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The Molecular Genetics and Major Concepts Underlying Whole Body Regeneration in the Animal World

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A special issue of Genes (ISSN 2073-4425). This special issue belongs to the section "Animal Genetics and Genomics".

Deadline for manuscript submissions: closed (15 September 2021) | Viewed by 53274

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Special Issue Editor

Dr. Uri Gat

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Guest Editor

Department of Cell and Developmental Biology, Life Sciences Institute, Hebrew University, Jerusalem, Israel
Interests: developmental biology; evolution of development; whole body regeneration; developmental pathways; Wnt pathway; spider silk fibers

Special Issue Information

Dear colleagues,

The major regeneration capabilities of some animals have likely intrigued the mind of nature observers from prehistoric times. Extensive regeneration is found in many phylogenetic clades, and the reason that some animal groups are almost devoid of regeneration powers while other excel in it is to date unclear. Whole body regeneration, which is the ability to regenerate all missing body parts, is considered the most extreme form of this process. In this Special Issue, researchers working on a wide variety of animals from different phylogenetic groups will present their work in the form of reviews and latest experimental research. Thus, the very different forms of regeneration that have evolved in the animal world can be compared, which may give new insights into this remarkable developmental phenomenon.

In recent yearsm we have gained new tools of molecular genetics and genomics, and their employment has allowed us to expose the basis of common molecular pathways that are involved in regeneration, on one hand, and the unique molecular mechanisms of different animals on the other. In this issue, the knowledge at the base of the most explored animal models will be discussed, and some of the most current "wet" work will be demonstrated, leading to possible further understanding of the most basic mysteries of regeneration. These include the relation of regeneration to embryonic development, its connection to the natural vegetative reproduction of some animals, and foremostly to the evolutionary, developmental, cellular, and molecular mechanisms underlying the paradigm. Hopefully, this will also contribute to enhancing our ability to comprehend the principles and concepts defining major body regeneration from the molecular genetics aspect and far beyond.

Dr. Uri Gat
Guest Editor

Manuscript Submission Information

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Keywords

Whole body regeneration
Molecular genetics of regeneration
Evolution of regeneration
Developmental pathways in regeneration
Morphallaxis
Epimorphosis
Body polarity
Embryonic development vs. regeneration

Published Papers (12 papers)

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Research

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17 pages, 2086 KiB

Open AccessArticle

Canalized Morphogenesis Driven by Inherited Tissue Asymmetries in Hydra Regeneration

by Lital Shani-Zerbib, Liora Garion, Yonit Maroudas-Sacks, Erez Braun and Kinneret Keren

Genes 2022, 13(2), 360; https://doi.org/10.3390/genes13020360 - 16 Feb 2022

Cited by 4 | Viewed by 2372

Abstract

The emergence and stabilization of a body axis is a major step in animal morphogenesis, determining the symmetry of the body plan as well as its polarity. To advance our understanding of the emergence of body axis polarity, we study regenerating Hydra. Axis polarity is strongly memorized in Hydra regeneration even in small tissue segments. What type of processes confer this memory? To gain insight into the emerging polarity, we utilize frustrating initial conditions by studying regenerating tissue strips which fold into hollow spheroids by adhering their distal ends of opposite original polarities. Despite the convoluted folding process and the tissue rearrangements during regeneration, these tissue strips develop in a reproducible manner, preserving the original polarity and yielding an ordered body plan. These observations suggest that the integration of mechanical and biochemical processes supported by their mutual feedback attracts the tissue dynamics towards a well-defined developmental trajectory biased by weak inherited cues from the parent animal. Hydra thus provide an example of dynamic canalization in which the dynamic rules are instilled, but, in contrast to the classical picture, the detailed developmental trajectory does not unfold in a programmatic manner. Full article

(This article belongs to the Special Issue The Molecular Genetics and Major Concepts Underlying Whole Body Regeneration in the Animal World)

