Maxixe (Cucumis anguria L.), also known as Burr gherkin and West Indian gherkin, was brought to Brazil from Africa during the slave trade. This crop was grown extensively in New England in the 18th and 19th centuries. There has been a tremendous increase of immigrants to the United States in recent years, and this has provided an opportunity for farmers to produce crops desired by these new and expanding markets. In order to benefit local farmers, two field experiments were implemented in 2009 and 2010 to address the effect of plant population, the use of a trellis and evaluate different seed sources of maxixe to assist producers interested in growing this crop in the Northeastern United States. The Trellis/Spacing trial was set up as a randomized–complete-block-split-plot design with five replications of ‘Trellis’ versus ‘No Trellis’ and within each trellis treatment there were five spacing between plants in the row: 15, 30, 45, 60, and 75 cm. The Seed Source trial was set up as a randomized complete block design with five replications and five sources of maxixe from five different seed companies: ‘Isla’, ‘Feltrin’, ‘Topseed’, ‘HF’, ‘Seed Savers Exchange’, and ‘Baker Creek Heirloom Seeds’. The five seed sources of maxixe are commercially viable for production in Massachusetts. The best plant spacing for marketable yield and marketable number of fruits was ‘15 cm’ in 2009; however, in 2010, the plant spacing that had the best marketable yield and the greater marketable number of fruits was ‘60 cm’ and ‘30 cm’, respectively. The use of trellis support indicated that the net returns on the ‘Trellis’ are higher than ‘No trellis’. However it is critical to understand the market preferences, such as size of the fruits and spines. This work speaks to the opportunities to supply the Brazilian markets and introduce this crop to non-Brazilian markets.

Fragile X Syndrome (FXS) is a prevalent monogenic disease, often presenting with cognitive and neurological disorders including autism and epilepsy. The Fmr1 gene - transcriptionally silenced in FXS - normally encodes the Fragile X Mental Retardation Protein (FMRP), which acts as an activity dependent translational regulator at the base of dendritic spines. In an attempt to understand its role, dendritic spines in the dentate gyrus (DG) and cornu ammonis 1 (CA1) hippocampal regions of three-week old Fmr1- mice were analyzed and compared to wildtype (WT) littermate controls using electron microscopy. Dendritic spines with a continuous profile of the parent dendrite, spine neck, and spine head complete with synaptic components (presynaptic vesicles and postsynaptic densities) were included in our morphological analyses. We observed no changes in postsynaptic density length (DG: 5.69±0.30/6.18±0.85; SR: 7.55±0.87/6,96±0.33 µm/100 µm2; p=0.627/0.620), synapse density (DG: 32.3±3.8/30.3±1.9; SR: 34.4±1.8/30.7±0.5 synapses/100 µm2; p=0.655/0.270), spine head diameters (DG: 0.524±0.016/0.529±0.014; SR: 0.524±0.014/0.515±0.014 µm; p=0.098/0.20) or spine neck lengths (DG: 0.457±0.016/0.485±0.019; SR: 0.421 ± 0.015/0.425±0.017 µm; p=0.14/0.26), but found that in the DG spine necks were significantly narrower in the Fmr1- mice (0.193±0.0062/0.167±0.0064 µm; p=0.0002), whereas there were no changes in CA1 spine neck widths (0.162±0.0049/0.161±0.0061 µm; p=0.073). Estimated resistance calculated from spine necks morphologies revealed a ~1.7 fold increase in the Fmr1- DG compared to WT DG. These findings support that FMRP plays a role in granule cell spine neck structure and may influence synaptic signal compartmentalization and propagation in a regionally dependent manner. / Graduate

Social isolation during adolescence can have long lasting negative effects in both humans and animal models. In mice, post-weaning social isolation leads to increased addiction-like behaviors in adulthood. However, little is known about how post-weaning social isolation alters the brain. Stress during development can lead to persistent restructuring of neurons. Changes in dendritic spines can be long-lasting and have been theorized to play an important role in the maintenance of cocaine craving. We found that post-weaning isolation led to a persistent increase in spine density in adulthood within both the core and shell regions of the nucleus accumbens in male mice, but not female mice. In contrast, in the infralimbic cortex, post-weaning social isolation led to an increase in spine density only in female mice. This study highlights the long-lasting, sex-specific effects of post-weaning isolation. Microglia have been shown to assist in