Transcriptional regulators of motor columnar specification

运动柱状规范的转录调节因子

• 批准号: 9900077
• 负责人: Soo-Kyung Lee
• 金额: $ 51.65万
• 依托单位: STATE UNIVERSITY OF NEW YORK AT BUFFALO
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-04-01 至 2024-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9900077
• 关键词: ATAC-seq; Antibodies; Axon; Binding; Biochemical Genetics; Biological Models; Cells; Chest; Chick; Chick Embryo; Chick model; Chromatin; Data; Data Set; Development; Eyelid structure; FOXP1 gene; Functional disorder; Ganglia; Gene Expression; Gene Expression Regulation; Generations; Genes; Genetic Transcription; Genomics; Gland; Goals; Heterogeneity; Homeostasis; Knockout Mice; Label; Location; Locomotion; Molecular; Motor; Motor Neurons; Movement; Mus; Muscle Fibers; Myocardium; Names; Nerve; Nervous System control; Neurites; Neurons; Newborn Infant; Organ; Pattern; Play; Population; Property; Ptosis; Regulator Genes; Research; Role; Seminal; Smooth Muscle; Specific qualifier value; Spinal; Spinal Cord; Sympathetic Ganglia; Sympathetic Nervous System; Synapses; Testing; Thoracic spinal cord structure; Validation; Visceral; bZIP Domain; conditional knockout; design; genome-wide; in vivo; migration; motor neuron development; mouse model; neural circuit; neurodevelopment; programs; single cell analysis; single-cell RNA sequencing; transcription factor; transcription factor USF; transcriptome

Our overarching research goal is to comprehensively understand the gene regulatory network that directs the development of various motor columns (MCs) in the spinal cord and how each MC contributes to the neural circuitry for locomotion. This proposal is designed to study a MC named PreGanglionic MC (PGC, aka CT for Column of Terni in chick), which is found only in thoracic levels of the spinal cord and contains visceral motor neurons (vMNs) that control the activity of the sympathetic nervous system (SymNS). In sympathetic ganglia, the axons of PGC motor neurons (MNs) form synapse with sympathetic neurons, which then regulate the activity of smooth muscle fibers, cardiac muscles, and glands. Given that vMNs in the PGC control the SymNS, which targets various internal organs, it is tempting to speculate that PGC is not a homogenous cell population and instead consists of multiple subtypes. However, despite recent advances in our generation mechanisms of spinal MCs, little is known about either that specify PGC identity. This study the cellular composition of PGC understanding of the MNs or the molecular will interrogate these two major issues in the field. Our strong preliminary findings led to our hypothesis: PGC MNs have multiple subtypes and Jun is a vital transcription factor in the gene regulatory network that directs fate-specification, differentiation, diversification, cell body migration, and axonal projection of PGC MNs.” To dissect this hypothesis, we will employ an ensemble of cellular, biochemical, genetic and unbiased genome-wide approaches.

我们的首要研究目标是全面了解基因调控网络，指导 脊髓中各种运动柱（MC）的发展以及每个MC如何促进神经功能的恢复。 用于运动的电路本研究旨在研究一种名为Preganglionic MC（PGC，又称CT）的MC， 鸡的Terni柱），仅见于脊髓的胸段，包含内脏运动 神经元（vMN）控制交感神经系统（SymNS）的活动。在交感神经节， PGC运动神经元（MN）的轴突与交感神经元形成突触，然后交感神经元调节PGC运动神经元的运动。 平滑肌纤维、心肌和腺体的活动。考虑到PGC中的vMN控制SymNS， 它靶向各种内脏器官，这很容易推测PGC不是一个同质的细胞群， 而是由多个子类型组成。然而，尽管我们的生成机制最近取得了进展， 脊髓MC，很少有人知道这两个指定PGC身份。本研究探讨了PGC的细胞组成 对MN或分子的理解将在该领域中询问这两个主要问题。 我们强有力的初步研究结果导致了我们的假设：PGC MN有多种亚型，Jun是一种 基因调控网络中的重要转录因子，指导命运特化，分化， PGC MNs的多样化、细胞体迁移和轴突投射。为了分析这个假设，我们 将采用细胞，生物化学，遗传和无偏见的全基因组方法的合奏。