Notch Functions in the Adult Nervous System

Notch信号传导在发育细胞命运决定中起着充分描述的作用， 调节干细胞增殖和许多疾病。Notch信号 对成年神经元的功能也至关重要。Notch在记忆保持中发挥作用， 小鼠和果蝇，但神经元中Notch信号传导的靶点尚不清楚。 我们证明了C.线虫lin-12 Notch受体在成虫中的作用 动物来调节行为。在这里提出的研究中，我们将确定 Notch信号改变神经元功能和行为的分子途径 利用C.优雅在试点屏幕中，我们 确定了五个在神经系统中表达的基因，这些基因可能是神经系统的直接靶点。 缺口。所有五个基因编码的蛋白质可能是关键的Notch信号， 脊椎动物的神经元也一样。在本提案中，我们讨论了 这些Notch靶基因在成人神经系统中起作用， 活动和行为。

Notch signaling plays well described roles in developmental cell fate decisions, in the regulation of stem cell proliferation and in numerous diseases. However, Notch signaling is also critical for the function of adult neurons. Notch plays a role in memory retention in mice and Drosophila, yet the targets of Notch signaling in neurons are unclear. We have demonstrated that the C. elegans lin-12 Notch receptor acts in adult animals to modulate behavior. In the studies proposed here, we will identify the molecular pathways by which Notch signaling alters neuronal function and behavior using the powerful genetic techniques available in C. elegans. In a pilot screen, we identified five genes expressed in the nervous system that are likely direct targets of Notch. All five genes encode proteins that are likely critical for Notch signaling in vertebrate neurons as well. In this proposal, we address the mechanisms and pathways by which these Notch target genes act in the adult nervous system to regulate neuronal activity and behavior.