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19 pages, 6244 KiB

Open AccessArticle

Expression of Piwi, MMP, TIMP, and Sox during Gut Regeneration in Holothurian Eupentacta fraudatrix (Holothuroidea, Dendrochirotida)

by Igor Yu. Dolmatov, Nadezhda V. Kalacheva, Ekaterina S. Tkacheva, Alena P. Shulga, Eugenia G. Zavalnaya, Ekaterina V. Shamshurina, Alexander S. Girich, Alexey V. Boyko and Marina G. Eliseikina

Genes 2021, 12(8), 1292; https://doi.org/10.3390/genes12081292 - 23 Aug 2021

Cited by 13 | Viewed by 2129

Abstract

Mesodermal cells of holothurian Eupentacta fraudatrix can transdifferentiate into enterocytes during the regeneration of the digestive system. In this study, we investigated the expression of several genes involved in gut regeneration in E. fraudatrix. Moreover, the localization of progenitor cells of coelomocytes, juvenile cells, and their participation in the formation of the luminal epithelium of the digestive tube were studied. It was shown that Piwi-positive cells were not involved in the formation of the luminal epithelium of the digestive tube. Ef-72 kDa type IV collagenase and Ef-MMP16 had an individual expression profile and possibly different functions. The Ef-tensilin3 gene exhibited the highest expression and indicates its potential role in regeneration. Ef-Sox9/10 and Ef-Sox17 in E. fraudatrix may participate in the mechanism of transdifferentiation of coelomic epithelial cells. Their transcripts mark the cells that plunge into the connective tissue of the gut anlage and give rise to enterocytes. Ef-Sox9/10 probably controls the switching of mesodermal cells to the enterocyte phenotype, while Ef-Sox17 may be involved in the regulation of the initial stages of transdifferentiation. Full article

(This article belongs to the Special Issue The Molecular Genetics and Major Concepts Underlying Whole Body Regeneration in the Animal World)

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20 pages, 6228 KiB

Open AccessArticle

Expression of Wnt and TGF-Beta Pathway Components during Whole-Body Regeneration from Cell Aggregates in Demosponge Halisarca dujardinii

by Ilya Borisenko, Fyodor V. Bolshakov, Alexander Ereskovsky and Andrey I. Lavrov

Genes 2021, 12(6), 944; https://doi.org/10.3390/genes12060944 - 20 Jun 2021

Cited by 6 | Viewed by 2108

Abstract

The phenomenon of whole-body regeneration means rebuilding of the whole body of an animal from a small fragment or even a group of cells. In this process, the old axial relationships are often lost, and new ones are established. An amazing model for studying this process is sponges, some of which are able to regenerate into a definitive organism after dissociation into cells. We hypothesized that during the development of cell aggregates, primmorphs, new axes are established due to the activation of the Wnt and TGF-beta signaling pathways. Using in silico analysis, RNA-seq, and whole-mount in situ hybridization, we identified the participants in these signaling pathways and determined the spatiotemporal changes in their expression in demosponge Halisarca dujardinii. It was shown that Wnt and TGF-beta ligands are differentially expressed during primmorph development, and transcripts of several genes are localized at the poles of primmorphs, in the form of a gradient. We suppose that the Wnt and TGF-beta signaling cascades are involved in the initial axial patterning of the sponge body, which develops from cells after dissociation. Full article

(This article belongs to the Special Issue The Molecular Genetics and Major Concepts Underlying Whole Body Regeneration in the Animal World)

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21 pages, 7201 KiB

Open AccessArticle

Structural and Functional Characterization of the FGF Signaling Pathway in Regeneration of the Polychaete Worm Alitta virens (Annelida, Errantia)

