Experimentally Manipulating the Thyroid Hormone Axis in Zebrafish

Thyroid hormone (TH) is an endocrine factor with a diverse array of developmental, metamorphic, and metabolic functions conserved across vertebrates. Zebrafish (Danio rerio) are a tractable model for endocrinology research, and recent research efforts focus on the roles of TH in zebrafish morphogenesis, growth and behavior. Several powerful approaches have been developed in zebrafish to modulate the TH axis and peripheral sensitivity to the hormone. These approaches include gain- and loss-of-function mutations that target components of the TH signaling pathways, as well as pharmacological treatments to modulate TH synthesis and availability. Here, we review some of these approaches for generating hypo- and hyperthyroid physiology and phenotypes during post-embryonic zebrafish development. In particular, we focus on a transgenic method of producing hypothyroid fish via metronidazole-based thyroid ablation. This approach can straightforwardly generate large numbers of hypothyroid individuals along with euthyroid sibling controls, and we survey some of the research applications in which this system has been used.