REGULATION OF NEURAL CAMS BY GROWTH FACTORS AND ACTIVITY

生长因子和活动对神经凸轮的调节

基本信息

批准号：
6639628
负责人：
GERALD EDELMAN
金额：
$ 32.41万
依托单位：
SCRIPPS RESEARCH INSTITUTE, THE
依托单位国家：
美国
项目类别：
财政年份：
2000
资助国家：
美国
起止时间：
2000-04-01 至 2005-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/6639628
关键词：
bone morphogenetic proteins cell line developmental neurobiology gel mobility shift assay genetically modified animals hippocampus homeobox genes laboratory mouse neural cell adhesion molecules transcription factor

项目摘要

DESCRIPTION (Adapted from applicant's abstract): A number of neural CAMs have been identified, and work in the applicant's laboratory and others has demonstrated the importance of these molecules in the formation and function of the nervous system. It is clear from these studies that when and where a given CAM is expressed during development are critical for its function. The applicant's recent studies have focused on determining the transcription factors that regulate the expression of N-CAM and another neural CAM, L1. He has shown that the genes for these molecules are targets of the homeodomain and paired domain (Pax) proteins that regulate overall neural patterning. He proposes to expand these studies by examining how growth factors of the bone morphogenetic protein (BMP) family and synaptic activity modulate the expression of the N-CAM and L1 genes. The specific aims of the application are: 1) To examine the regulation of N-CAM and L1 gene expression by BMP2 and BMP4 in neural cells; 2) To determine in transgenic mice the contributions of the homeodomain and paired domain binding elements in the N-CAM and L1 genes to their developmental expression patterns and BMP responses; 3) To identify the regulatory elements and transcription factor families involved in the induction of the L1 and N-CAM genes by neural activity. Transfected cells and hippocampal slice cultures from normal and transgenic mice will be used in conjunction with gel shift and supershift assays in these experiments. Overall, these studies will elucidate the role of BMP signaling and of specific homeodomain and Pax gene products in the regulation of the expression of two neural CAMs. It will also provide one of the first demonstrations of the links between transcriptional regulation of CAMs and synaptic activity. These results will be particularly significant in view of the central role of CAMs in brain development, neurological disease and synaptic plasticity.

描述（改编自申请人的摘要）：许多神经 CAM 具有已被确定，并且申请人的实验室和其他人的工作已经证明了这些分子在形成和功能中的重要性神经系统。从这些研究中可以清楚地看出，给定的时间和地点 CAM 在发育过程中表达对其功能至关重要。这申请人最近的研究重点是确定转录调节 N-CAM 和另一种神经 CAM L1 表达的因子。他已经表明这些分子的基因是同源域的目标并且调节整体神经模式的配对域 (Pax) 蛋白。他建议通过检查骨骼生长因子如何来扩展这些研究形态发生蛋白 (BMP) 家族和突触活动调节 N-CAM 和 L1 基因的表达。该应用程序的具体目标是： 1) 检查BMP2和BMP4对N-CAM和L1基因表达的调节在神经细胞中； 2) 确定转基因小鼠中的贡献 N-CAM 和 L1 基因中的同源域和配对域结合元件他们的发育表达模式和 BMP 反应； 3) 识别参与诱导的调控元件和转录因子家族 L1 和 N-CAM 基因的神经活动。转染细胞和海马来自正常和转基因小鼠的切片培养物将与这些实验中的凝胶位移和超位移测定。总体而言，这些研究将阐明 BMP 信号传导以及特定同源域和 Pax 的作用基因产物调节两个神经 CAM 的表达。它将还提供了第一个演示之间的联系 CAM 和突触活动的转录调控。这些结果将是鉴于 CAM 在大脑中的核心作用尤其重要发育、神经系统疾病和突触可塑性。

项目成果

期刊论文数量（11）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

A positive feedback vector for identification of nucleotide sequences that enhance translation.

用于鉴定增强翻译的核苷酸序列的正反馈载体。

DOI：
10.1073/pnas.0409892102
发表时间：
2005
期刊：
Proceedings of the National Academy of Sciences of the United States of America.
影响因子：
0
作者：
Zhou,Wei;Edelman,GeraldM;Mauro,VincentP
通讯作者：
Mauro,VincentP

Identification of two short internal ribosome entry sites selected from libraries of random oligonucleotides.

鉴定从随机寡核苷酸文库中选择的两个短内部核糖体进入位点。

DOI：
10.1073/pnas.98.4.1471
发表时间：
2001
期刊：
Proceedings of the National Academy of Sciences of the United States of America
影响因子：
11.1
作者：
Owens,GC;Chappell,SA;Mauro,VP;Edelman,GM
通讯作者：
Edelman,GM