Investigating the relationship between Sympathetic Nervous System Development and Neuroblastoma

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。的 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。

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.