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.
