A number of movements produced in everyday life require not only coordination of joints within a limb, but also coordination between one or more limbs. The aim of this dissertation was to examine the influence of biomechanical constraints on intralimb coordination, interlimb coordination, and learning. Experiment 1 sought to determine if principles of the Leading Joint Hypothesis, when applied to a multijoint bimanual coordination task, could provide insight into the contribution of intralimb dynamics to interlimb coordination. Participants repetitively traced ellipse templates in an asymmetrical coordination pattern (i.e. both limbs moving counter-clockwise). Kinematic data of the upper limbs were recorded with a VICON camera system. Ellipse templates were oriented either tilted right or tilted left; yielding a total of four left arm-right arm leading joint combinations. The findings indicated that stability of interlimb coordination patterns were found to be influenced by whether arm movements were produced with similar or different leading joints. Bimanual asymmetric ellipse-tracing produced with similar leading joints were more stable than patterns produced with different leading joints. For example, asymmetric coordination patterns produced with similar leading joints exhibited less transient behavior than coordination patterns produced with different leading joints (p < .01). Experiment 2 expanded on these findings by employing a similar task and incorporating a learning component to assess how intralimb dynamics are tuned with practice of a novel coordination pattern. Participants were randomly assigned to one of three groups. One group practiced tracing a pair of ellipse templates that were oriented in such a way that required similar leading joints while the other two groups practiced tracing ellipse templates that required different leading joints. Early in practice, the group learning the coordination pattern with similar leading joints exhibited greater interlimb stability than the two groups learning with different leading joints. However, following two days of practice, performance of the groups learning with different leading joints improved to match that of the group learning with similar leading joints. The findings suggest that initial biomechanical constraints can be overcome with practice, resulting in similar performance regardless of whether being produced with similar or different leading joints.

A number of movements produced in everyday life require not only coordination of joints within a limb, but also coordination between one or more limbs. The aim of this dissertation was to examine the influence of biomechanical constraints on intralimb coordination, interlimb coordination, and learning. Experiment 1 sought to determine if principles of the Leading Joint Hypothesis, when applied to a multijoint bimanual coordination task, could provide insight into the contribution of intralimb dynamics to interlimb coordination. Participants repetitively traced ellipse templates in an asymmetrical coordination pattern (i.e. both limbs moving counter-clockwise). Kinematic data of the upper limbs were recorded with a VICON camera system. Ellipse templates were oriented either tilted right or tilted left; yielding a total of four left arm-right arm leading joint combinations. The findings indicated that stability of interlimb coordination patterns were found to be influenced by whether arm movements were produced with similar or different leading joints. Bimanual asymmetric ellipse-tracing produced with similar leading joints were more stable than patterns produced with different leading joints. For example, asymmetric coordination patterns produced with similar leading joints exhibited less transient behavior than coordination patterns produced with different leading joints (p < .01). Experiment 2 expanded on these findings by employing a similar task and incorporating a learning component to assess how intralimb dynamics are tuned with practice of a novel coordination pattern. Participants were randomly assigned to one of three groups. One group practiced tracing a pair of ellipse templates that were oriented in such a way that required similar leading joints while the other two groups practiced tracing ellipse templates that required different leading joints. Early in practice, the group learning the coordination pattern with similar leading joints exhibited greater interlimb stability than the two groups learning with different leading joints. However, following two days of practice, performance of the groups learning with different leading joints improved to match that of the group learning with similar leading joints. The findings suggest that initial biomechanical constraints can be overcome with practice, resulting in similar performance regardless of whether being produced with similar or different leading joints.

