Investigating the relationship between Sympathetic Nervous System Development and Neuroblastoma

项目摘要 胚胎发育的一个共同特征是细胞在一个地方出生，必须成群移动 并在与不同位置的重要目标连接之前调节它们的分化。这样做的一个结果是 动态形态发生事件是交感神经系统的组装， 血压、心率和体温控制，发育不当导致出生缺陷， 婴儿神经母细胞瘤我们感兴趣的是了解调控集体的信号是如何 胚胎神经嵴细胞的细胞运动和分化在空间和时间上是协调的， 来驱动交感神经系统的出现。为了解决这个问题，我们将实施 生物学、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，其中大部分目前还不可能，但可以翻译为 发展哺乳动物系统。这项研究将是重要的，因为它将确定涉及的信号， 交感神经系统的发展，连接中枢和外周神经系统-与特殊的 重点是TrkB的作用，并确定介导迁移，分化，存活的信号， 确保交感神经系统回路形成的神经嵴细胞之间的分子串扰。的 本研究的结果将为外科手术方法提供关键信息，以通过神经修复和减轻 交感神经系统先天缺陷的影响，并转化为改善药物设计， 靶向受体酪氨酸激酶信号传导作为神经母细胞瘤治疗的努力， 婴儿存活率

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.