Дисертації з теми "Larves de poisson zèbre"
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Poirier, Jasmine. "Segmentation de neurones pour imagerie calcique du poisson zèbre : des méthodes classiques à l'apprentissage profond." Master's thesis, Université Laval, 2019. http://hdl.handle.net/20.500.11794/36452.
The experimental study of the resilience of a complex network lies on our capacity to reproduceits structural and functional organization. Having chosen the neuronal network of the larvalzebrafish as our animal model for its transparency, we can use techniques such as light-sheet microscopy combined with calcium imaging to image its whole brain more than twice every second, with a cellular spatial resolution. Having both those spatial and temporal resolutions, we have to process and segment a great quantity of data, which can’t be done manually. Wethus have to resort to numerical techniques to segment the neurons and extract their activity. Three segmentation techniques have been compared : adaptive threshold (AT), random deci-sion forests (ML), and a pretrained deep convolutional neural network. While the adaptive threshold technique allow rapid identification and with almost no error of the more active neurons, it generates many more false negatives than the two other methods. On the contrary, the deep convolutional neural network method identify more neurons, but generates more false positives which can be filtered later in the proces. Using the F1 score as our comparison metrics, the neural network (F1= 59,2%) out performs the adaptive threshold (F1= 25,4%) and random decision forests (F1= 48,8%). Even though the performances seem lower compared to results generally shown for deep neural network, we are competitive with the best technique known to this day for neurons segmentation, which is 3dCNN (F1= 65.9%), an algorithm presented in the neurofinder challenge.
Jouary, Adrien. "Comportement moteur induit visuellement et spontané chez la larve du poisson zèbre." Thesis, Paris 6, 2015. http://www.theses.fr/2015PA066605/document.
Behavior is often conceived as resulting from a stimulus-response association. Under this paradigm, understanding the nervous system is reduced to finding the relation between a sensory input and a motor output. Yet, in naturally behaving animals, motor actions influence sensory perceptions just as much as the other way around. Animals are continuously relying on sensory feedback to adjust motor commands. On the other hand, behavior is not only induced by the sensory environment, but can be generated by the brain's rich internal dynamics. My goal is to understand the sensory-motor dialogue by monitoring large brain regions, yet, with a single-neuron resolution. To tackle this question, I have used zebrafish larva to study visually induced and internally driven motor behaviors. Zebrafish larvae have a small and transparent body. These features enable using large-scale optical methods, such as selective plane illumination microscopy (SPIM), to record brain dynamics. In order to study goal-driven navigation in conditions compatible with imaging, I developed a visual virtual reality system for zebrafish larva. The visual feedback can be chosen to be similar to what the animal experiences in natural conditions. Alternatively, alteration of the visual feedback can be used to study how the brain adapts to perturbations. For this purpose, I first generated a library of free-swimming behaviors from which I learned the relationship between the trajectory of the larva and the shape of its tail. I then use this technique to infer the intended displacements of head-fixed larvae. The visual environment was updated accordingly. In the virtual environment, larvae were capable of maintaining the proper speed and orientation in the presence of whole-field motion and produced fine changes in orientation and position required to capture virtual preys. I demonstrate the sensitivity of larvae to visual feedback by updating the visual world only after the discrete swimming episodes. This feedback perturbation induced a decay in the performance of prey capture behavior, suggesting that larva rely on real-time visual feedback during swimming. Behavior can also be induced by the internal dynamics of the brain. In the absence of salient sensory cues, zebrafish larva spontaneously produces stereotypical tail movements, similar to those produced during goal-driven navigation. After having developed a new method to classify tail movements, I analyzed the sequence of spontaneously generated tail movements. The latter switched between period of quasi-rhythmic activity and long episodes of rest. Moreover, consecutive movements were more similar when executed at short time intervals (~10s). In order to study the mechanisms responsible for the spontaneous decisions to move, I coupled SPIM to tail movement analysis. Using dimensionality reduction, I identified clusters of neurons predicting the direction of spontaneous turn movements but not their timings. This Preliminary result suggests that distinct pathways could be responsible for the timing (when) and the selection (what) of spontaneous actions. Together, the results shed light on the role of feedback and internal dynamics in shaping behaviors and open the avenue for investigating complex sensorimotor process in simple systems
Yedji, Rodrigue. "Perturbateurs endocriniens de type phtalate et poisson zèbre Danio rerio : approche chémoprotéomique pour l'identification des cibles et recherche de signatures d'exposition." Electronic Thesis or Diss., Université de Lorraine, 2022. http://www.theses.fr/2022LORR0106.
Phthalate esters are a family of synthetic compounds widely used as plasticisers. They are used in a number of plastic products such as packaging, toys, cosmetics, plastic roofing system and furniture decoration materials. Phthalates are not covalently bonded to the polymer matrix and are therefore easily released into the environment, resulting in animal and human exposure. In the absence of non-toxic substitutes, phthalate compounds are still widely used in industry, despite the classification of some of them by the European Chemicals Agency (ECHA) as suspected toxic substances and as endocrine disruptors. In addition, they are carcinogenic and teratogenic. The deleterious effect of phthalate esters on organisms is established, but the multiple nature of the effects observed shows that the mechanisms of action of phthalates are only partially elucidated. We used two targeted proteomics approaches to shed light on the mechanisms of action of phthalate esters. Dibutyl phthalate (DBP) was used as a model phthalate and zebrafish (D. rerio) as a model organism. Using the first targeted proteomics approach, affinity-based protein profiling (AfBPP), the functional disruption of proteins by DBP with photoaffinity probes from aryl azide synthesis was demonstrated. Optimisation of the binding conditions for diazirine probes (Diazirine 2) should provide us with a probe that can be used to identify DBP protein targets in the zebrafish proteome. The second approach, activity-based protein profiling (ABPP), used a reactive probe specific for serine hydrolases (SHs) to map active SHs in the zebrafish proteome for the first time. The identification of deregulated SHs in the presence of DBP in zebrafish larvae was also reported in this study. Overall, our results indicate that targeted proteomics approaches such as ABPP or AfBPP can be an asset for understanding xenobiotic-related mechanisms of action in ecotoxicology
Olive, Raphaël. "Perception des écoulements et des vibrations chez la larve de poisson-zèbre : étude comportementale et imagerie." Thesis, Paris 6, 2015. http://www.theses.fr/2015PA066468/document.
The Zebrafish larva is a model for the study of vertebrate central nervous system. Mutants have been developped which express calcium reporter (GCaMP) in their neurons. These mutants are used in functional imaging experiments in which the activity of almost all the neurons is simultaneously recorded. The first chapter of this thesis is devoted to the conception of a behavioral experiment designed to record and analyse the swim movements of zebrafish larvae submitted to a succion flow. The contributions of lateral line (specific fish organ responsible for the perception of hydrodynamic stimulations) and visual system have been separated in order to describe the interactions between those two modalities and their respective effects on larvae reactions to aspiration, analysed through their swim patterns. This experiment was thought to prepare a study of neuronal responses to aspiration, thanks to the laser sheet microscopy setup developped in the laboratory since four years. The aim was to use calcium imaging to work on cross-modal experiment, by the dynamic observation of neural networks dedicated to the two sensory modalities when stimulated simultaneously or separatly. Facing difficulties to record lateral line response using calcium imaging, which are not been recorded yet, functional imaging experiments have adressed zebrafish larvae auditory system instead of hydrodynamic perception. The second part of this thesis describes protocols, analysis and results from these experiments. The results are still at an exploratoty stage but draw a scheme of neural networks involved in vibrations perception in zebrafish larvae : they present recordings of a huge part of central nervous system and the activity evoked by auditory stimulations
Perrichon, Prescilla. "Développement de tests embryonnaires prédictifs d’effets toxiques précoces et tardifs pour des molécules hydrophobes." Thesis, La Rochelle, 2014. http://www.theses.fr/2014LAROS040/document.
