Variations in cell plasticity and proliferation underlie distinct modes of regeneration along the antero-posterior axis in the annelid Platynereis.

The capacity to regenerate lost tissues varies significantly among animals. Some phyla, such as the annelids, display substantial regenerating abilities, although little is known about the cellular mechanisms underlying the process. To precisely determine the origin, plasticity and fate of the cells participating in blastema formation and posterior end regeneration after amputation in the annelid Platynereis dumerilii, we developed specific tools to track different cell populations. Using these tools, we find that regeneration is partly promoted by a population of proliferative gut cells whose regenerative potential varies as a function of their position along the antero-posterior axis of the worm. Gut progenitors from anterior differentiated tissues are lineage restricted, whereas gut progenitors from the less differentiated and more proliferative posterior tissues are much more plastic. However, they are unable to regenerate the stem cells responsible for the growth of the worms. Those stem cells are of local origin, deriving from the cells present in the segment abutting the amputation plane, as are most of the blastema cells. Our results favour a hybrid and flexible cellular model for posterior regeneration in Platynereis relying on different degrees of cell plasticity.

The compact genome of the sponge Oopsacas minuta (Hexactinellida) is lacking key metazoan core genes.

BACKGROUND: Explaining the emergence of the hallmarks of bilaterians is a central focus of evolutionary developmental biology-evodevo-and evolutionary genomics. For this purpose, we must both expand and also refine our knowledge of non-bilaterian genomes, especially by studying early branching animals, in particular those in the metazoan phylum Porifera. RESULTS: We present a comprehensive analysis of the first whole genome of a glass sponge, Oopsacas minuta, a member of the Hexactinellida. Studying this class of sponge is evolutionary relevant because it differs from the three other Porifera classes in terms of development, tissue organization, ecology, and physiology. Although O. minuta does not exhibit drastic body simplifications, its genome is among the smallest of animal genomes sequenced so far, and surprisingly lacks several metazoan core genes (including Wnt and several key transcription factors). Our study also provides the complete genome of a symbiotic Archaea dominating the associated microbial community: a new Thaumarchaeota species. CONCLUSIONS: The genome of the glass sponge O. minuta differs from all other available sponge genomes by its compactness and smaller number of encoded proteins. The unexpected loss of numerous genes previously considered ancestral and pivotal for metazoan morphogenetic processes most likely reflects the peculiar syncytial tissue organization in this group. Our work further documents the importance of convergence during animal evolution, with multiple convergent evolution of septate-like junctions, electrical-signaling and multiciliated cells in metazoans.

Transcriptomic landscape of posterior regeneration in the annelid Platynereis dumerilii.

BACKGROUND: Restorative regeneration, the capacity to reform a lost body part following amputation or injury, is an important and still poorly understood process in animals. Annelids, or segmented worms, show amazing regenerative capabilities, and as such are a crucial group to investigate. Elucidating the molecular mechanisms that underpin regeneration in this major group remains a key goal. Among annelids, the nereididae Platynereis dumerilii (re)emerged recently as a front-line regeneration model. Following amputation of its posterior part, Platynereis worms can regenerate both differentiated tissues of their terminal part as well as a growth zone that contains putative stem cells. While this regeneration process follows specific and reproducible stages that have been well characterized, the transcriptomic landscape of these stages remains to be uncovered. RESULTS: We generated a high-quality de novo Reference transcriptome for the annelid Platynereis dumerilii. We produced and analyzed three RNA-sequencing datasets, encompassing five stages of posterior regeneration, along with blastema stages and non-amputated tissues as controls. We included two of these regeneration RNA-seq datasets, as well as embryonic and tissue-specific datasets from the literature to produce a Reference transcriptome. We used this Reference transcriptome to perform in depth analyzes of RNA-seq data during the course of regeneration to reveal the important dynamics of the gene expression, process with thousands of genes differentially expressed between stages, as well as unique and specific gene expression at each regeneration stage. The study of these genes highlighted the importance of the nervous system at both early and late stages of regeneration, as well as the enrichment of RNA-binding proteins (RBPs) during almost the entire regeneration process. CONCLUSIONS: In this study, we provided a high-quality de novo Reference transcriptome for the annelid Platynereis that is useful for investigating various developmental processes, including regeneration. Our extensive stage-specific transcriptional analysis during the course of posterior regeneration sheds light upon major molecular mechanisms and pathways, and will foster many specific studies in the future.

On the hormonal control of posterior regeneration in the annelid Platynereis dumerilii.

