Investigating the relationship between Sympathetic Nervous System Development and Neuroblastoma

研究交感神经系统发育与神经母细胞瘤之间的关系

基本信息

批准号：
10658015
负责人：
PAUL KULESA
金额：
$ 39.13万
依托单位：
UNIVERSITY OF NOTRE DAME
依托单位国家：
美国
项目类别：
财政年份：
2023
资助国家：
美国
起止时间：
2023-05-15 至 2028-04-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10658015
关键词：
Acceleration Address Applied Research Architecture Axon Biological Biological Models Birds Blood Pressure Brain-Derived Neurotrophic Factor Cell Differentiation process Cell Line Cell Transplantation Cells Central Nervous System Chick Chick Embryo Clinical Research Compensation Complex Congenital Abnormality Data Detection Development Diagnostic Dorsal Down-Regulation Drug Design Embryo Embryonic Development Ensure Equilibrium Event Ganglia Glial Differentiation Heart Rate Human Image Individual Infant Knowledge Laboratories Lead Ligands Link Location Malignant Neoplasms Mediating Methods Modeling Molecular Neural Crest Cell Neuroblastoma Neuronal Differentiation Neurons Operative Surgical Procedures Pattern Peripheral Nervous System Positioning Attribute Process Proliferating Protein Tyrosine Kinase Qualifying RNA Receptor Protein-Tyrosine Kinases Role Signal Pathway Signal Transduction Slice Spinal Cord Sympathetic Ganglia Sympathetic Nervous System System Techniques Temperature Testing Time Translating Ventral Roots cancer cell cell motility developmental disease fighting flexibility ganglion cell improved in vivo imaging infancy innovation insight interest migration nervous system development neural neural circuit neural repair neuroblastoma cell novel novel therapeutics prevent progenitor prognostic protein expression receptor response screening panel single-cell RNA sequencing spatiotemporal stem stem cells tool transcriptomics transplant model tumor tumor initiation

项目摘要

Project Summary A common feature of embryonic development is that cells are born in one place and have to move as a cluster and regulate their differentiation before connecting with a vital target in a different location. One result of this dynamic morphogenetic event is assembly of the sympathetic nervous system that is essential for maintaining blood pressure, heart rate, and temperature control with improper development leading to birth defects and neuroblastoma cancer in infants. We are interested in understanding how the signals that regulate the collective cell movement and differentiation of the embryonic neural crest cells are orchestrated, spatially and temporally, to drive the emergence of the patterned sympathetic nervous system. To address this, we will implement an innovative combination of techniques from biological, in vivo imaging and single cell spatial transcriptomic sciences applied to the avian model system, most of which are not currently possible but may be translated to developing mammalian systems. This study will be significant because it will identify the signals involved in sympathetic nervous system development, linking the central and peripheral nervous systems -- with special focus on the role of TrkB and on determining the signals that mediate the migration, differentiation, survival, and molecular crosstalk between neural crest cells that ensure sympathetic nervous system circuit formation. The results of this study will provide critical information for surgical methods to correct by neural repair and mitigate the effects of sympathetic nervous system birth defects and translate into and inform improved drug design efforts targeting receptor tyrosine kinase signaling as a treatment for neuroblastoma and possible increase in infant survival.

项目概要胚胎发育的一个共同特征是细胞诞生在一个地方并且必须作为一个簇移动并在与不同位置的重要目标连接之前调节它们的差异。这样做的结果之一动态形态发生事件是交感神经系统的组装，对于维持血压、心率和体温控制不当会导致出生缺陷和婴儿神经母细胞瘤。我们有兴趣了解调节集体的信号如何胚胎神经嵴细胞的细胞运动和分化在空间和时间上是精心安排的，驱动模式交感神经系统的出现。为了解决这个问题，我们将实施生物、体内成像和单细胞空间转录组学技术的创新组合应用于鸟类模型系统的科学，其中大部分目前不可能，但可以转化为开发哺乳动物系统。这项研究意义重大，因为它将识别涉及的信号交感神经系统的发育，连接中枢和周围神经系统——具有特殊的重点关注 TrkB 的作用并确定介导迁移、分化、生存和生长的信号。神经嵴细胞之间的分子串扰确保交感神经系统回路的形成。这这项研究的结果将为手术方法提供关键信息，以通过神经修复来纠正和减轻交感神经系统出生缺陷的影响，并转化为改进的药物设计并为其提供信息针对受体酪氨酸激酶信号传导作为神经母细胞瘤治疗方法的努力，并可能增加婴儿的生存。