Comparative regenerative biology of spiny (Acomys cahirinus) and laboratory (Mus musculus) mouse skin

Abstract

Wound‐induced hair follicle neogenesis (WIHN) has been demonstrated in laboratory mice (Mus musculus) after large (>1.5 × 1.5 cm2) full‐thickness wounds. WIHN occurs more robustly in African spiny mice (Acomys cahirinus), which undergo autotomy to escape predation. Yet, the non‐WIHN regenerative ability of the spiny mouse skin has not been explored. To understand the regenerative ability of the spiny mouse, we characterized skin features such as hair types, hair cycling, and the response to small and large wounds. We found that spiny mouse skin contains a large portion of adipose tissue. The spiny mouse hair bulge is larger and shows high expression of stem cell markers, K15 and CD34. All hair types cycle synchronously. To our surprise, the hair cycle is longer and less frequent than in laboratory mice. Newborn hair follicles in anagen are more mature than C57Bl/6 and demonstrate molecular features similar to C57Bl/6 adult hairs. The second hair cycling wave begins at week 4 and lasts for 5 weeks, then telogen lasts for 30 weeks. The third wave has a 6‐week anagen, and even longer telogen. After plucking, spiny mouse hairs regenerate in about 5 days, similar to that of C57Bl/6. After large full‐thickness excisional wounding, there is more de novo hair formation than C57Bl/6. Also, all hair types are present and pigmented, in contrast to the unpigmented zigzag hairs in C57Bl/6 WIHN. These findings shed new light on the regenerative biology of WIHN and may help us understand the control of skin repair vs regeneration.

Molecular and histologic outcomes following spinal cord injury in spiny mice,Acomys cahirinus

“…In summary, the molecular and histologic data presented here are consistent with a growing literature that indicates that Acomys has a tissue response to injury that may be relatively unique among mammals. Prior work definitively establishes that Acomys does not undergo fibrosis and has remarkable regenerative capacity in dermis, smooth muscle, skeletal muscle, and other tissue following injury (Brant et al, 2019;Brant et al, 2016;Jiang, Harn, Ou, Lei, & Chuong, 2019;Seifert et al, 2012). Our current data support the hypothesis that this unique response to injury extends to the spinal cord.…”

Understanding skin morphogenesis across developmental, regenerative and evolutionary levels

“…Such studies can reveal conserved core morphogenetic modules vs embryonic and adult state specific components. Moreover, comparative studies between species with low and high capacity for wound‐induced regeneration can be a fruitful approach for identifying genetic, cellular and signalling determinants of clinically desirable high regenerative responses.…”

“…Particularly notable in this respect are the diverse follicle and follicle‐like ectodermal appendages that endow animal skin with its many functions, including thermoregulation, camouflage, defense and mechano‐sensing to name a few . Several articles in this issue examine evolutionary aspects of hair follicle neogenesis after wounding and hair and feather follicle repair after genotoxic damage . Mallarino and Barsh discuss the evolution and the mechanisms for periodic pigmentation pattern specification and implementation, focusing on stripe‐like patterns that evolved in a number of rodents …”

“…Powerful insights on morphogenesis can be learned from emerging model organisms, whose skin has distinct anatomical or physiological features. In this issue, several works show how research on African spiny mice, African striped mice, pigs and dogs can advance the understanding of skin morphogenesis and regeneration. Interestingly, the degree to which different mammalian species can activate wound‐induced neogenesis programs can vary substantially.…”

“…Some species, notably African spiny mice (Acomys) , have evolved particularly robust regenerative responses to severe wounding . In this issue, Maden's group outlines the current state of knowledge on the regenerative mechanisms in this emerging model organism, and a comparative morphological study by Chuong's group reports new insights on the differences in hair follicle development, cycling and wound‐induced neogenesis between Acomys and laboratory mouse models …”