Notch Functions in the Adult Nervous System

Notch信号在发育中的细胞命运决定中扮演着重要的角色，在 干细胞增殖和多种疾病的调控。然而，Notch信令 对成年神经元的功能也至关重要。Notch在记忆保持中起作用 小鼠和果蝇，然而Notch信号在神经元中的目标尚不清楚。 我们已经证明线虫LIN-12 Notch受体在成人中起作用 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 利用线虫强大的基因技术。在飞行员屏幕上，我们 确定了在神经系统中表达的五个基因，它们可能是 开槽。所有五个基因都编码可能对Notch信号转导至关重要的蛋白质。 脊椎动物的神经元也是如此。在这项提案中，我们讨论了机制和途径 这些Notch靶基因通过其在成人神经系统中作用来调节神经元 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.