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Theses

Rôle du cil primaire dans la migration des neuroblastes du courant de migration rostrale

Abstract : The aim of my thesis was to better understand the mechanisms underlying the role of the primary cilium (PC) in neuronal migration. Our study model is the tangential migration in the rostral migratory stream (RMS) in the postnatal and adult mice. Neuroblasts of the CMR show a saltatory migration with pause and nucleokinesis and a stereotyped centrosome movement. In a first study with preliminary results, we compared the migration between postnatal (P10) and young adult (P30) stages by live imaging on acute brain slices, as well as the effect of genetic ablation of the PC at these two ages. We showed that migrations are different between these two stages and that genetic ablation of the PC impaired differentially migration parameters. In a second study, submitted for publication soon, we analysed cAMP dynamics during postnatal migration. We observed a dynamic cAMP hotspot cyclically at the centrosome, at the basis of the PC. We show that ciliary-produced cAMP diffuses to the centrosome, where it activates locally the cAMP-dependent Protein Kinase A (PKA). Genetic ablation of the cilium and knock-down of the ciliary Adenylate Cyclase 3 lead to the hotspot disappearance. They also affect migration with defective centrosome/nucleus coupling leading to altered nucleokinesis, which is recapitulated by PKA genetic delocalization. We thus show that PC and centrosome act as a signalling unit, linked by ciliary cAMP diffusion regulating the rhythmicity of salutatory migration at the centrosome.
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Maxime Chaulet. Rôle du cil primaire dans la migration des neuroblastes du courant de migration rostrale. Neurosciences [q-bio.NC]. Sorbonne Université, 2019. Français. ⟨NNT : 2019SORUS191⟩. ⟨tel-02932151⟩

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