The WTX/AMER1 gene family: evolution, signature and function

<p>Abstract</p> <p>Background</p> <p><it>WTX </it>is a novel gene mutated in a proportion of Wilms' tumors and in patients suffering from sclerosing bone dysplasia. On the molecular level WTX has been shown to act as an antagonist of canonical <it>Wnt/β-catenin </it>signaling in fish and mammals thus linking it to an essential pathway involved in normal development and cancer formation. Interestingly, WTX seems to also localize to an intranuclear component called paraspeckles. In spite of the growing interest of molecular biologists in <it>WTX</it>, little is known about its paralogs and its phylogenetic history.</p> <p>Results</p> <p>Using the amino-acid sequence of <it>WTX/AMER1 </it>as a tool for the assignment of orthology and paralogy, we here identify two novel proteins, <it>AMER2 </it>and <it>AMER3</it>, as "<it>WTX</it>" related. This <it>Amer </it>gene family is present in all currently available vertebrate genome sequences, but not invertebrate genomes and is characterized by six conserved blocks of sequences. The phylogenetic analysis suggests that the <it>protoAmer </it>gene originated early in the vertebrate lineage and was then duplicated due to whole genome duplications (WGD) giving rise to the three different <it>Amer </it>genes.</p> <p>Conclusion</p> <p>Our study represents the first phylogenetic analysis of <it>Amer </it>genes and reveals a new vertebrate specific gene family that is likely to have played an important role in the evolution of this subphylum. Divergent and conserved molecular functions of <it>Wtx/Amer1</it>, <it>Amer2 </it>and <it>Amer3 </it>are discussed.</p

Bulletin des bibliothèques de France dans l’histoire des bibliothèques (Le)

Ce mémoire retrace l’évolution des bibliothèques françaises depuis 1980 telle que la restitue le BBF. L’historique de la revue rend compte de ses modifications structurelles et matérielles successives tandis que l’analyse de différents thèmes abordés par le BBF renseigne sur l’évolution de la réflexion des professionnels des bibliothèques

Snail1 factor behaves as a therapeutic target in renal fibrosis.

Kidney fibrosis is a devastating disease that leads to organ failure, and no specific treatment is available to preserve organ function. In fibrosis, myofibroblasts accumulate in the interstitium leading to massive deposition of extracellular matrix and organ disfunction. The origin of myofibroblasts is multiple and the contribution of renal epithelial cells after undergoing epithelial-to-mesenchymal transition (EMT) is still debated. In a model unable to reactivate the EMT inducer Snail1 upon damage, we show that Snail1 is required in renal epithelial cells for the development of fibrosis. Damage-mediated Snail1 reactivation induces a partial EMT that relays fibrotic and inflammatory signals to the interstitium through the activation of TGF-β and NF-B pathways. Snail1-induced fibrosis can be reverted in vivo and inhibiting Snail1 in a model of obstructive nephropathy highly ameliorates fibrosis. These results reconcile conflicting data on the role of EMT in renal fibrosis and provide avenues for the design of antifibrotic therapies.pre-print8435 K

The evolution of asymmetric photosensitive structures in metazoans and the Nodal connection

International audienceAsymmetries are observed in a great number of taxa in metazoans. More particularly, functional lateralization and neuroanatomical asymmetries within the central nervous system have been a matter of intense research for at least two hundred years. While asymmetries of some paired structures/organs (e.g. eyes, ears, kidneys, legs, arms) constitute random deviations from a pure bilateral symmetry, brain asymmetries such as those observed in the cortex and epithalamus are directional. This means that molecular and anatomical features located on one side of a given structure are observed in most individuals. For instance, in humans, the neuronal tract connecting the language areas is enlarged in the left hemisphere. When asymmetries are fixed, their molecular mechanisms can be studied using mutants displaying different phenotypes: left or right isomerism of the structure, reversed asymmetry or random asymmetry. Our understanding of asymmetry in the nervous system has been widely enriched thanks to the characterization of mutants affecting epithalamus asymmetry. Furthermore, two decades ago, pioneering studies revealed that a specific morphogen, Nodal, active only on one side of the embryo during development is an important molecule in asymmetry patterning. In this review, I have gathered important data bringing insight into the origin and evolution of epithalamus asymmetry and the role of Nodal in metazoans. After a short introduction on brain asymmetries (chapter I), I secondly focus on the molecular and anatomical characteristics of the epithalamus in vertebrates and explore some functional aspects such as its photosensitive ability related to the pineal complex (chapter II). Third, I discuss homology relationship of the parapineal organ among vertebrates (chapter III). Fourth, I discuss the possible origin of the epithalamus, presenting cells displaying photosensitive properties and/or asymmetry in the anterior part of the body in non-vertebrates (chapter IV). Finally, I report Nodal signaling expression data and functional experiments performed in different metazoan groups (chapter V)

Les gènes Snail et les maladies rénales-Les leçons de l’organogenèse

3 páginas, 2 figuras.Peer reviewe

Les gènes Snail et les maladies rénales-Les leçons de l’organogenèse

3 páginas, 2 figuras.Peer reviewe

Reactivation of Snail Genes in Renal Fibrosis and Carcinomas: A Process of Reversed Embryogenesis?

