Les éponges (Porifera) sont l'une des premières lignées d'animaux à avoir émergé. De ce fait, elles sont considérées comme des espèces clés pour retracer l’origine et l'évolution des gènes et des voies de signalisation qui ont sous-tendu l'apparition de la pluricellularité chez les métazoaires. Entre autres, les voies Wnt ont été décrites comme des cascades génétiques essentielles du control de nombreux mécanismes cellulaires (prolifération, communication, adhésion, motilité, etc.) au cours du développement précoce des bilatériens et des cnidaires. C’est pourquoi, l'étude de ces voies, chez les lignées d’émergences plus anciennes sont essentielles afin de comprendre l'origine des plans d’organisation des animaux.J’ai alors entrepris de nombreuses analyses bioinformatiques sur différentes bases de données d’éponges. Il apparait alors que l’ancêtre commun des éponges possédait déjà certainement tous les composants des voies Wnt. Néanmoins, à ce jour, puisque l’intégralité de ces composants n’a été identifiée que dans le genre Oscarella (lignée des Homoscleromorpha), différentes pertes secondaires sembleraient s’être produites chez les démosponges, les éponges calcaires et les hexactinellides. Afin de tester si ces gènes orthologues sont impliqués dans la mise en place du plan d’organisation des éponges, des études fonctionnelles ont été mises en œuvre. Ces approches fonctionnelles réalisées sur deux lignées d’éponges différentes tendent alors à confirmer la conservation des voies de signalisation Wnt dans les processus de mise en place des plans d’organisation des animaux, à la fois au cours de l'embryogenèse mais aussi lors du renouvellement cellulaire chez l'adulte. / Sponges (Porifera) are one of the earliest emerged animal lineages. They are thus considered as key species to retrace early evolution of genes and pathways underlying the emergence of multicellularity in metazoans. Among others, the Wnt pathways have been described as crucial modules controlling cell proliferation, cell communication, cell adhesion and cell motility during the early development of Bilaterians and Cnidarians. Therefore the study of these signaling pathways in more basally branching lineages is essential for unraveling the origin of animal body plans. I performed numerous bioinformatic analyses on different poriferan databases. One of my main results is that the last common ancestor of Porifera probably already possessed all the components of the Wnt pathways. Nevertheless, because, to date, all these components were only retrieved in the Oscarella genus (Homoscleromorpha lineage), several secondary gene losses would have occurred in other sponge lineages, namely Demospongia, Calcarea and Hexactinellida.In order to test whether or not these retrieved orthologous genes, are involved in patterning sponge body plan (as they do in Bilateria and Cnidaria), functional studies were implemented. These functional studies performed on two different lineages tend to confirm that Wnt signaling pathways were conserved from sponges to vertebrates to pattern animal body plan during both embryogenesis and cell renewal in adult.

O cristalino de vertebrados se origina a partir da invaginação do ectoderme que recobre a vesícula óptica. A invaginação epitelial em diversos modelos é causada pela constrição celular apical, mediada pela contração apical de actina e miosina II e regulada pela GTPase RhoA. Neste trabalho nós investigamos se a invaginação do cristalino em embriões de galinha ocorre devido à constrição celular apical e se este evento é controlado por RhoA. Actina filamentosa e miosina II são expressas na porção apical do cristalino durante a invaginação. Quando a polimerização de actina é inibida por Citocalasina D, o cristalino não invagina, sugerindo que a constrição celular apical poderia contribuir para a invaginação do cristalino. RhoA também é expressa durante o desenvolvimento do cristalino, mas a inibição de RhoA, por eletroporação da forma dominante-negativo, não impediu a invaginação do placóide do cristalino, não alterou a distribuição de miosina II na porção apical do cristalino nem sua ativação, indicando que a invaginação do cristalino independe de RhoA. / Vertebrate lens derives from invagination of the ectoderm that overlies optic vesicles. Epithelial invagination in many model systems is driven by apical cell constriction, mediated by actin and myosin II contraction regulated by GTPase RhoA. Here we investigate the possibility that chick lens placode invagination could also be driven by apical cell constriction and controlled by RhoA. We show that actin and myosin II are expressed at lens apical side during lens invagination. Actin polymerization inhibition by in ovo Cytochalasin D treatment prevents lens placode invagination, suggesting that lens placode invagination could be driven by apical cell constriction. RhoA GTPase is also expressed at apical portion of lens placode and during lens invagination. However, when we overexpressed by electroporation the dominant-negative RhoA in the pre-lens ectoderm invagination was not affected. Furthermore, dominant-negative RhoA didnt affect myosin II apical localization nor myosin II phosphorilation, indicating that in lens invagination this process is not regulated by GTPase RhoA.

