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

成体哺乳动物中枢神经系统(CNS)中广泛存在具有向神经元和神经胶质细胞分化潜能的增殖细胞。然而，由于目前对控制成人神经干细胞分化的分子信号通路缺乏了解，这些神经干细胞(NSCs)的招募用于修复患病的成人CNS是受到阻碍的。我的初步结果表明，Wnt蛋白在成年神经干细胞的神经元和多巴胺能分化的调节中起主要作用。在这个项目中，我建议在体外和体内从细胞和分子水平上研究Wnt信号在这些过程中的作用。此外，我建议在成人中枢神经系统中操纵Wnt信号，目的是刺激在神经退行性疾病中常见的非神经源性区域内内源性神经干细胞的神经元和多巴胺能分化。这些研究不仅有助于更好地了解控制成年NSCs行为的分子信号，而且最终可能对设计新的退行性中枢神经系统疾病的治疗方法产生影响，目的是招募内源性NSCs来替代濒临死亡的神经元。

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.