Cellular and transcriptomic programs linking amygdala progenitors to mature neuronal identity

将杏仁核祖细胞与成熟神经元身份联系起来的细胞和转录组程序

• 批准号: 10751113
• 负责人: JOSHUA G CORBIN
• 金额: $ 10.26万
• 依托单位: CHILDREN'S RESEARCH INSTITUTE
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-02-11 至 2024-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10751113
• 关键词: Adhesions; Adult; Aggressive behavior; Amygdaloid structure; Automobile Driving; Behavior; Behavior Control; Behavioral; Biology; Brain; Cell division; Cells; Cerebral cortex; Complex; Cues; Data; Development; Discrimination; Early identification; Electrophysiology (science); Electroporation; Embryo; Embryonic Development; Emotional; Emotional disorder; Endowment; Event; Exhibits; Experimental Models; FOXP2 gene; Gene Expression; Genes; Genetic; Goals; Human; Hypothalamic structure; Instinct; Intervention; Ion Channel; Knowledge; Label; Link; Medial; Mental disorders; Molecular; Molecular Profiling; Morphology; Neurons; Neurotransmitters; Olfactory Pathways; Output; Partner in relationship; Pattern; Phenotype; Process; Proliferating; Property; Regulation; Social Behavior; Specific qualifier value; Specificity; Structure of terminal stria nuclei of preoptic region; System; Testing; Therapeutic; Transcription Process; Vertebrates; Work; autism spectrum disorder; cohort; developmental disease; experimental study; in utero; in vivo; inhibitory neuron; innovation; multiphoton imaging; nerve stem cell; neuroepithelium; neurogenesis; neuronal patterning; neuropathology; novel; postmitotic; postnatal; progenitor; programs; rational design; receptor; segregation; single nucleus RNA-sequencing; social; social deficits; time use; transcription factor; transcriptomics; ultrasound

Project Summary The complex cellular and molecular events driving embryonic brain development are becoming better understood. However, how and to what extent these early processes are linked to the later emergence of neuronal identity and circuit specific patterns of neuronal wiring controlling diverse behaviors remains unknown. Our previous studies of development of medial subnucleus of the amygdala (MeA), a central hub for processing olfactory cues essential for innate (unlearned) social behavior, suggests a direct link between embryonic patterning and later subtype neuronal identity, lineage-specific patterns of output connectivity and innate behavioral regulation. Leveraging the advantages of studying the MeA, a developmentally hard-wired system, the goal of our proposed studies is elucidate the cellular and molecular mechanisms that bridge embryonic brain development with later functional outputs. Based on our previous data, we hypothesize that the mature properties of MeA neuronal subtype identity and subcircuit wiring patterns are preconfigured via cellular and molecular sequalae that unfold as lineages diverge in the VZ/SVZ. We propose to test this hypothesis by determining: the cellular mechanisms underlying early MeA lineage diversification (Specific Aim 1) and 2) linking emerging embryonic transcriptomic programs with the acquisition of genetic identifiers of neuronal identity and circuit assembly and connectivity (Specific Aim 2). This will be achieved by combining the expertise of the Haydar lab in cellular and transcriptomic mechanisms of early progenitor specification and the Corbin lab in the genetic basis of amygdala development and function. We propose to utilize innovative approaches including in utero ultrasound precision guided labeling of MeA progenitor pools, multiphoton imaging to follow neurons as they emerge, and cutting-edge unsupervised single-nuclei (sn) RNA-seq to identify the full repertoire of cellular and molecular factors operating as MeA progenitors generate functionally connected postnatal neurons.

项目总结