PAHs are ubiquitous widespread contaminants which emissions are overgrowing with increasing anthropogenic activities. These semi-persistent chemicals are threatening organisms in the environment. Ecosystems health and resilience are essential to life and societal functioning. Impact assessment of these chemicals is a real requirement for society thereby establishing the european legislative (DCE, Water Framework Directive) and regulations (REACH, Registration, Evaluation, Authorisation and Restriction of Chemicals) for better (eco)toxicological risk management. In this context, many bioassays have been developed to assess environmental quality, the toxicity of chemicals (including mixture) on organisms and its underlying mechanisms. This study aimed to identify (eco)toxicological risks in the context of fish embryo-larval assay, using a relevant and well-known model : the zebrafish Danio rerio. Two complementary approaches (chemical and biological) were used to assess transfer, fate and toxicity of PAHs. Induced-responses were evaluated at different levels of biological organization, from molecular (oxidative stress, DNA damage, EROD) to physiological (cardiac activity), behavioral (PhotoMotor Response) and morphological levels. Among the three exposure routes tested, the sediment contact exposure was not suitable for PAHs toxicity assessment. In contrast, exposures to water-accommodated fractions (WAF) of petroleum products represented a more reproducible, sensitive and integrative approach for testing multiscale toxic effects. Following these experiments, the observation scope of induced effects should be broadened beyond the standard duration recommended by the Organization for Economic Cooperation and Development in order not to underestimate the acute effect of the tested-compounds. Furthermore, our multigenerational study showed physiological and behavioral disturbances on the first generation of offspring providing from parents exposed to contaminated-food with three aromatic extracts pyrolytic and petrogenic origin (heavy and light). Although the contamination transfer of PAHs has not been revealed, the observed alterations (probably due to a transfer through genetic and epigenetic modifications) in the early stages of zebrafish could have adverse effects on survival and recruitment populations. Multigenerational studies prove to be an integrated approach for the toxicity assessment of chemicals and strengthen the predictive effects. These ecotoxicological studies should be widely undertaken to evaluate the potential for exposed-population to maintain in the future time
Terras, Fériel. "Développement d’une méthode de mesure et d’analyse du transport intraneuronal dans le cerveau de larve de poissons-zèbre par suivi de nanocristaux non-linéaires en microscopie de second-harmonique : application à l’étude d’anomalies de transport chez des poissons portant une mutation retrouvée dans des neuropathies humaines." Thesis, université Paris-Saclay, 2020. http://www.theses.fr/2020UPASP050.
Molecular transport in neurons plays an essential role in their development and the maintenance of their functions, due in particular to their long branches. The consequences of axonal transport abnormalities have long been associated with Alzheimer's disease, such as the swelling of axons caused by the accumulation of transported organelles. However, there are few tools allowing the detailed long-term study of this transport in culture and even less in vivo.The team in which this work was conducted has developed a method for measuring intraneuronal transport in mouse cultured neurons based on the tracking of endosomes having spontaneously internalized fluorescent nanodiamonds. This technique was able to detect genetic risk factors of neuropsychiatric diseases, proving its high sensitivity.The objective of my thesis was to extend this measurement method to the neuronal circuit of the zebrafish larvae’s brain. For this purpose, I have used nanocrystals (NCs) with non-linear optical response, which can be excited in a tissue transparency window at a wavelength ≈1 µm, and generate a second harmonic signal. We have used the multiphoton microscope of the Emerg'In facility (INRAE, Jouy-en-Josas), which is installed next to a fish farming and has resonant galvanometric scanners and hybrid detectors, which allowed us to maintain a frame rate of 20 fps despite the need to scan the laser beam, unlike in culture studies conducted in wide field.We have developed a new measurement protocol, from the injection of the NC to the extraction of transport parameters from the videos data. To do this, I have optimized and automated the data analysis by developing two programs written in Python: one that automatically reconstructs the trajectories of the NCs as faithfully as possible and the other that segments the trajectories into motion and pause phases in order to extract transport parameters.I have applied these new tools to study, in a transgenic zebrafish model, the functional impact of a mutation present in neuropathies including hereditary spastic paraplegia and peripheral Charcot-Marie-Tooth disease. In patients suffering from one of these diseases, several mutations have been identified in the KIF5A gene coding for the heavy chain of the kinesin 1 molecular motor which ensures anterograde movements (from the cell body to the periphery). We have measured endosome transport in axons of neurons in the brain of transgenic zebrafish larvae bearing a mutation on kif5a, and we observed subtle changes in this transport. More than 500 endosome trajectories (acquired at a depth of ≈100 µm below the surface of the head) were analyzed from 40 larvae.As a control, we also studied endosomal transport in mutants deprived of dynein motors, the only ones to ensure retrograde transport, and observed that bi-directional transport was totally stopped in the mutants.This methodology can be used to screen for functional abnormalities resulting from genetic factors of neurological or neurodegenerative disorders
Bertrand, Christelle. "L' acétylcholinestérase du poisson zèbre, "Danio rerio"." Montpellier 2, 2000. http://www.theses.fr/2000MON20188.
Pruvot, Benoist. "Développement de modèles de cancer par xénotransplantation chez le poisson zèbre." Dijon, 2009. http://www.theses.fr/2009DIJOS065.
New cancer model development allowed new approach to understand important mechanisms involved in tumour progression and to develop new treatments. Due to its advantages, such as embryos transparency, zebrafish (Danio rerio) is more and more used in biological experimentation, and recently in cancer research. By transplanting mammalian tumour cells in zebrafish larvae, several models have been obtained. Such models allowed cancer cells development and response to several treatment , considering cancer cells and tumour interactions. We developed leukaemia models based on human cell lines transplantations. We also validated our models in pharmacological assays. Another model was obtain by injecting human leukaemia primary cells extract from patient blood and allowed us to define leukaemia cell fraction that can colonize zebrafish larvae. Nitric oxide (NO) involvement during tumour progression is ambivalent and still discussed. We developed a new in vivo model to analyse nitric oxide production and roles in tumour environment by using diaminofluorophores in a rat glioma xenograft model. By following tumour cell in vivo, we are able to study proteins that may be involved in tumour progression. We characterized a protein family called nonaspanins
Campario, Hugo. "Rôle du facteur de transcription hsf1 dans l’érythropoïèse du poisson zèbre." Thesis, Bourgogne Franche-Comté, 2020. http://www.theses.fr/2020UBFCI004.
Heat shock proteins (HSPs) are reported to play an important role in erythropoiesis. The expression of HSP genes is mainly controlled by Heat shock factor 1 (HSF1), a highly conserved transcription factor. So far, a detailed understanding of the function of HSF1 in erythropoiesis remains uncharacterized. This study has employed zebrafish as a relevant model to investigate the role of Hsf1 during embryonic erythropoiesis. We established hsf1-disrupted zebrafish lines using the CRISPR/Cas9 technology and performed phenotypic analyses throughout embryogenesis. We found that Hsf1 deficient embryos had a decreased number of primitive erythrocytes, while erythrocyte number in adults was unchanged. In Hsf1 deficient embryos, expression of embryonic a and b-globin genes was reduced as well as gata1 expression. In addition, the morphology of erythrocytes suggested an inhibition of erythrocyte maturation. On the other hand, no significant changes were observed in myeloid cells.Altogether our results support a key role for Hsf1 in erythrocyte maturation in vivo
Heuzé, Aurélie. "Processus régénératifs du cerveau moyen dorsal chez le poisson zèbre adulte." Thesis, Université Paris-Saclay (ComUE), 2017. http://www.theses.fr/2017SACLS508/document.
Unlike mammals, the adult teleost brain exhibits widespread neurogenic activity and can regenerate after injury. The adult zebrafish has the capacity to regenerate neurons from constitutive or latent progenitors. During my PhD, I studied the neuronal regeneration in the zebrafish dorsal midbrain (optic tectum, OT). At adult stage, neuroepithelial-like progenitors at the OT periphery contribute to neuronal and glial lineages during homeostasis.I identified a putative enhancer of meis2a, which allowed me to trace the progeny of neuroepithelial-like progenitors. In a non-regenerative context I showed that enhancer-targeted progenitors were at the origin of the whole structure during development and of its continued neurogenesis during post-embryonic growth.Following lesion, OT displayed reactive neurogenesis, at larval and adult stages, nevertheless its topographical structure remained altered. In adults, I showed that both constitutive neuroepithelial-like progenitors and latent ependymoglial progenitors were activated in a regenerative context
Cormier, Bettie. "Toxicité des microplastiques chez les poissons, au-delà de simple vecteurs de polluants?" Thesis, Bordeaux, 2020. http://www.theses.fr/2020BORD0036.
