Salamanders are capable of full-thickness skin regeneration where removal of epidermis, dermis and hypodermis results in scar-free repair. What remains unclear is whether regeneration of these tissues recapitulates the cellular events of skin development or occurs through a process unique to regenerative healing. Unfortunately, information on the post-embryonic development of salamander skin is severely lacking, having focused on compartments or cell types, but never on the skin as a complete organ. By examining coordinated development of the epidermis and dermis in axolotls we establish six distinct stages of skin development (I-VI): I–V for normally paedomorphic adults and a sixth stage following metamorphosis. Raising animals either in isolation (zero density pressure) or in groups (density pressure) we find that skin development progresses as a function of animal size and that density directly effects developmental rate. Using keratins, p63, and proliferative markers, we show that when the dermis transforms into the stratum spongiosum and stratum compactum, keratinocytes differentiate into at least three distinct phenotypes that reveal a cryptic stratification program uncoupled from metamorphosis. Lastly, comparing skin regeneration to skin development, we find that dermal regeneration occurs through a unique process, relying heavily on remodeling of the wound extracellular matrix, rather than proceeding through direct development of a dermal lamella produced by the epidermis. By preventing fibroblast influx into the wound bed using beryllium nitrate, we show that in the absence of fibroblast generated ECM production skin regeneration occurs through an alternate route that recapitulates development.
|Number of pages||13|
|State||Published - Nov 1 2019|
Bibliographical noteFunding Information:
This work was supported by the University of Kentucky Office of the Vice President for Research and a Gertrude Ribble Award to D.S.
This work was supported by the University of Kentucky Office of the Vice President for Research and a Gertrude Ribble Award to D.S. We would like to thank Katherine Thompson for statistical consultation, members of the Seifert lab for insightful discussions and three anonymous reviewers for constructive comments. We also thank Laura and Chris Muzinic of the Ambystoma Genetic Stock Center at the University of Kentucky for supplying some of the embryos used in this study.
© 2019 Elsevier Inc.
ASJC Scopus subject areas
- Molecular Biology
- Developmental Biology
- Cell Biology