We constructed a model of the coordination of segmental heart motor neurons driving blood circulation in leeches. The heart motor neuron models were conductance-based; conductances of voltage-gated and synaptic currents were adjusted to match the firing pattern of heart motor neurons from the living system. Each motor neuron receives a specific pattern of inhibitory input from rhythmic premotor heart interneurons and translates this spatiotemporal pattern into the fictive heartbeat motor pattern. The temporal pattern of synaptic input to the model was derived from extracellularly recorded spikes of the premotor heart interneurons. We focused on determining the components necessary to produce side-to-side asymmetry in the motor pattern: motor neurons on one side fire nearly in synchrony (synchronous coordination), while on the other they fire in a rear-to-front progression (peristaltic coordination). The model reproduces the general trends in phasing and was used to investigate the effective contribution of several synaptic and cellular properties of the motor neurons. The spatial and temporal pattern of premotor synaptic input, the electrical coupling between the segmental motor neurons, intra-burst, short-term synaptic plasticity of the synaptic inputs, and the axonal conduction delays all were integrated with the intrinsic membrane properties to influence intersegmental phasing.

TAMBORINDEGUY, A. C. Avaliação da força e do momento tibiofemoral durante a pedalada: uma orientação para a reabilitação. Dissertação de Mestrado. Programa de pós-graduação em ciências do movimento humano. Escola de Educação Física. Universidade Federal do Rio Grande do Sul. Durante o processo de reabilitação de lesões na articulação do joelho o ciclo ergômetro tem sido amplamente utilizado. No entanto, existem poucos estudos que orientem a sua utilização de forma a evitar sobrecargas às estruturas lesionadas. O presente estudo tem como objetivo comparar o comportamento das componentes de compressão e de cisalhamento anterior e posterior da força intersegmentar e do momento resultante tibiofemoral durante a pedalada no ciclo ergômetro em situações usuais da reabilitação de lesões do joelho. Participaram deste estudo nove sujeitos saudáveis do sexo masculino. O protocolo constou da avaliação de três diferentes alturas do selim (altura do trocânter, 3 cm para baixo e 3 cm para cima desta), duas cadências (40 e 70 rpm) e três cargas de trabalho (0, 5 e 10 N) relacionadas à realidade da reabilitação. Um pedal instrumentado e um sistema de cinemetria foram utilizados para o cálculo do modelo biomecânico bidimensional. Foram analisadas as médias do pico de compressão da força intersegmentar, dos picos do valor máximo e mínimo de cisalhamento da força intersegmentar e o pico dos momentos flexor e extensor durante oito ciclos de pedalada. Os resultados obtidos demonstram que o aumento da carga de trabalho causa um aumento na média do pico de compressão e do pico máximo de cisalhamento da força intersegmentar. As médias do pico de compressão foram de -44,94 (±3,12) N para 0 N, -53,21 (±4,56) N para 5 N e -76,50 (±5,69) N para 10 N. As médias do pico máximo de cisalhamento foram de 61,32 (±5,60) N para O N, 71,21 (±7,73) N para 5 N e 93,89 (±9,10) N para 10 N. O aumento das cargas de trabalho também causou um aumento do pico do momento flexor resultante que teve valores médios de 12,77 (±1,68) Nm para 0 N, 16,90 (±2,49) Nm para 5 N e 25,40 (±3,25) Nm para 10 N. O pico do momento extensor aumentou com a diminuição da altura do selim. As médias do pico do momento extensor nas posições do selim na altura do trocânter, 3 cm abaixo e 3 cm acima foram de, -10,15 (±0,58) Nm, -11,09 (±0,55) Nm e -9,68 (±0,58) Nm, respectivamente. O pico do momento extensor aumentou com o aumento da cadência de pedalada e com o incremento da