Die Rolle von Wnt-Proteinen in der neuronalen und dopaminergen Differenzierung adulter neuraler Stammzellen

具有分化为神经元和神经胶质细胞潜能的分化细胞存在于整个成年哺乳动物中枢神经系统（CNS）中。然而，招募这些神经干细胞（NSC）修复的患病的成年中枢神经系统受到阻碍，目前缺乏知识的分子信号通路，控制成人NSC的分化。我的初步研究结果表明，Wnt蛋白在调节成年神经干细胞的神经元和多巴胺能分化中起着重要作用。在这个项目中，我建议在体外和体内的细胞和分子水平上研究Wnt信号在这些过程中的作用。此外，我建议操纵Wnt信号在成人中枢神经系统的目标是刺激神经元和多巴胺能分化的内源性神经干细胞在非神经原性地区通常影响神经退行性疾病。这些研究不仅会导致更好地了解控制成人神经干细胞的行为的分子信号，但最终可能有后果的设计新的治疗方法，在退行性中枢神经系统疾病的目的是招募内源性神经干细胞替代垂死的神经元。

Proliferating cells with the potential to differentiate into neurons and glia are present throughout the adult mammalian central nervous system (CNS). However, recruitment of these neural stem cells (NSCs) for repair of the diseased adult CNS is hampered by the current lack of knowledge about the molecular signaling pathways that control the differentiation of adult NSCs. My preliminary results suggest that Wnt-proteins play a major role in the regulation of neuronal and dopaminergic differentiation of adult NSCs. In this project, I propose to examine the role of Wnt-signaling in these processes on the cellular and molecular level in vitro and in vivo. Moreover, I propose to manipulate Wnt-signaling in the adult CNS with the goal to stimulate the neuronal and dopaminergic differentiation of endogenous NSCs in non-neurogenic regions commonly affected in neurodegenerative diseases. These studies will not only lead to a better understanding of the molecular signals controlling the behavior of adult NSCs but may ultimately have consequences for the design of novel therapeutic approaches in degenerative CNS disorders which aim at the recruitment of endogenous NSCs for replacement of dying neurons.