Thyroid regulation of fish development: physiological, cellular and molecular responses with evolutionary considerations

点击翻译按钮获取中文摘要

This research program combines studies in thyroid hormone physiology, molecular biology and gene regulation to decipher the internal signals that regulate the dramatic developmental event of metamorphosis in lampreys. Lamprey metamorphosis is analogous to the metamorphosis that transforms a fish-like tadpole into a frog. Lampreys are one of the most ancient living vertebrates (animals with a spinal column, including humans) and are a good model to study the evolution of developmental regulation and vertebrate ancestry. Interestingly, the start of lamprey metamorphosis coincides with a dramatic drop in thyroid hormone levels. This drop is opposite to the surge in thyroid hormone levels seen at the beginning of major developmental events in other vertebrates. The aims of this research program are to determine if this paradox of lamprey metamorphosis represents a fundamental difference in how thyroid hormones control development in lamprey (i.e. gene regulation) or more simply a difference in the physiological and cellular regulation of active hormone. Specifically this program will decipher the function and role in development of: a) systems in lamprey blood that transport thyroid hormones b) the enzymes that activate and inactivate the hormones in the cell and c) the receptors to which hormones bind to modulate gene activity. Lastly, we will also identify the lamrpey genes that are controlled by thyroid hormones and potentially drive metamorphosis. My research program will advance our understanding of the regulation of thyroid hormones and their role in the development of ancient vertebrates. Thyroid hormones are involved in many important biological processes in vertebrates including: development, growth, fat metabolism, temperature regulation, immune defense and reproduction. The unique nature of the lamprey thyroid system and its role in lamprey development may offer new insights into vertebrate thyroid physiology and dysfunction. Lastly, a better understanding of the factors that control lamprey development will provide novel opportunities to develop environmentally benign measures to control sea lamprey populations in the Great Lakes and reduce our reliance on current chemical treatments.