Caractérisation du rôle d'ephrineB1 et ephrineB2 dans la mise en place du système sensori-moteur chez la souris

Le système sensori-moteur permet à un organisme d'interagir avec le monde extérieur par le biais des neurones sensoriels et de réagir à ces informations par le biais des neurones moteurs. La motricité dépend de la connexion stéréotypique des neurones moteurs avec leurs muscles cibles. Ces motoneurones se situent dans la corne ventrale de la moelle épinière et se regroupent en unités fonctionnelles appelées colonnes motrices. Chaque colonne contient des neurones ayant la même identité et allant innerver des tissus cibles périphériques. Cette topographie semble importante pour une innervation correcte car à chaque groupe de motoneurones donné correspond un seul muscle cible. En parallèle, les neurones sensoriels du ganglion rachidien dorsal (DRG) émettent aussi des prolongements pour aller innerver les muscles mais aussi l'épiderme. Cette croissance axonale motrice et sensorielle se fait grâce à un système de guidance moléculaire. De récentes études ont montré que ces molécules de guidance établissaient une interaction entre les motoneurones et les neurones sensoriels permettant une innervation précise. De plus, plusieurs études suggèrent un potentiel rôle du système vasculaire, mis en place plus tôt, dans l'agencement du réseau nerveux à travers certaines de ces protéines. Les récepteurs Eph et leurs ligands, les ephrines constituent l'une de ces familles de molécules de guidance axonale. La signalisation bidirectionnelle qui résulte de leur liaison, est impliquée dans de nombreux processus développementaux chez les Vertébrés et les Invertébrés. Bien que le rôle des Eph/ephrine A ait été bien établi dans la mise ne place du système sensori-moteur in vivo, peu de choses sont connues à propos de l'implication des Eph/ephrine de classe B et de leurs cibles moléculaires dans ce processus développemental. Mes travaux de thèse ont permis de caractériser le rôle de deux membres de la famille des ephrineBs dans la mise en place du système sensori-moteur. En particulier, nous avons montré qu'ephrineB2 jouait un rôle autonome dans la position du soma des motoneurones dans le tube neural, en corrélation avec une modification dans le choix de l'innervation dorso/ventrale. De plus, nous avons également mis en évidence le rôle non autonome d'ephrineB1 sur les axones afin de permettre leur fasciculation. Cette fonction semble passer par une action répulsive de la signalisation au niveau du cône de croissance, en agissant sur la dynamique des microtubules. En effet, des expériences en culture cellulaire ont montré un lien direct entre la signalisation EphB2/ephrineB1et la dynamique de microtubules individuels. De plus, afin de tester la potentielle implication du système vasculaire dans l'innervation, en particulier à travers l'expression de molécules de guidance, nous avons généré une lignée transgénique de souris surexprimant ephrineB2 spécifiquement dans les cellules endothéliales. Au cours de ces deux dernières années, un certain nombre d'études a montré que l'expression des récepteurs Eph et ephrines est augmentée après une lésion dans le système nerveux ou dans certaines pathologies tumorales. Ces résultats suggèrent que cette voie de signalisation pourrait jouer un rôle significatif dans la réparation après une lésion nerveuse ainsi que dans l'angiogenèse tumorale. Ces travaux récents soulignent l'importance de nos études visant à comprendre le rôle et les mécanismes moléculaires de la signalisation Eph/ephrine dans le développement du système sensori-moteur.The sensori-motor system allows an organism to interact with the environnement through sensory neurons and respond to this information via motor neurons. Motricity depends on the stereotypical connection of motor neurons with their target muscles. These neurons are located in the ventral horn of the spinal cord and are grouped into functional units called motor columns. Each column contains neurons with the same identity that innervate the same peripheral target tissues. This topography appears to be important for proper nerve supply for each group of neurons is given a single muscle target. Simultaneously, the sensory neurons of the spinal dorsal ganglion (DRG) also emit extensions to innervate the muscles but also the epidermis. The motor and sensory axonal growth is achieved through a system of guidance molecules. Recent studies have shown that these guidance molecules establishe an interaction between motor neurons and sensory neurons allowing a specific innervation. In addition, several studies suggest a potential role of the vascular system, established earlier, in the arrangement of the nervous system through some of these proteins. Eph receptors and their ligands, ephrins are one of the families of axon guidance molecules. Bidirectional signaling resulting from their binding is involved in many developmental processes in Vertebrates and Invertebrates. Although the role of Eph / ephrin A has been well established in the establishment of sensori-motor system in vivo, little is known about the involvement of Eph / ephrin B class and their molecular targets in this developmental process. During my PhD, we characterized the role of two family members of the ephrin B in the establishment of sensori-motor system. In particular, we showed that ephrinB2 plays an independent role in the position of the soma of motor neurons in the neural tube, in connection with a change in the choice of dorso/ventral innervation. In addition, we also highlighted the non-autonomous role of ephrineB1 to allow axon fasciculation. This function seems to go through a repellent signaling at the growth cone, by acting on microtubule dynamics. Indeed, experiments in cell culture have shown a direct link between EphB2/ephrineB1 signaling and individual microtubule dynamics. In addition, to test the potential involvement of the vascular system in innervation, especially through the expression of guidance molecules, we generated a transgenic line of mice overexpressing ephrineB2 specifically in endothelial cells. During the past two years, a number of studies showed that the expression of Eph receptors and ephrins is increased after injury in the nervous system or in tumors. These results suggest that this signaling pathway could play a significant role in repair after nerve injury as well as in tumor angiogenesis. These recent studies highlight the importance of our studies aimed at understanding the role and molecular mechanisms of Eph / ephrin signaling in the development of the sensori-motor system

