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RUI: Elucidating the signaling interactions that control spinal cord fate specification

RUI：阐明控制脊髓命运规范的信号相互作用

基本信息

批准号：
1755386
负责人：
Isaac Skromne
金额：
$ 39.95万
依托单位：
University of Richmond
依托单位国家：
美国
项目类别：
Standard Grant
财政年份：
2018
资助国家：
美国
起止时间：
2018-07-15 至 2023-06-30
项目状态：
已结题

来源：
https://www.nsf.gov/awardsearch/showAward?AWD_ID=1755386&HistoricalAwards=false
关键词：
RUI Elucidating signaling interactions control

项目摘要

This project advances understanding of how cells in embryos interpret localized signaling cues to decide their fate, that is, the type of tissue to become. This complex problem is simplified by investigating a simple binary decision event: the specification of posterior neural precursor cells to become either hindbrain or spinal cord. This decision is controlled by three signaling molecules regulating the expression of one gene family. Because developmental signal interactions are conserved across organisms, this research will expand our knowledge of signal interactions in the nervous system specifically, while also providing a foundational framework to understand vertebrate head-trunk evolution more generally. This work will have broad intellectual implications in neurobiology, developmental biology, and evolutionary biology. The project will also support the training of undergraduate students, fostering inquiry-based research essential to developing the skills needed in a thriving US scientific workforce.A remarkably small number of signaling factors specify a large number of cell fates during the development of vertebrate tissues, and the nervous system is no exception. A striking example occurs in the caudal neural plate, where inputs of the signaling molecules FGF, Wnt and Retinoic Acid are required to specify which portion of the tissue will become spinal cord and not hindbrain. Previous studies have shown that FGF-Wnt, FGF-RA and Wnt-RA all contribute to regulation of the spinal cord specification gene cdx4. This project will focus on determining the individual and collective contribution of these three signals to spinal cord specification. By determining these interactions, the project will produce a detailed map of the signaling networks coordinating hindbrain-spinal cord specification, an important step for further analysis of nervous system development and evolutionThis 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.

该项目增进了对胚胎细胞如何解释局部信号线索来决定其命运（即形成的组织类型）的理解。通过研究一个简单的二元决策事件可以简化这个复杂的问题：将后神经前体细胞指定为后脑或脊髓。这一决定由调节一个基因家族表达的三个信号分子控制。由于发育信号相互作用在生物体中是保守的，因此这项研究将专门扩展我们对神经系统中信号相互作用的了解，同时也为更广泛地理解脊椎动物头躯干进化提供了一个基础框架。这项工作将对神经生物学、发育生物学和进化生物学产生广泛的智力影响。该项目还将支持本科生的培训，促进基于探究的研究，这对于发展美国蓬勃发展的科学队伍所需的技能至关重要。在脊椎动物组织的发育过程中，极少数的信号因子决定了大量的细胞命运，神经系统也不例外。一个引人注目的例子发生在尾神经板，其中需要输入信号分子 FGF、Wnt 和视黄酸来指定组织的哪一部分将成为脊髓而不是后脑。先前的研究表明，FGF-Wnt、FGF-RA 和 Wnt-RA 均有助于脊髓规范基因 cdx4 的调节。该项目将重点确定这三个信号对脊髓规范的单独和集体贡献。通过确定这些相互作用，该项目将生成协调后脑-脊髓规范的信号网络的详细图谱，这是进一步分析神经系统发育和进化的重要一步。该奖项反映了 NSF 的法定使命，并通过使用基金会的智力价值和更广泛的影响审查标准进行评估，被认为值得支持。