carga de trabalho de 5 para 10 N. As médias do pico do momento extensor foram de -10,12 (±0,57) Nm para 40 rpm, de - 10,49 (±0,56) Nm para 70 rpm, -10,19 (±0,57) Nm para 5 N e de -10,53 (±0,60) Nm para 10 N. Portanto, pedalar com uma carga de 0 N, com o selim posicionado 3 cm acima da altura do trocânter e na cadência de 40 rpm resulta em menor sobrecarga articular e muscular. / TAMBORINDEGUY, A. C. Assessment of force and moment during cycling: an orientation to rehabilitation. Master thesis. Graduation Program in Human Movement Sciences. School of Physical Education. Federal University of Rio Grande do Sul. During knee injuries rehabilitation process the cycle ergometer has been largely used. However, there are few studies orienting their use avoiding overload damaged structures. The aim of the present study was to compare the effects of compression and shear force components and resultant joint moment in ergometer cycling at different saddle height, cadence and workload during rehabilitation seasons. Nine healthy male volunteers participated in this study. Protocol consisted of evaluation of three differents saddle heights (trochanter height, 3 cm downward and 3 cm upward from trochanter height), two cadences (40 and 70 rpm) and three workloads (0, 5 and 10 N). An instrumented pedal and a motion system were used to calculate the twodimensional biomechanical model. Mean peak compressive intersegmental force, maximum and minimum mean peak shear force, and mean peak extensor and flexor moment during eight pedaling cycles were analyzed. Results demonstrated that changes in workload interfere in mean peak compressive force as well in maximum mean peak shear intersegmentar force. Mean peak compressive were -44.94 (±3.12) N for 0 N, -53.21 (±4.56) N for 5 N and -76.50 (±5.69) N for 10 N. Maximum mean peak shear were 61.32 (±5.60) N for O N, 71.21 (±7.73) N for 5 N and 93.89 (±9.10) N for 10 N. Mean peak flexor moment increased as workload increase (12.77 (±1.68) Nm for 0 N, 16.90 (±2.49) Nm for 5 N and 25.40 (±3.25) Nm for 10 N). Mean peak extensor moment increased at saddle positioned 3 cm downward. Results were - 10.15 (±0.58) Nm, -11.09 (±0.55) Nm, and -9.68 (±0.58) Nm, for trochanteric height, 3 cm downward, and 3 cm upward, respectively. Mean peak extensor moment increased as cadence and workload increased (from -10.12 (±0.57) Nm at 40 rpm to - 10.49 (±0.56) Nm at 70 rpm; from -10.19 (±0.57) Nm at 5 N to -10.53 (±0.60) Nm at 10 N, respectively). Therefore, pedaling at 0 N with saddle positioned 3 cm upward from trochanter height at 40 rpm results in lower joint and muscle overload.

TAMBORINDEGUY, A. C. Avaliação da força e do momento tibiofemoral durante a pedalada: uma orientação para a reabilitação. Dissertação de Mestrado. Programa de pós-graduação em ciências do movimento humano. Escola de Educação Física. Universidade Federal do Rio Grande do Sul. Durante o processo de reabilitação de lesões na articulação do joelho o ciclo ergômetro tem sido amplamente utilizado. No entanto, existem poucos estudos que orientem a sua utilização de forma a evitar sobrecargas às estruturas lesionadas. O presente estudo tem como objetivo comparar o comportamento das componentes de compressão e de cisalhamento anterior e posterior da força intersegmentar e do momento resultante tibiofemoral durante a pedalada no ciclo ergômetro em situações usuais da reabilitação de lesões do joelho. Participaram deste estudo nove sujeitos saudáveis do sexo masculino. O protocolo constou da avaliação de três diferentes alturas do selim (altura do trocânter, 3 cm para baixo e 3 cm para cima desta), duas cadências (40 e 70 rpm) e três cargas de trabalho (0, 5 e 10 N) relacionadas à realidade da reabilitação. Um pedal instrumentado e um sistema de cinemetria foram utilizados para o cálculo do modelo biomecânico