenerate almost complete skin structures including the dermis and secretion glands without forming a remarkable scar after a deep skin injury. In skin regeneration of a metamorphosed Xenopus laevis, an amphibian, cells that resemble limb blastema cells accumulate under the epidermis after injury and cells from subcutaneous tissues (tissues underlying the skin) contribute to skin regeneration. The skin of urodele amphibians and that of anuran amphibians provide valuable models for studying skin regeneration as adults. Recent progress in transgenesis and genome editing techniques with whole genome sequencing in Xenopus and an axolotl have enabled comparative analyses by molecular genetics of mammal skin and amphibian skin. Such comparative analyses would enable direct comparison of scar-forming myofibroblasts in mammals and blastema-like cells that contribute to skin regeneration in amphibians, ultimately leading to realization of skin regeneration in adult mammals. Amphibian skin regeneration will also be useful for determining how to step up skin regeneration to a higher level of regeneration such as limb regeneration in the future.

Frog Skin Innate Immune Defences: Sensing and Surviving Pathogens

“…Frog skin is no exception; it acts as a critical immune organ constituting a complex network of physical, chemical, immunological, and microbiological barriers to pathogen insult. Striking commonalities exist between frog, fish, and mammalian skin and exemplify the importance of endeavours in comparative vertebrate skin biology to address numerous research areas (7, 8). As a consequence of their reliance on terrestrial or aquatic habitats, or a combination thereof, amphibian skin is a sophisticated mucosal organ with specialized adaptations required to perform various critical physiological functions (e.g., ion transport, respiration, water uptake, etc.…”

“…), while still maintaining a selective barrier to the external environment (2, 3, 9). Other than the presence of a sophisticated glandular system, a miraculous feature of amphibian skin that sets frogs apart from other vertebrates is their ability to rapidly heal deep wounds which protrude through the dermal layers without scar formation, including complete regeneration of any glands affected by the injury (8). Despite extensive studies showing that amphibian skin is vital to survival, and apart from antimicrobial peptides (AMPs) (10, 11), relatively little focus has been placed on examining the role of frog skin epithelium to pathogen defence.…”

Copy number variation in HOXB7 and HOXB8 involves in the formation of beard trait in chickens

“…These findings indicated that the HOXB8 may perform different functions between fishes and avians, amphibians, reptilians and mammalians. Compared with the simple skin structure of fish, the amphibians, reptilians, avians and mammalians evolved sophisticated structures such as mitochondria, well-designed active ion transport systems and keratinous appendages in their skin (Yokoyama et al 2018). Feather development involves a series of interactions between epithelium and mesenchyme, resulting in the formation of a specialized keratinous appendage, the feather.…”

Conserved keratin gene clusters in ancient fish: An evolutionary seed for terrestrial adaptation

“…Vertebrate skin structure dramatically changed during the evolutionary transition of vertebrates from aquatic living as fish to terrestrial living as mammals. In the process of terrestrial adaptation, amniotes (e.g., mammals, birds, and reptiles) acquired the stratum corneum, an outer epidermal layer that is filled with keratinous fibers, to guard the skin against drying (Schempp et al, 2009;Yokoyama et al, 2018). By contrast, the skin of bony fish is covered with bony scales to protect them from predators.…”