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

可塑性尾巴：诱导蝌蚪尾巴生长和吸收的发育内分泌学

基本信息

批准号：
2035732
负责人：
Daniel Buchholz
金额：
$ 47.99万
依托单位：
University of Cincinnati Main Campus
依托单位国家：
美国
项目类别：
Standard Grant
财政年份：
2021
资助国家：
美国
起止时间：
2021-03-01 至 2025-02-28
项目状态：
未结题

来源：
https://www.nsf.gov/awardsearch/showAward?AWD_ID=2035732&HistoricalAwards=false
关键词：
tail plasticity developmental endocrinology induced

项目摘要

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.

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对环境条件做出反应，然后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组织水平的反应。该项目的目标是揭示特定激素如何在分子水平上决定青蛙蝌蚪在变态过程中尾巴生长和尾巴吸收过程中产生哪些蛋白质以及实现哪些发育结果。这些基本知识对于评估环境条件的变化，如气候变化和各种化学物质的存在，可能如何影响生物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，这项研究将开辟新的途径，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。在这些研究过程中，研究生和本科生将接受与两栖动物衰退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室课程，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、创新的科学工作队伍的目标。两栖蝌蚪通过激素信号调节生长和发育的生死变化来对环境做出反应。关于荷尔蒙如何在分子水平上起作用来决定影响个体健康的生理和发育结果，存在着一个关键的知识缺口。这项建议的目的是解释糖皮质激素如何作用于非洲爪哇蝌蚪的尾巴，以促进尾巴大小的增加或减少。为此，拟议的研究将确定涉及的组织、激素受体、细胞变化、基因调控和激素相互作用。中心假设是，对糖皮质激素的替代尾部反应源于受体对尾部组织的特定作用，这是由甲状腺激素信号控制的。在验证这一假说的过程中，研究将：1)通过鉴定在尾巴生长和吸收过程中哪些细胞表达糖皮质激素受体(S)来识别尾部糖皮质激素靶组织；2)确定在调节生长和吸收过程中对糖皮质激素受体(S)的需求；3)检测组织特异性和受体特异性糖皮质激素反应基因调节受甲状腺激素信号的影响。这些分析将使用糖皮质激素受体突变的蝌蚪来显示受体特定的作用，调节改变的尾巴大小。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的反应基因)阻碍了解释发育过程中的应激如何影响青蛙和其他脊椎动物的表型的进展。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的知识将推动解释环境如何通过改变激素水平来调节发育过程和结果，从而塑造健康和健身的表型结果的长期目标。这项研究的教育影响更广泛，包括培养研究生和本科生，开发一门新的基因操纵技术本科课程，以及为当地高中生提供实践活动。该奖项反映了NSF的法定使命，并通过使用基金会的智力优势和更广泛的影响审查标准进行评估，被认为值得支持。