Reconfigurable dual band microstrip patch antenna for software defined radio applications

In this paper, a reconfigurable microstrip patch antenna with RF pin diode switches is implemented for dual band of 2.4 GHz and 5.6 GHz Software Defined Radio (SDR) applications. For the dual band SDR system, the use of a single antenna with a wide bandwidth to cover both of the bands can be limiting for low power level signal applications due to wideband noise. A reconfigurable nested microstrip patch antenna is designed on a Rogers 5880 RT/DUROID substrate which is fed by a coaxial probe from the back side of the grounded substrate. RF switching circuitry involves four RF pin diodes at each side of the inner patch. The dual bands of 2.4 GHz and 5.6 GHz frequency operation can be simply obtained by switching the PIN diodes on and off. The antenna is well matched and achieves approximately 7 dBi simulated gain at both frequency bands. Simulation results show that the nested patch antenna is suitable for dual band SDR applications

Design of Multi-Antenna System for UMTS Clamshell Mobile Phones with Ground Plane Effects Considerations

In this paper, the influence of the ground plane dimensions on the port-to-port isolation of two closely-spaced Universal Mobile Telecommunications System (UMTS) Planar Inverted-F Antennas (PIFAs) with and without neutralization line is first presented. Parametric studies show the existence of an optimal size of the ground plane allowing optimizing the isolation and the efficiency of the considered antenna-system. The results obtained with this study are used in the second part to develop an efficient neutralized multi-antenna system for clamshell-type mobile phones. The obtained results, in terms of isolation, matching and diversity for the two possible configurations of the clamshell system in use namely the open and the closed states, show that good performance are obtained in the open state and preserved in the closed state. Prototypes of these two configurations are realized and measurement results are in good agreement with the simulations

Conformal Antenna Array for Millimeter-Wave Communications: Performance Evaluation

In this paper, we study the influence of the radius of a cylindrical supporting structure on radiation properties of a conformal millimeter-wave antenna array. Bent antenna array structures on cylindrical surfaces may have important applications in future mobile devices. Small radii may be needed if the antenna is printed on the edges of mobile devices and in items which human beings are wearing, such as wrist watches, bracelets and rings. The antenna under study consists of four linear series-fed arrays of four patch elements and is operating at 58.8 GHz with linear polarization. The antenna array is fabricated on polytetrafluoroethylene substrate with thickness of 0.127 mm due to its good plasticity properties and low losses. Results for both planar and conformal antenna arrays show rather good agreement between simulation and measurements. The results show that conformal antenna structures allow achieving large angular coverage and may allow beam-steering implementations if switches are used to select between different arrays around a cylindrical supporting structure.Comment: Keywords: conformal antenna, millimeter-wave communications, patch antenna array. 11 pages, 10 figures, 1 tabl

A method to investigate muscle target-specific transcriptional signatures of single motor neurons

Motor neurons in the vertebrate spinal cord have long served as a paradigm to study the transcriptional logic of cell type specification and differentiation. At limb levels, pool-specific transcriptional signatures first restrict innervation to only one particular muscle in the periphery, and get refined, once muscle connection has been established. Accordingly, to study the transcriptional dynamics and specificity of the system, a method for establishing muscle target-specific motor neuron transcriptomes would be required.; To investigate target-specific transcriptional signatures of single motor neurons, here we combine ex-ovo retrograde axonal labeling in mid-gestation chicken embryos with manual isolation of individual fluorescent cells and Smart-seq2 single-cell RNA-sequencing. We validate our method by injecting the dorsal extensor metacarpi radialis and ventral flexor digiti quarti wing muscles and harvesting a total of 50 fluorescently labeled cells, in which we detect up to 12,000 transcribed genes. Additionally, we present visual cues and cDNA metrics predictive of sequencing success.; Our method provides a unique approach to study muscle target-specific motor neuron transcriptomes at a single-cell resolution. We anticipate that our method will provide key insights into the transcriptional logic underlying motor neuron pool specialization and proper neuromuscular circuit assembly and refinement

Smanjenje sprege između dviju planarnih obrnutih-F antena s područjem rada u bliskim frekvencijskim pojasima

