Temperature Scaling of Animal Development

动物从单细胞发育到成年是一个复杂的过程，需要数十亿个分子事件的极端协调。值得注意的是，大多数动物物种的发育都是正常的，尽管环境可能会发生根本性的变化，这些变化会单独影响这些分子反应。这一特性表明，尽管条件变化，进化已经选择并可以编码产生相似发育结果的基因调控网络。这一提议旨在了解动物在不同温度下发育时如何保持基因表达的正确时间。具体来说，研究人员已经开发出了直接测量动物如何以及何时开启和关闭关键发育基因的工具。他们将使用这个系统来剖析在不同温度下不同细胞和组织的发育过程中如何维持全局基因表达的变化。这将使研究人员能够确定基因表达的未知结构，以确保不同环境下的发育产生相似的结果。作为该项目的一部分，他们还将为一名本科生提供研究经验，并将在纽约市少数族裔高中开展外展活动。温度影响所有的生化反应。对于多细胞发育系统，温度波动带来了特殊的挑战，因为有序的形态进展取决于空间和时间上协调的细胞决定。研究表明，尽管尺度参数与属甚至种有关，但变温动物的总体发育速率服从阿伦尼乌斯尺度。尽管涉及无数不同的化学反应，但这种温度缩放是一致的，使得关键发育里程碑的相对时间不变。目前尚不清楚这是如何实现的，更一般地说，控制发育过程的单个分子决策是如何缓冲温度并在组织内和组织间同步以保持发育精度的。该项目的目标是揭示赋予这种健壮性的组织策略和分子机制。研究人员开发了一种独特的微流体方法，可以在胚胎发育过程中同时对多个秀丽隐杆线虫幼虫的基因表达进行高分辨率成像。这项技术将使研究人员能够确定关键调控分子的转录模式在不同温度下是如何组织的，并使他们能够模拟产生这些模式的基因调控网络（grn）如何工作。这些研究使研究人员现在能够率先对GRN的时间模式进行定量体内研究。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

The development of animals from a single cell to adulthood is a complex operation requiring extreme coordination of billions of molecular events. Remarkably, development of most animal species occurs normally despite radical changes that may occur in the environment that would individually impact these molecular reactions. This property suggests that evolution has selected for and can encode gene regulatory networks that generate similar developmental outcomes despite changing conditions. This proposal aims to understand how animals can maintain the correct timing of gene expression when developing at different temperatures. Specifically, the investigators have developed tools to directly measure how and when animals turn on and off key developmental genes. They will use this system to dissect how changes in global gene expression are maintained across different cells and tissues during development at variable temperatures. This will allow the investigators to determine the unknown architectures of gene expression that are in place to make sure development in varying environments generates similar outcomes. As part of this project they will also provide research experiences for an undergraduate student, and they will perform outreach to minority-serving high schools in New York City.Temperature impacts all biochemical reactions. For multicellular developmental systems, temperature fluctuations pose particular challenges because the orderly morphological progression depends on both spatially and temporally coordinated cellular decisions. It has been shown that overall developmental rates of poikilothermic animals obey Arrhenius scaling, though scaling parameters are genus and even species dependent. Despite the myriad diverse chemical reactions involved, this temperature scaling is uniform, leaving the relative timing of key developmental milestones unchanged. It remains unknown how this is achieved and, more generally, how individual molecular decisions that control developmental processes are buffered against temperature and synchronized within and across tissues to maintain developmental precision. The goal of this project is to uncover the organizational strategy and molecular mechanisms that confer this robustness. The investigators have developed a unique microfluidics methodology that allows high-resolution imaging of gene expression in multiple C. elegans larvae simultaneously throughout post-embryonic development. This technology will enable the investigators to determine how transcriptional patterns of key regulatory molecules are organized at different temperatures and enable them to model how Gene Regulatory Networks (GRNs) that generate these patterns work. The studies put the investigators in a position to now pioneer quantitative in-vivo studies of the temporal patterning GRN.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.