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Rôle des gènes de la voie de biosynthèse des purines au cours du développement embryonnaire de Xenopus laevis

Abstract : The purine biosynthesis pathway is a conserved metabolic pathway essential for many cell functions. In Human, several mutations in genes involved in this pathway lead to severe neuromuscular diseases, which are at least in part caused by unknown developmental impairments. We established a Xenopus laevis model to decipher the role of the purine biosynthesis genes during vertebrate development. As no data was available regarding this pathway, the main Xenopus purine genes were first identified in silico and functionally validated in vivo using the yeast Saccharomyces cerevisiae as a heterologous system. Spatio-temporal analyses revealed that these genes are expressed all along the development, especially in neuromuscular tissues, suggesting an important role during their formation. The knock-down of ppat, adsl or hprt, three key purine genes, leads in each case to severe defects in skeletal muscles embryonic defects, in particular in somites and hypaxial muscles. These muscular phenotypes are the consequence of an early alteration in expression of some crucial Myogenic Regulatory Factors (MRF), such as myoD and myf5. Moreover, an alteration of the hypaxial muscles precursors was observed. In conclusion our results establish X. laevis as an ideal model to get new insights into the neuromuscular developmental alterations associated to purine deficiencies.
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Maëlle Duperray. Rôle des gènes de la voie de biosynthèse des purines au cours du développement embryonnaire de Xenopus laevis. Génétique. Université de Bordeaux, 2017. Français. ⟨NNT : 2017BORD0750⟩. ⟨tel-01714572⟩

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