Insights from zebrafish deficiency models to understand the impact of local thyroid hormone regulator action on early development

General and Comparative Endocrinology
Pieter VancampVeerle M Darras

Abstract

Thyroid hormones (THs) stimulate and coordinate a wide range of processes to ensure normal development, mainly by binding of the most active TH 3,5,3'-triiodothyronine (T3) to nuclear receptors resulting in changes in gene transcription. Local TH action is monitored at three distinct levels by different types of regulators: transmembrane transporters (TH influx and efflux), deiodinases (TH activation and inactivation) and nuclear receptors (TH signalling). Since TH regulators are strongly conserved among vertebrate species, the externally and rapidly developing zebrafish (Danio rerio) has become one of the favourite models to study their role in TH-dependent development. Most regulators are expressed in zebrafish from early stages in development in a dynamic and tissue-specific pattern. Transient or permanent disruption of a given regulator severely perturbs development of multiple organs. These zebrafish deficiency models help to explain why, next to overall hypo-/hyperthyroidism, inactivating mutations in the genes encoding TH regulators such as MCT8 and THRA/B have irreversible adverse effects on human development. Zebrafish are also increasingly used as a high-throughput model to assess the toxicity of various xenobiotics a...Continue Reading

Citations

May 24, 2019·Acta Physiologica·Jean-David GothiéSylvie Remaud
Jun 2, 2020·Frontiers in Endocrinology·Pieter VancampSylvie Remaud
Mar 10, 2020·Molecular and Cellular Endocrinology·Stephan CouderqJean-Baptiste Fini
Oct 19, 2019·Chemical Research in Toxicology·Steven CassarLeonard I Zon

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