by Alexandra Y. Shalaeva, Roman P. Kostyuchenko and Vitaly V. Kozin

Genes 2021, 12(6), 788; https://doi.org/10.3390/genes12060788 - 21 May 2021

Cited by 7 | Viewed by 3549

Abstract

Epimorphic regeneration of lost body segments is a widespread phenomenon across annelids. However, the molecular inducers of the cell sources for this reparative morphogenesis have not been identified. In this study, we focused on the role of fibroblast growth factor (FGF) signaling in the posterior regeneration of Alitta virens. For the first time, we showed an early activation of FGF ligands and receptor expression in an annelid regenerating after amputation. The expression patterns indicate that the entire regenerative bud is competent to FGFs, whose activity precedes the initiation of cell proliferation. The critical requirement of FGF signaling, especially at early stages, is also supported by inhibitor treatments followed by proliferation assay, demonstrating that induction of blastemal cells depends on FGFs. Our results show that FGF signaling pathway is a key player in regenerative response, while the FGF-positive wound epithelium, ventral nerve cord and some mesodermal cells around the gut could be the inducing tissues. This mechanism resembles reparative regeneration of vertebrate appendages suggesting such a response to the injury may be ancestral for all bilaterians. Full article

(This article belongs to the Special Issue The Molecular Genetics and Major Concepts Underlying Whole Body Regeneration in the Animal World)

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Review

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19 pages, 3052 KiB

Open AccessReview

Regeneration in the Segmented Annelid Capitella teleta

by Elaine C. Seaver and Danielle M. de Jong

Genes 2021, 12(11), 1769; https://doi.org/10.3390/genes12111769 - 08 Nov 2021

Cited by 4 | Viewed by 2793

Abstract

The segmented worms, or annelids, are a clade within the Lophotrochozoa, one of the three bilaterian superclades. Annelids have long been models for regeneration studies due to their impressive regenerative abilities. Furthermore, the group exhibits variation in adult regeneration abilities with some species able to replace anterior segments, posterior segments, both or neither. Successful regeneration includes regrowth of complex organ systems, including the centralized nervous system, gut, musculature, nephridia and gonads. Here, regenerative capabilities of the annelid Capitella teleta are reviewed. C. teleta exhibits robust posterior regeneration and benefits from having an available sequenced genome and functional genomic tools available to study the molecular and cellular control of the regeneration response. The highly stereotypic developmental program of C. teleta provides opportunities to study adult regeneration and generate robust comparisons between development and regeneration. Full article

(This article belongs to the Special Issue The Molecular Genetics and Major Concepts Underlying Whole Body Regeneration in the Animal World)

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23 pages, 3161 KiB

Open AccessReview

Comparative Aspects of Annelid Regeneration: Towards Understanding the Mechanisms of Regeneration

by Roman P. Kostyuchenko and Vitaly V. Kozin

Genes 2021, 12(8), 1148; https://doi.org/10.3390/genes12081148 - 28 Jul 2021

Cited by 20 | Viewed by 4111

Abstract

The question of why animals vary in their ability to regenerate remains one of the most intriguing questions in biology. Annelids are a large and diverse phylum, many members of which are capable of extensive regeneration such as regrowth of a complete head or tail and whole-body regeneration, even from few segments. On the other hand, some representatives of both of the two major annelid clades show very limited tissue regeneration and are completely incapable of segmental regeneration. Here we review experimental and descriptive data on annelid regeneration, obtained at different levels of organization, from data on organs and tissues to intracellular and transcriptomic data. Understanding the variety of the cellular and molecular basis of regeneration in annelids can help one to address important questions about the role of stem/dedifferentiated cells and “molecular morphallaxis” in annelid regeneration as well as the evolution of regeneration in general. Full article

(This article belongs to the Special Issue The Molecular Genetics and Major Concepts Underlying Whole Body Regeneration in the Animal World)

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19 pages, 2644 KiB

Open AccessReview

The Tentacular Spectacular: Evolution of Regeneration in Sea Anemones

by Chloé A. van der Burg and Peter J. Prentis

Genes 2021, 12(7), 1072; https://doi.org/10.3390/genes12071072 - 14 Jul 2021

Cited by 5 | Viewed by 3979

Abstract

Sea anemones vary immensely in life history strategies, environmental niches and their ability to regenerate. While the sea anemone Nematostella vectensis is the starlet of many key regeneration studies, recent work is emerging on the diverse regeneration strategies employed by other sea anemones. This manuscript will explore current molecular mechanisms of regeneration employed by non-model sea anemones Exaiptasia diaphana (an emerging model species for coral symbiosis studies) and Calliactis polypus (a less well-studied species) and examine how these species compare to the model sea anemone N. vectensis. We summarize the field of regeneration within sea anemones, within the greater context of phylum Cnidaria and in other invertebrate models of regeneration. We also address the current knowledge on two key systems that may be implemented in regeneration: the innate immune system and developmental pathways, including future aspects of work and current limitations. Full article

