Beyond Adult Stem Cells: Dedifferentiation as a Unifying Mechanism Underlying Regeneration in Invertebrate Deuterostomes

Abstract

The diversity of regenerative phenomena seen in adult metazoans, as well as their underlying mechanistic bases, are still far from being comprehensively understood. Reviewing both ultrastructural and molecular data, the present work aims to showcase the increasing relevance of invertebrate deuterostomes, i.e., echinoderms, hemichordates, cephalochordates and tunicates, as invaluable models to study cellular aspects of adult regeneration. Our comparative approach suggests a fundamental contribution of local dedifferentiation -rather than mobilization of resident undifferentiated stem cells-as an important cellular mechanism contributing to regeneration in these groups. Thus, elucidating the cellular origins, recruitment and fate of cells, as well as the molecular signals underpinning tissue regrowth in regenerationcompetent deuterostomes, will provide the foundation for future research in tackling the relatively limited regenerative abilities of vertebrates, with clear applications in regenerative medicine.

Whole-Body Regeneration in Sponges: Diversity, Fine Mechanisms, and Future Prospects

“…This type of WBR is close to a typical reparative regeneration known in many other animals, e.g., Hydra [ 10 ], Platyhelminthes [ 13 ], and Asteroides [ 19 ]. It is worth noting that WBR after body dissection can occur either with the retention of the parental sponge’s polarity or with complete re-building of involved tissues, i.e., through somatic embryogenesis.…”

“…The described examples are few and mostly restricted to basal metazoans: sponges [ 3 , 6 ], placozoans [ 7 , 8 ], ctenophores [ 9 ], and cnidarians [ 10 , 11 ]. However, WBR is also known in acoels [ 12 ], flat worms [ 13 ], nemerteans [ 14 , 15 ], annelids [ 16 , 17 ], echinoderms [ 18 , 19 ], hemichordates [ 20 ], and colonial botryllid ascidians [ 5 , 21 , 22 ].…”

And Then There Were Three…: Extreme Regeneration Ability of the Solitary Chordate Polycarpa mytiligera

“…The majority of solitary ascidians reproduce sexually by releasing gametes into the seawater for external fertilization, while colonial species also propagate by asexual reproduction or budding ( Berrill, 1975 ). These asexual strategies has evolved independently several times across the Ascidiacea, and has been shown to involve a variety of cellular mechanisms in different species ( Gutierrez and Brown, 2017 ; Manni et al, 2019 ; Scelzo et al, 2019 ; Ferrario et al, 2020 ). Furthermore, some colonial species exhibit more than one budding strategy, activated by different stimuli ( Manni et al, 2019 ).…”

A New Protocol of Computer-Assisted Image Analysis Highlights the Presence of Hemocytes in the Regenerating Cephalic Tentacles of Adult Pomacea canaliculata

“…Invertebrates have provided important contributions to the understanding of human biology, and their usage in biological research has been increasing in the last few decades [ 1 , 2 , 3 ]. Among the biological issues addressed by comparative research, regeneration and its relationship with the immune system has attracted attention for a long time [ 1 , 4 ].…”

“…Among the biological issues addressed by comparative research, regeneration and its relationship with the immune system has attracted attention for a long time [ 1 , 4 ]. Many invertebrate models present relevant regeneration capabilities [ 2 , 5 , 6 ] while in Amniotes, this capability is significantly reduced [ 7 ] and the adaptive immune system is frequently considered as detrimental for a complete regeneration [ 8 ]. The innate immune components of invertebrates such as in annelids [ 9 , 10 ] and molluscs [ 11 , 12 , 13 ] seem to play a major role in regulating the regeneration process.…”