O capim-braquiária (Brachiaria decumbens Stapf. cv. Basilisk) tem grande importância para sistemas de produção pecuários no Brasil, notadamente em regiões com baixa fertilidade natural do solo. O objetivo do presente trabalho foi estudar efeitos de duas intensidades (5 e 10 cm de altura pós-pastejo) e duas frequências de desfolhação (descanso até 95 e 100% de interceptação luminosa, IL, para início do pastejo) como definidores da estrutura do dossel, da morfogênese e do valor nutritivo da B.decumbens cv. Basilisk sob lotação intermitente. O estudo foi conduzido em Brotas - SP. O período experimental foi de Jan 2007 a Ago 2008, compreendendo sete épocas (Verão/2007, Outono/2007, Inverno/2007, Final de primavera/2007, Verão/2008, Outono/2008 e Inverno/2008) para as variáveis: produção de forragem, composição morfológica, índice de área foliar (IAF), altura de dossel, IL e valor nutritivo de folhas. Para características morfogênicas, densidade e demografia de perfilhos, o período foi de Ago 2007 a Ago 2008 e para valor nutritivo da forragem de Jan 2008 a Ago 2008. Os tratamentos foram quatro combinações possíveis entre as duas intensidades e frequências de desfolhação, em arranjo fatorial, com quatro repetições num delineamento inteiramente casualizado.O manejo com 100% IL resultou em produção total de 17,1 Mg MS ha-1, enquanto que para 95% IL a produção foi de 14,2 Mg MS ha-1. Pastos sob a estratégia 100% IL resultaram em maior produção de colmos e material morto, e maior IAF-pré pastejo. A intensidade de 10 cm promoveu maior produção de forragem e colmos (16,6 e 4,4 Mg MS ha-1), e maior IL e IAF no pós-pastejo. As maiores taxas de aparecimento de folhas (TAPF) e menores taxas de senescência foliar (TSF), alongamento (TALC) e acúmulo de colmo (TAFCM), na primavera de 2007 até outono de 2008 foram obtidas para 95% IL.As maiores taxas de acúmulo de folhas (TAFLM)no final da primavera ocorreram em pastos submetidos a 95% de IL e no verão e outono para o tratamento 10/95 (24,3, 26,8 e 23,3 kg MS ha-1 dia-1). De forma geral, o tratamento 10/95 resultou em altas taxas de aparecimento e de sobrevivência de perfilhos basais nas épocas com maior disponibilidade nos fatores de crescimento, épocas em que também foram encontrados os maiores teoresem proteína bruta (PB) de folhas para 95% IL, enquanto adigestibilidade in vitro da matéria orgânica (DIVMO)de folhas foi maior para a intensidade de 10 cm. As menores DIVMOs da forragem foram encontradas nos pastos que receberam a combinação 5/100, indicando que períodos longos de descanso e intensidades altasde pastejo resultam na produção de forragem de baixo valor nutritivo. A altura de dossel no pré-pastejo para o manejo com 95% IL ficou próximo a 16 cm e para 100% IL em 22 cm. A desfolhação do capim-braquiária deve ser realizada até10 cm uma vez que isto resulta em rebrotações rápidas e, quando associado à frequência de 95% IL, permite que animais em pastejo tenham acesso a forragem com maior participação de folhas e menor de material morto e colmo. / Signalgrass (Brachiaria decumbens Stapf. cv. Basilisk) is an important forage resource in Brazilian livestock systems, mainly where soil natural fertility is low. The objective in this study was to investigate the effects of two intensities (5 and 10 cm stubble) and two frequencies of defoliation (rest periods determined by 95 or 100% light interception LI by the canopy) as determinants of sward structure, morphogenesis, and forage nutritive value of B.decumbens cv. Basilisk under intermittent grazing. The work was carried out in Brotas, SP. The experimental period was from Jan 2007 through Aug 2008, divided in seven seasons (Summer/2007, Autumn/2007, Winter/2007, Late Spring/2007, Summer/2008, Autumn/2008 and Winter/2008) for the response variables: forage production, plant-part composition, leaf area index (LAI), sward height, LI, and leaf nutritive value. For the morphogenetic characteristics, tiller density, and tiller demography, the experimental period was from Aug 2007 through Aug 2008. For forage nutritive value, it was from Jan 2008 through Aug 2008. Treatments included all possible