Research topics: current interests

Identification of novel thyroid hormone-regulated genes and proteins, and their role in the development of the chicken brain. Thyroid hormones (THs) are essential for a correct timing of the different steps of brain development. They influence the expression of TH-responsive genes by binding nuclear thyroid hormone receptors (TR). The responsivity of TH-responsive genes, however, is - depending on the gene - temporally and spatially limited. In this project, we use microarray technology and 2D-DIGE for the identification of TH-responsive genes or proteins in the developing chicken brain. We study their expression, cellular distribution, and colocalization with factors that influence TH abundance and activity. Ontogenic studies are done in euthyroid, hypothyroid and hyperthyroid embryos and in embryos treated with selected environmental neurotoxic pollutants such as PCBs. The function of novel interesting genes is studied by in ovo knock-out or knock-down technology.

Identification and characterization of factors involved in the tissue-specific and age-specific regulation of iodothyronine deiodinases. A correct spatiotemporal expression of the deiodinase enzymes, activating and inactivating THs, is crucial for the correct implementation of T3-mediated developmental programmes. Recent research has shown that glucocorticoids, steroid hormones produced by the adrenal glands, play an important role in the control of deiodinase expression. The goal of this project is to unravel the mechanisms that are responsible for the tissue- and age-specific regulation of deiodinases by glucocorticoids. First, we investigate how the tissue-specific inhibition of D3 is regulated during the embryonic development of the chicken. Second, we study the mechanisms underlying the age-specific control of D2 in the brain. The identification of factors involved in this glucocorticoid-mediated transrepression/transactivation is done by mRNA differential display and 2D-DIGE.

The use of zebrafish (Danio rerio) as a model organism to study the role of thyroid hormones in development and growth of teleost fish. Thyroid hormones play an important role in the growth and development of many vertebrate species, including fish. However, up till now most of the molecular mechanisms involved in thyroid hormone regulated growth and development remain to be elucidated. The goal of this project is to study the role of thyroid hormones in embryonic development and growth using the zebrafish as a model organism. In the first part of the project the different factors involved in thyroid hormone production, activation and degradation are characterized, whereas in the second phase the hormonal regulation of these parameters is investigated. In a third phase this knowledge is used to assess the role of and the mechanisms through which thyroid hormones regulate embryonic development and growth by means of the transient gene knock-out technique.

Feedback communication between the thyroid and pituitary gland in the chicken. In this research topic we focus on two receptors that play an important part within the hypothalamus-pituitary-thyroidal axis, namely thyroid hormone receptor ß2 (TRß2) and the thyrotropin receptor (TSHR). TRß2 is one of the three TRs that have been discovered in chicken, and acts as a nuclear transcription factor influencing gene expression in a negative or positive way. In mammals, TRß2 is found to regulate the transcription of TSH and is thus involved in the negative feedback mechanism of thyroid hormones (TH) on TSH. The TSHR could, besides from its function in the thyroid gland, play an important role in the ultra-short feedback control of pituitary TSH secretion. We therefore investigate in which way these receptors take part in regulating TSH and TH secretion in the developing chicken, and in which way these receptors are influenced by the hypothalamic hormones and of course THs.

Central interactions between the thyroidal and adrenal axes: mode of action and role in the development of vertebrates. Corticotropin-releasing hormone (CRH) is thought to be a phylogenetically ancient signaling molecule in vertebrates that controls the developmental response of the larva, embryo or fetus on environmental stress factors (so-called phenotypic developmental plasticity) by the regulation of both thyroid and adrenal function. The interaction of CRH with the thyroidal axis is a role of this hypothalamic hormone that - in contrast to its role in homeostatic and behavioural responses to stress - relatively unknown, even though the TSH-releasing capacity of CRH has been demonstrated in representatives of all non-mammalian vertebrates. We want to identify the different components that are involved in the interaction of CRH with the thyroidal axis in the chicken. Furthermore, we investigate the role of this interaction in developmental processes of different vertebrate species, such as hatching in birds and amphibian metamorphosis.

Control mechanisms of energy homeostasis: the chicken as a model (collaboration with Prof. J. Buyse of the Faculty of Bioscience Engineering). With this project we want to unravel the mechanisms that play a role in the control and regulation of the energy homeostasis with the chicken as experimental animal model. Energy homeostasis is the net result of energy intake on the one hand, and energy deposition (mainly as fat) and energy expenditure on the other hand. As problems such as obesity, ascites, heart failure etc. are hampering the poultry industry, the main objective of this research is to gather more insight in the mechanisms that are involved in the regulation of food intake in relation to body composition and energy expenditure in avian species. We investigate which peripheral signaling molecules are modulated in relation to the food intake pattern and how these signals affect the control system in the hypothalamus. We also look into the effect of these appetite-regulating molecules on energy deposition and expenditure. Finally, we try to elucidate the functional role of leptin expression in the chicken liver, which is unique for this species.