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Etude des mécanismes moléculaires contrôlant le développement des projections commissurales

Abstract : In all bilaterians, the connections linking the left and the right part of the central nervous system (CNS) are called the commissures. Understanding molecular mechanisms involved in the formation of these circuits is a major issue in developmental neurobiology. The guidance of commissural projections lay on two major couples of ligand- receptors: Netrin-1/DCC and Slits/Robos. Netrin-1 and Slits are expressed in the floor plate whereas their respective receptors, DCC and Robo1/2, are present in the neurons and commissural axons of the spinal cord and the hindbrain during the development. Analysis of mice deficient for these genes lead to establish a model: a Netrin-1 gradient would act through long distances in order to attract commissural axons to the ventral midline, then Slits would repulse axons outside the floor plate. During my thesis, I used genetic mouse models to study the setting of commissural axons and the migration of precerebellar neurons in vivo. We have specifically inactivated the expression of Netrin-1 Slits and Robo1/2 genes in different region of the CNS. We showed that floor plate-derived Netrin-1 was not necessary for the attraction of commissural axons and that the principal source of Netrin-1 was the radial glia. We also showed that the Slit/Robo couple was not essential for the migration of precerebellar neurons. These results reassess the model firstly provided and suggest the presence of other molecular mechanisms involved in commissural axon guidance.
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Chloé Dominici. Etude des mécanismes moléculaires contrôlant le développement des projections commissurales. Neurosciences [q-bio.NC]. Université Pierre et Marie Curie - Paris VI, 2016. Français. ⟨NNT : 2016PA066382⟩. ⟨tel-01885492⟩

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