(This article belongs to the Special Issue The Molecular Genetics and Major Concepts Underlying Whole Body Regeneration in the Animal World)

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9 pages, 1171 KiB

Open AccessReview

The Use of Larval Sea Stars and Sea Urchins in the Discovery of Shared Mechanisms of Metazoan Whole-Body Regeneration

by Andrew Wolff and Veronica Hinman

Genes 2021, 12(7), 1063; https://doi.org/10.3390/genes12071063 - 13 Jul 2021

Cited by 3 | Viewed by 4581

Abstract

The ability to regenerate is scattered among the metazoan tree of life. Further still, regenerative capacity varies widely within these specific organisms. Numerous organisms, all with different regenerative capabilities, have been studied at length and key similarities and disparities in how regeneration occurs have been identified. In order to get a better grasp on understanding regeneration as a whole, we must search for new models that are capable of extensive regeneration, as well as those that have been under sampled in the literature. As invertebrate deuterostomes, echinoderms fit both of these requirements. Multiple members regenerate various tissue types at all life stages, including examples of whole-body regeneration. Interrogations in two highly studied echinoderms, the sea urchin and the sea star, have provided knowledge of tissue and whole-body regeneration at various life stages. Work has begun to examine regeneration in echinoderm larvae, a potential new system for understanding regenerative mechanisms in a basal deuterostome. Here, we review the ways these two animals’ larvae have been utilized as a model of regeneration. Full article

(This article belongs to the Special Issue The Molecular Genetics and Major Concepts Underlying Whole Body Regeneration in the Animal World)

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15 pages, 2815 KiB

Open AccessReview

Whole-Body Regeneration in the Lobate Ctenophore Mnemiopsis leidyi

by Allison Edgar, Dorothy G. Mitchell and Mark Q. Martindale

Genes 2021, 12(6), 867; https://doi.org/10.3390/genes12060867 - 05 Jun 2021

Cited by 11 | Viewed by 8446

Abstract

Ctenophores (a.k.a. comb jellies) are one of the earliest branching extant metazoan phyla. Adult regenerative ability varies greatly within the group, with platyctenes undergoing both sexual and asexual reproduction by fission while others in the genus Beroe having completely lost the ability to replace missing body parts. We focus on the unique regenerative aspects of the lobate ctenophore, Mnemiopsis leidyi, which has become a popular model for its rapid wound healing and tissue replacement, optical clarity, and sequenced genome. M. leidyi’s highly mosaic, stereotyped development has been leveraged to reveal the polar coordinate system that directs whole-body regeneration as well as lineage restriction of replacement cells in various regenerating organs. Several cell signaling pathways known to function in regeneration in other animals are absent from the ctenophore’s genome. Further research will either reveal ancient principles of the regenerative process common to all animals or reveal novel solutions to the stability of cell fates and whole-body regeneration. Full article

(This article belongs to the Special Issue The Molecular Genetics and Major Concepts Underlying Whole Body Regeneration in the Animal World)

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18 pages, 7053 KiB

Open AccessEditor’s ChoiceReview

Regeneration Potential of Jellyfish: Cellular Mechanisms and Molecular Insights

by Sosuke Fujita, Erina Kuranaga and Yu-ichiro Nakajima

Genes 2021, 12(5), 758; https://doi.org/10.3390/genes12050758 - 17 May 2021

Cited by 17 | Viewed by 9168

Abstract

Medusozoans, the Cnidarian subphylum, have multiple life stages including sessile polyps and free-swimming medusae or jellyfish, which are typically bell-shaped gelatinous zooplanktons that exhibit diverse morphologies. Despite having a relatively complex body structure with well-developed muscles and nervous systems, the adult medusa stage maintains a high regenerative ability that enables organ regeneration as well as whole body reconstitution from the part of the body. This remarkable regeneration potential of jellyfish has long been acknowledged in different species; however, recent studies have begun dissecting the exact processes underpinning regeneration events. In this article, we introduce the current understanding of regeneration mechanisms in medusae, particularly focusing on cellular behaviors during regeneration such as wound healing, blastema formation by stem/progenitor cells or cell fate plasticity, and the organism-level patterning that restores radial symmetry. We also discuss putative molecular mechanisms involved in regeneration processes and introduce a variety of novel model jellyfish species in the effort to understand common principles and diverse mechanisms underlying the regeneration of complex organs and the entire body. Full article