During the last decades, plastics have gained interest from media, public and scientists. Plastics have been categorized as emerging pollutants particularly in the marine environment due to their ubiquity and persistence, particularly microplastics (< 5 mm, MPs). Numerous studies reported the occurrence of MPs in the marine environment (surface water, sediments). However, neither there exist standardized nor harmonized methods to evaluate their potential toxicity and their role as vector of hazardous chemicals into organism. This thesis had three main objectives, (1) the investigation of sorption of chemicals models on MPs, (2) the study of the toxic potential of these sorbed chemicals on zebrafish and (3) the characterization and the study of the toxicity of environmental MPs. The first part of the thesis aimed at the investigation of the sorption processes of three model pollutants - perfluorooctanesulfonic acid (PFOS), benzo[a]pyrene (BaP) and oxybenzone (BP3) - on pristine MPs using different sizes and polymer types. The second part studied the vectorization of the three compounds sorbed on MPs toward zebrafish (Danio rerio) embryos, juveniles and adults through direct or trophic exposures, and their toxicities. The third part investigated the toxicity of environmental samples of MPs from two sandy beaches (Guadeloupe Island, France), using the same procedure as above, as well as the characterization of additives and adsorbed chemicals through a non-target approach. Study of pollutants sorption demonstrated differences in pattern (e.g. kinetics, sorption efficiency), depending on size particles and chemical used. Potential adverse effects of MPs associated with chemicals were investigated in zebrafish embryos using OECD 236 guideline and by using a chronic exposure from larvae or juveniles up to 5-months old adults through trophic exposure. Molecular and individual toxicological endpoints were monitored during exposure. Main findings were the low acute toxicity of MPs on early life stages (embryos and larvae) exposed to particles, organic extracts or leachates. Nevertheless, the ingestion of MPs by juveniles and adults led to a significant long-term toxicity for all tested MPs albeit with different intensity according to the spiked chemicals and to the environmental samples. Deleterious effects included growth alteration, reprotoxicity, behavioral disturbances as well as hyperactivity observed in offspring of exposed fish. In conclusion, the present work revealed that (1) MPs may play a role in the vectorization of pollutants and (2) may induce significant sublethal effects in juveniles of zebrafish chronically fed with pristine MPs or MPs artificially spiked with pollutants. Same conclusions were observed (3) with environmental MPs
Yousfi, Nadhir. "Rôle du monoxyde d'azote dans le développement tumoral chez le poisson zèbre. Rôle de HSF1 dans le développement chez le poisson zèbre en absence de choc thermique." Thesis, Dijon, 2014. http://www.theses.fr/2014DIJOS085/document.
The use of animal models has led to the discovery of important mechanisms of biology development in general, and tumor development in particular, to establish and develop new treatments. The Zebrafish (Danio rerio) is increasingly used nowadays as part of this research because of its many advantages such as the transparency of the larvae, and the high homology with human. Several approaches have been developed in this fish, as the gene-knockdown in order to identify the role of a protein in the development, or the tumor transplantation of mammalian cells to study anti-tumor treatments response.It is in one of these two contexts that we studied the role of nitric oxide in tumor development in zebrafish. We used a fluorescent probe and were able to detect in vivo the production of nitric oxide associated with xenograft tumor cells. The use of an NO scanvenger, the cPTIO resulted in a loss of tumor cells and a decrease in the expression of an angiogenic factor VEGF, showing a potential in the use of cPTIO as antitumor molecule.We used also the transitory invalidation of hsf1 gene, in order to explore a potential new role in the development and red blood cells differentiation in zebrafish as an experimental model, in non heat-shocked conditions. We found that HSF1 was important for the differentiation of erythrocytes, and its inactivation also reflected defects in development
Fontagné, Stéphanie. "Utilisation des acides gras à chaîne moyenne par les larves de poisson." Bordeaux 1, 2000. http://www.theses.fr/2000BOR10543.
Rondy-Turcotte, Jean-Christophe. "Détection des potentiels d'action par la fluorescence calcique chez le poisson zèbre." Master's thesis, Université Laval, 2020. http://hdl.handle.net/20.500.11794/66419.
Quillien, Aurélie. "Spécification des sous-types neuronaux dans la glande pinéale du poisson zèbre." Toulouse 3, 2010. http://www.theses.fr/2010TOU30211.
Cell fate diversification is a prerequisite for the formation of a functional vertebrate nervous system. Given the high level of complexity of the vertebrate nervous system, understanding the bases of neuronal subtype diversification, as well as the mechanisms by which future neurons simultaneously process information from multiple pathways to establish their identity remain challenging issues. The zebrafish pineal gland offers a simple system to address questions concerning the integration of signaling pathways during neural specification as it contains only two types of neurons - photoreceptors and projection neurons. The aim of my thesis was to characterize which mechanisms are implicated during the specification of these neurons. We have recently shown that the Notch pathway is involved in the specification of these neuronal subtypes. However, while Notch appears sufficient to inhibit the projection neuron specification program it is not able to induce a photoreceptor fate, leading us to postulate the existence of a photoreceptor-inducing signal (Cau et al. , 2008). To search for this signal we performed a small unbiased screen, thus the activity of seven signalling pathways knonw to be involved in neuronal subtype specification (Wnt, BMP, Retinoic Acid, FGF, EGF, Shh and TGFbeta) was impaired. The BMP, Wnt and EGF signaling pathway emerged as interesting regulators of neuronal specification in the pineal gland. Indeed, the BMP signaling pathway promotes the photoreceptor fate, and is moreover required as a competence factor for Notch to inhibit the PN fate. Furthermore, my preliminary results suggest that the Wnt signaling pathway could function as a projection neuron-inducing signal and that EGF signaling acts upstream of Notch to inhibit a projection neuron program. Finally, specification of epiphysial neurons required at least four signaling pathways whose interactions probably enable a fine-grained regulation of the number of neurons and their identity
Aleksejeva, Elina. "Défenses innées antivirales du poisson zèbre : de la signalisation aux cellules specialisées." Thesis, Université Paris-Saclay (ComUE), 2016. http://www.theses.fr/2016SACLV016/document.
This thesis is based on the studies of two aspects of innate immunity in zebrafish: 1) proteins involved in the regulation of type I interferon (Ifn) and 2) specialized myeloid cells that patrol neuromasts – mechano-sensory organs embed in the skin that could be pathogen entry sites. In this thesis two different proteins are described for the capability to enhance Ifn production. In one part, two zebrafish orthologues of mammalian transcription factor PLZF (Promyelocytic leukemia zinc finger) are shown to augment type I Ifn and ISG in response to double-stranded RNA viruses. PLZF is a BTB/POZ transcription factor that was recently shown to induce a subset of ISG, in human and mouse. Thus, zebrafish Plzf proteins can operate at multiple steps in the Ifn system. Furthermore, their activity was not dependent on the presence of BTB-domain implying that the underlying mechanism is different from the usual mode of action of BTB/POZ transcription factors. In the second part, fish-specific TRIM ubiquitin ligase - Ftr83 (Fish novel tripartite motif protein 83), mounted a strong anti-viral protection through the upregulation of Ifn. Interestingly a strong correlation between the expression of Ftr83 and Ifn was seen in the gills suggesting that Ftr83 might maintain a low basal level of Ifn signalling in organs constantly exposed to pathogens. In the second part, a GFP reporter transgenic line called medaktin:EGFP has been characterized. It marks leukocytes in the skin surrounding neuromasts. Deep sequencing revealed that these cells express several macrophage and dendritic cell markers, including genes involved in autophagy, microbicidial functions and antigen presentation, thus highlighting them as possible sentinel cells
Bouzaffour, Mohamed. "Voies de signalisation impliquées dans la régénération chez le poisson zèbre adulte." Paris 7, 2010. http://www.theses.fr/2010PA077065.