bidimensional. Foram analisadas as médias do pico de compressão da força intersegmentar, dos picos do valor máximo e mínimo de cisalhamento da força intersegmentar e o pico dos momentos flexor e extensor durante oito ciclos de pedalada. Os resultados obtidos demonstram que o aumento da carga de trabalho causa um aumento na média do pico de compressão e do pico máximo de cisalhamento da força intersegmentar. As médias do pico de compressão foram de -44,94 (±3,12) N para 0 N, -53,21 (±4,56) N para 5 N e -76,50 (±5,69) N para 10 N. As médias do pico máximo de cisalhamento foram de 61,32 (±5,60) N para O N, 71,21 (±7,73) N para 5 N e 93,89 (±9,10) N para 10 N. O aumento das cargas de trabalho também causou um aumento do pico do momento flexor resultante que teve valores médios de 12,77 (±1,68) Nm para 0 N, 16,90 (±2,49) Nm para 5 N e 25,40 (±3,25) Nm para 10 N. O pico do momento extensor aumentou com a diminuição da altura do selim. As médias do pico do momento extensor nas posições do selim na altura do trocânter, 3 cm abaixo e 3 cm acima foram de, -10,15 (±0,58) Nm, -11,09 (±0,55) Nm e -9,68 (±0,58) Nm, respectivamente. O pico do momento extensor aumentou com o aumento da cadência de pedalada e com o incremento da carga de trabalho de 5 para 10 N. As médias do pico do momento extensor foram de -10,12 (±0,57) Nm para 40 rpm, de - 10,49 (±0,56) Nm para 70 rpm, -10,19 (±0,57) Nm para 5 N e de -10,53 (±0,60) Nm para 10 N. Portanto, pedalar com uma carga de 0 N, com o selim posicionado 3 cm acima da altura do trocânter e na cadência de 40 rpm resulta em menor sobrecarga articular e muscular. / TAMBORINDEGUY, A. C. Assessment of force and moment during cycling: an orientation to rehabilitation. Master thesis. Graduation Program in Human Movement Sciences. School of Physical Education. Federal University of Rio Grande do Sul. During knee injuries rehabilitation process the cycle ergometer has been largely used. However, there are few studies orienting their use avoiding overload damaged structures. The aim of the present study was to compare the effects of compression and shear force components and resultant joint moment in ergometer cycling at different saddle height, cadence and workload during rehabilitation seasons. Nine healthy male volunteers participated in this study. Protocol consisted of evaluation of three differents saddle heights (trochanter height, 3 cm downward and 3 cm upward from trochanter height), two cadences (40 and 70 rpm) and three workloads (0, 5 and 10 N). An instrumented pedal and a motion system were used to calculate the twodimensional biomechanical model. Mean peak compressive intersegmental force, maximum and minimum mean peak shear force, and mean peak extensor and flexor moment during eight pedaling cycles were analyzed. Results demonstrated that changes in workload interfere in mean peak compressive force as well in maximum mean peak shear intersegmentar force. Mean peak compressive were -44.94 (±3.12) N for 0 N, -53.21 (±4.56) N for 5 N and -76.50 (±5.69) N for 10 N. Maximum mean peak shear were 61.32 (±5.60) N for O N, 71.21 (±7.73) N for 5 N and 93.89 (±9.10) N for 10 N. Mean peak flexor moment increased as workload increase (12.77 (±1.68) Nm for 0 N, 16.90 (±2.49) Nm for 5 N and 25.40 (±3.25) Nm for 10 N). Mean peak extensor moment increased at saddle positioned 3 cm downward. Results were - 10.15 (±0.58) Nm, -11.09 (±0.55) Nm, and -9.68 (±0.58) Nm, for trochanteric height, 3 cm downward, and 3 cm upward, respectively. Mean peak extensor moment increased as cadence and workload increased (from -10.12 (±0.57) Nm at 40 rpm to - 10.49 (±0.56) Nm at 70 rpm; from -10.19 (±0.57) Nm at 5 N to -10.53 (±0.60) Nm at 10 N, respectively). Therefore, pedaling at 0 N with saddle positioned 3 cm upward from trochanter height at 40 rpm results in lower joint and muscle overload.

