GROWTH FACTOR SIGNALS THROUGH BHLH TRANSCRIPTION FACTORS

描述（改编自申请人摘要）：长期研究 本项目的目的是了解bHLH和bHLH的功能 阻遏物和bHLH激活剂在神经营养生长因子信号传导中的作用。 该实验室先前的研究表明， 果蝇多毛和分裂增强蛋白，HES-1，作为一个阻遏物 的神经分化。他们的工作表明，HES-1是 神经生长因子信号传导的核靶点和效应物。在目前的提案中， 研究人员将扩大他们的bHLH蛋白在神经营养 通过进行旨在研究HES-1在 来源于PNS和CNS的原代神经元培养物。此外他们 计划研究MASH-1（一种bHLH激活剂）在介导NGF信号传导中的作用。 拟议项目的实验目标是测试以下内容 假设：1）HES-1是在来自神经元的原代神经元中NGF信号传导的关键介质。 PNS和CNS。2)HES-1还介导其他神经营养生长的作用， H19-7细胞中的因子。3)MASH-1是一种必要的中介物， 并且足以在PC 12细胞中发生NGF依赖性神经分化。 4)MASH-1是HES-1在PC 12细胞中的功能性靶点。

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.