Mineralocorticoid signaling in frog metamorphosis

This project focusses on how the hormone aldosterone functions to facilitate aquatic to terrestrial transitions in vertebrate animals. The processes of birth in humans, hatching in birds, and metamorphosis in frogs all involve a critical transition from an aquatic environment (womb, egg, pond) to a terrestrial existence with vastly different physiological, locomotor, and feeding demands.

All vertebrates use the same hormones to control the transition, which must be carefully orchestrated to ensure survival of life on land. The project fills a gap in knowledge about function of the role of aldosterone in the timing of metamorphosis in frogs. The research results will help evaluate how man-made environmental conditions, such as climate change and the presence of endocrine disrupting chemicals, may pose health threats to the processes of birth, hatching, and metamorphosis.

In addition, this research will open new avenues to study why individuals may respond differently to changing environmental conditions, identify novel genes and hormone interactions, and develop new assays for endocrinology studies. During these studies, graduate and undergraduate students will be trained in basic research with applications relating to amphibian declines and climate change, which advances the National Science Foundation's goal to create a well-prepared, innovative scientific workforce.

In addition, an undergraduate laboratory course will be developed to teach hands-on skills in gene disruption technology and bring research to high school students.

The complex endocrine regulation of vertebrate developmental transitions has been challenging to unravel. Many hormones act and interact simultaneously on multiple cell types at different time points throughout the organism. The goal of the current proposal is to reveal how one such hormone, the corticosteroid aldosterone, regulates frog metamorphosis.

Aldosterone is implicated in amphibian development, but lack of appropriate experimental tools has previously precluded conclusions about its precise role in the process. The project’s central hypothesis is that aldosterone is the primary mineralocorticoid in tadpole plasma and acts through the mineralocorticoid receptor to regulate genes required for normal developmental progression through metamorphosis.

To address this hypothesis, the approach is to: 1) measure the levels of 11 corticosteroids in plasma and tail tissue throughout the larval period, 2) compare growth and development at molecular and morphological levels in tadpoles wild-type and mutant for the mineralocorticoid receptor, and 3) use RNA-sequencing to identify mineralocorticoid receptor response genes in tail, kidney, and brain. Knowledge of the identity and quantity of steroid hormones and induced genes during development and the consequences for development in the absence of aldosterone signaling will advance the long-term goal of explaining how hormones modulate developmental processes that shape adult health and fitness.

This project is co-funded by the BIO-IOS Physiological Mechanisms and Biomechanics and Animal Developmental Mechanisms programs.

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.