TAMBORINDEGUY, A. C. Avaliação da força e do momento tibiofemoral durante a pedalada: uma orientação para a reabilitação. Dissertação de Mestrado. Programa de pós-graduação em ciências do movimento humano. Escola de Educação Física. Universidade Federal do Rio Grande do Sul. Durante o processo de reabilitação de lesões na articulação do joelho o ciclo ergômetro tem sido amplamente utilizado. No entanto, existem poucos estudos que orientem a sua utilização de forma a evitar sobrecargas às estruturas lesionadas. O presente estudo tem como objetivo comparar o comportamento das componentes de compressão e de cisalhamento anterior e posterior da força intersegmentar e do momento resultante tibiofemoral durante a pedalada no ciclo ergômetro em situações usuais da reabilitação de lesões do joelho. Participaram deste estudo nove sujeitos saudáveis do sexo masculino. O protocolo constou da avaliação de três diferentes alturas do selim (altura do trocânter, 3 cm para baixo e 3 cm para cima desta), duas cadências (40 e 70 rpm) e três cargas de trabalho (0, 5 e 10 N) relacionadas à realidade da reabilitação. Um pedal instrumentado e um sistema de cinemetria foram utilizados para o cálculo do modelo biomecânico bidimensional. Foram analisadas as médias do pico de compressão da força intersegmentar, dos picos do valor máximo e mínimo de cisalhamento da força intersegmentar e o pico dos momentos flexor e extensor durante oito ciclos de pedalada. Os resultados obtidos demonstram que o aumento da carga de trabalho causa um aumento na média do pico de compressão e do pico máximo de cisalhamento da força intersegmentar. As médias do pico de compressão foram de -44,94 (±3,12) N para 0 N, -53,21 (±4,56) N para 5 N e -76,50 (±5,69) N para 10 N. As médias do pico máximo de cisalhamento foram de 61,32 (±5,60) N para O N, 71,21 (±7,73) N para 5 N e 93,89 (±9,10) N para 10 N. O aumento das cargas de trabalho também causou um aumento do pico do momento flexor resultante que teve valores médios de 12,77 (±1,68) Nm para 0 N, 16,90 (±2,49) Nm para 5 N e 25,40 (±3,25) Nm para 10 N. O pico do momento extensor aumentou com a diminuição da altura do selim. As médias do pico do momento extensor nas posições do selim na altura do trocânter, 3 cm abaixo e 3 cm acima foram de, -10,15 (±0,58) Nm, -11,09 (±0,55) Nm e -9,68 (±0,58) Nm, respectivamente. O pico do momento extensor aumentou com o aumento da cadência de pedalada e com o incremento da carga de trabalho de 5 para 10 N. As médias do pico do momento extensor foram de -10,12 (±0,57) Nm para 40 rpm, de - 10,49 (±0,56) Nm para 70 rpm, -10,19 (±0,57) Nm para 5 N e de -10,53 (±0,60) Nm para 10 N. Portanto, pedalar com uma carga de 0 N, com o selim posicionado 3 cm acima da altura do trocânter e na cadência de 40 rpm resulta em menor sobrecarga articular e muscular. / TAMBORINDEGUY, A. C. Assessment of force and moment during cycling: an orientation to rehabilitation. Master thesis. Graduation Program in Human Movement Sciences. School of Physical Education. Federal University of Rio Grande do Sul. During knee injuries rehabilitation process the cycle ergometer has been largely used. However, there are few studies orienting their use avoiding overload damaged structures. The aim of the present study was to compare the effects of compression and shear force components and resultant joint moment in ergometer cycling at different saddle height, cadence and workload during rehabilitation seasons. Nine healthy male volunteers participated in this study. Protocol consisted of evaluation of three differents saddle heights (trochanter height, 3 cm downward and 3 cm upward from trochanter height), two cadences (40 and 70 rpm) and three workloads (0, 5 and 10 N). An instrumented pedal and a motion system were used to calculate the twodimensional biomechanical model. Mean peak compressive intersegmental force, maximum and minimum mean peak shear force, and mean peak extensor and flexor moment during eight pedaling cycles were analyzed. Results demonstrated that changes in workload interfere in mean peak compressive force as well in maximum mean peak shear intersegmentar force. Mean peak compressive were -44.94 (±3.12) N for 0 N, -53.21 (±4.56) N for 5 N and -76.50 (±5.69) N for 10 N. Maximum mean peak shear were 61.32 (±5.60) N for O N, 71.21 (±7.73) N for 5 N and 93.89 (±9.10) N for 10 N. Mean peak flexor moment increased as workload increase (12.77 (±1.68) Nm for 0 N, 16.90 (±2.49) Nm for 5 N and 25.40 (±3.25) Nm for 10 N). Mean peak extensor moment increased at saddle positioned 3 cm downward. Results were - 10.15 (±0.58) Nm, -11.09 (±0.55) Nm, and -9.68 (±0.58) Nm, for trochanteric height, 3 cm downward, and 3 cm upward, respectively. Mean peak extensor moment increased as cadence and workload increased (from -10.12 (±0.57) Nm at 40 rpm to - 10.49 (±0.56) Nm at 70 rpm; from -10.19 (±0.57) Nm at 5 N to -10.53 (±0.60) Nm at 10 N, respectively). Therefore, pedaling at 0 N with saddle positioned 3 cm upward from trochanter height at 40 rpm results in lower joint and muscle overload.

