Endocrine Regulation of Epimorphic Regeneration

Easterling, Marietta R.; Crespi, Erica J.

doi:10.1210/en.2019-00321

Cited by 12 publications

(11 citation statements)

References 151 publications

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“…The most parsimonious explanation for these findings could be that, at least in the context of repeated amputations, there are as yet unidentified systemic components regulating mammalian digit tip regeneration. While local effectors of epimorphic regeneration have been the primary focus in the last decades, both cellular and humoral systemic mediators of epimorphic regeneration have been explored [ 43 , 44 ]. With the exception of deer antler regeneration [ 45 ], no such studies exist for mammalian epimorphic regeneration until now.…”

Section: Discussionmentioning

confidence: 99%

Epimorphic regeneration of the mouse digit tip is finite

et al. 2022

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Background Structural regeneration of amputated appendages by blastema-mediated, epimorphic regeneration is a process whose mechanisms are beginning to be employed for inducing regeneration. While epimorphic regeneration is classically studied in non-amniote vertebrates such as salamanders, mammals also possess a limited ability for epimorphic regeneration, best exemplified by the regeneration of the distal mouse digit tip. A fundamental, but still unresolved question is whether epimorphic regeneration and blastema formation is exhaustible, similar to the finite limits of stem-cell mediated tissue regeneration. Methods In this study, distal mouse digits were amputated, allowed to regenerate and then repeatedly amputated. To quantify the extent and patterning of the regenerated digit, the digit bone as the most prominent regenerating element in the mouse digit was followed by in vivo µCT. Results Analyses revealed that digit regeneration is indeed progressively attenuated, beginning after the second regeneration cycle, but that the pattern is faithfully restored until the end of the fourth regeneration cycle. Surprisingly, when unamputated digits in the vicinity of repeatedly amputated digits were themselves amputated, these new amputations also exhibited a similarly attenuated regeneration response, suggesting a systemic component to the amputation injury response. Conclusions In sum, these data suggest that epimorphic regeneration in mammals is finite and due to the exhaustion of the proliferation and differentiation capacity of the blastema cell source.

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Section: Discussionmentioning

confidence: 99%

Epimorphic regeneration of the mouse digit tip is finite

et al. 2022

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“…In vertebrates, the main signaling factors involved in blastema were Wnts, fibroblast growth factor 8 (FGF8), and FGF10, similar to the signaling factors involved in the growth of the regenerative limbs of larval Xenopus laevis (Yokoyama et al, 2011). Wnt activated FGF8, which in turn activated FGF10, forming a positive feedback pathway during AEC formation that promotes cell proliferation and the reconstruction of limb morphology (Easterling et al, 2019). A distal to proximal gradient of Wnt proteins was not detected using immunolabeling in S. tsinlingensis and P. muralis (Hutchins et al, 2014).…”

Section: Discussionmentioning

confidence: 99%

Wnt1 and Wnt2b Immunodetection of the Regenerating Tail and Comparative Ultrastructure of Tail Spinal Cord in the Scincella tsinlingensis

et al. 2022

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The Wnt pathway is essential for the initiation of lizard tail regeneration. The regenerated lizard tails exhibit obvious morphological differences compared to the original ones. The expression of Wnt1 and Wnt2b proteins in the regenerating tail of Scincella tsinlingensis was detected by immunohistochemistry and then comparatively analyzed for ultrastructural changes in the original and regenerated spinal cord. The ependymal layer of the original spinal cord was pseudostratified with multiciliated cells and primary monociliated cells, while the cells of the ependymal layer of the regenerated spinal cord were organized in a monolayer with a few biciliated cells. Immunolocalization indicated that Wnt1 and Wnt2b were mainly distributed in the dermis near the original tail stump, spinal cord, and clot-positive migratory cells during Stage I, 0-1 days post-amputation (dpa). Wnt1 and Wnt2b were predominantly detected in the epaxial and hypaxial musculature near the original tail stump, wound epithelium, and spinal cord in the original tail during Stage II, 1-7 dpa. Mesenchymal cells and wound epithelium showed immunostaining during Stage III and IV, 7-15 dpa. The ependymal tubes contained these signaling proteins during Stage V and VI, 20-30 dpa. Labeling was mainly observed in nearby regenerative blood vessels, ependymal cells, epaxial and hypaxial musculature in the apical epithelial layer (AEC) after 45-160 dpa. These findings indicated that Wnt1 and Wnt2b proteins presented primarily in regenerating epidermis and nerve tissues were a critical signal for tail regeneration in S. tsinlingensis.

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“…Other studies find that age coincides with slower or faster regeneration (60-62) but also find other secondary factors (e.g., nutrition, seasonal variation, or stress) are associated with slower regeneration (63,64). A small study in Acomys found that older Acomys (≥3 years) regenerated 2mm biopsy punches to the ears slower than younger Acomys (2months) (65).…”

Section: Phenotypic Diversity In Ear-hole Closurementioning

confidence: 99%

Social dominance status and social stability in spiny mice (Acomys cahirinus) and its relation to ear-hole regeneration and glucocorticoids

Varholick

Godinez

Mobin

et al. 2022

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Spiny mice (Acomys cahirinus) are an emerging animal model in studies measuring tissue regeneration, but decades of research on social dominance in other animals indicates the relationships animals form in their home-cage may affect phenotypic plasticity in tissue regeneration and glucocorticoids. Studies in baboons and mice, for example, indicate that subordinate ranked animals heal wounds slower than their dominant group-mates, and have increased levels of basal glucocorticoids. Recent studies in tissue regeneration with salamanders and zebrafish indicate that increased glucocorticoids can delay tissue regeneration, but whether this effect extends to Acomys is unknown, especially regarding their social dominance relationships. Here we report that most adult Acomys had a social dominance status, but many groups had unclear social stability, with more frequent huddling than fighting during their active cycle. We also found no sex differences in social dominance behavior, and that Acomys more frequently fled than froze when chased or approached. After a 4mm ear-pinna biopsy, we found that social stability significantly accounted for variability in time to close the ear-hole but adding age to the statistical model removed the effect of social stability. When investigating glucocorticoid blood levels, there were no significant effects of social dominance status or social stability. A transcriptional enhancer for StAR, Nr5a1 had a significant effect for the interaction of social dominance status and social stability. This effect, however, was not reflected in StAR and unclear groups mostly had unclear social statuses, so this effect should be considered with caution. This is the first study to investigate home-cage social dominance behaviors in Acomys since the 1970s or measure any associations with their ability to regenerate tissue. This provides a platform for further work on their social dominance and glucocorticoids and highlights the need to consider the role of aging in their ability to regenerate tissue.

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Endocrine Regulation of Epimorphic Regeneration

Cited by 12 publications

References 151 publications

Epimorphic regeneration of the mouse digit tip is finite

Epimorphic regeneration of the mouse digit tip is finite

Wnt1 and Wnt2b Immunodetection of the Regenerating Tail and Comparative Ultrastructure of Tail Spinal Cord in the Scincella tsinlingensis

Social dominance status and social stability in spiny mice (Acomys cahirinus) and its relation to ear-hole regeneration and glucocorticoids

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