both the formation and elimination of dendritic spines, and are activated following exposure to stress and cocaine. Therefore, we hypothesized that microglia may be involved in the restructuring of dendritic spines during post-weaning isolation, and contribute to addiction-like behavior in adulthood. We examined whether inhibiting microglia with minocycline during the first three weeks of post-weaning isolation altered the impact of isolation in cocaine seeking. Isolated animals that received minocycline showed increased cocaine seeking in adulthood compared to group housed mice and isolated mice that received saline. Minocycline and isolation also caused sex-specific alterations in spine density. The findings of these studies provide insight into the mechanisms by which social isolation during adolescence increases vulnerability to addiction later in life. / Psychology

Neurodevelopmental disorders (NDDs) are a heterogeneous set of disorders that are characterized by early disruptions to brain development and include autism spectrum disorder (ASD), attention deficit/hyperactivity disorder (ADHD), developmental delay (DD), intellectual disability (ID), epilepsy and schizophrenia (SZ). Although thousands of genetic risk variants have been identified, there is a lack of understanding of how they impact cellular and molecular mechanisms that underlie the clinical presentation and heterogeneity of NDDs. To investigate this, we used a combination of cellular, molecular, bioinformatic and omics methods to study NDD-associated molecular pathways in distinct neuronal populations. First, we studied the interaction between the high-confidence SZ risk genes DISC1 and NRG1-ErbB4 in cortical inhibitory neurons and found that NRG1-ErbB4 functions through DISC1 to regulate dendrite growth and excitatory synapses onto inhibitory neurons. Next, we studied the 15q13.3 microdeletion, a recurrent copy number variation (CNV) that is associated with multiple NDDs. Using a heterozygous mouse model [Df(h15q13)/+] and human sequencing data we identified OTUD7A (encoding a deubiquitinase) as an important gene driving neurodevelopmental phenotypes in the 15q13.3 microdeletion syndrome. Due to the paucity of literature on the function of OTUD7A in the brain, we used a proximity-labeling approach (BioID2) to elucidate the OTUD7A protein interaction network (PIN) in cortical neurons, and to examine how patient mutations affect the OTUD7A PIN. We found that the OTUD7A PIN was enriched for postsynaptic and axon initial segment proteins, and that distinct patient mutations have shared and distinct effects on the OTUD7A PIN. Further, we identified the interaction of OTUD7A with a high-confidence bipolar risk gene ANK3, which encodes AnkyrinG. We identified decreased levels of AnkyrinG in Df(h15q13)/+ neurons, and synaptic phenotypes were rescued by increasing AnkyrinG levels or targeting the Wnt pathway. Future investigation should include examination of the role of OTUD7A deubiquitinase activity in neural development. / Dissertation / Doctor of Philosophy (PhD) / Neurodevelopmental disorders result from disruptions to early brain development and include autism spectrum disorder (ASD), developmental delay (DD), epilepsy, and schizophrenia (SZ). These disorders affect more than 3% of children worldwide and can have a significant impact on an individual’s quality of life, including an increased risk of death in some cases. There is currently a lack of understanding of how these disorders develop and how to effectively treat them. Neurodevelopmental disorders are thought to arise from alterations in the connections between brain cells (neurons) and one of the major risk factors for these disorders is having certain variations in regions of the genome (DNA sequences), with more than 1000 of these risk variants having been identified so far. In this thesis, we analyzed how genetic risk factors interact in neurons to regulate neural connectivity. We discovered that risk variants found in individuals with different disorders actually work together to regulate similar processes important for neural connectivity, which suggests that distinct disorders may share a common underlying cause. Additionally, we established the importance of a new ASD risk gene and discovered that it interacts with other known risk genes to regulate neural connectivity. This thesis provides new insights into the processes in the brain that lead to neurodevelopmental disorders and has implications for future development of effective therapies for individuals affected by these disorders.

No description available.

