A tail of plasticity: developmental endocrinology of induced tadpole tail growth and resorption

包括人类在内的发育中的动物通过改变血液中存在的激素水平来应对环境条件，从而改变影响健康和健身的发育结果。值得注意的是，激素对发育生理过程的作用是复杂的，涉及多种激素作用于一个或多个器官以实现机体水平的反应。该项目的目的是揭示在分子水平上，特定的激素如何决定蝌蚪在蜕变过程中尾巴生长和尾巴吸收过程中产生哪些蛋白质和实现哪些发育结果。这些基本知识对于评估气候变化和各种化学品的存在等环境条件的变化如何影响生物体形态和生理并可能威胁人类健康至关重要。通过识别新的基因和激素相互作用，这项研究将为研究个体如何以及为什么对不断变化的环境条件做出不同的反应开辟新的途径。在这些研究的过程中，研究生和本科生将接受与两栖动物数量减少和气候变化有关的应用基础研究的培训。将开发一门本科实验课程，教授基因破坏技术的实践技能，并为高中生提供实践研究经验。这些教育活动将支持建立一支准备充分、具有创新精神的科学劳动力队伍的目标。两栖动物蝌蚪对环境的反应是通过激素信号介导的生长发育的生死变化。关于激素如何在分子水平上决定影响个体适应性的生理和发育结果，存在一个关键的知识缺口。这一建议的目的是解释糖皮质激素如何作用于爪蟾蝌蚪尾巴，以促进尾巴大小的增加或减少。为此，本研究将确定组织、激素受体、细胞变化、基因调控和激素相互作用。核心假设是，尾巴对糖皮质激素的选择性反应源于尾巴组织上的受体特异性作用，由甲状腺激素信号控制。在验证这一假设的过程中，本研究将：1)通过识别尾部生长和吸收过程中哪些细胞表达糖皮质激素受体来识别尾部糖皮质激素靶组织；2)确定调节生长和吸收过程中糖皮质激素受体的需求；3)在甲状腺激素信号的影响下，研究组织特异性和受体特异性糖皮质激素反应基因调控。这些分析将使用糖皮质激素受体突变的蝌蚪来显示调节尾巴大小变化的受体特异性作用。先前缺乏基本的分子遗传学工具（即糖皮质激素受体突变体和相关反应基因），这阻碍了解释青蛙和其他脊椎动物发育过程中压力如何影响表型的进展。了解糖皮质激素反应基因调控的组织、受体、基因和甲状腺激素依赖性，将有助于解释环境如何通过改变激素水平调节发育过程，并导致塑造健康和适应性的表型结果。这项研究对教育的广泛影响包括培养研究生和本科生，开发新的基因操作技术本科课程，并为当地高中学生提供实践活动。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。

Developing animals including humans respond to environmental conditions by changing the level of hormones present in the blood, which then alters developmental outcomes affecting health and fitness. Significantly, hormone actions on developmental physiological processes are complex, involving multiple hormones acting on one or more organs to achieve organismal-level responses. The goal of this project is to reveal how, at the molecular level, specific hormones determine which proteins are made and which development outcomes are achieved in the process of tail growth and tail resorption during metamorphosis in frog tadpoles. Such basic knowledge is critical for evaluating how changes in environmental conditions, such as climate change and the presence of various chemicals, may affect organismal morphology and physiology and may threaten human health. By identifying novel genes and hormone interactions, this research will open new avenues to study how and why individuals may respond differently to changing environmental conditions. In the course of these studies, graduate and undergraduate students will be trained in basic research with applications relating to amphibian declines and climate change. An undergraduate laboratory course to teach hands-on skills in gene disruption technology, and hands-on research experiences for high school students, will be developed. These educational activities will support the goal of creating a well-prepared, innovative scientific workforce.Amphibian tadpoles respond to the environment with life-or-death changes in growth and development mediated by hormone signaling. A critical knowledge gap exists as to how hormones act at the molecular level to determine physiological and developmental outcomes that affect individual fitness. The objective of this proposal is to explain how glucocorticoid hormones act on Xenopus tadpole tails to promote either an increase or decrease in tail size. Towards this end, the proposed research will identify the tissues, hormone receptors, cell changes, gene regulation, and hormone interactions involved. The central hypothesis is that alternative tail responses to glucocorticoids stem from receptor-specific actions on tail tissues, as governed by thyroid hormone signaling. In the course of testing this hypothesis, the research will: 1) identify glucocorticoid target tissues in the tail by identifying which cells express glucocorticoid receptor(s) during tail growth and resorption, 2) determine the requirement for glucocorticoid receptor(s) in regulating growth and resorption, and 3) examine tissue-specific and receptor-specific glucocorticoid-response gene regulation as influenced by thyroid hormone signaling. These analyses will use glucocorticoid-receptor mutant tadpoles to show receptor-specific actions regulating altered tail size. Prior lack of basic molecular genetic tools (i.e., glucocorticoid-receptor mutants and associated response genes) has impaired progress to explain how stress during development affects phenotypes in frogs and other vertebrates. Knowledge of the tissues, receptors, genes, and thyroid hormone-dependence of glucocorticoid response gene regulation will advance the long-term goal of explaining how the environment, via altered hormone levels, modulates developmental processes and results in phenotypic outcomes that shape health and fitness. The educational broader impacts of this research include training of graduate and undergraduate research students, development of a new undergraduate course in gene-manipulation technology, and providing hands-on activities for local high school students.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.