combinations among two grazing frequencies and two intensities, in a factorial arrangement of a completely randomized design. The 100% LI management resulted in total yield of 17.1 Mg DM ha-1, whereas for the 95% LI treatments total production was 14.2 Mg DM ha-1. Pastures under the 100% LI strategy produced more stem and dead material, as well as higher pregraze LAI. The 10-cm stubble resulted in higher forage and stem yield (16.6 and 4.4 Mg DM ha-1, respectively), as well as higher postgraze LI and LAI.The highest leaf appearance rates and lowest rates of leaf senescence, leaf elongation, and stem accumulation from Spring 2007 through Autumn 2008 were recorded for 95%LI. The highest rates of leaf accumulation in late spring were found in pastures under 95% LI, and in the summer and autumn for the 10/95 treatment (24.3, 26.8 and 23.3 kg DM ha-1 d-1, respectively). In general, the 10/95 treatment resulted in high rates of basal tiller appearance and survival, when the environmental conditions were favorable, which was also when crude protein concentration in leaves was highest under 95% LI, whereas in vitroorganic matter digestibility (IVOMD) of leaves was higher for the 10 cm stubble. The lowest IVOMDs were found in pastures receiving the 5/100 treatment combination, indicating that long rest periods combined with high grazing intensities result in forage of low nutritive value. Pregraze sward height for the 95%-LI managements was around 16 cm and for the 100%-LI, around 22 cm. Defoliation of signalgrass should not be lower than 10 cm height, since this results in rapid regrowth and, when associated with the 95%-LI frequency, allows animals to harvest forage with high proportion of leaves and low proportion of stem and dead material.

Comment les cellules établissent leurs formes et organisations internes est un problème biologique fondamental. Au cours de cette thèse, j’ai étudié le développement de la forme cellulaire et de la polarité chez la cellule de levure fissipare. Ces études sont fondées sur l’exploration de la façon dont les petites spores symétriques de levures se développent et s’organisent pour briser la symétrie pour la définition de leur tout premier axe de polarité. Dans une première partie, j’ai étudié les couplages entre la mécanique de surface de la paroi cellulaire des spores et la stabilité de domaines de polarité de Cdc42 qui contrôlent les aspects spatio-temporelles de la brisure de symétrie de ces spores. Dans une seconde partie, j’ai étudié les mécanismes par lesquels ces domaines de polarité contrôlent leur taille et l'adapte à la géométrie de la cellule, un processus vraisemblablement pertinents pour comprendre comment des domaines fonctionnels corticaux s’adaptent à la taille des cellules. Globalement, ces nouvelles recherches focalisant sur la façon dont les cellules développent dynamiquement leur forme et polarité de novo, permettent de mettre en évidence des couplages complexes dans la morphogenèse qui ne peuvent pas être testés en regardant les cellules à « l’état stationnaire» ou avec des outils génétiques. / How cells establish their proper shapes and organization is a fundamental biological problem. In this thesis, I investigated the dynamic development of cellular form and polarity in the rod-shape fission yeast cell. These studies are based on monitoring how small symmetric fission yeast spores grow and self-organize to break symmetry for the definition of their very first polarity axis. In a first part, I studied interplays between surface mechanics of the spore cell wall and the stability of Cdc42-based polarity domains which control spatio-temporal aspects of spore symmetry breaking. In a second part, I studied mechanisms by which these polarity domains control their width and adapt it to cell surface geometry, a process likely relevant to understand how functional cortical domains scale to cell size. Overall these novel investigations focusing on how cells dynamically develop their form and polarity de novo highlight complex feedbacks in morphogenesis that cannot be evidenced by looking at cells at “steady state” or with genetics.