Regeneration is the process by which many animals are able to restore lost or injured body parts. After amputation of the posterior part of its body, the annelid Platynereis dumerilii is able to regenerate the pygidium, the posteriormost part of its body that bears the anus, and a subterminal growth zone containing stem cells that allows the subsequent addition of new segments. The ability to regenerate their posterior part (posterior regeneration) is promoted, in juvenile worms, by a hormone produced by the brain and is lost when this hormonal activity becomes low at the time the worms undergo their sexual maturation. By characterizing posterior regeneration at the morphological and molecular levels in worms that have been decapitated, we show that the presence of the head is essential for multiple aspects of posterior regeneration, as well as for the subsequent production of new segments. We also show that methylfarnesoate, the molecule proposed to be the brain hormone, can partially rescue the posterior regeneration defects observed in decapitated worms. Our results are therefore consistent with a key role of brain hormonal activity in the control of regeneration and growth in P. dumerilii, and support the hypothesis of the involvement of methylfarnesoate in this control.

Non-invasive neurally adjusted ventilatory assist in preterm infants with RDS: effect of changing NAVA levels.

We aimed to examine the effect of changing levels of support (NAVA level) during non-invasive neurally adjusted ventilatory assist (NIV-NAVA) in preterm infants with respiratory distress syndrome (RDS) on electrical diaphragm activity. This is a prospective, single-centre, interventional, exploratory study in a convenience sample. Clinically stable preterm infants supported with NIV-NAVA for RDS were eligible. Patients were recruited in the first 24 h after the start of NIV-NAVA. Following a predefined titration protocol, NAVA levels were progressively increased starting from a level of 0.5 cmH2O/µV and with increments of 0.5 cmH2O/µV every 3 min, up to a maximum level of 4.0 cmH2O/µV. We measured the evolution of peak inspiratory pressure and the electrical signal of the diaphragm (Edi) during NAVA level titration. Twelve infants with a mean (SD) gestational age at birth of 30.6 (3.5) weeks and birth weight of 1454 (667) g were enrolled. For all patients a breakpoint could be identified during the titration study. The breakpoint was on average (SD) at a level of 2.33 (0.58) cmH2O/µV. With increasing NAVA levels, the respiratory rate decreased significantly. No severe complications occurred.Conclusions: Preterm neonates with RDS supported with NIV-NAVA display a biphasic response to changing NAVA levels with an identifiable breakpoint. This breakpoint was at a higher NAVA level than commonly used in this clinical situation. Immature neural feedback mechanisms warrant careful monitoring of preterm infants when supported with NIV-NAVA.Trial registration: clinicaltrials.gov NCT03780842. Date of registration December 12, 2018. What is Known: • Non-invasive neurally adjusted ventilatory assist (NIV-NAVA) is a safe, feasible and effective way to support respiration in preterm infants. • Intact neural feedback mechanisms are needed to protect the lung from overdistension in neurally adjusted ventilatory assist. What is New: • Preterm infants with acute RDS have a similar pattern of respiratory unloading as previously described. • Neural feedback mechanisms seem to be immature with the risk of insufficient support and lung injury due to overdistension of the lung.

Animal regeneration in the era of transcriptomics.

Animal regeneration, the ability to restore a lost body part, is a process that has fascinated scientists for centuries. In this review, we first present what regeneration is and how it relates to development, as well as the widespread and diverse nature of regeneration in animals. Despite this diversity, animal regeneration includes three common mechanistic steps: initiation, induction and activation of progenitors, and morphogenesis. In this review article, we summarize and discuss, from an evolutionary perspective, the recent data obtained for a variety of regeneration models which have allowed to identify key shared mechanisms that control these main steps of animal regeneration. This review also synthesizes the wealth of high-throughput mRNA sequencing data (bulk mRNA-seq) concerning regeneration which have been obtained in recent years, highlighting the major advances in the regeneration field that these studies have revealed. We stress out that, through a comparative approach, these data provide opportunities to further shed light on the evolution of regeneration in animals. Finally, we point out how the use of single-cell mRNA-seq technology and integration with epigenomic approaches may further help researchers to decipher mechanisms controlling regeneration and their evolution in animals.

DNA methylation atlas and machinery in the developing and regenerating annelid Platynereis dumerilii.

