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Project 1 Genetic Networks Establishing Serontonergic Neuronal Idenity

项目 1 建立血清素能神经元身份的遗传网络

基本信息

批准号：
7921653
负责人：
EVAN S DENERIS
金额：
$ 23.71万
依托单位：
VANDERBILT UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-07-01 至 2012-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7921653
关键词：
Address Adult Alleles Anxiety Area Behavior Behavioral Bioinformatics Characteristics Circadian Rhythms Collaborations Databases Development Disease Embryo Emotional Flow Cytometry Foundations Future Gene Expression Gene Expression Profile Genes Genetic Genetic Variation Glucocorticoid Receptor Goals Ice Immunohistochemistry In Situ Hybridization Knock-out Knockout Mice Label Mental disorders Methodology Molecular Genetics Molecular Profiling Moods Mus Neurodevelopmental Disorder Neurologic Neurons Pain Pathogenesis Pattern Perception Play Predisposition Preparation Proteins Proteomics Regulation Research Research Personnel Resources Respiration Risk Risk Factors Role Serotonin Signal Transduction Sleep Staging Stress System Tamoxifen Testing Time Transgenic Organisms Variant axon growth axonal guidance base biological adaptation to stress clinically relevant energy balance follow-up gene function genetic variant nerve supply nervous system disorder neurochemistry neuron development novel marker postnatal programs receptor function recombinase spatiotemporal synaptogenesis tool

项目摘要

Altered 5HT signaling has been implicated in the pathogenesis of numerous neurological and psychiatric disorders. Many of these disorders are neurodevelopmental in origin and risk for acquiring them is likely to be influenced by multiple heritable susceptibility factors. In Project 1: Genetic Networks Establishing Serotonergic Neuronal Identity, Evan Deneris hypothesizes that some of these susceptibility factors may be allelic variants of genes that govern 5HT neuron development and that these alleles may contribute to behavioral pathogenesis by adversely increasing or decreasing 5HT system activity. Although some SERT variants are identifiable risk factors for mental health disorders, the majority of genes involved in 5HT neuron development have not yet been investigated for the presence of disease-associated alleles. Advances in this area have not been made because 5HT neurons are difficult to access for molecular genetic studies. Consequently, only a small number of genes that compose the 5HT neuron developmental program have been identified. An additional critical factor that has hindered progress is that diverse methodology and expertise is required to investigate the function of 5HT neuron developmental control genes. Deneris has developed transgenic-based tools that enable direct and highly specific access to embryonic and adult 5HT neurons. The research proposed here will take advantage of these tools to interrogate the 5HT neuron transcriptome and thereby identify genes that may control 5HT neuron development and function. His proposed aims will address the following questions: What network of genes is expressed during critical stages of embryonic and postnatal 5HT neuron development? What are the differences between the rostral and caudal 5HT neuron expressed gene networks? Are different stages of 5HT neuron development marked by expression of certain sets of genes? What role does the glucocorticoid receptor (GR) play in embryonic and adult 5HT neurons? Deneris expects to identify a diverse network of fTa3ctors that govern different facets of 5HT neuron development and function. Integration of this research into ¿hearCacotnetreistCicesntoefrcapnrodjiedcatewisllergorteoantelyrgfaicimlitartkeesrstuadniedsfuanimcteiodnaltsdtuedteierms ionfinGgRththerosupgahtioctaermepfuollryalpleaxnpnredssaiondn orchestrated collaborations with P. Levitt (Project 2), R. Blakely (Project 3), E. Sanders-Bush (Project 4), D. McMahon (Project 6) and the three Conte Center Cores. Deneris' transgenic lines will provide new tools to facilitate studies proposed in Projects 2-4 and 6. Project 1's transcriptome databases will provide critical reference information for studies of mouse 5HT neuron transcriptome function and regulation proposed in Projects 2-6. Project 1 studies will enable future screens for disease relevant genetic variants in validated 5HT neuron developmental control genes.

5HT信号的改变与许多神经和神经疾病的发病机制有关