(This article belongs to the Special Issue The Molecular Genetics and Major Concepts Underlying Whole Body Regeneration in the Animal World)

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25 pages, 8475 KiB

Open AccessEditor’s ChoiceReview

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

by Alexander Ereskovsky, Ilya E. Borisenko, Fyodor V. Bolshakov and Andrey I. Lavrov

Genes 2021, 12(4), 506; https://doi.org/10.3390/genes12040506 - 29 Mar 2021

Cited by 24 | Viewed by 5071

Abstract

While virtually all animals show certain abilities for regeneration after an injury, these abilities vary greatly among metazoans. Porifera (Sponges) is basal metazoans characterized by a wide variety of different regenerative processes, including whole-body regeneration (WBR). Considering phylogenetic position and unique body organization, sponges are highly promising models, as they can shed light on the origin and early evolution of regeneration in general and WBR in particular. The present review summarizes available data on the morphogenetic and cellular mechanisms accompanying different types of WBR in sponges. Sponges show a high diversity of WBR, which principally could be divided into (1) WBR from a body fragment and (2) WBR by aggregation of dissociated cells. Sponges belonging to different phylogenetic clades and even to different species and/or differing in the anatomical structure undergo different morphogeneses after similar operations. A common characteristic feature of WBR in sponges is the instability of the main body axis: a change of the organism polarity is described during all types of WBR. The cellular mechanisms of WBR are different across sponge classes, while cell dedifferentiations and transdifferentiations are involved in regeneration processes in all sponges. Data considering molecular regulation of WBR in sponges are extremely scarce. However, the possibility to achieve various types of WBR ensured by common morphogenetic and cellular basis in a single species makes sponges highly accessible for future comprehensive physiological, biochemical, and molecular studies of regeneration processes. Full article

(This article belongs to the Special Issue The Molecular Genetics and Major Concepts Underlying Whole Body Regeneration in the Animal World)

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Graphical abstract

31 pages, 2533 KiB

Open AccessEditor’s ChoiceReview

Molecular Aspects of Regeneration Mechanisms in Holothurians

by Igor Yu. Dolmatov

Genes 2021, 12(2), 250; https://doi.org/10.3390/genes12020250 - 10 Feb 2021

Cited by 26 | Viewed by 3156

Abstract

Holothurians, or sea cucumbers, belong to the phylum Echinodermata. They show good regenerative abilities. The present review provides an analysis of available data on the molecular aspects of regeneration mechanisms in holothurians. The genes and signaling pathways activated during the asexual reproduction and the formation of the anterior and posterior parts of the body, as well as the molecular mechanisms that provide regeneration of the nervous and digestive systems, are considered here. Damage causes a strong stress response, the signs of which are recorded even at late regeneration stages. In holothurian tissues, the concentrations of reactive oxygen species and antioxidant enzymes increase. Furthermore, the cellular and humoral components of the immune system are activated. Extracellular matrix remodeling and Wnt signaling play a major role in the regeneration in holothurians. All available morphological and molecular data show that the dedifferentiation of specialized cells in the remnant of the organ and the epithelial morphogenesis constitute the basis of regeneration in holothurians. However, depending on the type of damage, the mechanisms of regeneration may differ significantly in the spatial organization of regeneration process, the involvement of different cell types, and the depth of reprogramming of their genome (dedifferentiation or transdifferentiation). Full article

(This article belongs to the Special Issue The Molecular Genetics and Major Concepts Underlying Whole Body Regeneration in the Animal World)

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