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Understanding Early Organogenesis Using a Simplified In Situ Hybridization Protocol in Xenopus
Published on: January 12, 2015
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A biologically based computational model for the hypothalamic-pituitary-thyroid (HPT) axis in Xenopus laevis larvae
Jonathan T Haselman1, John W Nichols1, Kali Z Mattingly2
1U.S. Environmental Protection Agency, Office of Research and Development, Center for Computational Toxicology and Exposure, Great Lakes Toxicology and Ecology Division, 6201 Congdon Boulevard, Duluth, MN, 55804, United States of America.
Mathematical Biosciences
|May 18, 2023
Summary
A new computational model simulates the thyroid axis in Xenopus laevis, aiding the study of thyroid hormone disruption and metamorphosis. This tool predicts chemical impacts on development by modeling the hypothalamic-pituitary-thyroid axis.
Area of Science:
- Endocrinology
- Computational Biology
- Developmental Biology
Background:
- The hypothalamic-pituitary-thyroid (HPT) axis regulates crucial developmental processes, including metamorphosis.
- Understanding HPT axis function in developing organisms like Xenopus laevis is vital for assessing environmental impacts.
- Existing models often lack organism-specific details crucial for accurate predictions.
Purpose of the Study:
- To develop a biologically based computational model of the HPT axis in developing Xenopus laevis.
- To create a predictive tool for understanding thyroid hormone-mediated metamorphosis and chemical toxicant effects.
- To simulate normal HPT axis function and calibrate the model against observed developmental data.
Main Methods:
- Developed a computational model incorporating HPT axis dynamics, organism growth, thyroid gland growth, and developmental regulation of thyroid-stimulating hormone (TSH).
- Modeled key biochemical processes and calibrated the model using data from Xenopus laevis larvae during a critical developmental window (Nieuwkoop and Faber stages 54-57).
- Integrated the HPT axis model with a toxicokinetic model to predict chemical effects from in vitro assay data.
Main Results:
- The model successfully simulates normal HPT axis function and thyroid hormone levels during development.
- Predictions indicate that homeostatic mechanisms can preserve circulating thyroid hormone levels despite impaired synthesis.
- The model incorporates biochemical processes amenable to high-throughput in vitro screening.
Conclusions:
- The developed computational model serves as a valuable tool for studying thyroid hormone regulation and metamorphosis in Xenopus laevis.
- This model can predict organismal outcomes following exposure to chemical toxicants by linking in vitro and in vivo data.
- The approach facilitates a better understanding of endocrine disruption and its developmental consequences in aquatic organisms.
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