Purpose: Several studies have examined intralimb coordination between the shoulder and elbow joints during target-oriented movements. These studies have observed consistent patterns in coordination despite changes in movement variables such as speed, direction, and inertia. Researchers used intersegmental dynamics to quantitatively analyze these patterns between shoulder and elbow joints while systematically changing values of these movement variables. Some studies have examined central nervous system adaptations to inertial changes at the elbow and entire arm during a movement, but none have examined inertial changes to the upper limb. Methods: Five male and five female participants aged 27 to 39 years (mean age = 33 ± 4.3 standard deviation) performed a maximal speed, point-to-point, reversal hand movement in the sagittal plane with and without a 2.2 kg. weight attached to their dominant, right upper arm. To determine the effects of the added mass, dependent t-tests were performed on elbow and shoulder peak muscular torques generated during the reversal region of the movement. Results: A significant increase in shoulder joint torque (p < 0.05), a significant increase in movement time (p < 0.05) and a non-significant decrease in elbow muscular torque (p = 0.1074) was shown to achieve the movement objective with the added weight. Conclusions: While future studies may result in more conclusive findings, this study showed a pattern of increased shoulder torque and decreased elbow torque due to the added inertia. Larger shoulder torque was needed to overcome the added inertia and move at high speed. As a result of the higher shoulder force, interaction torque at the elbow increased, and a reduction in elbow torque was needed to control the hand path and accurately hit the targets. This pattern supports Bernstein’s proposal that passively arising phenomena (i.e., interaction torque) is exploited during multi-segment movement.

The purpose of this study was to identify dimensions of synergy in the College Going Initiative of Imperial County, California. The instrument through which this intersegmental partnership was examined was the Partnership Self-Assessment Tool. This study found that leadership is the strongest contributor to synergy, and that leadership facilitates the use of other dimensions, such as administration/management activities and the efficiency and sufficiency of resources in a partnership. This study identified how leadership spans organizational boundaries to filter and combine information from each educational segment in a manner useful and appeasing to all segments. This study extended existing research by identifying a new model, the Three Phases of Synergy, which describes how the activities and outcomes produced in a synergistic partnership occur in three distinct phases: the convening phase, the implementation phase, and the sustainability phase. Each phase requires leaders take special consideration regarding how to influence the administrative activities and resources of the partnership. The ultimate goal of this three-phase continuum is to maximize and sustain results in a synergistic partnership. This study recommends educational professionals maximize the benefits of partnership by developing their boundary spanning abilities. Such recommendations are made for educational professionals engaging in partnership during each of the three phases of synergy identified in this study. In addition, the benefit of creating educational policy which reinforces synergistic partnerships and recommendations for implementation are discussed. Finally, this study makes recommendations regarding replicating this study, utilizing the Partnership Self-Assessment Tool in education, and future research of boundary spanning activities and synergistic partnerships.

