Egr genes in sympathetic nervous system development

描述(申请人提供)：早期生长反应(Egr)基因可能在哺乳动物交感神经系统发育中发挥重要作用。EGR介导的基因转录对交感神经系统来源的PC12和神经母细胞瘤细胞系的分化至关重要。然而，它们在交感神经元发育中的作用在体内从未被研究过。我们概述了一个训练和研究计划，该计划将：1)鉴定Egr3基因缺陷小鼠的交感神经系统缺陷；2)确定哪些Egr基因家族成员在体内交感神经元中表达；3)探索涉及神经营养素-3(NT-3)和上游转录调节因子(如CREB)的信号转导通路在交感神经元发育过程中调节Egr基因表达的作用。进一步了解与生长因子介导的分化和存活相关的信号转导机制，可能会为肿瘤和交感神经退行性疾病的发病机制提供重要的见解。

DESCRIPTION (provided by applicant): Early Growth Response (Egr) genes may have an important role in mammalian sympathetic nervous system development. Egr mediated gene transcription is essential for differentiation of sympathetic nervous system derived PC12 and neuroblastoma cell lines. However, their role in sympathetic neuron development has never been addressed in vivo. We have outlined a training and research program that will: 1) Characterize the sympathetic nervous system defects in Egr3-deficient mice; 2) determine which Egr gene family members are expressed in sympathetic neurons in vivo; and 3) explore the role of signal transduction pathways involving neurotrophin-3 (NT-3) and upstream transcriptional regulators such as CREB in regulating Egr gene expression during sympathetic neuron development. A greater understanding of the signal transduction mechanisms related to growth factor mediated differentiation and survival may provide important insights into the pathogenesis of tumors and neurodegenerative diseases involving sympathetic neurons.