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Neurogenesis regulation and homeostasis : role of Pax6 signalling and mathematical modelling

Abstract : A tight control of the organization of the cerebral cortex is vital for most species. Understanding the regulatory mechanisms supporting these processes is an important endeavor in developmental biology. We focused on the processes taking place during neurogenesis of the cerebral cortex, and took a multi-disciplinary approach combining biological experiments and mathematical models. We start with a model describing the probability of progenitor divisions sequence as a function of time during the neurogenesis. It is parsimonious, but sufficient to explain and draw predictions on the phenotype observed in Lhx2 conditional knock-out mutant that precocious neurogenesis affected cortical surface and thickness. The second topic we studied is how the brain compensates cell death to maintain homeostasis during development. In two mutant mouse models with neuronal death between embryonic days 11 to 14, different compensation phenotypes are observed. Here, we develop a unified mathematical model that reconciles those two opposite observations. This model is based on two fundamental compensation mechanisms: 1) an increase in the probability and maximal number of intermediate progenitor proliferative divisions; 2) a delay in the switching time between upper- and deep-layer neurons generation by a maximum of 24h. The third topic we studied is the role of extracellular Pax6 on neurogenesis. Pax6 is one of the master regulators of neuronal progenitor proliferative division and differentiation. With its homeodomain, it can transfer between cells and exert non-cell autonomous activities. We showed that blocking extracellular Pax6 induces Cajal-Retzius neurons generation ectopically.
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  • HAL Id : tel-02864832, version 1

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Yi Cui. Neurogenesis regulation and homeostasis : role of Pax6 signalling and mathematical modelling. Neurons and Cognition [q-bio.NC]. Sorbonne Université, 2018. English. ⟨NNT : 2018SORUS309⟩. ⟨tel-02864832⟩

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