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

该项目推进了对胚胎细胞如何解释局部信号线索以决定其命运的理解，即成为组织的类型。这个复杂的问题通过研究一个简单的二元决策事件来简化：后部神经前体细胞的指定成为后脑或脊髓。 这一决定是由三个信号分子调节一个基因家族的表达。 由于发育信号相互作用在生物体中是保守的，这项研究将扩大我们对神经系统中信号相互作用的认识，同时也为更普遍地理解脊椎动物头-躯干进化提供了一个基础框架。这项工作将在神经生物学、发育生物学和进化生物学方面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，这对于培养蓬勃发展的美国科学工作者所需的技能至关重要。在脊椎动物组织的发育过程中，数量非常少的信号因子指定了大量细胞的命运，神经系统也不例外。一个突出的例子发生在尾神经板，其中需要信号分子FGF、Wnt和视黄酸的输入来指定组织的哪一部分将成为脊髓而不是后脑。以往的研究表明，FGF-Wnt、FGF-RA和Wnt-RA均参与脊髓特异性基因cdx 4的调控。 该项目将集中于确定这三个信号对脊髓特化的个体和集体贡献。通过确定这些相互作用，该项目将产生协调后脑脊髓规范的信号网络的详细地图，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，并被认为值得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来支持。

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.