This paper presents a solution to reduce the mutual coupling between two Planar Inverted-F Antennas (PIFAs) working in close frequency bands: DCS1800 (1710-1880 MHz) and UMTS (1920-2170 MHz). The antennas are positioned on the top corner of a ground plane whose size is representative of the Printed Circuit Board (PCB) of a typical mobile phone. Two antenna-systems are designed and several arrangements are studied, especially when suspended line is inserted between the radiators. This line is intended to act as a neutralization device and then reduce the mutual coupling. Several prototypes are fabricated and measured to validate the proposed solution.U radu je predstavljeno rješenje smanjenja sprege dviju planarnih obrnutih-F antena (PIFA) s područjem rada u bliskim frekvencijskim pojasima: DCS1800 (1710–1880 MHz) i UMTS (1920–2170 MHz). Antene su postavljene u vrh uzemljene ravnine čija je veličina predstavnik tiskanih pločica (PCB) tipičnih mobilnih telefonskih uređaja. Tri antene su konstruirane i nekoliko modifikacija je proučavano, posebice u vezi postavljanja neaktivne prijenosne linije između njih. Ta prijenosna linija je zamišljena da služi kao neutralizirajuća komponenta i da stoga smanjuje međusobnu spregu. Nekoliko prototipova je izvedeno i izmjereno u cilju verifikacije predloženog rješenja

Development of the chick wing and leg neuromuscular systems and their plasticity in response to changes in digit numbers

The tetrapod limb has long served as a paradigm to study vertebrate pattern formation. During limb morphogenesis, a number of distinct tissue types are patterned and subsequently must be integrated to form coherent functional units. For example, the musculoskeletal apparatus of the limb requires the coordinated development of the skeletal elements, connective tissues, muscles and nerves. Here, using light-sheet microscopy and 3D-reconstructions, we concomitantly follow the developmental emergence of nerve and muscle patterns in chicken wings and legs, two appendages with highly specialized locomotor outputs. Despite a comparable flexor/extensor-arrangement of their embryonic muscles, wings and legs show a rotated innervation pattern for their three main motor nerve branches. To test the functional implications of these distinct neuromuscular topologies, we challenge their ability to adapt and connect to an experimentally altered skeletal pattern in the distal limb, the autopod. Our results show that, unlike autopod muscle groups, motor nerves are unable to fully adjust to a changed peripheral organisation, potentially constrained by their original projection routes. As the autopod has undergone substantial morphological diversifications over the course of tetrapod evolution, our results have implications for the coordinated modification of the distal limb musculoskeletal apparatus, as well as for our understanding of the varying degrees of motor functionality associated with human hand and foot malformations

Eph:ephrin-B1 forward signaling controls fasciculation of sensory and motor axons

AbstractAxon fasciculation is one of the processes controlling topographic innervation during embryonic development. While axon guidance steers extending axons in the accurate direction, axon fasciculation allows sets of co-extending axons to grow in tight bundles. The Eph:ephrin family has been involved both in axon guidance and fasciculation, yet it remains unclear how these two distinct types of responses are elicited. Herein we have characterized the role of ephrin-B1, a member of the ephrinB family in sensory and motor innervation of the limb. We show that ephrin-B1 is expressed in sensory axons and in the limb bud mesenchyme while EphB2 is expressed in motor and sensory axons. Loss of ephrin-B1 had no impact on the accurate dorso-ventral innervation of the limb by motor axons, yet EfnB1 mutants exhibited decreased fasciculation of peripheral motor and sensory nerves. Using tissue-specific excision of EfnB1 and in vitro experiments, we demonstrate that ephrin-B1 controls fasciculation of axons via a surround repulsion mechanism involving growth cone collapse of EphB2-expressing axons. Altogether, our results highlight the complex role of Eph:ephrin signaling in the development of the sensory-motor circuit innervating the limb

Two-Element PIFA Array Structure for Polarization Diversity in UMTS Mobile Phones

In this paper, we demonstrate the possibility to strongly modify the radiated fields of a UMTS handset by using a phased two-element PIFA array. The structure is composed of a 100x40 mm2 metallic ground plane acting as the Printed Circuit Board (PCB) of the mobile phone. Two UMTS PIFAs are located at the top edge of this PCB. They are fed by a double Quasi-Lumped Coupler able to provide a 360° phase difference between its two outputs. By properly choosing the DC bias of the double QuasiLumped Coupler, we can set a specific phase difference between the two PIFAs. In this way the two-element array is able to radiate different electromagnetic fields. Simulated and measured radiation patterns in the two main planes of the chassis are presented for different phase differences. It is especially revealed that the novel twoantenna structure is able to radiate vertically-polarized electric fields in the azimuthal plane of the phone and horizontally-polarized electric fields in the same plane when changing the phase shift between the antennas from 0° to 180°. Potential applications are polarization-diversity techniques and Specific Absorption Rate reduction for handsets