The majority of fast excitatory neurotransmission in the brain occurs at glutamatergic synapses. The extensive dendritic arborisations of pyramidal neurons in the neocortex and hippocampus harbor thousands of synaptic connections, each formed on tiny protrusions called dendritic spines. Spine synapses are rapidly established during early postnatal development – a key period in neural circuit assembly – and are subject to dynamic activity-dependent plasticity mechanisms that are believed to underlie neural information storage and processing for learning and memory. Recent decades have seen remarkable progress in identifying diverse plasticity mechanisms responsible for regulating synapse structure and function, and in understanding the processes underlying computation of synaptic inputs in the dendrites of individual neurons. These advances have strengthened our understanding of the biological mechanisms underlying brain function but, not surprisingly, they have also raised many new questions. Using a combination of whole-cell electrophysiology, 2-photon imaging and glutamate uncaging in rodent brain slice preparations, I have helped to document the subtype-specific regulation of glutamate receptors during a homeostatic form of synaptic plasticity at CA1 pyramidal neurons of the hippocampus, and have discovered novel synaptic calcium dynamics during a critical period of neural circuit formation. First, we found that during a homeostatic response to prolonged inactivity, both AMPA and NMDA subtypes of glutamate receptors undergo a switch in subunit composition at synapses, but exhibit a divergence in their subcellular localization at extrasynaptic regions of the plasma membrane (this work was published in the Journal of Neuroscience in 2013). In separate series of experiments using 2-photon calcium imaging, I discovered a functional coupling between NMDA receptor activation and intracellular calcium release at dendritic spines and dendrites that is selectively expressed during a critical period of synapse formation. This synaptic calcium signaling mechanism enabled the transformation of distinct spatiotemporal patterns of synaptic input into salient biochemical signals, and is thus apt to locally regulate synapse development along individual dendritic branches. Consistent with this hypothesis, I found evidence for non-random clustering of synapse development between neighboring dendritic spines. Together, these experimental results expand the current understanding of the dynamics of synapse function during homeostatic plasticity and early postnatal development. --- Les synapses glutamatergiques soutiennent la majorité de la neurotransmission excitatrice rapide du cerveau. Des milliers de ces synapses, localisées sur de minuscules saillies appelées épines dendritiques, décorent les vastes arborisations dendritiques des neurones pyramidaux du néocortex et de l'hippocampe. Ces synapses sont formées tôt lors du développement postnatal et sont soumises à des mécanismes dynamiques de plasticité qui sous-tendent, croit-on, les capacités d'apprentissage et de mémoire du cerveau. Les dernières décennies ont vu des progrès remarquables dans l'identification de divers mécanismes de régulation de la structure et de la fonction des synapses sur différentes échelles de temps, et dans la compréhension des processus qui régissent l’intégration des inputs synaptiques au niveau des dendrites individuelles. Ces progrès ont renforcé notre compréhension des éléments fondamentaux régissant la fonction cérébrale et ont ouvert de nouvelles voies d’investigations neurophysiologiques. En utilisant une combinaison d’électrophysiologie cellulaire, d'imagerie à deux-photons et de photolibération de glutamate sur des neurones pyramidaux de la région CA1 de l'hippocampe de rats, j’ai contribué à la découverte et à la caractérisation de nouvelles régulations des récepteurs du glutamate durant la plasticité synaptique homéostatique. J’ai également découvert un nouveau type de dynamique de calcium synaptique relié à une organisation spatiale du développement des synapses pendant une période critique de l’ontogénie des circuits neuronaux. Dans la première étude, nous avons constaté que lors d'une plasticité de type homéostatique induite par une inactivité prolongée, les récepteurs de glutamate de types AMPA et NMDA sont soumis à un changement important dans la composition de leurs sous-unités. De plus, nous avons observé un ciblage différentiel de ces récepteurs vers des compartiments subcellulaires spécifiques des neurones. Dans une série d'expériences séparée utilisant l’imagerie calcique à deux-photons, j’ai découvert un couplage fonctionnel durant le développent entre l'activation des récepteurs NMDA et une libération de calcium intracellulaire qui envahit tant les épines dendritiques que les dendrites. J’ai également trouvé que ce mécanisme de signalisation de calcium synaptique transforme des motifs spatiotemporels d’activités synaptiques spécifiques en signaux biochimiques post-synaptiques de manière à potentiellement réguler l’organisation spatiale des synapses durant le développement. Conformément à cette hypothèse, j’ai observé des manifestations fonctionnelles claires de regroupement dans l’espace de synapses de forces similaires le long de branches dendritiques individuelles. Ensemble, ces résultats expérimentaux élargissent notre compréhension actuelle de de la fonction des synapses durant la plasticité homéostatique ainsi que durant le développement postnatal du cerveau. En étudiant les mécanismes neurophysiologiques de base, il sera possible d'avoir un aperçu plus profond du fonctionnement du cerveau et de ses pathologies.