No description available.

The work presented in the thesis was carried with the aim to understand how Widerborst (Wdb) regulate planar cell polarity in Drosophila wing. In search of proteins interacting with Wdb I carried a Yeast Two Hybrid screen and identified a protein, bitesize, with tandem C2 domains in its C terminus interacting with Wdb. Wdb also interacts with btsz genetically and removal of one copy each of Wdb and btsz enhances the truncated hair phenotype observed in Wdb EMS mutants and btsz P element insertion mutants. There are at least three predicted isoforms of bitesize and loss of the btsz-II isoform is lethal. Clonal analysis of a btsz mutant, btszJ5-2, which removes the btsz II isoform resulted in truncated wing hair outgrowth. On the other hand over expression of a myc-btsz-II construct resulted in hair duplication phenotype. However, over expression of the GFP-CT is sufficient to give wing hair duplication phenotype and this hair duplication phenotype is stronger than that caused by myc-btsz-II over expression. The Myc tagged btsz-II protein shows apical localization. Though most of the protein is confined to cytoplasm, btsz-II also marks the plasma membrane. The GFP-CT construct marks the plasma membrane strongly and is enriched in the apical region. The over expression of CT domain is sufficient to give hair duplication phenotype and the strong difference observed in the localization pattern of full length btsz-II protein and GFP-CT together suggest that regulation of membrane localization of btsz through its CT region is important to regulate hair morphogenesis. As the loss of function (truncated wing hair) and gain of function (hair duplication) both affect the process of hair morphogenesis, it can be said that btsz is a positive regulator of hair morphogenesis. Since no defect in cortical polarization of Fmi was observed in cells lacking btsz-II, btsz is required for establishment of cortical domains. However with the present study it remains unknown how exactly the C2 domains might regulate hair morphogenesis and whether Wdb targets btsz for dephophorylation to PP2A catalytic subunit.

Development of functional neural circuits involves a series of complicated steps, including neurogenesis and neuronal morphogenesis. To understand the molecular mechasnims of neurite complexity, especially neurite branching/arborization, the Drosophila brain, especially MBNs (mushroom body neurons) and PNs (projection neurons) in olfactory circuitry, was used in this dissertation work as the model system to study how two molecules, Dscam and Kr-h1 affect neurite complexity in the Drosophilabrain. For the Drosophila Dscam, through alternative splicing it could encode up to 152,064 distinct immunoglobulin/fibronectin type cell adhesion molecules. Each Dscam isoform is derived from one of the 19,008 ectodomain variants connected with one of the two alternative transmembrane segments and one of the four possible endodomain portions. Recent studies revealed that Dscam was widely required for neurite branching/arborizaiton. However, due to the technical difficulty, the functional roles of Dscam transmembrane variants and ectodomain variants remain unclear. In this thesis work, a microRNA based RNA interference was used to knock down distinct subsets of Dscam isoform. First, loss of Dscam[TM1] versus Dscam[TM2], two distinct Dscam transmembrane variants, disrupted the dendritic versus axonal morphogenesis, respectively. Furthermore, structural analysis suggested that the juxtamembrane portion of transmembrane segment was required for the Dscam protein targeting in dendrites/axons and this differential protein targeting might account for the functional distinction between Dscam[TM1] and Dscam[TM2]. Second, to further address the functional significance of having two Dscam transmembrane variants in axons versus dendrites, the possibility that there might be different usage of Dscam repertoire between axons and dendrites that lead to different levels of morphological complexity between axons and dendrites in the same neuron was examined. To this end, end-in targeting approaches were used to exchange Dscam populations between axons and dendrites. Though the genetic data suggested that Dscam populations were exchanged between axons and dendrites, the phenotypic analysis in various neuronal types revealed that depending on the neuronal types, exchange of Dscam populations between axons