BACKGROUND: Methylation of cytosines in DNA (5mC methylation) is a major epigenetic modification that modulates gene expression and constitutes the basis for mechanisms regulating multiple aspects of embryonic development and cell reprogramming in vertebrates. In mammals, 5mC methylation of promoter regions is linked to transcriptional repression. Transcription regulation by 5mC methylation notably involves the nucleosome remodeling and deacetylase complex (NuRD complex) which bridges DNA methylation and histone modifications. However, less is known about regulatory mechanisms involving 5mC methylation and their function in non-vertebrate animals. In this paper, we study 5mC methylation in the marine annelid worm Platynereis dumerilii, an emerging evolutionary and developmental biology model capable of regenerating the posterior part of its body post-amputation. RESULTS: Using in silico and experimental approaches, we show that P. dumerilii displays a high level of DNA methylation comparable to that of mammalian somatic cells. 5mC methylation in P. dumerilii is dynamic along the life cycle of the animal and markedly decreases at the transition between larval to post-larval stages. We identify a full repertoire of mainly single-copy genes encoding the machinery associated with 5mC methylation or members of the NuRD complex in P. dumerilii and show that this repertoire is close to the one inferred for the last common ancestor of bilaterians. These genes are dynamically expressed during P. dumerilii development and regeneration. Treatment with the DNA hypomethylating agent Decitabine impairs P. dumerilii larval development and regeneration and has long-term effects on post-regenerative growth. CONCLUSIONS: Our data reveal high levels of 5mC methylation in the annelid P. dumerilii, highlighting that this feature is not specific to vertebrates in the bilaterian clade. Analysis of DNA methylation levels and machinery gene expression during development and regeneration, as well as the use of a chemical inhibitor of DNA methylation, suggest an involvement of 5mC methylation in P. dumerilii development and regeneration. We also present data indicating that P. dumerilii constitutes a promising model to study biological roles and mechanisms of DNA methylation in non-vertebrate bilaterians and to provide new knowledge about evolution of the functions of this key epigenetic modification in bilaterian animals.

Morphological, cellular and molecular characterization of posterior regeneration in the marine annelid Platynereis dumerilii.

Regeneration, the ability to restore body parts after an injury or an amputation, is a widespread but highly variable and complex phenomenon in animals. While having fascinated scientists for centuries, fundamental questions about the cellular basis of animal regeneration as well as its evolutionary history remain largely unanswered. Here, we present a study of regeneration of the marine annelid Platynereis dumerilii, an emerging comparative developmental biology model, which, like many other annelids, displays important regenerative abilities. When P. dumerilii worms are amputated, they are able to regenerate the posteriormost differentiated part of their body and a stem cell-rich growth zone that allows the production of new segments replacing the amputated ones. We show that posterior regeneration is a rapid process that follows a well reproducible path and timeline, going through specific stages that we thoroughly defined. Wound healing is achieved one day after amputation and a regeneration blastema forms one day later. At this time point, some tissue specification already occurs, and a functional posterior growth zone is re-established as early as three days after amputation. Regeneration timing is only influenced, in a minor manner, by worm size. Comparable regenerative abilities are found for amputations performed at different positions along the antero-posterior axis of the worm, except when amputation planes are very close to the pharynx. Regenerative abilities persist upon repeated amputations without important alterations of the process. We also show that intense cell proliferation occurs during regeneration and that cell divisions are required for regeneration to proceed normally. Finally, 5-ethynyl-2'-deoxyuridine (EdU) pulse and chase experiments suggest that blastemal cells mostly derive from the segment immediately abutting the amputation plane. The detailed characterization of P. dumerilii posterior body regeneration presented in this article provides the foundation for future mechanistic and comparative studies of regeneration in this species.

Evolution of Prdm Genes in Animals: Insights from Comparative Genomics.

Prdm genes encode transcription factors with a subtype of SET domain known as the PRDF1-RIZ (PR) homology domain and a variable number of zinc finger motifs. These genes are involved in a wide variety of functions during animal development. As most Prdm genes have been studied in vertebrates, especially in mice, little is known about the evolution of this gene family. We searched for Prdm genes in the fully sequenced genomes of 93 different species representative of all the main metazoan lineages. A total of 976 Prdm genes were identified in these species. The number of Prdm genes per species ranges from 2 to 19. To better understand how the Prdm gene family has evolved in metazoans, we performed phylogenetic analyses using this large set of identified Prdm genes. These analyses allowed us to define 14 different subfamilies of Prdm genes and to establish, through ancestral state reconstruction, that 11 of them are ancestral to bilaterian animals. Three additional subfamilies were acquired during early vertebrate evolution (Prdm5, Prdm11, and Prdm17). Several gene duplication and gene loss events were identified and mapped onto the metazoan phylogenetic tree. By studying a large number of nonmetazoan genomes, we confirmed that Prdm genes likely constitute a metazoan-specific gene family. Our data also suggest that Prdm genes originated before the diversification of animals through the association of a single ancestral SET domain encoding gene with one or several zinc finger encoding genes.

Local effect of enhancer of zeste-like reveals cooperation of epigenetic and cis-acting determinants for zygotic genome rearrangements.

In the ciliate Paramecium tetraurelia, differentiation of the somatic nucleus from the zygotic nucleus is characterized by massive and reproducible deletion of transposable elements and of 45,000 short, dispersed, single-copy sequences. A specific class of small RNAs produced by the germline during meiosis, the scnRNAs, are involved in the epigenetic regulation of DNA deletion but the underlying mechanisms are poorly understood. Here, we show that trimethylation of histone H3 (H3K27me3 and H3K9me3) displays a dynamic nuclear localization that is altered when the endonuclease required for DNA elimination is depleted. We identified the putative histone methyltransferase Ezl1 necessary for H3K27me3 and H3K9me3 establishment and show that it is required for correct genome rearrangements. Genome-wide analyses show that scnRNA-mediated H3 trimethylation is necessary for the elimination of long, repeated germline DNA, while single copy sequences display differential sensitivity to depletion of proteins involved in the scnRNA pathway, Ezl1- a putative histone methyltransferase and Dcl5- a protein required for iesRNA biogenesis. Our study reveals cis-acting determinants, such as DNA length, also contribute to the definition of germline sequences to delete. We further show that precise excision of single copy DNA elements, as short as 26 bp, requires Ezl1, suggesting that development specific H3K27me3 and H3K9me3 ensure specific demarcation of very short germline sequences from the adjacent somatic sequences.

The Amphimedon queenslandica genome and the evolution of animal complexity.

Sponges are an ancient group of animals that diverged from other metazoans over 600 million years ago. Here we present the draft genome sequence of Amphimedon queenslandica, a demosponge from the Great Barrier Reef, and show that it is remarkably similar to other animal genomes in content, structure and organization. Comparative analysis enabled by the sequencing of the sponge genome reveals genomic events linked to the origin and early evolution of animals, including the appearance, expansion and diversification of pan-metazoan transcription factor, signalling pathway and structural genes. This diverse 'toolkit' of genes correlates with critical aspects of all metazoan body plans, and comprises cell cycle control and growth, development, somatic- and germ-cell specification, cell adhesion, innate immunity and allorecognition. Notably, many of the genes associated with the emergence of animals are also implicated in cancer, which arises from defects in basic processes associated with metazoan multicellularity.

A metameric origin for the annelid pygidium?

BACKGROUND: Segmented body organizations are widely represented in the animal kingdom. Whether the last common bilaterian ancestor was already segmented is intensely debated. Annelids display broad morphological diversity but many species are among the most homonomous metameric animals. The front end (prostomium) and tail piece (pygidium) of annelids are classically described as non-segmental. However, the pygidium structure and development remain poorly studied. RESULTS: Using different methods of microscopy, immunolabelling and a number of molecular markers, we describe the neural and mesodermal structures of the pygidium of Platynereis dumerilii. We establish that the pygidium possesses a complicated nervous system with a nerve ring and a pair of sensory ganglia, a complex intrinsic musculature, a large terminal circular blood sinus and an unusual unpaired torus-shaped coelomic cavity. We also describe some earlier steps of pygidial development and pygidial structure of mature animals after epitokous transformation. CONCLUSIONS: We describe a much more complex organization of the pygidium of P. dumerilii than previously suggested. Many of the characteristics are strikingly similar to those found in the trunk segments, opening the debate on whether the pygidium and trunk segments derive from the same ancestral metameric unit. We analyze these scenarios in the context of two classical theories on the origin of segmentation: the cyclomeric/archicoelomate concept and the colonial theory. Both theories provide possible explanations for the partial or complete homology of trunk segments and pygidium.

Posterior elongation in the annelid Platynereis dumerilii involves stem cells molecularly related to primordial germ cells.

Like most bilaterian animals, the annelid Platynereis dumerilii generates the majority of its body axis in an anterior to posterior temporal progression with new segments added sequentially. This process relies on a posterior subterminal proliferative body region, known as the "segment addition zone" (SAZ). We explored some of the molecular and cellular aspects of posterior elongation in Platynereis, in particular to test the hypothesis that the SAZ contains a specific set of stem cells dedicated to posterior elongation. We cloned and characterized the developmental expression patterns of orthologs of 17 genes known to be involved in the formation, behavior, or maintenance of stem cells in other metazoan models. These genes encode RNA-binding proteins (e.g., tudor, musashi, pumilio) or transcription factors (e.g., myc, id, runx) widely conserved in eumetazoans. Most of these genes are expressed both in the migrating primordial germ cells and in overlapping ring-like patterns in the SAZ, similar to some previously analyzed genes (piwi, vasa). The SAZ patterns are coincident with the expression of proliferation markers cyclin B and PCNA. EdU pulse and chase experiments suggest that new segments are produced through many rounds of divisions from small populations of teloblast-like posterior stem cells. The shared molecular signature between primordial germ cells and posterior stem cells in Platynereis thus corresponds to an ancestral "stemness" program.

Expanding roles for the evolutionarily conserved Dmrt sex transcriptional regulators during embryogenesis.

Dmrt genes encode a large family of transcription factors characterized by the presence of a DM domain, an unusual zinc finger DNA binding domain. While Dmrt genes are well known for their important role in sexual development in arthropodes, nematodes and vertebrates, several new findings indicate emerging functions of this gene family in other developmental processes. Here, we provide an overview of the evolution, structure and mechanisms of action of Dmrt genes. We summarize recent findings on their function in sexual regulation and discuss more extensively the role played by these proteins in somitogenesis and neural development.

Evolution of apoptotic signalling pathways within lophotrochozoans.

Apoptosis is the main form of regulated cell death in metazoans. Apoptotic pathways are well characterised in nematode, fly and mammals, leading to a vision of the conservation of apoptotic pathways in metazoans. However, we recently showed that intrinsic apoptosis is in fact divergent among metazoans. In addition, extrinsic apoptosis is poorly studied in non-mammalian animals, making its evolution unclear. Consequently, our understanding of apoptotic signalling pathways evolution is a black-box which must be illuminated by extending research to new biological systems. Lophotrochozoans are a major clade of metazoans which, despite their considerable biological diversity and key phylogenetic position as sister group of ecdysozoans (i.e. fly, nematode), are poorly explored, especially regarding apoptosis mechanisms. Traditionally each apoptotic signalling pathway was considered to rely on a specific initiator Caspase, associated with an activator. To shed light on apoptosis evolution in animals, we explored the evolutionary history of initiator Caspases, Caspase activators and the BCL-2 family (which control mitochondrial apoptotic pathway) in lophotrochozoans using phylogenetic analysis and protein interaction predictions. We discovered a diversification of initiator Caspases in molluscs, annelids and brachiopods, and the loss of key extrinsic apoptosis components in platyhelminths, along with the emergence of a clade specific Caspase with an ankyrin pro-domain. Taken together, our data show a specific history of apoptotic actors' evolution in lophotrochozoans, further demonstrating the appearance of distinct apoptotic signalling pathways during metazoan evolution.

A genome resource for the marine annelid Platynereis dumerilii.

The marine annelid Platynereis dumerilii is a model organism used in many research areas including evolution and development, neurobiology, ecology and regeneration. Here we present the genomes of P. dumerilii and of the closely related P. massiliensis and P. megalops, to facilitate comparative genomic approaches and help explore Platynereis biology. We used long-read sequencing technology and chromosomal-conformation capture along with extensive transcriptomic resources to obtain and annotate a draft genome assembly of ~1.47 Gbp for P. dumerilii, of which more than half represent repeat elements. We predict around 29,000 protein-coding genes, with relatively large intron sizes, over 38,000 non-coding genes, and 580 miRNA loci. We further explore the high genetic variation (~3% heterozygosity) within the Platynereis species complex. Gene ontology reveals the most variable loci to be associated with pigmentation, development and immunity. The current work sets the stage for further development of Platynereis genomic resources.

Evolution of RNA-binding proteins in animals: insights from genome-wide analysis in the sponge Amphimedon queenslandica.

