Nous étudions la migration radiale des étoiles, et testons son impact sur l’évolution chimique de la Voie Lactée. Pour cela nous utilisons une simulation N-corps+SPH (Gadget-3) de galaxie fortement barrée, afin d’étudier la migration radiale induite par la barre. Nous examinons un nouveau mécanisme de migration radiale: une fraction des étoiles piégées à la corotation de la barre, se déplacent avec le rayon de corotation lorsque celui-ci va vers l’extérieur (quand la vitesse de rotation de la barre diminue, du fait de son évolution séculaire). Nous montrons que ce mécanisme affecte principalement les régions externes du disque, à condition que la corotation atteigne ces régions. Nous montrons également que ce mécanisme n’a pas d’effets dans la Voie Lactée, car les estimations observationnelles des caractéristiques de la barre, indiquent que la corotation est loin des zones externes. Nous analysons également la migration radiale dans cette simulation, afin de construire un modèle empirique de diffusion stellaire dans le disque, et nous incluons ce modèle dans un code semi-analytique d’évolution chimique de galaxie. Nous testons la validité de cette approche en vérifiant que les galaxies simulées N-corps+SPH et semi-analytique ont des propriétés morphologiques et chimiques similaires. Nous appliquons ensuite notre modèle à la Voie Lactée, en adaptant les paramètres du modèle. Puis, nous comparons les résultats obtenus avec un grand nombre d’observations concernant le voisinage solaire (relation âge-métallicité, distribution de métallicité, relation a/Fe vs Fe/H et la bimodalité disque mince - disque épais) , et les gradients radiaux d’abondance. / We study the radial migration of stars, and test its impact on the chemical evolution of the Milky Way. For this we use a simulation-body + SPH (Gadget-3) strongly barred galaxy to study the radial migration induced by the bar. We examine a new mechanism of radial migration: a fraction of stars trapped at corotation with the bar, move with the corotation radius when it goes outwards (when the rotational speed of the bar decreases, because of its secular evolution). We show that this mechanism affects mainly the outer regions of the disc, provided that the corotation reaches these regions. We also show that the mechanism has no effects in the Milky Way, as the observational estimates of the characteristics of the bar indicates that the corotation is not in the outer regions. We also analyze the radial migration in this simulation to construct an empirical model of diffusion in the stellar disk, and we include this model in a semi-analytic code of chemical evolution of galaxy. We test the validity of this approach by ensuring that the galaxies simulated with N-body + SPH and semi-analytic have similar morphological and chemical properties. We then apply our model to the Milky Way, by adapting the model parameters. Then, we compare the results obtained with a large number of observations on the solar neighborhood (age-metallicity relation, metallicity distribution, relationship O/Fe vs. Fe/H and bimodality thin disk - thick disk), and radial gradients of abundances.

Pocket proteins (pRb, p107 and p130) are well studied in the role of regulating cell proliferation by controlling progression through the G1/S phase of the cell cycle. Increasing genetic and anatomical evidence suggests that these proteins also control early differentiation and even later stages of cell maturation including neural migration. However, the multifaceted functions of pocket proteins in the regulation of cell proliferation and cell death has complicated our interpretation of their role during development. As a result, the mechanisms through which pocket proteins regulate neuronal migration and neural maturation remain unknown. Using a pRb and p107 double knock out model, we show that a population of upper layer cortical neurons fails to pass through the intermediate zone into the cortical plate. Importantly, these neurons are born at the appropriate time and have exited the cell cycle. In addition, the role of pocket proteins in radial migration is independent cell death, since this migration defect cannot be rescued by eliminating ectopic cell death through Bax deletion. We also show a novel role of pRb and p107 in development of the dorsal midline and guidance of callosal axons. In the absence of pRb and p107, the structures of the commissural plate are highly disorganized and the callosal axons fail to cross the midline. We identify primary defects in axon extension and expression of multiple guidance cues, which can be observed prior to the disorganization of the midline axon guidance structures. Through the use of in vitro cortical explants and in utero electroporation, we identify defects in the rate of axon extension and directional guidance independent from the midline. In addition, protein levels of Netrin and Neuropilin-1 are decreased in the absence of pRb and p107, which could mediate the function of pocket proteins in guiding callosal axons. Indeed, we identify a previously undescribed population of Netrin expressing cells in the cingulate cortex of control embryos which is lost in the pRb/p107 deficient littermates. We propose that these cells play a significant role in callosal axon guidance during normal development. The results presented in this dissertation define multiple novel roles of pRb and p107 in the regulation of radial migration and axon guidance, independent from the role of these pocket proteins in cell death and proliferation.

La cytoarchitecture du néocortex repose sur la coordination spatiotemporelle des taux de production des neurones ‐via la régulation du cycle cellulaire de leurs progéniteurs‐ et de leur migration radiale vers la surface corticale. Chez le primate, les couches supragranulaires de l'aire 17 sont plus développées que celles de l'aire 18, conséquence d'une prolifération et d'une production neuronale accrues dans l'aire 17 à E77‐80. Des observations en vidéomicroscopie bi‐photonique, sur tranches organotypiques de cortex, révèlent que la migration radiale est plus rapide dans l'aire 17. Les variations aire‐spécifiques des taux de prolifération et de migration neuronale sont donc congruentes. L'étude des mécanismes moléculaires qui sous‐tendent la régulation coordonnée de la prolifération et de la migration est centrée sur le régulateur du cycle cellulaire p27kip1, qui via son domaine C‐terminal promeut la migration en inhibant la GTPase RhoA. Ce rôle pléiotrope de p27 a été exploré dans la migration nucléaire intercinétique (INM) qu'effectuent les précurseurs de la zone ventriculaire corticale, en synchronie avec les phases du cycle cellulaire. Des formes mutantes de p27 ou des shRNA ont été électroporés spécifiquement dans les neuroblastes d'embryons murins à E14‐15. Des observations en vidéomicroscopie bi‐photonique sur tranches organotypiques révèlent que le domaine C-terminal de p27 affecte l'INM, promeut les décisions différenciatives et la migration radiale. P27 se place donc au sein d'un réseau moléculaire contrôlant conjointement, et de façon aire-spécifique, les divisions successives des précurseurs corticaux, ainsi que la migration des neurones qui en sont issus / Cortical cytoarchitecture relies on the spatiotemporal coordination of neuronal production rate, precursors cell-cycle control and neuronal radial migration towards the cortical plate. In the primate, area 17 supragranular layers are more developed than in area 18, due to higher proliferation and neuronal production rates in area 17 between E77-80. Two-photon videomicroscopy observations on cortical organotypic slices revealed that radial migration is faster in area 17 than 18. This indicates that area-specific variations of proliferation and migration rates are congruent during corticogenesis. The study of molecular mechanisms underlying the coordinated regulation of proliferation and migration focused on the cell-cycle regulator p27kip1, which promotes migration, via inhibition of the Rhoa GTPase by its C-terminal domain. This p27 dual function could play a major role during the Interkinetic Nuclear Migration (INM) performed by cortical precursor cells from the ventricular zone, in synchrony with the cell-cycle phases. Mutant forms of p27 or shRNA were electroporated into neuroblasts of E14-15 mice embryos. Two-photon videomicroscopy observations on organotypic slices revealed that p27 affects INM, promotes differentiative divisions and neuronal radial migration, though its C-terminal domain. P27 is thus part of a molecular network which finely tunes, in an area-specific manner, the successive rounds of divisions of precursor, as well as the migratory behavior of the newborn neurons

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