Morphogens are secreted signalling molecules that are expressed in restricted groups of cells within the developing tissue. From there, they are secreted and travel throughout the target field and form concentration gradients. These concentration profiles endow receiving cells with positional information. A number of experiments in Drosophila demonstrated that the morphogen Decapentaplegic (Dpp) forms activity gradients by inducing the expression of several target genes above distinct concentration thresholds at different distances from the source. This way, Dpp contributes to developmental fates in the target field such as the Drosophila wing disc. Although the tissue distribution as well as the actual shape and size of the Dpp morphogen concentration gradient has been visualized, the cell biological mechanisms through which the morphogen forms and maintains a gradient are still a subject of debate. Two hypotheses as to the dominant mechanism of movement have been proposed that can account for Dpp spreading throughout the Drosophila wing imaginal target tissue: extracellular diffusion and planar transcytosis, i. e. endocytosis and resecretion of the ligand that is thereby transported through the cells. Here, I present data indicating that implications of a theoreticalanalysis of Dpp spreading, where Dpp transport through the target tissue is solely based on extracellular diffusion taking into account receptor binding and subsequent internalization, are inconsistent with experimental results. By performing Fluorescence Recovery After Photobleaching (FRAP) experiments, I demonstrate a key role of Dynamin-mediated endocytosis for Dpp gradient formation. In addition, I show that most of GFP-Dpp traffics through endocytic compartments at the receiving epithelial cells, probably recycled through apical recycling endosomes (ARE). Finally, a Dpp recycling assay based on subcellular photouncage of ligand is presented to address specifically the Dpp recycling event at the receiving cells.

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Différents éléments vasculo-nerveux participent à la constitution de l'angle ponto-cérébelleux. Dans certaines conditions pathologiques dont la genèse est encore imparfaitement connue actuellement, des conflits peuvent apparaître entre des vaisseaux battants autour du tronc cérébral et des nerfs crâniens. L'objectif de ce travail en trois parties distinctes est consacré à certaines bases anatomiques et physiologiques permettant de mieux appréhender ces conflits vasculo-nerveux. La première partie s'intéresse à la morphogenèse du système vertébrobasilaire. La conception d'un logiciel original de reconstruction tridimensionnelle a permis la modélisation de quatre embryons à partir de coupes histologiques. Les images obtenues permettent de confirmer la morphogenèse décrite dans la littérature et jette les bases d'une étude plus exhaustive. La deuxième partie démontre pour la première fois la mobilité physiologique du nerf vestibulo-cochléaire au niveau de l'angle ponto-cérébelleux, par l'utilisation d'une séquence IRM en contraste de phase. Les directions crânio-caudale et antéro-postérieure et leur amplitude ont été étudiées. Ces mouvements sont dépendants de l'onde de pouls. De façon plus générale, ils peuvent être modélisés sous la forme d'une corde oscillant entre le tronc cérébral et le fond du méat acoustique interne. La troisième partie traite d'une étude de faisabilité qui jette les bases informatiques permettant d'apprécier le vieillissement artériel par la variabilité morphologique du point de confluence des artères vertébrales. Au laboratoire, nous avons conçu un programme de normalisation à partir des scanographies de neuf patients. Il autorise ainsi la création d'un tronc cérébral moyen, et la comparaison de la topographie de ces points de confluence. / Several vascular and nervous structures are located within the cerebello-pontine angle. In certain pathological conditions, microvascular compression syndroms may occur, where an artery or a vein is compressing a cranial nerve. The purpose of this work in three parts is to investigate some anatomical and physiological bases of these microvascular compression syndroms. The first part focuses on the vertebrobasilar system morphogenesis. A special designed 3D reconstruction original software allowed us to reformate four human embryos from histological serial sections. The three-dimensional views are confirming the classical features thus creating the basis of a larger study based on multiple embryos. The second part shows for the first time the physiological motion of the vestibulo-cochlear nerve at the level of the cerebello-pontine angle, with the help of a phase-contrast MRI sequence. The cranio-caudal and antero-posterior directions and their amplitudes have been studied. These motions are cardiac-cycle-dependant. We used an "oscillating string" model to explain the VCN motion between the brain stem and the fundus of the internal acoustic meatus. The third part of this work is focused on a preliminary study of the variability of the vertebro-basilar arterial fusion along the lifetime. An original software has been designed and allowing the normalisation from nine post-contrast cerebral CT scanners. A ?mean? brain stem was obtained and visualized in front of nine arterial fusion points.

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