Excitotoxic calcium influx and activation of calcium-regulated systems is a common event in several types of neuronal injury. This mechanism has been the focus of intense research, with the hope that a more complete understanding of how neuronal injury affects calcium-regulated systems will provide effective treatment options. This study examines one such calcium-stimulated enzyme, calcineurin, in the context of two common neurological pathologies, status epilepticus and traumatic brain injury.Status epilepticus was induced by pilocarpine injection. NMDA-dependent increases in calcineurin activity were observed in cortical and hippocampal homogenates. Upon closer examination, the most profound increases in activity were found to be present in crude synaptoplasmic membrane fractions isolated from cortex and hippocampus. A concurrent status epilepticus-induced increase in calcineurin concentration was observed in membrane fractions from cortex and hippocampus. Immunohistochemical analysis revealed an increase in calcineurin immunoreactivity in apical dendrites of hippocampal pyramidal neurons. We examined a cellular effect of increased dendritic calcineurin activity by characterizing a calcineurin-dependent loss of dendritic spines. Increased dendritic calcineurin led to increased dephosphorylation and activation of cofilin, an actin-depolymerizing factor. Calcineurin-activated cofilin induced an increase in actin depolymerization, a mechanism shown to cause spine loss in other models. Finally, via Golgi impregnation, we demonstrated that status epilepticus-induced spine loss is blocked by calcineurin inhibitors.To demonstrate that the increase in dendritic calcineurin activity was not model-specific, we examined a moderate fluid-percussion model of brain injury. Calcineurin activity was significantly increased in hippocampal and cortical homogenates. This increased activity persisted for several weeks post-injury, and may be involved in injury-induced neuronal pathologies. Also similar to the SE model, calcineurin immunoreactivity was dramatically increased in synaptoplasmic membrane fractions from cortex and hippocampus, and immunohistochemistry revealed increased calcineurin content in dendrites of hippocampal CA1-3 pyramidal neurons. These changes in calcineurin distribution also persisted for several weeks post-injury.These studies demonstrate a novel, cellular mechanism of calcium-mediated pathology in two models of neuronal injury. Elucidation of cellular events involved in the acute and chronic effects of brain trauma is essential for the development of more effective treatment options.

La cellule de Purkinje (PC) est l'élément central du réseau neuronal du cortex cérébelleux et possède un arbre dendritique très développé qui se développe au cours des trois premières semaines post-natales chez la souris. Cette arborisation nécessite de nombreux réarrangement du cytosquelette, un processus contrôlé par les GTPases et leurs régulateurs, les GEFs et les GAPs, dans de nombreux types cellulaires. Au cours de ma thèse, j'ai étudié l'implication de la signalisation des RhoGTPases dans le développement post-natal du cervelet, et plus particulièrement des PCs chez la souris. Afin d'identifier de nouveaux acteurs de la signalisation des RhoGTPases impliqués dans la différenciation des PCs, nous avons établi le profil d'expression de toutes les GTPases et des GEFs de la famille DOCK à différents stades de développement de ces cellules (P3, P7, P15, P20) par Q-PCR en temps réel. Cette approche globale nous a permis d'identifier une GTPase, RhoQ, et un GEF, DOCK10, dont l'expression est très fortement augmentée au cours du développement des PCs. Nous avons montré que l'extinction de leur expression par infection lentivirale dans un modèle de coupes organotypiques de cervelet ou dans des neurones d'hippocampe entraine une très forte diminution du nombre d'épines dendritiques, révélant un rôle crucial de ces protéines dans la différenciation des PCs. / Purkinje cell (PC) occupy a central and integrative position in the synaptic network of the cerebellum and have the most elaborate dendritic tree among CNS neurons, which develops remarkably in the first three postnatal weeks in mice. This arborization requires intensive actin cytoskeleton remodeling, a process known in many cell types to be controlled by Rho GTPases and their regulators, GEFs and GAPs. During my thesis, I investigated the importance of Rho signaling during postnatal mouse cerebellar development, focusing on PC differentiation.In order to identify novel regulators of PC differentiation among members of the Rho signaling pathway, I undertook a global approach, comparing gene expression profiles of all mammalian Rho GTPases and all GEFs of the DOCK family at various stages of postnatal PC differentiation (P3, P7, P15 and P20) using real-time quantitative PCR. My global approach has allowed the identification of two Rho signaling actors, the GTPase RhoQ and the RhoGEF DOCK10, whose expressions increase dramatically during cerebellar development. Lentiviral shRNA-mediated knock down of their expression in organotypic cerebellar cultures and in hippocampal neurons showed strong dendritic spine defects, revealing an essential role for these proteins in PC differentiation.

