Mechanisms of cell recruitment in echinoderm regeneration: pluripotent versus dedifferentiated cells

Regenerative abilities are remarkably widespread among echinoderms. Indeed, at all life stages these marine deuterostomes are capable of regenerating both external and internal body parts following self-induced or traumatic mutilations. Although two different mechanisms are usually employed to describe the regenerative processes, namely epimorphosis and morphallaxis, in the case of echinoderm regeneration the origin and fate of the involved cells are still unclear. An up-to-date overview of the cell recruitment during this process in all the five echinoderm classes is here provided in order to clarify the state of the art on this topic and therefore highlight the necessary future steps to cover this gap of knowledge. Among stellate echinoderms, crinoids are the only group clearly displaying the recruitment of morphologically undifferentiated cells stocked in the stump tissues (i.e. coelom and brachial nerve) and their active migration to form a true blastema where they massively proliferate and differentiate to regenerate the lost tissues. Dedifferentiation occurs only in specific cases, such as basal arm amputations or stress situations. Both brittle stars and starfish do not show a true regenerative blastema, apparently mainly relying on dedifferentiation phenomena with subsequent cell re/trans-differentiation. In starfish, dedifferentiation is massively employed in muscle tissues. Additionally, scarcely differentiated cells are apparently recruited via epithelial-mesenchymal transition (EMT) from distant sources (i.e. coelomic epithelium, pyloric caeca). The same occurs for brittle star cell recruitment with an important contribution of the coelomic epithelium as source of progenitor-like cells after EMT. Sea cucumbers are studied mainly for nervous system and gut regeneration. In the former, the absence of “stemness” marker in the transcriptome suggests that radial nerve cord regeneration depends on dedifferentiation of the supporting cells that re-differentiate in both the same cytotype and new neurons. Massive myocyte dedifferentiation is employed during gut regeneration. In sea urchins, damaged test and broken spines are reformed through dedifferentiation of stump cells with only minor local cell proliferation, whereas totally removed spines are regenerated via undifferentiated (pluripotent) cells. Overall, echinoderm regeneration mainly relies on dedifferentiation phenomena rather than recruitment of pluripotent cells already stocked in the stump tissues but the precise origin and fate of the involved cells are still largely unknown. Echinoderm tissues, especially coelomic epithelium and muscles, show a high level of plasticity and cell proliferation, migration, and EMT play key roles in this process. Cell tracking, and coupled molecular and microscopy approaches will be strongly necessary to define the main challenge of echinoderm (and, in general, animal) regeneration, namely the understanding of the origin and fate of the recruited cells.