GROWTH FACTOR SIGNALS THROUGH BHLH TRANSCRIPTION FACTORS

描述(摘自申请者摘要)：长期研究 本项目的目的是了解bhlh和bhlh的功能。 神经营养生长因子信号转导中的抑制物和bHLH激活物。 该实验室之前的研究表明，与人类同源的哺乳动物 果蝇毛发和分裂蛋白增强子HES-1是一种抑制因子 PC12细胞的神经分化。他们的研究表明，HES-1是 NGF信号的核靶标和效应器。在目前的提案中， 研究人员将扩展他们对神经营养中bHLH蛋白的分析 通过实验研究HES-1在信号转导中的作用 原代神经元培养来源于三叉神经节和中枢神经系统。此外，他们还 计划研究碱性成纤维细胞生长因子激活剂MASH-1在调节NGF信号中的作用。 提议的项目的实验目标是测试以下内容 假设：1)HES-1是原代神经元NGF信号的关键介体。 PNS和CNS。2)HES-1还介导了其他神经营养生长的作用 影响H19-7细胞生长的因素。3)MASH-1是一种必不可少的调节剂 并且足以在PC12细胞中发生神经生长因子依赖的神经分化。 4)MASH-1是HES-1在PC12细胞中的功能靶点。

DESCRIPTION (adapted from applicant's abstract): The long-term research objective of this project is to understand the functions of both bHLH repressors and bHLH activators in neurotrophic growth factor signaling. Previous studies by this laboratory have shown that the mammalian homolog of the Drosophila Hairy and Enhancer of Split proteins, HES-1, acts as a repressor of neural differentiation in PC12 cells. Their work demonstrated that HES-1 is a nuclear target and effector of NGF signaling. In the current proposal, the investigators will extend their analysis of bHLH proteins in neurotrophic signaling by carrying out experiments aimed at studying the role of HES-1 in primary neuronal cultures derived from both the PNS and CNS. In addition, they plan to study the role of MASH-1, a bHLH activator, in mediating NGF signaling. The experimental goals for the proposed project are to test the following hypotheses: 1) HES-1 is a key mediator of NGF signaling in primary neurons from the PNS and CNS. 2) HES-1 also mediates the effect of other neurotrophic growth factors in H19-7 cells. 3) MASH-1 is an essential mediator that is necessary and sufficient for NGF-dependent neural differentiation to occur in PC12 cells. 4) MASH-1 is a functional target for HES-1 in PC12 cells.