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Étude du rôle de la Nétrine-1 dans l'ontogénèse et le maintien de l'homéostasie de l'épithélium intestinal murin

Abstract : The adult intestinal epithelium is a highly organized tissue, which is completely self-renewed every 5 to 7 days, due to a pool of multipotent intestinal stem cells (ISC). Located at the base of intestinal crypts, ISC have the ability to self- renew and to give rise to all epithelial intestinal cell types. To preserve the balance between their self-renewal and their differentiation, and therefore to maintain the epithelial tissue homeostasis, ISC reside in a tightly regulated microenvironment - called “niche”- that provides them all factors required for their functions. Netrin-1, a laminin-related secreted protein, is expressed in the microenvironment of the crypt, and is also expressed during intestinal development. Initially described as an axonal guidance cue, Netrin-1 is now considered as a pleiotropic molecule involved in many different processes such as morphogenesis, cell migration, cell adhesion, proliferation and also tumorigenesis. Based on these observations, we hypothesized that Netrin-1 could play a role in the maintenance of the adult intestinal stem cell compartment, and also in the intestinal ontogenesis. In a first part, we showed that Netrin-1 promotes the growth of enteroids ex vivo while regulating gene expression of specific intestinal stem cell markers. In the second part, we demonstrated, by using two novel genetically engineered mouse models, that Netrin-1 is involved in the embryonic development of the intestinal epithelium and that its deletion leads to a delay in villi emergence
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Pauline Vieugué. Étude du rôle de la Nétrine-1 dans l'ontogénèse et le maintien de l'homéostasie de l'épithélium intestinal murin. Biologie cellulaire. Université de Lyon, 2017. Français. ⟨NNT : 2017LYSE1283⟩. ⟨tel-02003609⟩

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