Skin shedding and tissue regeneration in African spiny mice (Acomys)

Abstract

SUMMARYEvolutionary modification has produced a spectrum of animal defense traits to escape predation, including the ability to autotomize body parts to elude capture1,2. Following autotomy, the missing part is either replaced through regeneration (e.g. urodeles, lizards, arthropods, crustaceans) or is permanently lost (mammals). While most autotomy involves the loss of appendages (e.g. leg, cheliped, antennae, tail), skin autotomy can occur in certain taxa of scincid and gekkonid lizards3. Here we report the first demonstration of skin autotomy in Mammalia (African spiny mice, Acomys). Mechanical testing revealed a propensity for skin to tear under very low tension and the absence of a fracture plane. Following skin loss, rapid wound contraction was followed by hair follicle regeneration in dorsal skin wounds. Surprisingly, we found regenerative capacity in Acomys extended to ear holes where they exhibited complete regeneration of hair follicles, sebaceous glands, dermis, and cartilage. Salamanders capable of limb regeneration form a blastema (a mass of lineage-restricted progenitor cells4) following limb loss, and our findings suggest that ear tissue regeneration in Acomys may proceed through assembly of a similar structure. This study underscores the importance of investigating regenerative phenomena outside of traditional model organisms and suggests that mammals may retain a higher capacity for regeneration than previously believed. As re-emergent interest in regenerative medicine seeks to isolate molecular pathways controlling tissue regeneration in mammals, Acomys may prove useful in identifying mechanisms to promote regeneration in lieu of fibrosis and scarring.

Macrophages are required for adult salamander limb regeneration

“…S9). α-Smooth muscle actin (α-SMA) is an established marker for differentiated myofibroblasts displaying subepithelial localization (31)(32)(33) in several species. Macrophage-depleted animals showed increased numbers of α-SMA-positive cells compared with the normally low levels observed in control animals at 20 dpa (Fig.…”

“…The regenerative blastema features mainly collagen type III (thin fibers), with a distinctive lack of collagen IV (48, 49), whereas collagen I (thick fibers) is normally down-regulated. Disruption of collagen production in macrophage-depleted limb stumps is presumably due to the activation of myofibroblasts, which are mainly absent in normal axolotl limb and scar-free skin regeneration (31), contributes to scarring in mammals (50,51), and represents a major difference between fibrotic and scar-free repair in the mouse (32).…”

A primer on regeneration

“…Since, descriptions of regeneration events in vertebrates have been reported widely, ranging from limbs, tails and retinas of Urodele amphibians [i.e. newts, salamanders] (Spallanzani, 1768; Todd, 1823;Colluci, 1891;Wolff, 1895;Thorton, 1938;Oberpriller and Oberpriller, 1974) to hearts and fins of fish (Morgan, 1900;Poss et al, 2002), deer antlers (Goss, 1961), and skin of spiny mice (Seifert et al, 2012).…”

Amphioxus regeneration: evolutionary and biomedical implications

“…For instance, African spiny mice of the Acomys genus are capable of true epimorphic tissue regeneration of ear hole pinnae, an ability lacking in standard laboratory mice (Gawriluk et al, 2016). The predator escape behaviour of skin shedding in spiny mice is thought to be a true case of mammalian autotomy resulting from structural adaptations that favour ease of tissue tearing and healing over scarring (Seifert et al, 2012). Similar proximate causes may explain why zebrafish can regenerate fins but not the tail proper (Gemberling et al, 2013), whereas many gymnotiform electric fish can replace the entire tail, including spinal cord and electroreceptors (Unguez et al, 2013).…”