Origine évolutive de la segmentation chez les bilateriens (étude de la formation des segments chez l'annélide platynereis dumerilii)

PARIS7-Bibliothèque centrale (751132105) / SudocSudocFranceF

Contribution à l'étude du mode d'action des protéines à homéodomaine Engrailed chez la Souris

PARIS-BIUSJ-Thèses (751052125) / SudocCentre Technique Livre Ens. Sup. (774682301) / SudocPARIS-BIUSJ-Physique recherche (751052113) / SudocSudocFranceF

Role of epigenetics in critical periods of plasticity

La plasticité cérébrale existe à l âge adulte mais est particulièrement forte au cours de périodes critiques de développement pendant lesquelles l anatomie et la physiologie du système nerveux sont extrêmement sensibles à l expérience sensorielle. Les mécanismes contrôlant le début et la durée de ces périodes critiques sont multiples. Parmi eux, la régulation épigénétique des gènes de transcription a récemment été mis en évidence comme étant un nouveau mécanisme fondamental impliqué dans la plasticité cérébrale. Ainsi, dans le but d identifier de nouveaux acteurs sensibles à ces périodes de forte plasticité, nous avons émis l hypothèse que l analyse des profils de méthylation d ADN pourrait être une méthode intéressante. L étude 1 a révélé que le profil de méthylation de CYP2E1 différait chez le nouveau-né en fonction de la consommation d antidépresseurs de sa mère pendant la grossesse. L étude 2 a recherché si des marqueurs de méthylation d ADN étaient associés à la capacité de discrimination de consonnes chez le foetus. L étude 3, pour sa part, a suggéré que la régulation du méthylome était dynamique et pouvait être différente d un mois à un autre. L étude 4 a identifié certains candidats qui pourraient participer à avoir l oreille absolue. L étude 5 a identifié F2RL2, un recepteur de thrombine, comme nouveau candidat impliqué dans la période critique du système visuel. Ensemble, ces résultats ont montré l importance du rôle de la méthylation d ADN dans diverses périodes critiques de plasticitéInadequate sensory input and/or drug exposure during specific developmental stage, called critical periods of plasticity, can affect their timing and can lead to long-term developmental outcomes. The aim of this thesis was to understand the role played by epigenetic mechanisms in this form of plasticity in using a DNA methylation microarray approach. Study 1 showed the impact of selective reuptake inhibitors prenatal exposure in the methylome of neonates. Study 2 investigated whether DNA methylation patterns could be involved in the speech perception critical period. Study 3 demonstrated that methylation patterns for some CpGs could be different within a month suggesting the existence of a dynamic regulation mechanism for them. Study 4 identified CpGs that could be involved in absolute pitch and CpGs that might be associated with valproate exposure in young healthy adults. Study 5 identified a thrombin receptor F2RL2 as a new candidate gene involved in visual cortical plasticity. Together the results of these studies have highlighted the importance of DNA methylation in several critical periods of plasticityPARIS-BIUSJ-Biologie recherche (751052107) / SudocSudocFranceF

Hydrogen Peroxide and Redox Regulation of Developments

Reactive oxygen species (ROS), which were originally classified as exclusively deleterious compounds, have gained increasing interest in the recent years given their action as bona fide signalling molecules. The main target of ROS action is the reversible oxidation of cysteines, leading to the formation of disulfide bonds, which modulate protein conformation and activity. ROS, endowed with signalling properties, are mainly produced by NADPH oxidases (NOXs) at the plasma membrane, but their action also involves a complex machinery of multiple redox-sensitive protein families that differ in their subcellular localization and their activity. Given that the levels and distribution of ROS are highly dynamic, in part due to their limited stability, the development of various fluorescent ROS sensors, some of which are quantitative (ratiometric), represents a clear breakthrough in the field and have been adapted to both ex vivo and in vivo applications. The physiological implication of ROS signalling will be presented mainly in the frame of morphogenetic processes, embryogenesis, regeneration, and stem cell differentiation. Gain and loss of function, as well as pharmacological strategies, have demonstrated the wide but specific requirement of ROS signalling at multiple stages of these processes and its intricate relationship with other well-known signalling pathways

Direct non-cell autonomous Pax6 activity regulates eye development in the zebrafish

Abstract Background Modifications in Pax6 homeogene expression produce strong eye phenotypes. This suggested to us that eye development might be an appropriate model to verify if homeoprotein intercellular passage has important functions in early development. Similar to other homeoproteins, Pax6 has two domains that enable secretion and internalization by live cells and, thus, intercellular passage. In principle, a straightforward way to test the hypothesis would be to mutate one of the two sequences to produce a 'cell autonomous only' Pax6. However, this was not possible because these sequences are in the homeodomain and their modification would affect Pax6 transcriptional properties. We have thus developed an approach aimed at blocking Pax6 only in the extracellular milieu of developing zebrafish embryos. Results A first strategy was to inject a one-cell embryo with a mRNA encoding a secreted single-chain anti-Pax6 antibody. A second, complementary, strategy was to inject a Pax6 antibody in the blastula extracellular milieu. In both cases, 'dissymmetric eyes', 'one eye only' and 'no eye' phenotypes were produced. In most cases, lens phenotypes paralleled retina malformations. Although eye phenotypes were analyzed 30 hours post-fertilization, there was a strong correlation between early eye field asymmetry, early asymmetry in Pax6 expression and later-occurring eye malformations. Several controls were introduced, demonstrating that the effect is specific to Pax6 and cannot be explained by intracellular antibody activities. Conclusion This study supports the hypothesis that the Pax6 transcription factor is also a signaling molecule with direct non-cell autonomous activity.</p

Nerves Control Redox Levels in Mature Tissues Through Schwann Cells and Hedgehog Signaling

Plume Geyser, erupts about every 20 minutes; The geothermal areas of Yellowstone include several geyser basins in Yellowstone National Park as well as other geothermal features such as hot springs, mud pots, and fumaroles. The number of thermal features in Yellowstone is estimated at 10,000. South of Norris along the rim of the caldera is the Upper Geyser Basin which has 410 geysers including Old Faithful, a cone geyser. Old Faithful was named in 1870 during the Washburn-Langford-Doane Expedition and was the first geyser in the park to receive a name. It is one of the most predictable geographical features on Earth, erupting every 35 to 120 minutes. Source: Wikipedia; http://en.wikipedia.org/wiki/Main_Page (accessed 9/6/2015

Dendritic localization and activity-dependent translation of Engrailed1 transcription factor

International audienceEngrailed1 (En1) is a homeoprotein transcription factor expressed throughout adulthood in several midbrain cells, including the dopami-nergic neurons of the substantia nigra. Here we report the presence of Engrailed protein and En1 mRNA in proximal dendrites of these neurons and of En1 mRNA in ventral midbrain synaptoneurosomes. We show that the 3′ untranslated region of En1 mRNA contains a functional cytoplasmic polyadenylation element (CPE), suggesting that its dendritic localization is regulated by CPE binding protein (CPEB). In order to evaluate activity-regulated translation, conditions were developed using primary midbrain neurons. With this in vitro model, En1 mRNA translation is increased by depolarization in a polyadenylation dependent manner. Furthermore, En1 translation is prevented by rapamycin, implicating the mTOR pathway, which is known to regulate dendritic translation. Together, these results suggest an activity-dependent role for Engrailed in midbrain dopaminergic neuron physiology