PAR-Complex and Crumbs Function During Photoreceptor Morphogenesis and Retinal Degeneration

The fly photoreceptor has long been used as a model to study sensory neuron morphogenesis and retinal degeneration. In particular, elucidating how these cells are built continues to help further our understanding of the mechanisms of polarized cell morphogenesis, intracellular trafficking and the causes of human retinal pathologies. The conserved PAR complex, which in flies consists of Cdc42-PAR6-aPKC-Bazooka, and the transmembrane protein Crumbs (Crb) are key players during photoreceptor morphogenesis. While the PAR complex regulates polarity in many cell types, Crb function in polarity is relatively specific to epithelial cells. Together Cdc42-PAR6-aPKC-Bazooka and Crb orchestrate the differentiation of the photoreceptor apical membrane (AM) and zonula adherens (ZA), thus allowing these cells to assemble into a neuro-epithelial lattice. In addition to its function in epithelial polarity, Crb has also been shown to protect fly photoreceptors from light-induced degeneration, a process linked to Rhodopsin expression and trafficking. Remarkably, mutations in the human Crumbs1 (CRB1) gene lead to retinal degeneration, making the fly photoreceptor a powerful disease model system

Orthodenticle Is Required for the Expression of Principal Recognition Molecules That Control Axon Targeting in the Drosophila Retina

Parallel processing of neuronal inputs relies on assembling neural circuits into distinct synaptic-columns and layers. This is orchestrated by matching recognition molecules between afferent growth cones and target areas. Controlling the expression of these molecules during development is crucial but not well understood. The developing Drosophila visual system is a powerful genetic model for addressing this question. In this model system, the achromatic R1-6 photoreceptors project their axons in the lamina while the R7 and R8 photoreceptors, which are involved in colour detection, project their axons to two distinct synaptic-layers in the medulla. Here we show that the conserved homeodomain transcription factor Orthodenticle (Otd), which in the eye is a main regulator of rhodopsin expression, is also required for R1-6 photoreceptor synaptic-column specific innervation of the lamina. Our data indicate that otd function in these photoreceptors is largely mediated by the recognition molecules flamingo (fmi) and golden goal (gogo). In addition, we find that otd regulates synaptic-layer targeting of R8. We demonstrate that during this process, otd and the R8-specific transcription factor senseless/Gfi1 (sens) function as independent transcriptional inputs that are required for the expression of fmi, gogo and the adhesion molecule capricious (caps), which govern R8 synaptic-layer targeting. Our work therefore demonstrates that otd is a main component of the gene regulatory network that regulates synaptic-column and layer targeting in the fly visual system

Identification of Burgers vectors along <111> in In-doped GaAs, by X-ray transmission topography andimage simulation.

International audienceLong dislocations with Burgers vectors along are unusual in f.c.c. lattices. X-ray topographs have beenobtained of as-grown GaAs crystals doped with 1020 atoms cm -3 of In, where the usual extinction criterion g.b = 0leads to this type of defect. However, for several g satisfying the condition g.b = 0 with b = a [111], the images of thesedislocations were still clearly visible. Comparison between experimental and computer-simulated X-ray topographicsections of these defects confirms the existence of Burgers vectors along

Roles of local He concentration and Si sample orientation on cavity growth in amorphous silicon

International audience(111)- and (100)-oriented Si samples are implanted with Si+ ions at 1 MeV to a dose of 1×1016 cm-2 and with 5×1016 He+ cm-2 at 10keV or 50 keV and eventually annealed in the 800 °C-1000 °C temperature range. Sample characterization is carried out by cross section transmission electron microscopy, positron annihilation spectroscopy, and nuclear reaction analysis. In addition to the formation of He bubbles at the projected range of He, bubbles are observed after solid phase epitaxial growth (SPEG) of the embedded amorphous Si layer. The He threshold concentration required to get thermally stable bubbles in amorphized Si is between one and four orders of magnitude lower than in c-Si. Since bubble formation and growth take place in the a-Si phase, the interaction with SPEG during annealing is studied by considering (100) and (111) Si. Both the SPEG velocity and the resulting defects play a role on bubble spatial distribution and size, resulting in bigger bubbles in (111) Si with respect to (100) Si

Lire Deborah Hay

Paris 8 Danse in Translation [On line] www.danse.univ-paris8.frTranslated by Jacqueline Cousineau from the slightly revised version (with some updates from Deborah Hay) of "Lire Deborah Hay", postface to the French translation of Deborah Hay's book My Body, the Buddhist: Mon corps, ce bouddhiste, extended edition, co-translation: Laurent Pichaud and Lucie Perineau, Dijon/Lausanne, Les presses du réel/La Manufacture, coll. Nouvelles scènes, 2017. «Deborah Hay writes. Since in the field of French choreography one can “write” [écrire] dance composition, we specify here that Deborah Hay “writes” both choreography and texts. Deborah Hay is prolific. She has published four books (and there is an additional unpublished manuscript in her archives), has almost twenty articles to her name, and has elaborated numerous scores for her pieces in textual form […]». This text attempts to unfold the question of language as a tool within Deborah Hay’s choreographic practice

