Di-μ2-bromido-bis­[bromido(η6-1,2,4,5-tetra­methyl­benzene)ruthenium(II)]

The asymmetric unit of the title compound, [Ru2Br4(C10H14)2], contains one half of the centrosymmetric mol­ecule. Each Ru center is coordinated by tetra­methyl­benzene ring in a η6-coordination mode, and one terminal and two bridging bromine atoms. The aromatic rings and the Ru2Br2 four-membered ring form a dihedral angle of 55.99 (8)°. In the crystal structure, weak inter­molecular C—H⋯Br inter­actions link mol­ecules into chains propagated in [001]

Species-specific contribution of volumetric growth and tissue convergence to posterior body elongation in vertebrates.

Posterior body elongation is a widespread mechanism propelling the generation of the metazoan body plan. The posterior growth model predicts that a posterior growth zone generates sufficient tissue volume to elongate the posterior body. However, there are energy supply-related differences between vertebrates in the degree to which growth occurs concomitantly with embryogenesis. By applying a multi-scalar morphometric analysis in zebrafish embryos, we show that posterior body elongation is generated by an influx of cells from lateral regions, by convergence-extension of cells as they exit the tailbud, and finally by a late volumetric growth in the spinal cord and notochord. Importantly, the unsegmented region does not generate additional tissue volume. Fibroblast growth factor inhibition blocks tissue convergence rather than volumetric growth, showing that a conserved molecular mechanism can control convergent morphogenesis through different cell behaviours. Finally, via a comparative morphometric analysis in lamprey, dogfish, zebrafish and mouse, we propose that elongation via posterior volumetric growth is linked to increased energy supply and is associated with an overall increase in volumetric growth and elongation.Jean-François Nicolas, Estelle Hirsinger: Core funding from the Institut Pasteur and Agence Nationale de la Recherche (ANR-10-BLAN-121801 DEVPROCESS). Estelle Hirsinger and Sylvie Mazan are from the Centre National de la Recherche Scientifique (CNRS). Benjamin Steventon was funded by the Agence Nationale de la Recherche (ANR- 10-BLAN-121801 DEVPROCESS), then a Roux fellowship (Institut Pasteur) then an AFM-Téléthon fellowship (number 16829).This is the author accepted manuscript. The final version is available from The Company of Biologists via http://dx.doi.org/10.1242/dev.12637

Di-μ2-chlorido-bis­[chlorido(η6-hexa­methyl­benzene)ruthenium(II)]

Dimeric mol­ecules of the title compound, [Ru2Cl4(C12H18)2], are located on a crystallographic centre of inversion with one mol­ecule in the asymmetric unit. The hexa­methyl­benzene rings are in an η6-coordination to the ruthenium centres, which are bridged by two chloride ligands. In addition, the ruthenium centres are bonded to another chloride ligand. The aromatic rings and the Ru2Cl2 four-membered ring enclose a dihedral angle of 55.85 (6)°

Mitral cell development in the olfactory bulb of sharks: evidences of a conserved pattern of glutamatergic neurogenesis

In mammals, the development of the olfactory bulb (OB) relies in part on the expression of transcription factors involved in the specifications/differentiation of glutamatergic cells. In a previous study from our group, a high molecular similarity was reported between mammals and cartilaginous fishes regarding the neurogenic mechanisms underlying the development of glutamatergic cells in the telencephalon. However, information about the transcriptional program operating in the development of the glutamatergic system (mainly represented by mitral cells) in the OB is lacking in the catshark Scyliorhinus canicula, a cartilaginous fish. Using immunohistochemistry and in situ hybridization techniques, we have found that, previously to the appearance of the olfactory primordium (OP), proliferating cells expressing Pax6 with molecular hallmarks of progenitor radial glia were located in the ventrolateral pallial ventricular zone. Later in development, when the OP is recognizable, a stream of Pax6-positive cells were observed between the ventricular zone and the OP, where transcription factors involved in mitral cell development in mammals (ScTbr2, ScNeuroD, Tbr1) are expressed. Later in development, these transcription factors became expressed in a layered-like structure where ScVglut1, a marker of mitral cells, is also present. Our data suggest that the transcriptional program related with the specification/differentiation of glutamatergic cells in the telencephalon has been conserved throughout the evolution of vertebrates. These results, in combination with previous studies concerning GABAergic neurogenesis in sharks, have evidenced that the OB of mammals and sharks shares similarities in the timing and molecular programs of development.This work was supported by the Spanish Ministerio de Economía y Competitividad-FEDER (BFU2014-5863-1P and BFU2017-8986-1P) and CNRS Université Pierre et Marie Curie Grant No. ANR-16-CE13-0013-02S