Zebrafish present the ability to faithfully regenerate organs and fins after an injury by a process called epimorphic regeneration. During caudal fin regeneration, the amputation triggers the recruitment of progenitor cells towards the lesion to form a mass of undifferentiated cells, the blastema, which gives rise to the lost part of the fin. Its formation and its fate involve a coordinated regulation of cell proliferation, morphogenesis and patterning. Previous studies highlight the crucial role of signalling pathways like Fgf, Wnt, Sdfl, Shh or Bmp for the blastemal cell formation and proliferation. During this study, we show that the chemokine Sdfl a has a dual role throughout the first steps of caudal fin regeneration. First, it relays the Fgf Signalling for the formation of the blastema and then it exerts, with the Wnt pathway, a negative feedback on the Fgf pathway through the inhibition of fgfZOa expression. This negative feedback permits the regulation of the blastema size in order to regenerate a fin with the same length that the original one. Another aspect of this work was the identification of novel signalling pathways involved in blastema formation. We demonstrate that thyroid hormones signalling and apoptosis are involved in this process. The amputation triggers the expression of Deiodinase 3. This enzyme regulates locally the thyroid hormones concentration and is essential for blastema formation. The analysis of apoptotic cell death shows that this process is highly regulated in time and in space. Its inhibition by caspases activation inhibitor or its induction by retinoic acid inhibits the regeneration
Seiliez, Iban. "Nutrition lipidique des larves de daurade Sparus aurata." Bordeaux 1, 2003. http://www.theses.fr/2003BOR12649.
Gagnon, Karine. "Distribution et abondance des larves d'éperlan arc-en-ciel (Osmerus mordax) au lac Saint-Jean /." Thèse, Chicoutimi : Université du Québec à Chicoutimi, 2005. http://theses.uqac.ca.
Barillet, Sabrina. "Toxicocinétique, toxicité chimique et radiologique de l'uranium chez le poisson zèbre (Danio rerio)." Phd thesis, Université de Metz, 2007. http://tel.archives-ouvertes.fr/tel-00274850.
Fontaine, Romain. "Etude du système dopaminergique inhibiteur de la fonction gonadotrope chez le poisson-zèbre." Thesis, Paris 11, 2014. http://www.theses.fr/2014PA11T104/document.
It was first demonstrated in a teleost fish that the stimulatory control of the gonadotrope axis by GnRH can be counterbalanced by an inhibitory control exerted by dopamine (DA). Later on, this inhibitory dopaminergic control was found in various vertebrate species. However the functional importance of this regulatory pathway varies according to the species. To deepen our knowledge on this inhibitory dopaminergic system, we used the zebrafish (Danio rerio) as a model, in which numerous molecular tools are available.First we demonstrated that DA indeed plays a role in the neuroendocrine control of zebrafish reproduction. By injecting a dopamine receptor antagonist together with an agonist of the GnRH (GnRHa), we were able to stimulate LH expression in the pituitary, and to reactivate the spawning cycles in sexually regressed old females, an effect of which was not produced by the GnRHa alone.We then studied the neuroanatomical basis of this inhibitory control. After observing the expression of the D2-DA receptors subtypes in LH cells, we highlighted numerous dopaminergic terminals on- or in the vicinity of- these cells. We then localized, by DiI retrograde tracing experiments in adult zebrafish, the dopaminergic cell bodies giving rise to these projections in the most antero-Ventral part of the preoptic area. We have called these hypophysiotropic neurons the preoptico-Hypophysial (POH) DA neurons.We next studied the development of POHDA neurons. Taking advantage of early anatomical landmarks, we followed the embryonic development of these cells. We showed that the first POHDA neurons arise at around 72 hours post fertilization (hpf), more than 24 hours later that the DA neurons in the neighbor suprachiasmatic nucleus (SCDA). This late differentiation would explain why POHDA neurons have not been studied in the developing embryo so far. We showed that contrary to the number of the SCDA neurons, which is constant all along the fish life, that of POHDA neurons increases proportionally to the growth of the fish due to continuous neurogenesis. Finally, we examined the expression profiles of developmental genes related to the regionalization of the anterior forebrain. We showed that the genetic networks involved in the development of POHDA and SCDA populations are at least partly different. To summarize, this work demonstrates for the first time the existence of a dopaminergic inhibitory control of gonadotrope function in zebrafish. It describes the anatomy of the preoptico-Hypophyseal dopaminergic system supporting these DA actions and the setting up of these neurons during embryonic development. We show that these neuroendocrine population displays neurogenesis even during adulthood. Our findings also provide the genetic bases for future functional studies on the development of POHDA, a poorly studied neuroendocrine DA population
Barillet, Sabrina Aurélia. "Toxicocinétique, toxicité chimique et radiologique de l'uranium chez le poisson zèbre (Danio rerio)." Metz, 2007. http://docnum.univ-lorraine.fr/public/UPV-M/Theses/2007/Barillet.Sabrina.SMZ0712.pdf.
This thesis explores the toxicokinetic and toxicologic aspects of uranium in fish. Uranium appears to be highly bioaccumulated and bioconcentrated in fish. It spreads all through the whole organism. Nevertheless, its distribution is heterogeneous (gills and liver being the main sites of accumulation). From a toxicologic point of view, we notice perturbations of the antioxidant system (inhibitions of hepatic SOD, CAT and GPx activities; depletion of total GSH) and of the cholinergic system (inhibition/over-activation of brain AChE). Genotoxic effects also appear in red blood cells, hepatocytes and gonadic cells. The kinetics of these biochemical perturbations depend on the radiological activity of uranium, responses appearing earlier with increasing delivered activity. Histological effects (differing in types depending on delivered radiological activity) are also observed (in gills and muscles)
Barbereau, Clément. "Neurotoxicité précoce et mécanismes de neuroprotection dans des modèles poisson‐zèbre de tauopathies." Thesis, Université Paris sciences et lettres, 2020. https://tel.archives-ouvertes.fr/tel-03179669.
Tauopathies are a group of neurodegenerative diseases, associated with pathological Tau proteins. The Tau protein is expressed in the nervous system cells and is involved in microtubule network stabilization, via specific binding domains. Abnormal post-translational processes can lead to the loss of Tau stabilizing function. Therefore, acquisition of aggregative and neurotoxic properties results into the accumulation of neurofibrillary tangles in neurons, which are histopathological markers of tauopathies and Alzheimer’s disease. Oligomer formation and aggregation is also associated with Tau mutations specific of different pathologies with distinct etiology. One of the projects led by the team is to characterize the involvement of the neurotrophic factor BDNF in zebrafish models of tauopathies. A decrease in BDNF induced by the peptide Aβ has been observed in patients with Alzheimer’s disease, but few studies have focused on the possible links between BDNF and pathological Tau proteins. Initial results evidenced a decrease in BDNF in zebrafish larvae expressing the pathological protein TauP301L. The main objective of my thesis was the analysis of the neuronal and sensory-motor phenotypes of zebrafish larvae with overexpression of wild type or mutated Tau proteins (TauWT, TauA152T and TauP301L). Tau phosphorylation, neurotoxicity and sensory-motor defects induced by this overexpression were characterized. We next evaluated the neuroprotective role of an exogenous treatment of BDNF on neurotoxicity at the cellular and functional levels. In addition, other signaling pathways that may be involved in the observed deficits were investigated. Our results showed that overexpression of human Tau protein in zebrafish larvae induces Tau hyperphosphorylation, neuronal death and/or axonal retraction, associated with sensory and locomotor deficits. Overexpression of TauWT, or mutated proteins (TauA152T, TauP301L) lead to different locomotor responses: TauWT induced a decrease in locomotor activity, decrease even more pronounced for TauA152T, while TauP301L leads to locomotor hyperactivity of the larvae. In order to rescue the observed phenotypes, we tested neuroprotective factors including lithium chloride (LiCl), known as a GSK3β inhibitor described to improve the deficits induced by TauP301L. LiCl resulted in the recovery of a locomotor phenotype for the TauP301L lineage, similar to the controls. At the same time, an exogenous supply of BDNF, or a TrkB receptor agonist, partially alleviated neurotoxicity and fully restored locomotor defects. The BDNF and LiCl treatments had no beneficial effect on locomotor alterations in larvae expressing the TauWT and TauA152T proteins. In order to test other signaling pathways involved in tauopathies, we next investigated the endoplasmic reticulum stress pathway, or UPR. Our preliminary data indicate several alterations of UPR effectors in larvae, such as an increase in the PERK protein level for larvae expressing TauWT and TauA152T. However, no beneficial effect was observed with a PERK inhibitor on TauWT or TauA152T larvae. In conclusion, our results demonstrate that overexpression of TauA152T or TauP301L proteins leads to Tau protein hyperphosphorylation, and a similar neurotoxicity. Sensory-motor tests were able to discriminate the effects induced by these two mutations. Furthermore, only TauP301L larvae displayed a decrease in the expression of the neurotrophic factor BDNF, that could be rescued by a pharmacological approach with the recovery of the locomotor phenotype. The two mutations studied have different aggregation and propagation properties and our data provide a complementary functional aspect in the perspective of testing new neuroprotective compounds
Siméon, Ségolène. "Modélisation pharmacocinétique et pharmacodynamique de la toxicité développementale de l'embryon de poisson zèbre." Thesis, Paris, Institut agronomique, vétérinaire et forestier de France, 2020. http://www.theses.fr/2020IAVF0020.