Shaping an optical dome: The size and shape of the insect compound eye

The insect compound eye is the most abundant eye architecture on earth. It comes in a wide variety of shapes and sizes, which are exquisitely adapted to specific ecosystems. Here, we explore the organisational principles and pathways, from molecular to tissular, that underpin the building of this organ and highlight why it is an excellent model system to investigate the relationship between genes and tissue form. The compound eye offers wide fields of view, high sensitivity in motion detection and infinite depth of field. It is made of an array of visual units called ommatidia, which are precisely tiled in 3D to shape the retinal tissue as a dome-like structure. The eye starts off as a 2D epithelium, and it acquires its 3D organisation as ommatidia get into shape. Each ommatidium is made of a complement of retinal cells, including light-detecting photoreceptors and lens-secreting cells. The lens cells generate the typical hexagonal facet lens that lies atop the photoreceptors so that the eye surface consists of a quasi-crystalline array of these hexagonal facet-lenses. This array is curved to various degree, depending on the size and shape of the eye, and on the region of the retina. This curvature sets the resolution and visual field of the eye and is determined by i) the number and size of the facet lens – large ommatidial lenses can be used to generate flat, higher resolution areas, while smaller facets allow for stronger curvature of the eye, and ii) precise control of the inter facet-lens angle, which determines the optical axis of the each ommatidium. In this review we discuss how combinatorial variation in eye primordium shape, ommatidial number, facet lens size and inter facet-lens angle underpins the wide variety of insect eye shapes, and we explore what is known about the mechanisms that might control these parameters

Some assembly required: building the fly eye for motion detection and colour discrimination

Among the many eyes that have evolved on Earth, the insect compound eye is the most abundant. Its crystal-like lattice structure is a feat of engineering that has evolved over millions of years, and is exquisitely adapted to detect moving objects and discriminate colours. This enables many behaviours, including foraging for food, finding a mate and avoiding predators. Our understanding of how the compound eye is built and works has been greatly expanded by studying the humble fruit fly, Drosophila melanogaster. The simple outward appearance of the fly eye belies a host of sophisticated features. Through the precise arrangement of photosensitive cells in the retina and their connections to the brain, the fly eye packs an astonishing amount of hardware into a very tiny volume. In this primer, we introduce the molecular pathways that underpin the building and inner workings of the fly eye

Adaptation génétique et changement climatique : une expérience de plantations de chêne-liège dans les Maures

Bernard Pichaud est propriétaire forestier dans le Var, il est adhérent de l’Association syndicale libre de la suberaie varoise. Il nous apporte son témoignage sur une expérimentation de plantations menée avec plusieurs provenances de chêne-liège et montre comment un propriétaire peut ainsi contribuer à une meilleure connaissance sur l’adaptation des arbres au changement climatique

Relation entre phénotype et génotype mitochondrial : mesure du métabolisme mitochondrial en fonction de la température chez deux haplotypes de Drosophila simulans

