PUBLICATION
Insights from zebrafish deficiency models to understand the impact of local thyroid hormone regulator action on early development
- Authors
- Vancamp, P., Houbrechts, A.M., Darras, V.M.
- ID
- ZDB-PUB-180924-3
- Date
- 2018
- Source
- General and comparative endocrinology 279: 45-52 (Other)
- Registered Authors
- Darras, Veerle
- Keywords
- Deficiency models, Development, Endocrine disrupting chemicals, Thyroid hormones, Zebrafish
- MeSH Terms
-
- Animals
- Embryonic Development/drug effects
- Endocrine Disruptors/toxicity
- Humans
- Models, Animal
- Thyroid Hormones/metabolism*
- Zebrafish/embryology*
- Zebrafish/metabolism*
- PubMed
- 30244055 Full text @ Gen. Comp. Endocrinol.
Citation
Vancamp, P., Houbrechts, A.M., Darras, V.M. (2018) Insights from zebrafish deficiency models to understand the impact of local thyroid hormone regulator action on early development. General and comparative endocrinology. 279:45-52.
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 and their impact on development. While adverse effects on TH metabolism and gene expression have been shown, information on direct interaction with TH regulators is scarce, albeit essential to fully understand their mechanism of action. For the future, the combination of novel gene silencing tools, fluorescent reporter lines and (single-cell) transcriptomics holds promise for new zebrafish models to further elucidate the role of each TH regulator in vertebrate development.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping