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Stem cells and regeneration in the annelid Platynereis dumerilii
Evolution of posterior elongation in bilaterian animals
Evolution of stemness and pluripotency in animals

signature_GMP

Stem cells and regeneration in the annelid Platynereis dumerilii

Regeneration, the ability to restore lost parts of the body, is a widespread phenomenon in animals. Whilst this ability is somehow limited in classical developmental model organisms, a variety of animals (for example sponges, cnidarians, planarians, annelids, salamanders …) are able to regenerate, upon injury (for example amputation), complex structures such as limbs or important parts of their body (Grillo et al., 2016). While there have been plenty of studies about regeneration in a large variety of animals, we still lack a general view of the evolution of animal regeneration and we still do not know whether there would be general principles and genetic programs that underlie regeneration in animals. We have started to work on Platynereis regeneration because we think it may constitute, due to its phylogenetic position, its belonging to a slow-evolving lineage, and the available tools to study its regeneration, an outstanding model to address fundamental questions about the evolution of regeneration in animals. After amputation of the posterior part of their body, Platynereis worms form a regeneration blastema (a structure made of undifferentiated proliferative cells) and regenerate both the pygidium (the posteriormost part of the body, which bears the anus) and the stem cell-rich subterminal growth zone. We called this process posterior regeneration. Platynereis, unlike other annelids, is unable to regenerate its head. Platynereis is also able to regenerate the various outgrowths of its body such as cirri (on both the head and the pygidium) and swimming/crawling appendages (parapodia). Parapodial regeneration also involves the formation of a regeneration blastema. We currently characterize, with a large variety of molecular, cellular and genomic tools, the different steps of posterior regeneration in Platynereis and to define the respective roles of pre-existing stem cells and dedifferentiation in the process. We also try to identify the signals that trigger regeneration in Platynereis and to understand how the capability to regenerate is regulated.(↑top)

Evolution of posterior elongation in bilaterian animals

We are interested in the evolution of posterior elongation (PE) and of the stem cells involved in this process. PE is the process by which animals such as chordates, annelids, and arthropods elongate their body axis through the addition of tissue in an anterior to posterior sequential progression. Using molecular and cellular tools, we previously showed that Platynereis PE relies on the presence of a subterminal growth zone that contains stem cells whose sustained proliferation allows the worms to grow during most of their life (Gazave et al., 2013). These posterior stem cells express several genes whose orthologs are known to be expressed in pluripotent somatic stem cells and primordial germ cells in other animals, and that constitute the so-called ‘GMP signature’. We aim to define whether the presence of posterior stem cells crucial to PE and expressing the GMP signature, is an ancestral feature of bilaterians. With this aim, we plan to characterize, at the molecular and cellular levels, PE in two species that belong to the other main bilaterian evolutionary lineages, the amphioxus Branchiostoma lanceolatum, a chordate (this work will be done in collaboration with Hector Escriva’s team; Banyuls sur mer), and a few crustacean species, which are arthropods (collaboration with Nicolas Rabet; Paris – Terri Williams; Hartford USA).(↑top)

Evolution of stemness and pluripotency in animals

Pluripotent stem cells, which are able to produce most or all tissues of the body, are the subject of considerable attention in biology and medicine. In many animals, including the main model species of developmental biology, pluripotency is a transient property that is only displayed by early embryonic cells. In mammals, for example, the epiblast cells of the mature blastocyst are capable of engendering all the tissues of the embryo, including the germline. Their pluripotency can be captured in culture, the resulting cells being the embryonic stem cells (ESCs). Primordial Germ Cells (PGCs), the stem cells that will produce the germinal cells, do also exhibit pluripotency properties (Johnson and Alberio, 2015). While artificial manipulations can lead to the conversion of somatic cells into pluripotent stem cells (iPS, induced pluripotent stem cells), ‘natural’ pluripotent stem cells do not exist at post-embryonic stages in mammals. This is, however, not a general rule: in several species belonging to distantly-related animal groups, the presence of pluripotent stem cells in adults has been demonstrated (or determined to be highly likely). This is for example the case in flatworms, cnidarians, sponges, colonial urochordates and annelids. The presence of these adult pluripotent stem cells endows these organisms with fundamental biological properties, such as continuous growth, ability to regenerate important parts of their body and asexual reproduction. The molecular analysis of these stem cells, such as flatworm neoblasts and cnidarian interstitial cells (i-cells), has shown that they share a common molecular signature known as the Germline Multipotency Program (GMP) (e.g., Juliano et al., 2010; Solana, 2013; Gazave et al., 2013). It consists of the expression of dozen of genes in the adult pluripotent stem cells among which the best known are piwi, vasa, and nanos. Those genes were previously thought to be germline-specific based on their expression in model systems such as mouse and Drosophila. This shared signature led to the hypothesis that pluripotent stems cells may have evolved from an ancestral stem cell type present in the very early animals, and which would also have been at the origin of PGCs. Further work is however required to test this hypothesis and to establish the evolutionary relationships between the different types of pluripotent stem cells found in animals (Collaboration with Lucie Laplace, CNRS, IHPST-Université Paris I Panthéon-Sorbonne). We aim at establishing a conserved molecular program for pluripotency and at understanding the evolution of pluripotent stem cells and germ cells at the metazoan scale.(↑top)

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