Entender como as interações ecológicas moldaram a dinâmica evolutiva dos caracteres das espécies continua sendo um desafio em ecologia evolutiva. Combinando modelos de evolução de caracteres e filogenias, nós analisamos a evolução de caracteres associadas à dispersão de sementes (tamanho e cor do fruto) e herbivoria (espinhos) em palmeiras neotropicais para inferir o papel das interações positivas e negativas entre plantas e animais na condução dos padrões evolutivos. Nós encontramos que o tamanho e a coloração dos frutos é evolutivamente correlacionada ao longo da história evolutiva das palmeiras neotropicais, suportando a interpretação adaptativa das síndromes de dispersão e destacando o papel de frugívoros em moldar caracteres de plantas. Além disso, nós encontramos uma associação positiva nas linhagens de palmeiras entre o tamanho de fruto e a presença de espinhos nas folhas e caule. Nós hipotetizamos que interações entre palmeiras e grandes mamíferos extintos podem explicar a relação entre tamanho de frutos e espinhos nas linhagens de palmeiras. Frugívoros de grande porte, como a megafauna extinta, além de consumir os frutos e dispersar sementes grandes, também podem consumir e/ou danificar outras partes da planta, favorecendo simultaneamente a evolução de grandes frutos e estruturas de defesa. Nossos resultados mostram como os padrões de caracteres atuais de um determinado clado podem ser entendidos como o resultado da interação entre interações antagonistas e mutualistas que aconteceram ao longo da história evolutiva do clado / Understanding how ecological interactions have shaped the evolutionary dynamics of species traits remains a challenge in evolutionary ecology. Combining trait evolution models and phylogenies, we analyzed the evolution of traits associated with seed dispersal (fruit size and color) and herbivory (spines) in Neotropical palms to infer the role of opposing animal-plant interactions in driving evolutionary patterns. We found that the evolution of fruit color and fruit size were associated in Neotropical palms, supporting the adaptive interpretation of seed-dispersal syndromes and highlighting the role of frugivores in shaping plant evolution. Furthermore, we reveal a positive association between fruit size and the presence of spines on palm leaves and stems. We hypothesize that interactions between palms and extinct large-bodied frugivores may explain the relationship between fruit size and spines. Large-bodied frugivores, such as extinct megafauna, besides consuming the fruits and dispersing large seeds, may also have consumed the leaves or damaged the plants, thus simultaneously favoring the evolution of large fruits and defensive structures. Our findings show how current trait patterns can be understood as the result of the interplay between antagonistic and mutualistic interactions that have happened throughout the evolutionary history of a clade

Engrailed (En) est un facteur de transcription important pour la mise en place de la segmentation de l’embryon et du plan d’organisation antéro-postérieur. Comme d’autres membres de la famille des homéoprotéines, Engrailed peut aussi agir comme une molécule de signalisation extracellulaire, internalisable grâce à son domaine « pénétratine » et stimulant dans la cellule cible la transcription ou la traduction des ARNm. De cette façon, Engrailed guide les axones en modifiant la traduction dans le cône de croissance axonal et l’infusion cérébrale d’Engrailed protège les neurones dopaminergiques dans un modèle de la maladie de Parkinson en augmentant la traduction de protéines mitochondriales. Des troubles cognitifs et un déficit des interactions sociales ont été observés chez les souris En1+/- et les souris En2-/-. Une augmentation de l’expression d’En2 a aussi été observée chez des patients atteints de troubles du spectre autistique. Néanmoins, le lien entre les modifications de l’expression d’Engrailed et l’autisme ne sont pas compris. L’objectif de cette thèse a été d’étendre notre connaissance des fonctions d’Engrailed dans une région télencéphalique où elle est a priori peu exprimée (l’hippocampe). Nos résultats confirment l’expression d’En1 et En2 dans l’hippocampe mature et décrivent les variations de l’expression de ces gènes au cours du développement de cette structure. En1 et En2 présentent des patrons d’expression différents pendant la première semaine postnatale et chez l’adulte suggérant que des variations du dosage génique d’Engrailed sont liées à certaines phases du développement, en particulier au début de la synaptogenèse. Nous avons également découvert que dans les cultures de cellules d’hippocampe Engrailed est exprimé dans les neurones et que son expression est plus forte dans les neurones GABA-ergiques, notamment dans leurs prolongements dendritiques et axonaux. Nous avons constaté qu’un excès d’Engrailed (décrit dans certains cas de TSA) augmente la complexité dendritique ainsi que la densité des épines dendritiques plastiques mais sans augmenter parallèlement la formation de synapses matures excitatrices. Nous avons observé des variations de densité des épines dendritiques chez les