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The role of Foxp1-regulated signaling pathways in brain development and behavior

Foxp1调节的信号通路在大脑发育和行为中的作用

基本信息

批准号：
9273628
负责人：
Genevieve Konopka
金额：
$ 40.5万
依托单位：
UT SOUTHWESTERN MEDICAL CENTER
依托单位国家：
美国
项目类别：
财政年份：
2015
资助国家：
美国
起止时间：
2015-09-01 至 2020-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9273628
关键词：
Acute Address Affect Alleles Autistic Disorder Automobile Driving Behavior Behavioral Brain Brain Diseases Brain region Cells Childhood Comorbidity Corpus striatum structure Data Data Set Development Developmental Delay Disorders Disease Electrophysiology (science)Embryo Etiology FMR1 FOXP1 gene Fragile X Syndrome Gene Expression Gene Expression Regulation Gene Targeting Genes Genetic Models Genetic Transcription Goals Heritability Hippocampus (Brain)Human Individual Injectable Intellectual functioning disability Knock-out Knockout Mice Knowledge Laboratories Molecular Mus Mutation Neurodevelopmental Disorder Neurons Pathway interactions Patients Play Regional Disease Regulator Genes Reporting Research Personnel Risk Risk Behaviors Rodent Rodent Model Role Signal Pathway Signal Transduction Slice Therapeutic Time Ultrasonics Viral autism spectrum disorder base cognitive function conditioned fear functional genomics insight loss of function mutation mind control nerve stem cell neuropsychiatric disorder novel therapeutic intervention postnatal programs public health relevance synaptic function targeted treatment transcription factor transcriptome transcriptome sequencing vocalization

项目摘要

DESCRIPTION (provided by applicant): Complete knowledge of the signaling pathways underlying brain development still remains unknown. The long- term goal of our laboratory is to elucidate the molecular signaling pathways disrupted in neurodevelopmental disorders that are important for brain development. Mutations in the gene encoding FOXP1 have previously been identified in individuals with developmental delay, intellectual disability, and autism. Our preliminary studies have shown that the transcription factor FOXP1 regulates genes important in brain development, and reduction in FOXP1 levels leads to behavioral changes in rodents. In addition, our data show that Foxp1 is a critical regulator of genes important for neuronal activity and loss of Foxp1 results in altered neuronal function. Based on these data, the central hypothesis driving this proposal is that FOXP1 is an orchestrator of transcriptional signaling cascades that are important for neuronal function and are at risk in neurodevelopmental disorders such as ASD. We propose to identify the developmental and regional disease-relevant targets of FOXP1 in the developing brain by using a combination of rodent models and human transcriptome data through three specific aims: 1) Identify the developmental transcriptional program regulated by Foxp1 in the brain; 2) Assess the role of Foxp1 and target genes in activity-dependent neuronal function; and 3) Determine the regional contribution of Foxp1 in the brain to specific ASD-relevant behaviors. Together, these aims will determine the transcriptional program regulated by Foxp1 throughout brain development and how Foxp1 gene regulation may be related to neuronal function and specific disease- relevant behaviors. Completion of the proposed aims will provide increased knowledge as to the molecular pathways that can be targeted for treatment in individuals with autism. The generated rodent models can be utilized to examine new therapeutic approaches for reversing autism-relevant behaviors. These data will also provide insight into the basic molecular mechanisms governing normal brain development.