Prosomeric organization of the hypothalamus in an elasmobranch, the catshark Scyliorhinus canicula

The hypothalamus has been a central topic in neuroanatomy because of its important physiological functions, but its mature organization remains elusive. Deciphering its embryonic and adult organization is crucial in an evolutionary approach of the organization of the vertebrate forebrain. Here we studied the molecular organization of the hypothalamus and neighboring telencephalic domains in a cartilaginous fish, the catshark, Scyliorhinus canicula, focusing on ScFoxg1a, ScShh, ScNkx2.1, ScDlx2/5, ScOtp, and ScTbr1 expression profiles and on the identification αacetylated-tubulin-immunoreactive (ir), TH-ir, 5-HT-ir, and GFAP-ir structures by means of immunohistochemistry. Analysis of the results within the updated prosomeric model framework support the existence of alar and basal histogenetic compartments in the hypothalamus similar to those described in the mouse, suggesting the ancestrality of these subdivisions in jawed vertebrates. These data provide new insights into hypothalamic organization in cartilaginous fishes and highlight the generality of key features of the prosomeric model in jawed vertebrates.This work was supported by grants from the Spanish Dirección General de Investigación-FEDER (BFU2010- 15816), the Xunta de Galicia (10PXIB200051PR, CN 2012/237), European Community-Research Infrastructure Action under the FP7 “Capacities” Specific Programme (ASSEMBLE 227799), the Région Centre, Région Bretagne (EVOVERT grant number 049755; PEPTISAN project), National Research Agency (grant ANR-09-BLAN-026201), CNRS, Université d’Orléans and Université Pierre et Marie Curie. GNSD would like to thank Spanish SEPE for its funding supportS

Mécanismes de latéralisation de l'épithalamus chez la lamproie et la roussette

Vertebrates are part of the bilaterally symmetric animals but this one is not perfect and numerous asymmetries can be seen between the left and right sides, especially in the nervous system. The epithalamus has proven itself to be the model system for brain lateralization mechanisms’ studies. This structure derived from the dorsal diencephalon contains by the bilaterally paired habenular nuclei and the pineal complex, which includes the pineal gland and parapineal organ. The habenulae exhibit more or less marked left-right asymmetries among most of the major vertebrate taxa. The parapineal is also asymmetrical but it is absent in many taxa. Zebrafish is the model system for the studies of the developmental mechanisms of epithalamic asymmetries. In this species, a lateralized parapineal migration is required for the establishment of habenular asymmetries. The underlying genetic mechanisms have also been partially decrypted. The first conspicuous asymmetry in the dorsal diencephalon corresponds to a left-sided expression of components of the Nodal signalling pathway. This asymmetric Nodal signalling activity is essential to induce an early neurogenetic asymmetry but not necessary the formation of epithalamic asymmetries per se. Its role is restricted to provide a bias to the parapineal organ’s lateralized migration, and thus influence the laterality of epithalamic asymmetries. Indeed, habenular asymmetries are induced by the final position of the parapineal organ. Conservation of these mechanisms described in zebrafish across vertebrates remains an open question. During this thesis, I tried to understand the evolution of these mechanisms by studying a Chondrichthyes, the catshark Scyliorhinus canicula and cyclostomes, the lampreys Petromyzon marinus and Lampetra planeri. Their phylogenetic position and the major asymmetries in size observed between their left and right habenulae make these species good model systems to understand the origin of these mechanisms in vertebrates. My work leads to three main conclusions:(1) As in zebrafish, we have found an asymmetric expression of the components of the Nodal signalling pathway in the left dorsal diencephalon of the catshark and the lamprey. The laterality of the asymmetry is conserved between these three species, which allows us to exclude a reversed laterality in lampreys like it was proposed on the basis of arguments related to the size of habenular nuclei.(2) The Nodal signalling pathway is requied for the establishment of habenular asymmetries in the catshark and lamprey thus suggesting an ancestral role in the development of epithalamic asymmetries.(3) A detailed analysis of proliferation-differentiation patterns in the catshark habenulae during their development highlighted multiple cellular and molecular asymmetries. In particular it showed the existence of an earlier left-sided asymmetric neurogenesis.These studies provide new insights about the origin and diversification of the mechanisms controlling the establishment of vertebrates’ brain asymmetries. The study of the lamprey and the dogfish, two unconventional model systems open new perspectives for their understanding.Les vertébrés font partie des animaux à symétrie bilatérale mais celle-ci n'est pas parfaite et de nombreuses asymétries sont visibles entre les côtés gauche et droit, notamment au niveau du système nerveux. L'épithalamus s'est imposé comme le modèle de référence pour l'étude des mécanismes de latéralisation du cerveau. Cette structure dérivée du diencéphale dorsal se compose de deux noyaux bilatéraux, les habénulæ et du complexe pinéal, qui regroupe les glandes pinéale et parapinéale. Les habénulæ présentent des asymétries plus ou moins marquées chez tous les grands groupes de vertébrés. La parapinéale est également asymétrique mais elle est absente dans de nombreux taxa. Chez le poisson zèbre, espèce modèle de référence pour l'étude des mécanismes de formation des asymétries épithalamiques, une migration latéralisée de la parapinéale est nécessaire à l'élaboration des asymétries habénulaires. Les mécanismes génétiques sous-jacents ont également été en partie décryptés. La première asymétrie visible dans le diencéphale dorsal correspond à une activité de la voie de signalisation Nodal à gauche. Si cette voie Nodal est essentielle pour induire une asymétrie neurogénétique précoce, elle ne l'est pas pour la formation des asymétries épithalamiques définitives. Son rôle se restreint à biaiser la directionnalité des asymétries en influençant la migration de la parapinéale. Les asymétries habénulaires sont induites par la position finale de la parapinéale. La conservation à l'échelle des vertébrés des mécanismes décrits chez le poisson-zèbre reste une question ouverte. Au cours de ce travail de thèse, j’ai cherché à comprendre l’évolution de ces mécanismes en étudiant un chondrichtyen, la roussette Scyliorhinus canicula et des cyclostomes, les lamproies Petromyzon marinus et Lampetra planeri. Leur position phylogénétique ainsi que les asymétries majeures en taille observées entre les habénulæ gauche et droite font de ces espèces de bons modèles pour comprendre leur origine chez les vertébrés. Mes travaux conduisent à trois conclusions principales :(1) on retrouve, comme chez le poisson zèbre, une expression asymétrique de la voie Nodal dans le diencéphale dorsal gauche de la lamproie et de la roussette; la directionnalité de cette asymétrie est conservée entre les trois espèces, ce qui permet d’exclure une inversion de latéralité précédemment proposée chez la lamproie sur la base d’arguments de taille relative des habénulæ(2) La voie Nodal est essentielle à la formation des asymétries habénulaires chez la roussette et la lamproie, ce qui suggère un rôle ancestral dans l’élaboration des asymétries épithalamiques.(3) une analyse détaillée des patrons de prolifération-différenciation des habénulæ au cours du développement de la roussette met en évidence des asymétries moléculaires et cellulaires multiples ; elle démontre en particulier l’existence d’une neurogenèse asymétrique qui débute plus précocement à gauche. Ces travaux donnent un éclairage nouveau sur l’origine et la diversification des mécanismes contrôlant la formation des asymétries cérébrales chez les vertébrés. L’étude de la roussette et la lamproie, deux organismes modèles non conventionnels, ouvrent de nouvelles perspectives pour leur compréhension

Lateralization mechanisms of the epithalamus in the lamprey and the catshark

Les vertébrés font partie des animaux à symétrie bilatérale mais celle-ci n'est pas parfaite et de nombreuses asymétries sont visibles entre les côtés gauche et droit, notamment au niveau du système nerveux. L'épithalamus s'est imposé comme le modèle de référence pour l'étude des mécanismes de latéralisation du cerveau. Cette structure dérivée du diencéphale dorsal se compose de deux noyaux bilatéraux, les habénulæ et du complexe pinéal, qui regroupe les glandes pinéale et parapinéale. Les habénulæ présentent des asymétries plus ou moins marquées chez tous les grands groupes de vertébrés. La parapinéale est également asymétrique mais elle est absente dans de nombreux taxa. Chez le poisson zèbre, espèce modèle de référence pour l'étude des mécanismes de formation des asymétries épithalamiques, une migration latéralisée de la parapinéale est nécessaire à l'élaboration des asymétries habénulaires. Les mécanismes génétiques sous-jacents ont également été en partie décryptés. La première asymétrie visible dans le diencéphale dorsal correspond à une activité de la voie de signalisation Nodal à gauche. Si cette voie Nodal est essentielle pour induire une asymétrie neurogénétique précoce, elle ne l'est pas pour la formation des asymétries épithalamiques définitives. Son rôle se restreint à biaiser la directionnalité des asymétries en influençant la migration de la parapinéale. Les asymétries habénulaires sont induites par la position finale de la parapinéale. La conservation à l'échelle des vertébrés des mécanismes décrits chez le poisson-zèbre reste une question ouverte. Au cours de ce travail de thèse, j’ai cherché à comprendre l’évolution de ces mécanismes en étudiant un chondrichtyen, la roussette Scyliorhinus canicula et des cyclostomes, les lamproies Petromyzon marinus et Lampetra planeri. Leur position phylogénétique ainsi que les asymétries majeures en taille observées entre les habénulæ gauche et droite font de ces espèces de bons modèles pour comprendre leur origine chez les vertébrés. Mes travaux conduisent à trois conclusions principales :(1) on retrouve, comme chez le poisson zèbre, une expression asymétrique de la voie Nodal dans le diencéphale dorsal gauche de la lamproie et de la roussette; la directionnalité de cette asymétrie est conservée entre les trois espèces, ce qui permet d’exclure une inversion de latéralité précédemment proposée chez la lamproie sur la base d’arguments de taille relative des habénulæ(2) La voie Nodal est essentielle à la formation des asymétries habénulaires chez la roussette et la lamproie, ce qui suggère un rôle ancestral dans l’élaboration des asymétries épithalamiques.(3) une analyse détaillée des patrons de prolifération-différenciation des habénulæ au cours du développement de la roussette met en évidence des asymétries moléculaires et cellulaires multiples ; elle démontre en particulier l’existence d’une neurogenèse asymétrique qui débute plus précocement à gauche. Ces travaux donnent un éclairage nouveau sur l’origine et la diversification des mécanismes contrôlant la formation des asymétries cérébrales chez les vertébrés. L’étude de la roussette et la lamproie, deux organismes modèles non conventionnels, ouvrent de nouvelles perspectives pour leur compréhension.Vertebrates are part of the bilaterally symmetric animals but this one is not perfect and numerous asymmetries can be seen between the left and right sides, especially in the nervous system. The epithalamus has proven itself to be the model system for brain lateralization mechanisms’ studies. This structure derived from the dorsal diencephalon contains by the bilaterally paired habenular nuclei and the pineal complex, which includes the pineal gland and parapineal organ. The habenulae exhibit more or less marked left-right asymmetries among most of the major vertebrate taxa. The parapineal is also asymmetrical but it is absent in many taxa. Zebrafish is the model system for the studies of the developmental mechanisms of epithalamic asymmetries. In this species, a lateralized parapineal migration is required for the establishment of habenular asymmetries. The underlying genetic mechanisms have also been partially decrypted. The first conspicuous asymmetry in the dorsal diencephalon corresponds to a left-sided expression of components of the Nodal signalling pathway. This asymmetric Nodal signalling activity is essential to induce an early neurogenetic asymmetry but not necessary the formation of epithalamic asymmetries per se. Its role is restricted to provide a bias to the parapineal organ’s lateralized migration, and thus influence the laterality of epithalamic asymmetries. Indeed, habenular asymmetries are induced by the final position of the parapineal organ. Conservation of these mechanisms described in zebrafish across vertebrates remains an open question. During this thesis, I tried to understand the evolution of these mechanisms by studying a Chondrichthyes, the catshark Scyliorhinus canicula and cyclostomes, the lampreys Petromyzon marinus and Lampetra planeri. Their phylogenetic position and the major asymmetries in size observed between their left and right habenulae make these species good model systems to understand the origin of these mechanisms in vertebrates. My work leads to three main conclusions:(1) As in zebrafish, we have found an asymmetric expression of the components of the Nodal signalling pathway in the left dorsal diencephalon of the catshark and the lamprey. The laterality of the asymmetry is conserved between these three species, which allows us to exclude a reversed laterality in lampreys like it was proposed on the basis of arguments related to the size of habenular nuclei.(2) The Nodal signalling pathway is requied for the establishment of habenular asymmetries in the catshark and lamprey thus suggesting an ancestral role in the development of epithalamic asymmetries.(3) A detailed analysis of proliferation-differentiation patterns in the catshark habenulae during their development highlighted multiple cellular and molecular asymmetries. In particular it showed the existence of an earlier left-sided asymmetric neurogenesis.These studies provide new insights about the origin and diversification of the mechanisms controlling the establishment of vertebrates’ brain asymmetries. The study of the lamprey and the dogfish, two unconventional model systems open new perspectives for their understanding

Targeting of the intracellular redox balance by metal complexes towards anticancer therapy.

International audienceThe development of cancers is often linked to the alteration of essential redox processes, and therefore, oxidoreductases involved in such mechanisms can be considered as attractive molecular targets for the development of new therapeutic strategies. On the other hand, for more than two decades, transition metals derivatives have been leading the research on drugs as alternatives to platinum-based treatments. The success of such compounds is particularly due to their attractive redox kinetics properties, favorable oxidation states, as well as routes of action different to interactions with DNA, in which redox interactions are crucial. For instance, the activity of oxidoreductases such as PHD2 (prolyl hydroxylase domain-containing protein) which can regulate angiogenesis in tumors, LDH (lactate dehydrogenase) related to glycolysis, and enzymes, such as catalases, SOD (superoxide dismutase), TRX (thioredoxin) or GSH (glutathione) involved in controlling oxidative stress, can be altered by metal effectors. In this review, we wish to discuss recent results on how transition metal complexes have been rationally designed to impact on redox processes, in search for effective and more specific cancer treatments

Recent Advances on O-Ethoxycarbonyl and O-Acyl Protected Cyanohydrins

Ethoxycarbonyl cyanohydrins and O-acyl cyanohydrins are examples of O-protected cyanohydrins in which the protecting group presents an electrophilic center, contributing to additional reaction pathways. The first section of this review describes recent advances on the synthesis of O-ethoxycarbonyl and O-acyl protected cyanohydrins. Reactions using KCN or alkyl cyanoformates as the cyanide ion source are described, as well as organic and transition metal catalysis used in their preparation, including asymmetric cyanation. In a second part, transformations, and synthetic applications of O-ethoxycarbonyl/acyl cyanohydrins are presented. A variety of structures has been obtained starting from such protected cyanohydrins and, in particular, the synthesis of oxazoles, 1,4-diketones, 1,3-diketones, 2-vinyl-2-cyclopentenones through various methods are discussed

Evolutionary Transition in the Regulation of Vertebrate Pronephros Development: A New Role for Retinoic Acid

The anterior-posterior (AP) axis in chordates is regulated by a conserved set of genes and signaling pathways, including Hox genes and retinoic acid (RA), which play well-characterized roles in the organization of the chordate body plan. The intermediate mesoderm (IM), which gives rise to all vertebrate kidneys, is an example of a tissue that differentiates sequentially along this axis. Yet, the conservation of the spatiotemporal regulation of the IM across vertebrates remains poorly understood. In this study, we used a comparative developmental approach focusing on non-conventional model organisms, a chondrichthyan (catshark), a cyclostome (lamprey), and a cephalochordate (amphioxus), to assess the involvement of RA in the regulation of chordate and vertebrate pronephros formation. We report that the anterior expression boundary of early pronephric markers (Pax2 and Lim1), positioned at the level of somite 6 in amniotes, is conserved in the catshark and the lamprey. Furthermore, RA, driving the expression of Hox4 genes like in amniotes, regulates the anterior pronephros boundary in the catshark. We find no evidence for the involvement of this regulatory hierarchy in the AP positioning of the lamprey pronephros and the amphioxus pronephros homolog, Hatschek’s nephridium. This suggests that despite the conservation of Pax2 and Lim1 expressions in chordate pronephros homologs, the responsiveness of the IM, and hence of pronephric genes, to RA- and Hox-dependent regulation is a gnathostome novelty