Les mitochondries possèdent leur propre matériel génétique (ADN mitochondrial ou ADNmt) qui code pour des peptides interagissant avec ceux codés par l'ADN nucléaire pour former les complexes du système de transport des électrons (ETS) ainsi que l'ATP synthase qui participent au processus de phosphorylation oxydative (OXPHOS). Il a été suggéré que la sélection sur l'ADNmt peut mener à des haplotypes adaptés à différents environnements. Dans cette thèse, Drosophila simulans a été choisie pour examiner le potentiel adaptatif des divergences de l'ADN mitochondrial. Cette espèce présente trois haplogroupes (siII, siII et siIII) subdivisés avec approximativement 3% de divergences inter-haplogroupes mais n'ayant aucune subdivision nucléaire observée au niveau des loci codés par l'ADN nucléaire. Le principal objectif de ce travail était d'examiner le rôle de l'ADN mitochondrial sur l'établissement de caractères phénotypiques tel que le métabolisme mitochondrial des haplotypes siII et silll de Drosophila simulans et de déterminer le potentiel adaptatif des divergences du génome mitochondrial sur les propriétés fonctionnelles des mitochondries en fonction des variations de température. Le premier objectif était d'identifier les différences au niveau des performances mitochondriales et de la thermosensibilité associées à la divergence des mitotypes sill et silll de Drosophila simulans en évaluant l'activité des différentes enzymes de l'ETS à quatre températures différentes grâce à une approche in vitro (isolations mitochondriales). Nous avons montré que les différentes enzymes de l'ETS ont différentes thermosensibilités, ce qui peut mener à une distribution différente du contrôle de la respiration par les composantes de l'ETS et par les déshydrogénases en amont de l'ETS à différentes températures. Par exemple, nous avons détecté un excès apparent au niveau du complexe IV d'environ 604% et 613% pour sill et silll respectivement, mais seulement à basse température (12°C), ce qui nous a amené à penser que cela était dû à un dysfonctionnement des déshydrogénases à basse température. Le second volet de cette thèse reprenait les mêmes objectifs que le premier. Cependant, pour ce chapitre, une nouvelle méthode (approche in situ) a été développée sur des fibres musculaires perméabilisées en utilisant un protocole en respirométrie à haute résolution. Nous avons montré, et ce pour la première fois, que l'approche in situ est très appropriée pour évaluer les performances mitochondriales chez des invertébrés et serait même plus pertinente que l'approche in vitro. De plus hautes capacités catalytiques des complexes de l'ETS ont été détectées à 24°C pour le mitotype siII. Cette capacité catalytique plus élevée pour siII peut lui donner un avantage en termes d'intensité du métabolisme aérobie, d'endurance, ou des deux si l'intensité de l'exercice qui peut être effectué au niveau aérobique est dictée par la capacité aérobique du tissu. De plus, les résultats obtenus sur la thermosensibilité ont montré que même si la température affecte les capacités catalytiques des différentes enzymes de l'ETS, les mitotypes sill et silll ont une grande tolérance aux variations de température. Le troisième volet de cette thèse se concentrait sur l'évaluation du potentiel adaptatif des divergences de l'ADNmt aux quatre températures déjà testées dans les chapitres précédents en utilisant des introgressions. Les performances mitochondriales des haplotypes ainsi créés (sill-introgressé et siIII-contrôle) ont ensuite été mesurée avec l'approche in situ. Nos résultats ont montré que les capacités catalytiques des différentes enzymes de l'ETS dans les organismes introgressés (sill-introgressé) étaient quasiment similaires à celles détectées dans le mitotype sill, du moins à 24°C. De plus, les différences entre sill et silll détectées à 24°C dans le second volet se retrouvent aussi entre sill-introgressé et siIII-contrôle, dénotant que les propriétés fonctionnelles des mitochondries sont principalement conférées par l'ADN mitochondrial. Cependant, l'impact de la température divergeait entre sill-introgressé et silIl-contrôle, principalement au niveau de l'excès apparent de COX à 12°C (excès d'environ 193% pour silIl-contrôle, mais pas d'excès pour sill-introgressé) et au niveau des coefficients de température (Q10) mesurés entre 12 et 18°C. Il est donc possible que les interactions entre ADN nucléaire et ADN mitochondrial soient nécessaires pour permettre aux organismes de faire face aux variations de température. C'est, selon nos connaissances, l'une des premières démonstrations claires du potentiel adaptatif de différents ADNmt sur les propriétés fonctionnelles des mitochondries. \ud ______________________________________________________________________________ \ud MOTS-CLÉS DE L’AUTEUR : respiration mitochondriale, système de transport des électrons, interactions mitonucléaires, ADNmt, température

Protein Complexes Structure Prediction by Combination of Binary Interactions Derived by Homology

Proteins are key participants in most cellular processes. However, they rarely function in isolation and usually they form multimolecular assemblies. The structural description of such an assembly provides critical details about the protein function. As the determination of such structures remains a great experimental challenge, only a small fraction of known protein complexes are currently available. This has created a need for alternative, predictive methods that can bridge the gap between complexes that are known to exist in the cell, and those for which structural information is available. This thesis presents a program to predict the structure of protein assemblies from the structures of their subunits. The method combines predictions of pairwise arrangements derived from homologous interaction templates to consider all possible assemblies. The problem of finding the best arrangement is modeled as a graph to allow fast graph traversing algorithms to be exploited. Individual predictions are evaluated by sequence identity or structural similarity between the subunits and the templates or by evaluation of the interfaces in the predictions. The method is benchmarked on three-domain assemblies derived from known structures and on nine complete structures that could possibly be re-assembled in a non-trivial fashion from previously determined structures. The method was also applied to complexes determined from high-throughput complex determination procedures, including RNA polymerase I and the Cdc48/Ufd1/Npl4 complex from the ubiquitin-proteasome pathway. The benchmark demonstrates that the approach can often work on small assemblies. For larger complexes, certain details can be predicted, and occassionaly large parts of the complex, though currently a lack of suitable templates limits applicability. Nevertheless, the method can now be applied to any protein complex and should be particularly useful when structures are difficult to obtain by experiments, and where additional information, such as pairwise interactions or stoichiometry, is available