In risk assessment, understanding and predicting the effects of chemical compounds on the development of living beings are needed to understand and manage environmental and therapeutic toxicity. Due to its many experimental and regulatory advantages, and genetic homologies with humans, the zebrafish embryo is widely used for toxicity testing. As part of the European project Eu-ToxRisk,the objective of this work was to improve the extrapolation of the zebrafish embryo data to humans by developingtwo mathematical models able to explain and predict the occurrence of malformations during the zebrafish embryo first five days of development, following exposure valproic acid (VPA), a notorious teratogen, and nine of its analogues.First, a generic physiology-based pharmacokinetic model (PBPK) able to predict the concentrations of neutral or ionizable compounds in ten embryonic organs of interest. Organ growth is considered and the culture medium to organ partition coefficients are predicted by a QSAR sub-model. Metabolic clearance and a partition coefficient correction factor weresimultaneously estimated by Bayesian calibration of the model with embryo and culture medium concentration data of VPA and its analogues over five days of repeated dosing. Second, a multi-state Markovian pharmacodynamic (PD) model to predict the occurrence of malformations as a function of time and VPA exposure concentration. Finally, to describe the behavior of VPA in the embryo and the impact of time and exposure on malformations, the two models were coupled to generate a PK-PD model. The average internal concentration of VPA, predicted by the PBPK model, controls random transitions between states. By Bayesian calibration with malformation data, the transition rates between states were estimated, allowing estimation oftransition probabilities and associated effective concentrations
Pezeron, Guillaume. "Aspects moléculaires et cellulaires de la formation de l'endoderme chez le poisson zèbre." Paris 7, 2007. http://www.theses.fr/2007PA077046.
During gastrulation, vertebrate embryos form the tree germ layer and develop antero-posterior and dorso-ventral axis. For my thesis, I have been working on molecular and cellular aspects of endoderm formation. The endoderm is the inner-most germ layer and give rise to digestive apparatus and respiratory epithelium. I studied the function of a new gene, rasl11b, selected for its expression within dorsal mesendoderme during gastrulation. 1 have shown that Rasll Ib is a negative modulator of Oep, a Nodal coreceptor, but also that Oep, beside its Nodal coreceptor function, can independently regulate the formation of the endoderm. Beside this study, using a transgenic line that express a fluorescent reporter protein, I analysed the behaviour of endodermal cells in vivo. I have shown that endoderm behave differently from mesoderm during gastrulation and migrate in a active random walk movement. This behaviour allow endodermal cell to colonise the yolk surface and thus to form the endodermal germ layer
Prudent, Julien. "Rôles des régulateurs de l’apoptose Bcl-wav et Nrz, au cours du développement embryonnaire du poisson zèbre." Thesis, Lyon 1, 2011. http://www.theses.fr/2011LYO10318.
Rabet, Nicolas. "Implications de la famille de gènes caudal dans la mise en place des tissus postérieurs chez les métazoaires." Paris 7, 2004. http://www.theses.fr/2004PA077147.
Xu, Lijun. "Contrôle spatio-temporel de l'activité de l'acide rétinoïque dans le rhombencephale du poisson zèbre." Phd thesis, Université Pierre et Marie Curie - Paris VI, 2012. http://tel.archives-ouvertes.fr/tel-00836933.
Panier, Thomas. "Imagerie par nappe laser de l'activité neuronale dans l'ensemble du cerveau d'un poisson-zèbre." Phd thesis, Université Pierre et Marie Curie - Paris VI, 2014. http://tel.archives-ouvertes.fr/tel-00979762.
Parmentier, Caroline. "Le système urophysaire et les urotensines : étude cytochimique et moléculaire chez le poisson zèbre." Paris 6, 2007. http://www.theses.fr/2007PA066484.
Behra, Martine. "Criblage d'une mutagenèse chimique dans les embryons de poisson-zèbre axé sur la mobilité." Université Louis Pasteur (Strasbourg) (1971-2008), 2002. http://www.theses.fr/2002STR13027.
During my PhD, I did a screen of a chemical mutagenesis in zebrafish embryos, inducing point mutations. We used two screening criteria's, the altered mobility of embryos and the presence of necroses in the neural tube, the structure giving rise to most of the adult nervous system. The goal was to find mutated genes implicated in the layout of a functional loco motor apparatus. In the first part of my thesis I analysed and characterized the mutant lines. In collaboration with an INRA group, we screened the lines for mutants in the acetylcholinesterase gene, coding for the enzyme (AChE) degrading the neuromuscular neurotransmitter acetylcholine (Ach). We called the mutant acetylcholinesterase (ache). We analysed the phenotype and by crossing it with the mutant nicotinic receptors (nic), lacking functional nicotinic receptors for Ach, we could show that the muscular phenotype is receptor dependant. Most of the insecticides and drugs against Alzheimer disease and myasthenis gravis are inhibitors of the AChE. So the mutant ache provides the first vertebrate model to test side effects of theses drugs. This mutant validates our screen and provides a model to tackle questions which can not be addressed in the mouse knock out. This work also provide a set of neuromuscular mutants, in which the molecular nature still remains to be determine, but which could improve our knowledge in the setting up of neuronal and muscular tissues. They might be of particular relevance in genetic diseases, like myopathies as some symptoms are highly reminiscent of some of the phenotypes of our lines
Rozmankova, Eliška. "Currently used pesticides and their mixtures : what are the risks to non-target aquatic organisms? Laboratory and in situ approaches." Thesis, Bordeaux, 2020. http://www.theses.fr/2020BORD0301.
