228 research outputs found
Cholet et l'industrie toilière au début du XVIIIe siècle
No full textDollé Pascal. Cholet et l'industrie toilière au début du XVIIIe siècle. In: Annales de Bretagne et des pays de l'Ouest. Tome 107, numéro 2, 2000. Les activités textiles dans l'Ouest XVIe-XIXe siècles. pp. 71-85
Defects of the Chorioallantoic Placenta in Mouse RXRα Null Fetuses
No full textAbstractThe active derivatives of vitamin A (the retinoids) play important and multiple roles in mammalian development and homeostasis. We have previously shown that specific retinoic acid receptors are expressed in the chorioallantoic placenta of the mouse and that among these, RXRα is strongly expressed in the developing labyrinthine zone (Sapin, V., Ward, S. J., Bronner, S., Chambon, P., Dollé, P.,Dev. Dyn.208, 199–210, 1997). Here, we show that mouse fetuses with a targeted disruption of the RXRα gene develop defects of the chorioallantoic placenta. Both morphological abnormalities and alterations in the expression of molecular markers were found, mostly confined to the labyrinthine zone of placentas from mid–late gestation mutants. This region exhibited edema, abnormal stasis of maternal blood, and signs of disruption of the endothelial layer of fetal vessels. We also detected a reduction in the number of lipid droplets in the trophoblastic layer and abnormal fibrin deposits in the junctional zone of the mutant placentas. These abnormalities most probably result in an impairment of the functional capacities of exchange between the maternal and fetal circulations in the mutant placentas. Thus, placental defects could represent an extraembryonic cause of lethality for RXRα null mutant fetuses, in addition to the previously described embryonic cardiac defects
Development of an organotypic model for characterizing axonal responses to In vitro strain injuries
No full textTraumatic brain injuries are the leading cause of disability each year in the US. The most common and devastating consequence is the stretching of axons caused by shear deformation that occurs during rotational acceleration of the brain during injury. These injuries often lead to unconsciousness and long-term impairment and unfortunately the effects on axonal molecular and functional events are not fully characterized. We have developed a strain injury model that maintains the three dimensional cell architecture and neuronal networks found in vivo with the ability to visualize individual axons and their response to a mechanical injury. The advantage of this model is that it can apply uniaxial strain injuries to axons that make functional connections between two organotypic slices and injury responses can be observed in real-time and over long term. This is accomplished using microfabrication techniques to produce micron-sized channels that direct axon growth originating from the periphery of organotypic hippocampal slices. This guidance of axonal growth allows for two organotypic slices to connect to each other. The dimension of these channels can be manipulated to control the number of entering axons allowing for observation of injury effects on both individual axons and axon bundles in real-time and long term following injury. These injury effects are assessed through the use of morphology, molecular, biochemical, and cellular techniques. This uniaxial strain injury model was designed to be capable of applying an array of mechanical strains at various rates of strain, thus replicating a range of modes of axonal injury. These applied uniaxial strains are reproducible and verified through finite element analysis. Long term culture, preservation of slice and cell orientation, and slice-slice connection on the device was demonstrated. The fidelity of the model was verified by observing characteristic responses to various strain injuries which included axonal beading, delayed elastic effects, microtubule degeneration, axonal transport, axonal degeneration and mitochondrial membrane potential. The axonal beading and delayed elastic effect responses to a strain injury are dependent on both the applied strain and the bundle diameter. As the diameter increases the number of beads that form decreases and the delayed elastic effect increases. Axonal bundle unraveling and primary axotomy at lower applied strains than previously reported are observed. The induced strain injury leads to a breakdown in axonal cytoskeleton resulting in a failure in axonal transport of essential proteins as seen by accumulations of amyloid precursor protein along the length of the axon. Both of these responses result in axonal degradation and are proportional to the degree of applied strain and time following injury. We observe an applied strain injury threshold with respect to mitochondrial membrane potential response, below which there is a delayed hyperpolarization and above which immediate depolarization. Using EIPA, a sodium / hydrogen exchanger inhibitor, we were able to attenuate both mitochondrial membrane hyperpolarization and depolarization, resulting in a decrease in axonal degeneration following injury. This model could prove to be a powerful tool in assessing strain injury effects on functional axon-axon connections by further characterizing axonal responses to controlled uniaxial strain injuries and the testing of additional potential traumatic brain injury therapeutics.Ph. D.Includes bibliographical referencesby Jean-Pierre Doll
