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

剖析无脊椎动物脊索动物神经元极化的内在调节程序

• 批准号: 1940743
• 负责人: Alberto Stolfi
• 金额: $ 86.39万
• 依托单位: Georgia Tech Research Corporation
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-05-15 至 2024-04-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1940743&HistoricalAwards=false
• 关键词: Dissecting; Intrinsic; Regulatory; Program; Neuronal

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.

该项目研究脑细胞形成并最终相互连接以确保正常大脑功能的过程。实验使用被囊动物，与脊椎动物关系最密切的无脊椎动物，因为它们特别适合这项工作的技术方面，而且因为它们的神经元与脊椎动物（包括人类）共享许多基因和结构特征。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，以收集有关神经细胞特征发育的新信息，这些特征控制神经系统中信息流的方向性。该项目还将通过教授高中生和大学生使用这些先进的遗传技术来更好地了解与动物大脑发育和功能有关的基因网络，研究简单脊索动物玻璃海鞘中神经元极化和轴突生长的内在、潜在保守调控程序的细胞内和细胞外组分的功能。该项目旨在实现两个主要目标：1）更好地理解细胞内和细胞外信号整合以指导体内神经元极性的方式; 2）阐明发育中调节神经元极性的转录网络。该项目将加深我们对进化上保守的分子途径的理解，这些分子途径协调分化神经元的极化形态发生过程，以及控制神经发育中细胞形态发生的调节机制。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接受的生物教育，该奖项反映了NSF的法定使命，并通过使用基金会的知识价值和更广泛的影响审查进行评估，被认为值得支持的搜索.

项目成果

A cis-regulatory change underlying the motor neuron-specific loss of Ebf expression in immotile tunicate larvae.

• DOI: 10.1111/ede.12364
• 发表时间: 2021-03
• 期刊: Evolution & development
• 影响因子: 2.9
• 作者: Lowe EK;Racioppi C;Peyriéras N;Ristoratore F;Christiaen L;Swalla BJ;Stolfi A
• 通讯作者: Stolfi A

Evolution of a chordate-specific mechanism for myoblast fusion

• DOI: 10.1126/sciadv.add2696
• 发表时间: 2022-09-02
• 期刊: SCIENCE ADVANCES
• 影响因子: 13.6
• 作者: Zhang，Haifeng;Shang，Renjie;Bi，Pengpeng
• 通讯作者: Bi，Pengpeng