and dendrites might primarily affect either axonal or dendritic morphology, suggesting that different usage of Dscam population between axons and dendrites might regulate complex patterns of neurite morphology. Finally, the functions of Dscam exon 4 variants had been addressed in different model neurons in the Drosophilabrain. First, 12 Dscam exon 4 variants were divided into three groups based on their phylogenetic distance. Then, three miRNA constructs were engineered to knock down one group at a time. The genetic data suggested that different Dscam exon 4 variants are differentially required in different neurons to support their proper neuronal morphogenesis. In summary, this part of my thesis work identified and characterized previously unrecognized functions of all these distinct Dscam variants and provided novel insights into how diverse Dscam isoforms regulate the different aspects of neuronal morphogenesis. In the honey bee brain, Kr-h1 is upregulated during the behavioral shift from nursing to foraging when there is increased neurite branching in the brain. To directly examine the hypothesis that altered Kr-h1 expression might regulate morphological complexity of neurites, this research work involved the MARCM (mosaic analysis with a repressible cell marker) and TARGET (temporal and regional gene expression targeting) techniques to analyze the roles of Kr-h1 in Drosophila neuronal morphogenesis. Interestingly, increased expression of Kr-h1 blocked the axon branching and further disrupted the lobe formation in the mushroom body whereas the loss-of-Kr-h1 did not show any apparent neuronal morphogenetic defects. In addition, it was observed that Kr-h1 was expressed when MB (mushroom body) did not undergo active morphogenesis, suggesting its potential anti-morphogenetic activity. Indeed, loss of Kr-h1 (Kruppel homolog 1) enhanced the neuronal morphogenesis that was otherwise delayed due to the defective TGF-beta signaling. Furthermore, Kr-h1 expression was closely linked to ecdysone dependent signaling: Kr-h1 was first regulated by usp (ultraspiracle), which dimerized with various ecdysone receptors and then Kr-h1 expression was essential for proper ecdysone patterning in the larval CNS (central nervous system). Together, though Kr-h1could potentially regulate the neurite complexity, it seems primarily involved in the coordinating ecdysone signaling. In conclusion, the powerful genetic toolkit available in the Drosophila has allowed the investigation in the molecular mechanisms of neuronal morphogenesis and understanding of these mechanisms will enhance our understanding of how the complex nervous system is wired to perform the delicate behaviors.

Tato dizertační práce se zabývá studiem morfogeneze dimethakrylátových sítí. V práci byly využity zjednodušené systémy založené na monomerech, které bývají typicky využívány jako složky matric pryskyřičných kompozitních materiálů využívaných v oblasti záchovné stomatologie. Kinetika a mechanismy formování polymerních sítí byly studovány především s ohledem na strukturu jednotlivých monomerů, jejich vzájemný molární poměr a koncentraci iniciačního systému využitého pro radikálovou polymeraci. Vypočtené profily konverze funkčních skupin a reakčních rychlostí byly využity jako základ pro pochopení a interpretaci mechanismů morfogeneze sítí a porovnání se známými modely. Dále byla studována kinetika termické degradace, která je s morfologií vytvrzených sítí přímo spjata. V rámci takto charakterizovaných systémů byla stanovena teplotní závislost dynamického modulu a byl popsán vztah mezi supra-molekulární strukturou dimethakrylátových sítí a jejich viskoelastickou odezvou v daném teplotním rozmezí. Kinetika polymerace byla studována pomocí diferenční kompenzační foto-kalorimetrie (DPC) a infračervené spektroskopie (FTIR). Proces termické degradace byl analyzován pomocí termo-gravimetrické analýzy (TGA). Viskoelastické parametry byly charakterizovány pomocí dynamicko-mechanické analýzy (DMA). Reaktivita jednotlivých systémů je přímo odvozena od molekulární struktury monomerů, která ovlivňuje mobilitu reagujících složek v průběhu polymerace. Kinetika polymerace je řízena především difúzí, přičemž její rychlost je dána tuhostí monomerní páteře, koncentrací funkčních skupin a vlivem fyzikálních interakcí. Omezená mobilita rostoucích řetězců, postranních funkčních skupin i samotných monomerů vede k monomolekulární terminaci makro-radikálů a