Nouveau rôle de la Sémaphorine 6D et de son récepteur Plexine-A1 dans le ciblage des axones rétiniens

Abstract : During development, axons branch at precise points to innervate a specific brain target, yet the mechanisms at hand are still unclear. To address this question, I used retinal axons forming the optic tract that innervate two principal targets of the visual system: the dorsal lateral geniculate nucleus (dLGN) and the superior colliculus. I investigated the role of the guidance receptor Plexin-A1and its ligand Semaphorin-6D (Sema6D) in this targeting process. Here I highlight a new type of phenotype in Plexin-A1-/- or Sema6D-/- mice. In these mice, the optic tract enters in the dLGN instead of circumscribing it and some retinal axons innervate ectopic regions at the other side of the optic tract. Furthermore, the analysis of simple or double heterozygotes mice reveals that Plexin-A1 and Sema6D interact together with a dose-dependent effect. Using loss and gain of function experiments (via retinal in utero electroporation), I showed that both are necessary in the retina for proper retinal innervation through non-cell autonomous effects. All these results reveal for the first time a dose-dependent mechanism, in which Sema6D and Plexin-A1 interact together. They monitor axon-axon communication to allow the correct innervation of the dLGN by a subpopulation of retinal axons.
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Delphine Prieur. Nouveau rôle de la Sémaphorine 6D et de son récepteur Plexine-A1 dans le ciblage des axones rétiniens. Neurosciences [q-bio.NC]. Sorbonne Université, 2018. Français. ⟨NNT : 2018SORUS285⟩. ⟨tel-02370105⟩

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