Pesticides have enabled humankind to protect its crops from pests, intensifying thus the crop yields to sustain the growing population. However, pesticides often end up in aquatic water bodies, e.g. via field runoff, where they may harm non-target organisms. The environmental concentrations of pesticides are often considered safe for aquatic ecosystems although they might induce sublethal changes in exposed organisms. Moreover, the organisms are generally not dealing with only one pesticide issued from a nearby field but with a complex mixture of various chemical compounds, interacting amongst themselves, and creating a toxic cocktail with unknown and hardly predictable impacts. These compounds, each with different environmental fate, eventually degrade and form more or less toxic and persistent metabolites aggravating the complexity of the mixtures.This dissertation thesis summarizes the state-of-the-art in pesticide mixture toxicity research and is composed of five research articles dealing with sublethal effects of selected pesticides on non-target aquatic species. Vulnerable embryo-larval stages of two model organisms: freshwater zebrafish (Danio rerio) and euryhaline bivalve Pacific oyster (Magallana gigas) were used to assess the sublethal toxicity of especially environmental concentrations (detected in selected European water bodies) of commonly used herbicide S metolachlor with its two metabolites metolachlor oxanilic acid and metolachlor ethanesulfonic acid, insecticide imidacloprid, and fungicide propiconazole, alone and in a mixture. A complementary in situ approach was carried out to evaluate a real impact on early-life stages of the Pacific oyster in Arcachon Bay in France, a final recipient of various substances including pesticides from respective watersheds.First, zebrafish embryo-larval stages were observed to be highly sensitive to environmentally relevant concentrations of propiconazole and to a lesser extent also to imidacloprid. In contrast, S-metolachlor and its metabolites had almost no effect on their development, neurobehavioral functions, or gene expression except for altered genes implicated in the thyroid system. A mixture of these compounds exhibited a concentration addition effect on zebrafish development. These observations imply that the development of freshwater fish may be at risk with current agricultural practice.Second, a study with Pacific oyster embryos and larvae revealed very low toxicity of propiconazole and imidacloprid on their development and locomotion patterns. Few effects caused by these compounds were observed at the molecular level, as well as the effects caused by the mixture. The environmental concentration of the mixture induced developmental malformations in oyster larvae, however, those exposed in situ in Arcachon Bay did not show higher proportions of abnormal larvae suggesting that the water quality of Arcachon Bay is sufficient for oyster development. Nevertheless, oyster larvae exposed in the inner part of Arcachon Bay showed different gene expression levels than larvae from the reference site located near the ocean entrance, which may indicate consequences of a potential long term impact.These results documented that embryo-larval stages of zebrafish and Pacific oysters are relevant tools for the assessment of low concentrations of pesticides and pesticides in a mixture, and that laboratory studies complemented with field research are useful for (eco)toxicity assessment and of high ecological relevance
Guillon, Emilie. "Étude fonctionnelle du collagène XV-B dans le développement du système neuromusculaire du poisson zèbre." Thesis, Lyon 1, 2014. http://www.theses.fr/2014LYO10123/document.
The extracellular matrix (ECM) provides positional information to guide motoneuron axons toward their muscle target. Collagen XV is a basement membrane component encoded by two paralogs in zebrafish, col15a1a and col15a1b. My PhD project consisted in the characterization of the expression pattern of the col15a1b paralog during development and in the analysis of the in vivo function of this paralog in developing zebrafish embryos. Interestingly, we showed that col15a1b paralog is expressed by slow muscle precursors that represent an important source of the ECM path. Using newly generated antibodies to collagen XV-B (COLXV-B), we found that COLXV-B paves the trajectory of motor axons. Loss and gain of function experiments showed that col15a1b expression and extracellular organization depends respectively on Hedgehog and unplugged/MuSK signaling. Col15a1b knockdown weakly affected slow muscle differentiation but provoked primary and secondary motoneuron axons truncation or pathfinding errors at the choice point where pathway selection takes place. This resulted in muscle atrophy and compromised swimming behavior. Our data identified an unexpected role for COLXV-B as an unplugged/MuSK-dependent cue that paves the axonal motor path to guide the decision of axons at the choice point. The conserved syntheny, the broad expression pattern of col15a1b similar to COL15A1 ortholog and the conservation of the primary sequence of COLXV-B with the mammalian counterparts suggested that the human protein COLXV could display similar function and represent a gene candidate for neuromuscular disorders
Dupret, Barbara. "Etude du rôle des protéines Polycomb Pcgf1 et Ezh2 chez le poisson zèbre Danio rerio." Thesis, Lille 1, 2017. http://www.theses.fr/2017LIL10115/document.
PCR1 and PRC2 are complexes that control gene expression via chromatin structure reorganization. This expression regulation is maintained by adding epigentics marks H2AK119ub1 by the PRC1 and adding of H3K27me3 by the PRC2. The study devotes to study the role of the protein Pcgf1 (part of the PRC1 complex) and of the Ezh2 protein (part of the PRC2 complex) during the zebrafish development. The PRC1 complex is formed by different proteins including Pcgf proteins. There are several Pcgf homologs that have different functions. The study reveals that some Pcgf proteins have a different expression during caudal fin regeneration and development. We are interested in Pcgf1 protein during the zebrafish development. The pcgf1 gene was inactivated by using TALEN. The fish pcgf1-/- are viable and fertile. However, the early development is delayed and adults show signs of accelerated aging. This mutant is the first vertebrate model showing the role of Pcgf1 in cells proliferation during development and aging. Ezh2 protein is involved in cell-fate decisions and differenciation. Inactivation of ezh2 gene by TALEN reveals the essential role of Ezh2 during development. Indeed, at the beginning embryos develop normally then larvae die at 12 days post-fertilization. Interestingly, zebrafish embryo can gastrulate without Ezh2. This contradicts with observations in mouse model. The organs are properly formed at 5 days postfertilization. Larvae show defects in the intestinal bulb wall. Ezh2 is important for exocrine pancreas maintenance. The absence of Ezh2 causes an increase in apoptic cells. Ezh2 is essential during caudale fin regeneration
Dubrana, Leslie. "Modèles poisson zèbre de l’intoxication aux organophosphorés cholinergiques et neuropathiques et évaluation de l’efficacité d’antidotes." Thesis, Bordeaux, 2020. http://www.theses.fr/2020BORD0187.
Organophosphates (OPs) are organic compounds used as pesticides, plasticizers, flame-retardants or chemical warfare nerve agent. They are responsible for several thousand deaths each year as well as induction of pathologies of the nervous system. Therefore, they represent a serious problem of public health and environmental toxicity. OPs interfere with important esterase activities for the degradation of active molecules in organisms. The most studied is acetylcholinesterase (AChE) which hydrolyses acetylcholine. This neurotransmitter is essential in the cholinergic synaptic transmission of nerve impulses in the peripheral and central nervous system (CNS). The acute toxicity of OPs is linked to the inhibition of AChE which generates a cholinergic syndrome. This syndrome induces paralysis, pulmonary and vascular damage, but also seizures, which can lead to death. The OPs responsible for this syndrome are called cholinergic OPs. As the current standard treatment is not sufficiently effective, it is necessary to find new antidotes to counteract the effects of these toxins, in particular on the CNS, due to their difficulty in crossing the blood-brain barrier. In this context, many new molecules must be evaluated for their therapeutic benefit. Moreover, certain OPs induce a distal degeneration of axons localised in the peripheral and central nervous systems. This pathology evolves several weeks after exposure and is named organophosphate-induced delayed neuropathy (OPIDN). These neuropathic OPs can target an enzyme called neuropathy target esterase (NTE / PNPLA6) but their mechanism of action is still unclear and controversial. Zebrafish is a recognized model with many advantages for in vivo experimentation, especially in the early stages of its development. This work develop an innovative strategy to assess the effects of cholinergic and neuropathic OPs intoxication and to search new antidotes using the zebrafish eleuthero-embryo. This methodology combines biochemical analysis and innovative locomotor tests. The results obtained provide a new system for in vivo evaluation of the antidote efficacy for cholinergic OP poisoning and new key events of the neuropathic OP mechanism of action
Mathieu, Juliette. "Régulation de la formation du mésoderme et de la ligne médiane chez le poisson zèbre." Paris 6, 2002. http://www.theses.fr/2002PA066253.
Aoki, Tazu. "Etude sur les mécanismes moléculaires de la détermination du destin endodermique chez le poisson zèbre." Paris 6, 2003. http://www.theses.fr/2003PA066006.
Brodoline, Alexey. "Holographie numérique appliquée à l’imagerie 3D rapide de la circulation sanguine chez le poisson-zèbre." Thesis, Montpellier, 2018. http://www.theses.fr/2018MONTS058/document.