omezení stupně konverze funkčních skupin. Vzhledem k tomu, že k zásadnímu omezení mobility dochází již v počáteční fázi polymerace, tj. v bodu gelace, je případná termodynamická nestabilita vedoucí k fázové separaci polymerujícího systému potlačena a proces kopolymerace je ve své podstatě náhodný. To bylo prokázáno i prostřednictvím identifikace jedné teploty skelného přechodu u charakterizovaných kopolymerů. Heterogenní charakter morfogeneze je spjat s rozdílnou reaktivitou postranních funkčních skupin. V počátečních fázích polymerace dochází k propagaci reakcí postranní funkční skupiny s radikálem na stejném rostoucím řetězci, což vede ke vzniku tzv. primárního cyklu. Pravděpodobnost cyklizace souvisí především s flexibilitou monomerní páteře. Heterogenita polymerace je charakterizována vznikem vnitřně zesítěných struktur, tzv. mikrogelů, a jejich následným spojováním. Tuhost monomeru naopak přispívá k vyšší efektivitě zesítění a více homogenní morfologii vytvrzené sítě. Heterogenita dimethakrylátových sítí se odráží v mechanismu termické degradace, přičemž přítomnost strukturně odlišných domén vede k rozkladu ve dvou krocích. Průběh soufázového modulu a teplota skelného přechodu korelují s tuhostí polymerních sítí, efektivitou zesítění a přítomností fyzikálních interakcí, které vyztužují strukturu sítě nad rámec kovalentního zesítění. Heterogenní morfologie sítí se projevuje rozšiřováním spektra relaxačních časů. Experimentální data jsou v kvalitativní shodě s existujícími numerickými modely popisujícími kinetiku radikálové polymerace multifunkčních monomerů.

L’environnement des cellules souches (CS) est appelé la niche. Les interactions entre la niche et les CS doivent être hautement régulées puisqu’un dérèglement de ces interactions peut entrainer la formation de tumeurs ou une stérilité. La découverte récente de niches pré-métastatiques rend l’étude de ces interactions cruciale pour mieux comprendre les processus tumoraux. L’ovaire de drosophile un excellent modèle pour étudier les voies de signalisation contrôlant le maintien des CS par leur niche. C’est dans ce modèle qu’il a été montré pour la première fois que le maintien des CS germinales (CSG) dépend d’un facteur secrété par les niches, Decapentaplegic (Dpp), homologue des protéines BMP (superfamille des TGF-β) chez les mammifères. La régulation fine de cette voie est cruciale pour empêcher une prolifération excessive de CSG (tumeur) ou bien leur perte (stérilité). La formation de ces niches et le recrutement des CSG a lieu durant le développement larvaire. Le locus bric-à-brac (bab) est le premier décrit comme étant nécessaire pour ce processus. Durant ma thèse, j’ai montré que Bab est nécessaire et suffisant pour réguler l’expression de dpp et par conséquent le recrutement des CSG ; et certains de mes résultats suggèrent également que le recrutement des CSG au sein de leur niche est régulé par un mécanisme différent de celui impliqué dans leur maintien (Miscopein-Saler et al,. en préparation). / The interactions between stem cells (SC) and their microenvironment called a niche are known to be crucial for SC behaviour. These interactions need to be highly regulated since abnormal SC behaviour is a leading cause of developmental diseases and tumourigenesis. The discovery of pre-metastatic niches makes the study of niche-to-SC interactions a crucial step for our understanding of cancer biology. The powerful genetic tools available render the Drosophila ovary an excellent model to study the signalling controlling germline SC (GSC) maintenance by a niche in an adult tissue. Using this model, it was shown for the first time that SC maintenance was dependent on a factor emanating from the niche. This factor is Decapentaplegic (Dpp), a Drosophila homolog of BMP proteins (family of TGF-β signalling molecules) and a tight regulation of this signalling pathway is very important to avoid an excess of GSC-like cells (tumour) or a loss of GSCs (sterility). Formation of the GSC niches occurs during the larval stages and the bric-à-brac (bab) locus was first discovered as being necessary for niche morphogenesis. During my doctoral studies, I have shown that Bab1 and Bab2 are necessary and sufficient for GSC recruitment by regulating dpp expression, and some of my results alos suggest that GSC recruitment might occurs according to a different mechanism that the one involved in their maintenance (Miscopein-Saler et al,. in preparation).