Role of retinoic acid during mouse cortical neurogenesis
No full textL’acide rétinoïque (AR), dérivé actif de la vitamine A (rétinol) circulante, est une petite molécule lipophile contrôlant divers aspects de la mise en place du système nerveux central des vertébrés. L'AR influence notamment le développement précoce du cerveau antérieur, où il contrôle la prolifération et la survie des cellules progénitrices dans l'épithélium neural prosencéphalique. Le développement neural est un processus qui s'articule en trois grandes étapes : la phase d'expansion latérale (E9,5-E10,5 chez la souris), la phase de neurogenèse (E11,5-stades périnataux) et la phase de gliogenèse (stades périnataux-adulte). Nous avons montré que l'AR produit par les méninges à partir de E13 influence la spécification et la migration neuronale au cours de la phase de neurogenèse. De plus, nos travaux suggèrent un rôle plus précoce de l'AR pour la formation et la prolifération des populations progénitrices et neuronales avant et au début de la phase de neurogenèse. Une combinaison de signaux intrinsèques et extrinsèques contrôle divers aspects du développement neural cortical. Nos travaux placent l'AR parmi ces facteurs modulateurs de la neurogenèse corticale.Retinoic acid (RA), an active vitamin A (retinol) metabolite, is a small lipophilic molecule controlling numerous events during central nervous system development in vertebrates. RA is involved in early forebrain development by controlling cell proliferation and survival in the prosencephalic neuroepithelium. Neural development is a process progressing through three key steps: a phase of lateral expansion (E9.5-E10.5 in the mouse), a phase of neurogenesis (E11.5-perinatal stages) and a gliogenic phase (perinatal stages-adult). My work has shown that RA produced by the developing meninges from E13 influences neuronal specification and migration during the phase of neurogenesis. Moreover, our data suggest an earlier role of RA during the production and proliferation of progenitor and neuronal populations, before and at the onset of the neurogenic phase. A combination of extrinsic and intrinsic signals is required to orchestrate the various aspects of cortical development. RA is likely to be one of such extrinsic factors modulating cortical neurogenesis
Developmental expression of retinoic acid receptors (RARs).
No full textInternational audienceHere, I review the developmental expression features of genes encoding the retinoic acid receptors (RARs) and the 'retinoid X' or rexinoid receptors (RXRs). The first detailed expression studies were performed in the mouse over two decades ago, following the cloning of the murine Rar genes. These studies revealed complex expression features at all stages of post-implantation development, one receptor gene (Rara) showing widespread expression, the two others (Rarb and Rarg) with highly regionalized and/or cell type-specific expression in both neural and non-neural tissues. Rxr genes also have either widespread (Rxra, Rxrb), or highly-restricted (Rxrg) expression patterns. Studies performed in zebrafish and Xenopus demonstrated expression of Rar and Rxr genes (both maternal and zygotic), at early pre-gastrulation stages. The eventual characterization of specific enzymes involved in the synthesis of retinoic acid (retinol/retinaldehyde dehydrogenases), or the triggering of its catabolism (CYP26 cytochrome P450s), all of them showing differential expression patterns, led to a clearer understanding of the phenomenons regulated by retinoic acid signaling during development. Functional studies involving targeted gene disruptions in the mouse, and additional approaches such as dominant negative receptor expression in other models, have pinpointed the specific, versus partly redundant, roles of the RARs and RXRs in many developing organ systems. These pleiotropic roles are summarized hereafter in relationship to the receptors' expression patterns
Retinoic acid in development: towards an integrated view.
No full textInternational audienceRetinoic acid (RA) has complex and pleiotropic functions during vertebrate development. Recent work in several species has increased our understanding of the roles of RA as a signalling molecule. These functions rely on a tight control of RA distribution within embryonic tissues through the combined action of synthesizing and metabolizing enzymes, possibly leading to diffusion gradients. Also important is the switching of nuclear receptors from a transcriptionally repressing state to an activating state. In addition, cross-talk with other key embryonic signals, especially fibroblast growth factors (FGFs) and sonic hedgehog (SHH), is being uncovered. Some of these functions could be maintained throughout the life of an organism to regulate cell-lineage decisions and/or the differentiation of stem cell populations, highlighting possibilities for regenerative medicine
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