title: Deiodinase knockdown during early zebrafish development affects growth, development, energy metabolism, motility and phototransduction.
abstract: Thyroid hormone (TH) balance is essential for vertebrate development. Deiodinase type 1 (D1) and type 2 (D2) increase and deiodinase type 3 (D3) decreases local intracellular levels of T3, the most important active TH. The role of deiodinase-mediated TH effects in early vertebrate development is only partially understood. Therefore, we investigated the role of deiodinases during early development of zebrafish until 96 hours post fertilization at the level of the transcriptome (microarray), biochemistry, morphology and physiology using morpholino (MO) knockdown. Knockdown of D1+D2 (D1D2MO) and knockdown of D3 (D3MO) both resulted in transcriptional regulation of energy metabolism and (muscle) development in abdomen and tail, together with reduced growth, impaired swim bladder inflation, reduced protein content and reduced motility. The reduced growth and impaired swim bladder inflation in D1D2MO could be due to lower levels of T3 which is known to drive growth and development. The pronounced upregulation of a large number of transcripts coding for key proteins in ATP-producing pathways in D1D2MO could reflect a compensatory response to a decreased metabolic rate, also typically linked to hypothyroidism. Compared to D1D2MO, the effects were more pronounced or more frequent in D3MO, in which hyperthyroidism is expected. More specifically, increased heart rate, delayed hatching and increased carbohydrate content were observed only in D3MO. An increase of the metabolic rate, a decrease of the metabolic efficiency and a stimulation of gluconeogenesis using amino acids as substrates may have been involved in the observed reduced protein content, growth and motility in D3MO larvae. Furthermore, expression of transcripts involved in purine metabolism coupled to vision was decreased in both knockdown conditions, suggesting that both may impair vision. This study provides new insights, not only into the role of deiodinases, but also into the importance of a correct TH balance during vertebrate embryonic development.
authors: Systemic Physiological and Ecotoxicological Research (SPHERE), Department of Biology, University of Antwerp, B-2020 Antwerpen, Belgium; Zebrafishlab, Veterinary Physiology and Biochemistry, Department of Veterinary Sciences, University of Antwerp, B-2160 Wilrijk, Belgium.
authors: Enise
authors: E
authors: Bagci
authors: Laboratory of Comparative Endocrinology, Animal Physiology and Neurobiology Section, Department of Biology, KU Leuven, B-3000 Leuven, Belgium.
authors: Marjolein
authors: M
authors: Heijlen
authors: Zebrafishlab, Veterinary Physiology and Biochemistry, Department of Veterinary Sciences, University of Antwerp, B-2160 Wilrijk, Belgium.
authors: Lucia
authors: L
authors: Vergauwen
authors: Zebrafishlab, Veterinary Physiology and Biochemistry, Department of Veterinary Sciences, University of Antwerp, B-2160 Wilrijk, Belgium.
authors: An
authors: A
authors: Hagenaars
authors: Laboratory of Comparative Endocrinology, Animal Physiology and Neurobiology Section, Department of Biology, KU Leuven, B-3000 Leuven, Belgium.
authors: Anne M
authors: AM
authors: Houbrechts
authors: Laboratory for Molecular Biodiscovery, Department of Pharmaceutical and Pharmacological Sciences, KU Leuven, B-3000 Leuven, Belgium.
authors: Camila V
authors: CV
authors: Esguerra
authors: Zebrafishlab, Veterinary Physiology and Biochemistry, Department of Veterinary Sciences, University of Antwerp, B-2160 Wilrijk, Belgium.
authors: Ronny
authors: R
authors: Blust
authors: Laboratory of Comparative Endocrinology, Animal Physiology and Neurobiology Section, Department of Biology, KU Leuven, B-3000 Leuven, Belgium.
authors: Veerle M
authors: VM
authors: Darras
authors: Zebrafishlab, Veterinary Physiology and Biochemistry, Department of Veterinary Sciences, University of Antwerp, B-2160 Wilrijk, Belgium; Systemic Physiological and Ecotoxicological Research (SPHERE), Department of Biology, University of Antwerp, B-2020 Antwerpen, Belgium.
authors: Dries
authors: D
authors: Knapen
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D004625:Embryo, Nonmammalian; D047108:Embryonic Development / Q000235:genetics*; D004734:Energy Metabolism / Q000235:genetics; D018507:Gene Expression Regulation, Developmental; D007453:Iodide Peroxidase / Q000235:genetics* / Q000378:metabolism; D055537:Light Signal Transduction; D024510:Muscle Development / Q000235:genetics; D013963:Thyroid Hormones / Q000235:genetics / Q000378:metabolism; D015027:Zebrafish / Q000235:genetics* / Q000254:growth & development; D000097564:Iodothyronine Deiodinase Type II
chemical_list: D000255:Adenosine Triphosphate; D007453:Iodide Peroxidase; D013963:Thyroid Hormones; D000097564:Iodothyronine Deiodinase Type II; C109812:iodothyronine deiodinase type I; C117274:iodothyronine deiodinase type III