L’obstruction des vaisseaux est responsable d’ischémie tissulaire dans différents territoires périphériques, cardiaques et cérébraux. Un des mécanismes d’adaptation du tissu à l’ischémie est la formation de néo-vaisseaux. Plusieurs données récentes mettent en évidence un rôle de la voie de signalisation Wnt/Frizzled (Fzd) dans le développement vasculaire. Le travail de cette thèse s’est focalisé sur l’étude du récepteur Frizzled7 (Fzd7) et de son rôle dans la formation des vaisseaux. Le modèle des corps embryoïdes, un modèle de différenciation des cellules souches embryonnaires vers le phénotype endothélial, nous a permis de démontrer que Fzd7 était exprimé au cours des différentes étapes de différenciation endothéliale. Des études sur des cellules endothéliales matures nous ont permis de montrer que Fzd7 régulait différentes propriétés des cellules endothéliales dont la migration et la formation de tubes endothéliaux, mais pas la prolifération. De plus, Fzd7 participe à la stabilité des jonctions cellulaires en interagissant avec la VE-cadhérine. Concernant les mécanismes moléculaires mis en jeu par Fzd7, nous avons pu montrer que celui-ci était capable d’activer la voie Wnt/PCP via la phosphorylation de la protéine JNK. Enfin, une étude in vivo dans le modèle du poisson Zèbre, nous a permis de mettre en évidence un rôle de Fzd7 dans la formation des vaisseaux intersomitiques. La deuxième partie de ce travail concerne le rôle de la voie Wnt/Fzd dans les propriétés angiogèniques des cellules souches mésenchymateuses (CSM). L’objectif de cette étude était de définir comment les CSM participaient à la formation des vaisseaux et si le système Wnt/Frizzled était nécessaire. Nous avons pu montrer que sFRP1, un modulateur de la voie Wnt, améliore la fonction cellulaire des CSM et contribue à la maturation des néo-vaisseaux. De plus, nous avons pu montrer que les CSM implantées dans un modèle d’ischémie du membre inférieur amélioraient la réponse angiogénique lorsque celles-ci étaient préconditionnées en hypoxie. Nous avons mis en évidence le rôle de Wnt4 dans ce processus. / The obstruction of the vessels is responsible for ischemia in various outlying areas, heart and brain. One of the mechanisms of tissue adaptation to ischemia is the formation of neo-vessels. Several recent data show a role of Wnt/Frizzled (Fzd) pathway in vascular development.The work of this thesis focused on the study of receptor Frizzled7 (Fzd7) and its role in vessel formation. Using the model of embryoid bodies, a model of embryonic stem cell differentiation toward the endothelial lineage, we demonstrated that Fzd7 was expressed during different stages of endothelial cell differentiation. Studies on mature endothelial cells have shown that Fzd7 regulates endothelial cells properties including migration and endothelial tube formation but not proliferation. In addition, Fzd7 participates in the stability of cell junctions by interacting with VE-cadherin. Regarding the molecular mechanisms involved in Fzd7 signalling, we could show that this receptor was capable of activating the Wnt/PCP pathway via phosphorylation of JNK protein. Finally, an in vivo study in zebrafish model, allowed us to highlight a role of Fzd7 in intersomitic vessel formation.The second part of this work concerns the role of the Wnt/Fzd pathway in the angiogenic properties of mesenchymal stem cells (MSC). The objective of this study was to determine how CSM participated in vessel formation and if the Wnt/Frizzled pathway was necessary. We show that sFRP1, a modulator of the Wnt pathway, improves cellular function of MSCs and contributes to the maturation of neo-vessels. In addition, we have shown that MSCs implanted in a model of lower limb ischemia improved the angiogenic response when they were preconditioned by hypoxia. We have highlighted the role of Wnt4 in this process.

No description available.