Cells from subcutaneous tissues contribute to scarless skin regeneration in Xenopus laevis froglets

Abstract

Cells derived from subcutaneous tissues, at least in the trunk region, contribute to and may be essential for skin regeneration. Characterizing the subcutaneous tissue-derived cells that contribute to skin regeneration in amphibians may lead to the induction of cells that can regenerate complete skin structures without scarring in mammals. Developmental Dynamics 246:585-597, 2017. © 2017 Wiley Periodicals, Inc.

Learning from regeneration research organisms: The circuitous road to scar free wound healing

“…A benefit to using Xenopus as a model is that they are able to regenerate skin appendages, such as exocrine glands. Additionally, Xenopus have a multi-layered epidermis, similar to that of mammals (Bertolotti et al, 2013; Caddy et al, 2010; Franchini and Bertolotti, 2014; Franchini et al, 2016; Otsuka-Yamaguchi et al, 2017; Yoshii et al, 2005). Just like frogs, urodele amphibians, such as newts and axolotls, also have the ability to regenerate skin appendages scar-free (Fig.…”

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

“…The epidermis covers the wound after an excisional full-thickness skin wound within 24 hrs both in axolotls (Levesque et al, 2010) and in Xenopus laevis froglets (Otsuka-Yamaguchi et al, 2017;Yokoyama et al, 2011). While it takes longer in axolotls with thyroxine-induced metamorphosis for re-epithelialization (Seifert, Monaghan, et al, 2012), re-epithelialization is much quicker than that in mammals, for example, mice in which it takes more than 10 days to complete re-epithelialization (Braiman-Wiksman, Solomonik, Spira & Tennenbaum, 2007).…”

“…After the accumulation of blastemalike cells with activation of the prx1 limb-specific enhancer around the original wound, nearly normal dermal tissue with maturating (newly formed) secretion glands is formed in a Xenopus laevis froglet (Yokoyama et al, 2011). Finally, almost complete skin including secretion glands and dermis is regenerated and subcutaneous myofibrillar organization around the original wound is recovered in an anuran amphibian, a Xenopus laevis froglet (Otsuka-Yamaguchi et al, 2017;Suzuki et al, 2005;Yokoyama et al, 2011), as well as in a urodele amphibian, an axolotl (Levesque et al, 2010;Seifert, Monaghan, et al, 2012), without formation of an obvious scar. Finally, almost complete skin including secretion glands and dermis is regenerated and subcutaneous myofibrillar organization around the original wound is recovered in an anuran amphibian, a Xenopus laevis froglet (Otsuka-Yamaguchi et al, 2017;Suzuki et al, 2005;Yokoyama et al, 2011), as well as in a urodele amphibian, an axolotl (Levesque et al, 2010;Seifert, Monaghan, et al, 2012), without formation of an obvious scar.…”

“…Firstly, it remains unclear whether these cells derived from subcutaneous tissues are identical to blastema-like cells with prx1 enhancer activity. A section of regenerating skin was stained with DAPI (g) for nuclei and was labeled with an anti-GFP antibody (h) as previously described (Otsuka-Yamaguchi et al, 2017;Yokoyama et al, 2011). These F I G U R E 3 Xenopus tropicalis prx1 enhancer sequence recapitulates the phenotype of Mprx1-GFP Tg X. laevis for limb development and skin regeneration.…”

“…For example, an axolotl (Ambystoma mexicanum), a neotenous Mexican salamander, regenerates its tail skin without scar formation after a full-thickness skin wound (Levesque, Villiard & Roy, 2010). Other recent studies have shown that the Xenopus laevis froglet (a spontaneously metamorphosed African clawed frog), the young adult frog, can regenerate skin including the dermis and secretion glands on the limb, trunk, and head after a full-thickness excisional skin wound (Otsuka-Yamaguchi et al, 2017;Yokoyama et al, 2011). Other recent studies have shown that the Xenopus laevis froglet (a spontaneously metamorphosed African clawed frog), the young adult frog, can regenerate skin including the dermis and secretion glands on the limb, trunk, and head after a full-thickness excisional skin wound (Otsuka-Yamaguchi et al, 2017;Yokoyama et al, 2011).…”