Une cellule reçoit et intègre une multitude de signaux physiques et biochimiques. Elle est capable de sentir et de répondre à ces signaux de sorte que ses fonctions s’accordent avec son environnement. Si l’intégration de ces signaux est hautement régulée par des voies de signalisation et de rétroaction, certaines étapes semblent résulter de processus d’auto-organisation géométrique et mécanique du réseau d’actine. Il est capable de s’auto-assembler et d’adopter différentes architectures. Celles-ci sont autant de modules qui coexistent dans la cellule avec une claire ségrégation spatiale et fonctionnelle. Notamment, le cytosquelette d’actine participe à l’intégration des signaux encodés par la matrice extracellulaire. Cette intégration suppose entre autre, une régulation des forces de tension entre la cellule et son environnement impliquant le cytosquelette d’actine, les adhésions cellulaire et la matrice. Afin d’explorer ces mécanismes, nous avons eu recours à des techniques avancées de micropatterning, de mesure de force de traction cellulaire et de microdissection laser. Nous avons ainsi montré en réprimant l’expression de l’ alpha-actinine, une des principales protéines de réticulation du cytosquelette d’actine, que la connectivité du réseau d’actine était essentielle à l’intégration des signaux émanant de la matrice extracellulaire. Elle participe à l’évaluation de la rigidité de la matrice et au mécanisme de migration dirigé haptotactique. Elle participe donc potentiellement aux mécanismes de différentiation cellulaire et au maintien de la polarité cellulaire. Dans le même esprit nous avons pris part à une étude portant sur l’organisation et la maturation des adhésions cellulaires, en participant à la caractérisation d’une protéine d’adhésion Kank2. Nous avons ainsi pu démontrer le rôle essentiel de cette protéine dans le phénomène de rigidity sensing. L’ensemble de l’étude ayant montré l’implication de cette protéine dans le processus de maturation des adhésions cellulaires et de mécano-transduction. / Cells sense and integrate a wealth of mechanical and biochemical signals. Signal integration is part of a process, which ensures that cellular functions are in accordance with the extracellular environment. While these processes are highly regulated by biochemical and mechanical signalling and feedback loops, some of the fundamental processes appear to rely on actin cytoskeleton autoassembly giving raise to modules with defined geometrical and mechanical properties. Thus the actin cytoskeleton is a modular architecture, and the modules co-exist within the cell with spatial and functional specificity. The actin cytoskeleton, notably, is involved in cell/matrice signalling. This interaction relies mainly on mechanical signalling involving the actin cytoskeleton, cell/matrix adhesions and the extracellular matrix. To characterize these mechanisms we took advantage of advanced micropatterning techniques, traction force measurements and laser microdissection. By downregulating the expression of α-actinin, one of the main actin crosslinking proteins, we demonstrated that actin cytoskeleton connectivity is essential for proper integration of cell/matrix signalling. Connectivity is essential for rigidity sensing and haptotaxis by ensuring balanced force distribution through the whole cell. Therefore connectivity might be crucial for cell differentiation processes and cellular polarity. Further, in the context of a collaborative project, we have contributed to the characterization of a novel cell adhesion protein, namely, Kank2. We showed, by traction force measurements, that this protein is essential for rigidity sensing. Globally this study demonstrated the implication of Kank2 in cell adhesion maturation and mecanotransduction.