RNA-binding proteins (RBPs) are key players in various biological processes, most notably regulation of gene expression at the posttranscriptional level. Although many RBPs have been carefully studied in model organisms, very few studies have addressed the evolution of these proteins at the scale of the animal kingdom. We identified a large set of putative RBPs encoded by the genome of the demosponge Amphimedon queenslandica, a species representing a basal animal lineage. We compared the Amphimedon RBPs with those encoded by the genomes of two bilaterians (human and Drosophila), representatives of two other basal metazoan lineages (a placozoan and a cnidarian), a choanoflagellate (probable sister group of animals), and two fungi. We established the evolutionary history of 32 families of RBPs and found that most of the diversity of RBPs present in contemporary metazoans, including humans, was already established in the last common ancestor (LCA) of animals. This includes RBPs known to be involved in key processes in bilaterians, such as development, stem and/or germ cells properties, and noncoding RNA pathways. From this analysis, we infer that a complex toolkit of RBPs was present in the LCA of animals and that it has been recruited to perform new functions during early animal evolution, in particular in relation to the acquisition of multicellularity.

Studying Annelida Regeneration Using Platynereis dumerilii.

Regeneration, the ability to restore body parts after an injury or an amputation, is a widespread property in the animal kingdom. This chapter describes methods used to study this fascinating process in the annelid Platynereis dumerilii. During most of its life, this segmented worm is able to regenerate upon amputation the posterior part of its body, including its pygidium (terminal non-segmented body region bearing the anus) and a subterminal posterior growth zone which contains stem cells required for the formation of new segments. Detailed description of Platynereis worm culture and how to obtain large quantity of regenerating worms is provided. We also describe the staging system that we established and three important methods to study regeneration: whole mount in situ hybridization to study gene expression, 5-ethynyl-2'-deoxyuridine (EdU) labeling to characterize cell proliferation, and use of pharmacological treatments to establish putative roles of defined signaling pathways and processes.

Sponge genes provide new insight into the evolutionary origin of the neurogenic circuit.

The nerve cell is a eumetazoan (cnidarians and bilaterians) synapomorphy [1]; this cell type is absent in sponges, a more ancient phyletic lineage. Here, we demonstrate that despite lacking neurons, the sponge Amphimedon queenslandica expresses the Notch-Delta signaling system and a proneural basic helix loop helix (bHLH) gene in a manner that resembles the conserved molecular mechanisms of primary neurogenesis in bilaterians. During Amphimedon development, a field of subepithelial cells expresses the Notch receptor, its ligand Delta, and a sponge bHLH gene, AmqbHLH1. Cells that migrate out of this field express AmqDelta1 and give rise to putative sensory cells that populate the larval epithelium. Phylogenetic analysis suggests that AmqbHLH1 is descendent from a single ancestral bHLH gene that later duplicated to produce the atonal/neurogenin-related bHLH gene families, which include most bilaterian proneural genes [2]. By way of functional studies in Xenopus and Drosophila, we demonstrate that AmqbHLH1 has a strong proneural activity in both species with properties displayed by both neurogenin and atonal genes. From these results, we infer that the bilaterian neurogenic circuit, comprising proneural atonal-related bHLH genes coupled with Notch-Delta signaling, was functional in the very first metazoans and was used to generate an ancient sensory cell type.

[A trio of mechanisms involved in regeneration initiation in animals]. / Un trio de mécanismes au cœur de l'initiationde la régénération chez les animaux.

Whole-body and complex structure regeneration is a widespread phenomenon in animals. While regenerative abilities vary greatly from one species to another, a number of mechanisms appear essential for regeneration in distantly related phylogenetic groups. In this review, we synthetize the knowledge gathered on the implication of three mechanisms that appear to be important for the initiation of regeneration in animals. Reactive Oxygen Species (ROS) are metabolic by-products involved in cell signalling, which are produced shortly after amputation in several species. ROS production may be responsible for triggering apoptosis, another recurring mechanism involved in regeneration initiation. In turn, apoptosis causes compensatory proliferation by setting off cellular division, thus contributing to the reconstitution of tissues. Inhibiting either ROS production, apoptosis or cellular proliferation impairs regeneration in a variety of model species.

TITLE: Un trio de mécanismes au cœur de l'initiationde la régénération chez les animaux. ABSTRACT: La régénération d'un membre ou du corps entier est un processus largement répandu chez les animaux. Même si les capacités régénératives varient d'une espèce à l'autre, trois mécanismes sont observés de façon récurrente lors de l'initiation de la régénération : la production de dérivés réactifs de l'oxygène (DRO), l'apoptose, et la prolifération cellulaire. De nombreux travaux ont mis en évidence le fait que ces trois mécanismes étaient nécessaires au bon déroulement de la régénération chez des espèces pourtant phylogénétiquement éloignées. Comprendre en détail les mécanismes moléculaires et cellulaires qui sous-tendent la coordination de ces trois processus dans l'initiation de la régénération pourrait aider à développer des thérapies pro-régénératives.