5 páginas, 4 figuras.While the activity oepithelialf Snail genes is required during embryonic development for the formation of different tissues and organs, they must be repressed in the adult in order to maintain epithelial integrity and homeostasis. Indeed, pathological activation of Snail in epithelial tumors induces malignancy and the recurrence of tumors. Here we show that in dedifferentiated areas of human renal carcinomas, Snail undergoes a process of reactivation. In addition to tumor progression, renal fibrosis is also linked to the activity of Snail genes and indeed, reactivation of Snail in the adult kidney is sufficient to induce fibrosis. Thus, Snail genes illustrate a paradigm whereby reactivation of crucial embryonic genes in adult tissues provokes the onset of devastating diseases.Peer reviewe

mTOR Signaling at the Crossroad between Metazoan Regeneration and Human Diseases

A major challenge in medical research resides in controlling the molecular processes of tissue regeneration, as organ and structure damage are central to several human diseases. A survey of the literature reveals that mTOR (mechanistic/mammalian target of rapamycin) is involved in a wide range of regeneration mechanisms in the animal kingdom. More particularly, cellular processes such as growth, proliferation, and differentiation are controlled by mTOR. In addition, autophagy, stem cell maintenance or the newly described intermediate quiescence state, Galert, imply upstream monitoring by the mTOR pathway. In this review, we report the role of mTOR signaling in reparative regenerations in different tissues and body parts (e.g., axon, skeletal muscle, liver, epithelia, appendages, kidney, and whole-body), and highlight how the mTOR kinase can be viewed as a therapeutic target to boost organ repair. Studies in this area have focused on modulating the mTOR pathway in various animal models to elucidate its contribution to regeneration. The diversity of metazoan species used to identify the implication of this pathway might then serve applied medicine (in better understanding what is required for efficient treatments in human diseases) but also evolutionary biology. Indeed, species-specific differences in mTOR modulation can contain the keys to appreciate why certain regeneration processes have been lost or conserved in the animal kingdom

Digital Marine: An online platform for blended learning in a marine experimental biology module, the Schmid Training Course

International audienceFor over 20 years, the Schmid Training Course (STC) has offered unique opportunities for marine biology students from European universities to learn about marine model organisms. While the topics of the course have continuously changed over the years with the advent of new research techniques and discoveries, the pedagogical approach has remained largely the same-a combination of lectures, lab practicals, and field excursions. Several life science researchers, who have taught in the STC for many years, sought to bring the course's pedagogical approach into the 21st century, and with the support of Erasmus+ Programme of the European Community funding, the DigitalMarine project was developed. DigitalMarine began in 2018 as an international partnership between the six research centers from which the STC instructors hail, and its main objective was to introduce a flipped, blended approach to learning and teaching with respect to established and emerging marine biological model systems. The DigitalMarine platform, which covers 12 marine model organisms, is now publicly available. The Schmid Training Course (STC) The Station Biologique de Roscoff, a marine station of Sorbonne Université (SU), in France (Northern Brittany) was founded in 1872 by Henri de Lacaze-Duthiers with the aim to develop a laboratory for both observational and experimental zoology. Since then, research has extended into additional fields, including ecology and oceanography, and several training courses linked to these areas have been established. One of these courses is the Schmid Training Course (STC) that focuses on experimental biology using marine organisms. The STC was named after the Swiss zoologist Volker Schmid, who was an iconic teacher for the course, and who passed away in 2008 [1]. The STC allows students to explore the diversity of marine model organisms and train them in using these models in experimental biology. More precisely, the goal is to show students the benefits of various marine organisms as alternative or complementary systems to the conventional model organisms (i.e. Drosophila melanogaster, Caenorhabditis elegans, Mus musculus, Saccharomyces cerevisiae) to address fundamental scientific questions

eIF4B mRNA Translation Contributes to Cleavage Dynamics in Early Sea Urchin Embryos

International audienceDuring the first steps of sea urchin development, fertilization elicits a marked increase in protein synthesis essential for subsequent cell divisions. While the translation of mitotic cyclin mRNAs is crucial, we hypothesized that additional mRNAs must be translated to finely regulate the onset into mitosis. One of the maternal mRNAs recruited onto active polysomes at this stage codes for the initiation factor eIF4B. Here, we show that the sea urchin eIF4B orthologs present the four specific domains essential for eIF4B function and that Paracentrotus lividus eIF4B copurifies with eIF4E in a heterologous system. In addition, we investigated the role of eIF4B mRNA de novo translation during the two first embryonic divisions of two species, P. lividus and Sphaerechinus granularis. Our results show that injection of a morpholino directed against eIF4B mRNA results in a downregulation of translational activity and delays cell division in these two echinoids. Conversely, injection of an mRNA encoding for P. lividus eIF4B stimulates translation and significantly accelerates cleavage rates. Taken together, our findings suggest that eIF4B mRNA de novo translation participates in a conserved regulatory loop that contributes to orchestrating protein synthesis and modulates cell division rhythm during early sea urchin development