权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Translational control in neurogenesis by ZNF804A

ZNF804A 对神经发生的翻译控制

基本信息

批准号：
10333413
负责人：
Yingwei Mao
金额：
$ 27.19万
依托单位：
PENNSYLVANIA STATE UNIVERSITY, THE
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-04-01 至 2025-01-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10333413
关键词：
Adolescence Adult Affect Age Behavior Behavioral Binding Binding Sites Biological Assay Bipolar Disorder Brain Brain Diseases Cells DNA-Binding Proteins Defect Development Developmental Delay Disorders Developmental Gene Disease Etiology Functional disorder Genes Genetic Genetic Risk Genomics Human Immunoprecipitation Knockout Mice Knowledge Life Maps Measures Mediating Medical Mental disorders Messenger RNA Molecular Mosaicism Mus Nervous system structure Neurons Neuropsychology Pathologic Patients Physiological Play Population Production Proteins Proteomics Publishing Puromycin RNA-Binding Proteins Regulation Reporting Research Proposals Risk Factors Role Schizophrenia Structure System Techniques Testing Transcript Translations Variant Wild Type Mouse Zinc Fingers autism spectrum disorder base crosslink crosslinking and immunoprecipitation sequencing gene interaction genetic association genetic predictors high throughput analysis in vivo innovation insight migration neocortical nerve stem cell nervous system disorder neurodevelopment neurogenesis neurogranin neuroimaging neuronal circuitry novel therapeutics progenitor public health relevance risk variant stem cell proliferation theories

项目摘要

Modified Project Summary/Abstract Section Mental illnesses like schizophrenia (SZ) and bipolar disease (BP) are devastating brain disorders with global unmet medical needs. The “neurodevelopmental” theory posits that disturbances in the production and differentiation of neural progenitor cells (NPCs) cause brain development to deviate from its normal path, leading to alterations in neuronal circuitry and behavioral deficits that first manifest themselves in adolescence or adulthood. Genetic risk plays a major role in the etiology of SZ and BP and several robust and replicable risk loci have been identified with significant overlap between these two disorders. Among the top genetic associations, ZNF804A encodes a zinc finger protein. Diverse chromosomal variants of ZNF804A, including deletions and duplications, have also been found in patients with autism and developmental delay. Moreover, neuroimaging and neuropsychological studies have confirmed ZNF804A as an important genetic predictor of abnormal changes in brain structures, connectivity and behavior. However, molecular functions of ZNF804A in the nervous system are completely unknown. Thus, there is a critical need to elucidate the impacts of ZNF804A dysfunction on brain development in early life. Our central hypothesis is that ZNF804A regulates neuronal determination through interacting with translational machinery, and genetic interactions of ZNF804A with other developmental genes. The objective of this application, therefore, is to further dissect the molecular details on how ZNF804A modulates neurogenesis, and to examine genetic functional interactions between ZNF804A and its interacting genes in the knockout mice. This central hypothesis will be tested by following Specific Aims: 1) Define the mechanism of ZNF804A-mediated regulation of protein translation; 2) Determine the role of ZNF804A in neuronal fate commitment in vivo. The research proposal is innovative because this strategy combines in vivo mouse experimental systems with cutting-edge genomic/proteomic techniques. This contribution will be significant because it allows us to measure the effect of ZNF804A on the trajectory of neurodevelopment, and to identify potential underlying mechanisms contributing to developmental brain disorders.

修改的项目摘要/摘要部分