In this manuscript, we present an imaging technique based on digital holography.It enables to image in 3D and in time the blood circulation in a zebrafish larva. The 3D information is acquired in a single frame of the camera, which makes possible to track the movement of red blood cells in the vascular system. We will first discuss the traditional techniques of bio and blood flow imaging, then we will remind the principles of holography. Afterwards, we will describe the imaging method we developed and the experimental results obtained. We will then present the improvements that have been made to the technique. Finally, we will briefly discuss the application of the compressed sensing to the blood flow imaging in zebrafish
Calhabeu, Frédérico. "NOV / CCN3 et CKIP-1 régulent respectivement la détermination et la migration des myoblastes au cours de la différenciation musculaire." Paris 6, 2006. http://www.theses.fr/2006PA066453.
Gangatharan, Girisaran. "Role of Tall and the immune system during zebrafish heart regeneration." Thesis, Montpellier, 2016. http://www.theses.fr/2016MONTT076.
Unlike mammals, zebrafish have the ability to regenerate their heart after substantial injury. A deeper understanding of this phenomenon could aid in the design of clinical therapies to enhance mammalian cardiac regeneration. In this study, we have identified signaling pathways in zebrafish heart regeneration using a chemical genetic screen. Furthermore, we identify the presence of a bHLH transcription factor, Tal1 and show its requirement during zebrafish cardiac regeneration. Finally, we examine the role of the immune system during zebrafish heart regeneration and demonstrate a model of scar removal by MMP14 positive macrophages and show that this process is required for successful heart regeneration to occur
Le, Fol Vincent. "Approche in vivo/in vitro du métabolisme de perturbateurs endocriniens chez le poisson zèbre (Danio rerio)." Phd thesis, Toulouse, INPT, 2015. http://oatao.univ-toulouse.fr/15125/1/lefol_1.pdf.
Nauroy, Pauline. "Matrice extracellulaire et régénération : une étude utilisant le modèle de la nageoire caudale du poisson zèbre." Thesis, Lyon, 2017. http://www.theses.fr/2017LYSEN082.
In addition to their role within tissues, extracellular matrix proteins are implicated in a large number of cellular processes. However, their role in regeneration is not well studied at the moment. A better understanding of the extracellular matrix proteins involvement in regeneration can have several future applications for regenerative and reconstructive medicine. The aim of my PhD project is to answer this question.To do this, we used the well-established zebrafish caudal fin model which have many advantages such as a simple structure, easily accessible and a quick regeneration in only few days. A global transcriptomic approach without a priori showed us that extracellular matrix proteins are playing a key role in regeneration. A first step of my work was to use an orthology-based approach to create the first list of extracellular matrix genes in zebrafish, called the matrisome. Our study revealed the unexpected role of a collagen during epidermal basement membrane reconstruction, an importance structure for the dermo-epidermal cohesion in skin. This protein which is expressed only during embryogenesis, is re-expressed in the regenerating epidermis and deposited in the basement membrane. Using an anti-sense strategy in vivo, I have demonstrated by atomic force microscopy and electron microscopy that the absence of this collagen impacts the biomechanics of this reconstructing basement membrane. These results were confirmed on a zebrafish line invalidated for this collagen that I have generated using the genome editing CRISPR/Cas9 technic. We showed that this collagen acts as a molecular spacer needed for the correct tridimensional organization of the other basement membrane components during regeneration
Ramspacher, Caroline. "Développement de modèles animaux de maladies génétiques des systèmes cardiovasculaire et musculaire chez le poisson-zèbre." Thesis, Strasbourg, 2014. http://www.theses.fr/2014STRAJ095/document.
The numerous advantages of zebrafish were used to study two hereditary diseases: desminopathy and pulmonary veno-occlusive disease (PVOD). Desminopathy is a myofibrillar myopathy characterized by the presence of granulofilamentous aggregates. Two models of loss and gain of function of desmin showed the implication of both loss of functional desmin and presence of desmin aggregates in desminopathy clinical manifestations. Phenotypes observed in these models include in particular a perturbation of the heart contraction biomechanics and of calcium propagation throughout the myocardium. Potential drugs, lowering the aggregate content, were proposed. After validating the use of zebrafish as a model of arterial hypertension, by verifying the implication of the elasticity of the aorta in blood flow regulation, we generated and characterized PVOD models. PVOD is a rare and severe form of pulmonary hypertension. The venous-specificity of the phenotypes observed in this pathology was confirmed
Lucas, Julie. "Intégrité fonctionnelle chez le poisson zèbre, Danio rerio, exposé à des concentrations sublétales d’hydrocarbures aromatiques polycycliques." Thesis, La Rochelle, 2013. http://www.theses.fr/2013LAROS422/document.
The increase of anthropogenic activities on coastal areas induces discharges of polycyclic aromatic hydrocarbons in aquatic ecosystem. PAHs effects depend on their concentration and the way of contamination, but also on the different developmental stages of the organism. In this context, the aim of our study was to observe the effects of an exposure to two PAHs mixes, pyrolytic and petrogenic, on the model species zebrafish Danio rerio. These chronicle exposures at sub-lethal concentrations were representative of contaminated areas. Biological responses of fish were estimated at individual levels through the assessment of aerobic metabolic scope, swimming and escape performance, which are considered to be relevant indirect measures of the fitness. Furthermore, measurements of cardiac frequency allowed observing PAHs impairments at sub-individual levels. These physiological performances were estimated (i) a several times of exposure (i.e. from 2-months juveniles to 6-months adults) and (ii) on their progeny, in order to observe parental effect of the PAHs exposure. An increase of aerobic metabolic scope was observed on the progeny of fish contaminated by pyrolytic mix. Regarding petrogenic PAHs exposure, the increase of aerobic metabolic scope was associated to increase of critical swimming speed in adults. This study will contribute to establishing a global vision of PAHs exposure impairments and to a better understanding of the regulating mechanisms of the main biological functions on which organism survival depends
Yossa, Nouaga Rodrigue. "Interactions entre la biotine et l'avidine dans la nutrition du poisson zèbre Danio rerio (HAMILTON-BUCHANAN)." Thesis, Université Laval, 2012. http://www.theses.ulaval.ca/2012/28898/28898.pdf.
Zebrafish Danio rerio was used as model organism in the first step of a project aiming at developing a biological confinement method of farmed fish based on the interactions between biotin and avidin. The objectives of this thesis were i) to estimate the dietary biotin requirements of zebrafish; ii) to study the effects of dietary biotin and avidin on growth, survival, feed conversion, biotin status and gene expression in zebrafish; iii) to assess the contribution of the intestinal microflora to biotin supply in zebrafish, and iv) to investigate the effects of biotin on zebrafish reproduction. The first study of this thesis has demonstrated that biotin is essential for zebrafish growth and that the optimum dietary biotin requirement for maximal growth is 0.51 mg kg-1 diet. The second study confirmed the essentiality of biotin for zebrafish growth found in the first study. This study also revealed that feeding zebrafish a diet containing avidin in 60-fold excess of biotin requirement induces biotin deficiency signs in zebrafish such as retarded growth, high mortality, low condition factor, and decreased steady-state level of acetyl CoA carboxylase-A (acca) transcripts in the liver. The third study suggested that intestinal microbial synthesis is a significant source of biotin to zebrafish. Fish fed the antibiotic-supplemented diet (1% succinylsulfathiazole, mass/mass) showed lower growth, health condition, whole-body biotin content, survival and feed utilization than fish fed the biotin unsupplemented and biotin supplemented diets. The results of the fourth study demonstrated that dietary biotin affect both male and female reproductive performances; the biotin-deficient male showed lower gonadosomatic index as well as lower sperm quality and quantity, while biotin-deficient female showed reduced fertility. The results of this thesis constitute a baseline in the understanding of the interactions between dietary biotin and avidin in zebrafish nutrition on the one hand, and in the potential use of these interactions in order to develop a biological confinement strategy of farmed fish on the other hand.
Alavi, Naini Seydeh Maryam. "Etude de la physiopathologie des tauopathies dans le modèle de poisson zèbre : Implication des héparanes sulfates." Paris 7, 2014. http://www.theses.fr/2014PA077215.