souris En2-/- et les souris En1+/-, ce qui confirme l’implication d’Engrailed dans leur formation ou leur stabilisation. Si dans nos conditions expérimentales l’excès d’Engrailed ne modifie pas la densité des synapses, un mutant d’Engrailed qui présente une interaction réduite avec eIF4E est moins efficace qu’Engrailed pour augmenter la densité des épines et diminue la densité des boutons présynaptiques et le synaptic matching. Ces résultats indiquent que l’interaction avec eIF4E régule au moins en partie les effets d’Engrailed sur la spinogenèse et suggèrent également une implication d’Engrailed dans la formation ou la stabilisation des boutons présynaptiques. Le rôle clef d’eIF4E dans la traduction permet de postuler que certains effets d’Engrailed observés dans notre étude pourraient dépendre de la synthèse protéique. Nos résultats montrent à cet égard qu’Engrailed augmente la synthèse protéique dans les neurones d’hippocampe. Cette traduction est différente de celle induite par la LTP chimique (LTPc) car insensible à l’action des oligomères synthétiques d’AβO, responsables sous leur forme naturelle de synaptopathies dans le contexte de la maladie d’Alzheimer. Engrailed permet également de restaurer la traduction défaillante de neurones issus de souris TG2576, modèles de la maladie d’Alzheimer. Dans leur ensemble, nos résultats identifient Engrailed comme un nouvel acteur de la plasticité dendritique. Ils révèlent qu’un excès d’Engrailed au cours de la synaptogenèse modifie les caractéristiques des dendrites, une situation susceptible d’altérer les caractéristiques fonctionnelles du réseau dendritique dans une situation de surexpression pathologique de la protéine. (...) / Engrailed (En) is an important transcription factor in embryo’s segmentation and anterior-posterior axis establishment during early embryogenesis. As several homeoproteins, Engrailed can act as an extracellular signalling molecule which can be internalized by target cells thanks to its penetratin domain and act through transcriptional and/or translation dependent mechanisms. Engrailed has for instance, translation-dependent effects on axonal guidance and cerebral infusion of Engrailed protects dopaminergic neurons in a Parkinson disease model by increasing mitochondrial protein translation. Also, cognitive defects were observed in En1+/+ and En2-/- and En2 expression is increased in ASD patients. This work consisted in extending the knowledge of Engrailed expression and functions. We explored the links with a telencephalic structure where it is a priori fewly expressed (hippocampus). Our results confirm En1 and En2 expression in the mature hippocampus and describe their respective expression along the development of this structure. En1 and En2 have different expression patterns during the first post-natal week as well as in the adulthood suggesting a genetic dosage of Engrailed during the development, specifically with the beginning of synaptogenesis. We also reveal that Engrailed, expressed in hippocampal neurons, is more expressed in GABA-ergic neurons, notably in their dendritic and axonal neurites. We observe that an excess of Engrailed (described in some ASD cases) increases dendritic complexity as well as plastic dendritic spine density, without affecting mature excitatory synapses. We show that En2-/- and heterozygote En1 mice have variations in dendritic spine density, which confirms that Engrailed is involved either in their formation or stabilization. Even though our experiments show no modification of synapse density with an excess of Engrailed, a mutant showing a decreased eIF4E interaction and less efficient than wild type Engrailed to increase dendritic spine density, decreases presynaptic button density and synaptic matching. Those results indicate that eIF4E interaction with Engrailed is, at least in part, responsible for its effects on spinogenesis and suggest a role of Engrailed in presynaptic button formation/stabilization. Key-role of eIF4E in translation allow to hypothesize that some of Engrailed effects we report could be translation dependent. In this sense, our results show that Engrailed is able to increase proteic synthesis in hippocampal neurons. This translation is different from the one induced by chemical LTP (LTPc): it is not altered by synthetic AβO, which are the main toxic agent when produced at abnormally high levels in Alzheimer disease. Engrailed is also able to restore defaulting translation in neurons from Alzheimer disease mice model (TG2576). As a whole, our results identify Engrailed as a novel actor in dendritic plasticity. They reveal that an excess of Engrailed during synaptogenesis can modify dendrite characteristics. This can lead to dendritic network dysfunction in a context of pathologic surexpression of Engrailed. Our observations open to new perspectives contributing to a better understanding of the relationship between Engrailed and ASD. Finally, this work lays the foundation to potentially fruitful links between Engrailed and AβOligomers signalling pathways, where modulation of protein synthesis could be a therapeutic lever in physiopathologic conditions.