Développement et évolution des systèmes commissuraux chez les vertébrés

Abstract : In most bilateria, some neurons, called commissural neurons, extend their axons across midline to connect with contralateral targets. Netrin-1, a protein secreted at the ventral midline by the floor plate, atracts commissural axons and guide them towards midline. It is thought that the DCC receptor mediates Netrin-1 attraction towards ventral midline. However, in the mouse, Robo3 receptor also participate to Netrin-1 attractive signaling, and is necessary for commissural axons to reach ventral mdline. In this work, we have been studiing Robo3 and DCC receptors conservation in vertebrates. Strickingly, we found that birds withinh two major groups, the Galliforms and Passeriforms, do not have a Dcc gene. However, our comparative analysis of commissure development in birds revealed no difference between birds having or not DCC. On the other hand, Robo3 gene is present in all vertebrates studied, but is divergent in mammals. Especially Robo3 does not bind its cananical lignads Slits in these group. In amniotes, Robo3 is specifically expressed in commissural axons before they cross the midline. In contrast, Robo3 expression in other vertebrates is broder, and its exact function in commissural axon guidance remains unclear. Finally, restoring Slit binding to Robo3 in mammals does not affect commissural guidance, and the rôle of Robo3-Slit signaling in other vertebrates remains unclear. These data shed a new light on commissures diversity and their guidance mechanism among vertebrates.
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François Friocourt. Développement et évolution des systèmes commissuraux chez les vertébrés. Neurosciences [q-bio.NC]. Université Pierre et Marie Curie - Paris VI, 2017. Français. ⟨NNT : 2017PA066149⟩. ⟨tel-02169199v2⟩

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