Tauopathies are a class of neurodegenerative diseases that include Alzheimer's disease and frontotemporal dementia. A cardinal feature of tauopathies is hyperphosphorylation and aggregation of tau protein in brain. The pathophysiology of tauopathies is poorly understood, and to date there is no measure to prevent or even slow the progression of disease. -Several studies indicate that heparan sulfates (polymers of sulfated polysaccharides attached to a core protein) play a significant role in tau hyperphosphorylation, but the nature of the heparan sulfates involved in the pathological processes and their precise function in the pathogenesis of tauopathy remains unknown. The aim of my thesis was to shed light on the role of heparan sulfates in tauopathies. For my work, I used the transgenic zebrafish line Tg[HuC::hTauP301L/DsRed] that expresses the human tau protein carrying the P301L mutation responsible for frontotemporal dementia and parkinsonism linked to chromosome 17. This transgenic line reproduces an important pathophysiological feature of tauopathies: abnormal hyperphosphorylation of the tau protein. In the first part of my thesis, I participated in research designed to investigate the role of 3-O-sulfotransferase-2 (an enzyme involved in the synthesis of heparan sulfate) in tau hyperphosphorylation, using the Tg[HuC::hTauP301L/DsRed] line. With a genetic approach,. Ie. Inactivation of 3-0- sulfotransferase-2 by injection of antisense morpholino oligonucleotides in Tg[HuC::hTauP301L/DsRed] embryos, I have shown that this enzyme (and therefore the heparan sulfates with sulfated residues in position 3 of glucosamine) play a key role in pathological tau hyperphosphorylation. Indeed, partial inactivation of the 3-0- sulfotransferase-2 in these embryos induces a 60% decrease in the accumulation of hyperphosphorylated forms of tau. This work points to heparan sulfates as a candidate therapeutic target for the treatment of tauopathies, including Alzheimer's disease. In the second part of my thesis, I worked on finding small molecule antagonists of heparan sulfates capable of inhibiting the abnormal hyperphosphorylation of tau protein. I discovered that two heparan sulfate antagonist molecules (surfen and oxalyl-surfen) not only significantly decrease tau hyperphosphorylation in Tg[HuC::hTauP301L/DsRed] embryos but can also partially rescue the axonal defects and fasciculation of primary motor neurons caused by expression of the mutated human tau. Taken together, my findings highlight the key role of heparan sulfate in the pathophysiology of tauopathies, and open promising perspectives in the search for therapeutic strategies for tackling these disorders
Poulain, Morgane. "Étude de la spécification des territoires endodermiques et mésodermiques au cours de l'embryogenèse du poisson zèbre." Nice, 2006. http://www.theses.fr/2006NICE4001.
During my PhD, J have focused on molecular mechanisms involved in endoderm and mesoderm specification. In zebrafish , endoderm and mesoderm are induced at the vegetal margin of the blastoderm by secreted TGFbeta molecules of Nodal family. J have characterized Mezzo, a novel homeobox transcription factor, which is regulated by Nodal signalling and acts in parallel with Mixer in the endoderm specification. These results highlight the complexity of the transcriptional network operating during endoderm formation. Mesoderm and endoderm originate from common precursors and segregate during gastrulation by mechanisms that are largely unknowm. I analyzed how the FGF and BMP pathways interact with Nodal signalling during the process of endoderm formation. I found that activation of the FGF/ERK pathway disrupts endoderm formation in the embryo and antagonizes the ability of Nodal signals to induce endoderm at the animal pole. Furthermore, I found that overexpression of BMPs compromises endoderm formation, suggesting that formation of endoderm precursors is negatively regulated by MPs on the ventral side. These data strongly suggest that BMP and FGF-ERK pathways cooperate to restrict the number of endodermal progenitors induced in response to Nodal signalling. I found that FGF/ERK signalling causes phosphorylation of Casanova, an important regulator of endoderm determination and provide evidence that this phosphorylation attenuates its activity. These results identify a molecular mechanism whereby FGF attenuates Nodal induced endodermal transcription factors and highlight a potential mechanism whereby mesoderm and endoderm fates could segregate from each other
Cotto, Emmanuelle. "Caractérisation moléculaire de la protéine prion de poisson-zèbre et expression génique au cours du développement." Bordeaux 1, 2004. http://www.theses.fr/2004BOR12817.
Prion diseases are characterized by the accumulation of an abnormal isoform (PrPsc) of a physiologic protein (PrPc) that is encoded by the Prnp gene in humans. A homologous protein has been characterized in different Mammal species and Birds, the turtle and Xenopus. Different prion-like proteins have been identified in Fish, but their orthologous and paralogous relationship to the human Prnp gene are unknown. Here, we characterized the prion protein (PrP1) of the zebrafish after cloning of its cDNA. Although its primary amino acid sequence is relatively divergent, the PrP1 protein shows preserved PrP-type characteristic motifs. The prp1 gene expression pattern has been determined in zebrafish embryos and larvae by using in situ in toto hybridization and compared to the expression of the prp2 gene. The latter exists also in the zebrafish genome and encodes for another protein of the PrP family. The prp1 gene is expressed in the zebrafish embryo from the beginning of zygotic activation, suggesting a pleiotropic role of this protein during early embryogenesis. Twenty-four hours after fertilization, transcripts of prp1 are localized in distinct anatomical structures, with a main expression in the central nervous system, lateral line neuromasts, different parts of kidney, liver, heart, posterior intestine and pectoral fins. The prp2 gene is mainly expressed in neuromasts and pectoral fins. In conclusion, we confirm the appearance of the PrP gene at the origin of Vertebrate evolution. Moreover, the differential expression pattern for PrP-type genes during development could be used as an additional argument to clarify phylogenetic relations emanating from the duplication of the prp gene in the Teleostean Fish genome
Vosges, Mélanie. "Effets neuroendocrines des perturbateurs endocriniens chez le poisson zèbre (Danio rerio) : étude du système à GnRH." Thesis, Tours, 2010. http://www.theses.fr/2010TOUR4035/document.
Until now, studies dedicated to the actions of endocrine disrupting chemicals (EDCs) on the reproductive axis have focused on the gonads and peripheral organs leaving virtually unexplored their actions on neuroendocrine circuits controlling reproduction. In vertebrates, gonadotropin-releasing hormone (GnRH) is the key factor controlling the activity of the reproductive axis. The development and functioning of GnRH neurons are finely tuned, notably by sex steroids, making these neurons potential targets of EDCs. The aim of this work was to explore the neuroendocrine effects of xenoestrogens in the zebrafish (Danio rerio). We show that 17α-ethinylestradiol (EE2) and nonylphenol (NP) disrupts the ontogeny of GnRH system during zebrafish early life stage. Moreover, we demonstrate that these effects involve functional estrogens receptors. In parallel, we report the inducing effects of EE2 and NP on the expression of brain aromatase protein, the enzyme responsible for estrogen biosynthesis. Altogether, these results highlight the need to consider neuroendocrine networks as critical and sensitive endpoints in the field of endocrine disruption
Rua, Ferreira Rita. "Etude du mécanisme de la sensation du flux ciliaire dans l'organiseur droite gauche du poisson zèbre." Thesis, Strasbourg, 2017. http://www.theses.fr/2017STRAJ001/document.
Both motile and immotile cilia play important roles in left-right (LR) axis determination, which generally involves cilia-mediated directional flows in organized structures (LR organizers, LRO) in which the LR symmetry is broken, thus driving asymmetric organogenesis in the developing embryos. In my PhD project we aimed to developed a method (3D-Cilia Map) and analyze the three-dimensional organization of ciliary implantation in order to extract the key parameters modulating the directional flow involved in breaking the axis of symmetry in the zebra fish LRO. Altogether, our results suggest the initial mechanism to break the LR symmetry is most likely to be based on the transport of achemical signal, while later, cells intrinsically provide their cilia the cues to orient asymmetrically. The work presented here represents an important contribution to our current understanding of cilia behaviors and flow-sensing mechanisms in the establishment of the left-right axis in the zebra fish LRO