Dissecting An Intrinsic Regulatory Program For Neuronal Polarization In An Invertebrate Chordate

这个项目研究脑细胞形成并最终相互连接的过程，以确保正常的大脑功能。这些实验使用了被囊动物，这是一种与脊椎动物关系最近的无脊椎动物，这既是因为它们特别适合这项工作的技术方面，也是因为它们的神经元与包括人类在内的脊椎动物有许多共同的基因和结构特征。这项工作将使用专门针对脑细胞的新型基因工程技术进行，以便收集有关神经细胞功能发展的新信息，这些功能控制神经系统中信息流的方向性。这个项目还将通过教高中生和大学生使用这些先进的基因技术来更好地了解动物大脑发育和功能所涉及的基因网络来吸引他们。这项工作将研究简单脊索状神经元中神经元极化和轴突生长的内在、潜在保守的调节程序的细胞内和细胞外成分的功能。该项目旨在实现两个主要目标：1)从机制上更好地理解细胞内和细胞外信号整合的方式，以指导体内神经元的极性；以及2)阐明调控神经元发育的转录网络(S)。这个项目将加深我们对进化保守的分子通路的理解，这些分子通路协调分化神经元中的极化形态发生过程，以及在神经发育中控制细胞形态发生的调控机制。这项研究计划与具体的研究相关活动相结合，以加强大学本科生和高中生所接受的生物教育，以及他们对基础研究和比较动物研究如何为科学知识做出贡献的欣赏。该奖项反映了NSF的法定使命，并通过使用基金会的智力优势和更广泛的影响审查标准进行评估，被认为值得支持。

This project examines the processes by which brain cells form and ultimately connect to one another to ensure proper brain function. The experiments use tunicates, the invertebrate animals most closely related to vertebrates, both because they are especially suitable for the technical aspects of this work, and because their neurons share many genes and structural features in common with vertebrates, including humans. The work will be carried out using novel genetic engineering techniques that specifically target brain cells in order to collect novel information about the development of nerve cell features that control the directionality of information flow in nervous systems. This project will also engage high school and college students by teaching them to use these advanced genetic techniques to better understand the networks of genes involved in animal brain development and function.The work will study the functions of both intracellular and extracellular components of an intrinsic, potentially conserved regulatory program for neuronal polarization and axon outgrowth in the simple chordate Ciona. This project is designed to achieve two main objectives: 1) To arrive at a better mechanistic understanding of the way(s) that intracellular and extracellular cues are integrated to instruct neuronal polarity in vivo; and 2) To elucidate the transcriptional network(s) regulating neuronal polarity in development. This project will deepen our understanding of evolutionarily conserved molecular pathways that coordinating polarized morphogenetic processes in differentiating neurons, as well as the regulatory mechanisms that control cellular morphogenesis in neural development. This research plan is integrated with specific research-related activities to enhance both the biological education that university undergraduates and high school students receive, as well as their appreciation for how fundamental research and comparative animal studies contribute to scientific knowledge.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.