Regeneration of Vertebrate Appendages

Abstract

Some vertebrates can faithfully replace complex parts of their body, a feature that is more commonly observed in invertebrates. They can perform this remarkable task because of their capacity to recruit progenitor cells and activate developmental programmes that largely parallel those used during embryogenesis. Tailed amphibians (urodeles), fish and deer provide the most striking examples of regeneration of appendages in adult animals. Frogs (anurans) can regenerate their limbs only at larval stages and can provide valuable models for studying loss of regenerative capability in the same species. Although birds and mammals cannot regenerate their limbs, digit tips display notable regenerative capability. The most striking example of mammalian appendage replacement is antler regeneration. Information on molecular landmarks of mature cell reprogramming in response to amputation is rapidly building up together with insights into the complex regulatory machinery controlling subsequent proliferation, differentiation and patterning of regenerating appendages. Key Concepts: Appendage regeneration can occur in some lower vertebrates, fish and amphibians. Wound healing modality and appropriate inflammatory responses are crucial for regeneration. Regeneration of vertebrate appendages occurs via formation of a growth zone, the blastema. Blastema formation in adult lower vertebrates involves a reversal of the differentiated state. Resident progenitor cells can contribute to regeneration. Blastemal cells in regenerating limbs largely maintain their original identity. The presence of a specialized wound epidermis is essential for regeneration throughout the process. The presence of the nerve is crucial for the initial stages of limb and fin regeneration and also for mammalian digit tip regeneration. Limb regeneration becomes nerve dependent after the developing limb is innervated. Redeployment of certain developmental mechanisms underlies patterning in regenerating appendages. Although, by and large, the same key signalling pathways are involved in regenerative responses across species, existence of species‐specific molecules may provide some rationale for differences in adult appendage regenerative capability.

Skeletal regeneration in the brittle star Amphiura filiformis

“…Skeletal regeneration is observed in other deuterostome groups: for example in cirri regeneration of amphioxus [ 56 ], and in appendage regeneration of different vertebrates (reviewed in [ 6 ]). It has even been suggested that adult bone repair and regeneration may recapitulate embryonic bone development at a molecular level [ 57 ].…”

“…In the context of adult organisms, this developmental process varies extensively among animals (reviewed in [ 1 ]) and also among different parts of the same organism. Some animals, such as cnidarians and flatworms, can regenerate the entire body from small fragments [ 2 – 5 ], while others can restore only some cell tissues or particular body parts, as in vertebrates (reviewed in [ 6 ]). Echinoderms are marine deuterostomes and constitute an invertebrate phylum containing five extant classes, all possessing extensive regenerative abilities in both adult and larval forms (reviewed in [ 7 ]).…”

FGF signalling plays similar roles in development and regeneration of the skeleton in the brittle star Amphiura filiformis

“…Skeletal regeneration is observed in other deuterostome groups: for example in cirri regeneration of amphioxus (Kaneto and Wada, 2011) and in appendage regeneration of different vertebrates (reviewed by Ferretti and Health, 2013). It has even been suggested that adult bone repair and regeneration may recapitulate embryonic bone development at a molecular level (Ferguson et al, 1999).…”

Ultrastructural and molecular analysis of the origin and differentiation of cells mediating brittle star skeletal regeneration

“…We have so far discussed in detail skeletal regeneration in the mature arms of A. filiformis and highlighted some similarities with sea urchin development. Other deuterostome groups, such as vertebrates, are in some cases able to regenerate the endoskeleton of their appendages [65][66][67].…”