Transcriptional regulators of motor columnar specification

运动柱状规范的转录调节因子

基本信息

批准号：
10625972
负责人：
Soo-Kyung Lee
金额：
$ 49.47万
依托单位：
STATE UNIVERSITY OF NEW YORK AT BUFFALO
依托单位国家：
美国
项目类别：
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/10625972
关键词：
ATAC-seq Antibodies Axon Binding Biochemical Biological Models Cells ChIP-seq 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 Genetic Transcription Genomics Gland Goals Heterogeneity Homeostasis Knockout Mice Label Location Locomotion Maps Molecular Motor Motor Neurons Movement Mus Muscle Fibers Myocardium Names Nerve Nervous System control Neurites Neurons Newborn Infant Organ Pattern Play Population Property Ptosis Research Role Seminal Smooth Muscle Specific qualifier value Spinal Spinal Cord Sympathetic Ganglia Sympathetic Nervous System Synapses System Testing Thoracic spinal cord structure Validation Vertebral column Visceral bZIP Domain conditional knockout design gene regulatory network 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

项目摘要

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.

我们的总体研究目标是全面了解指导该基因调节网络脊髓中各种运动柱（MC）的开发以及每个MC如何贡献中性运动电路。该建议旨在研究一个名为Preganglionic MC的MC（PGC，又名CT 小鸡中的terni柱），仅在脊髓的胸腔水平上发现，并包含内脏运动控制交感神经系统（SYMN）活性的神经元（VMN）。在同情神经节中， PGC运动神经元（MNS）的轴突与交感神经元形成突触，然后调节平滑肌纤维，心脏肌肉和腺体的活性。鉴于PGC中的VMN控制SEMN，针对各种内部器官的哪个，很容易推测PGC不是同质细胞种群而是由多种子类型组成。但是，目的地的最新进步我们的发电机制在脊柱MC中，对指定PGC身份的要么知之甚少。这项研究PGC的细胞组成对MN或分子的理解将询问该领域的这两个主要问题。我们强烈的初步发现导致了我们的假设：PGC MN具有多种亚型，Jun是一个基因调节网络中的生命转录因子，指导命运规格，分化， PGC MN的多样化，细胞体迁移和轴突投影。“剖析这一假设，我们将采用细胞，生化，遗传和无偏基因组的方法的合奏。