Zebrafish as a model to study peripheral thyroid hormone metabolism in vertebrate development

Heijlen, Marjolein; Houbrechts, Anne; Darras, Veerle

doi:10.1016/j.ygcen.2013.04.004

Cited by 53 publications

(31 citation statements)

References 65 publications

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“…The exposure concentrations for TPP were determined by a preliminary range-finding study. The zebrafish embryos were exposed until 7 days post-fertilization (dpf), by which time they have completed the development of most organs (Heijlen et al, 2013) and maintain relatively high levels of thyroid hormones (Chang et al, 2012). During the exposure, approximately 50% of the exposure solution was renewed daily.…”

Section: Zebrafish Culture and Embryo/larval Exposurementioning

confidence: 99%

Thyroid disruption by triphenyl phosphate, an organophosphate flame retardant, in zebrafish (Danio rerio) embryos/larvae, and in GH3 and FRTL-5 cell lines

et al. 2015

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Section: Zebrafish Culture and Embryo/larval Exposurementioning

confidence: 99%

Thyroid disruption by triphenyl phosphate, an organophosphate flame retardant, in zebrafish (Danio rerio) embryos/larvae, and in GH3 and FRTL-5 cell lines

et al. 2015

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“…deiodination (Heijlen et al, 2013;Infante et al, 2008;Itoh et al, 2010). Consequently, IDs are sensitive to T4/T3 concentrations ratio.…”

Section: Natural Hormones: Cross-talk Mechanismsmentioning

confidence: 99%

Deiodinases and thyroid metabolism disruption in teleost fish

Jarque

Piña

2014

Environmental Research

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“…In addition, the hypothalamic-pituitary-thyroid (HPT) axis is conserved in zebrafish [18], and zebrafish larvae have emerged as an attractive model for therapeutic drug screening [19]. In light of these advantages, we have recently isolated the zebrafish mct8 gene and promoter and showed that, as in humans, zebrafish mct8 is expressed primarily in the nervous and blood systems [20].…”

Section: Introductionmentioning

confidence: 99%

Altered Behavioral Performance and Live Imaging of Circuit-Specific Neural Deficiencies in a Zebrafish Model for Psychomotor Retardation

et al. 2014

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The mechanisms and treatment of psychomotor retardation, which includes motor and cognitive impairment, are indefinite. The Allan-Herndon-Dudley syndrome (AHDS) is an X-linked psychomotor retardation characterized by delayed development, severe intellectual disability, muscle hypotonia, and spastic paraplegia, in combination with disturbed thyroid hormone (TH) parameters. AHDS has been associated with mutations in the monocarboxylate transporter 8 (mct8/slc16a2) gene, which is a TH transporter. In order to determine the pathophysiological mechanisms of AHDS, MCT8 knockout mice were intensively studied. Although these mice faithfully replicated the abnormal serum TH levels, they failed to exhibit the neurological and behavioral symptoms of AHDS patients. Here, we generated an mct8 mutant (mct8−/−) zebrafish using zinc-finger nuclease (ZFN)-mediated targeted gene editing system. The elimination of MCT8 decreased the expression levels of TH receptors; however, it did not affect the expression of other TH-related genes. Similar to human patients, mct8−/− larvae exhibited neurological and behavioral deficiencies. High-throughput behavioral assays demonstrated that mct8−/− larvae exhibited reduced locomotor activity, altered response to external light and dark transitions and an increase in sleep time. These deficiencies in behavioral performance were associated with altered expression of myelin-related genes and neuron-specific deficiencies in circuit formation. Time-lapse imaging of single-axon arbors and synapses in live mct8−/− larvae revealed a reduction in filopodia dynamics and axon branching in sensory neurons and decreased synaptic density in motor neurons. These phenotypes enable assessment of the therapeutic potential of three TH analogs that can enter the cells in the absence of MCT8. The TH analogs restored the myelin and axon outgrowth deficiencies in mct8−/− larvae. These findings suggest a mechanism by which MCT8 regulates neural circuit assembly, ultimately mediating sensory and motor control of behavioral performance. We also propose that the administration of TH analogs early during embryo development can specifically reduce neurological damage in AHDS patients.

show abstract

Zebrafish as a model to study peripheral thyroid hormone metabolism in vertebrate development

Cited by 53 publications

References 65 publications

Thyroid disruption by triphenyl phosphate, an organophosphate flame retardant, in zebrafish (Danio rerio) embryos/larvae, and in GH3 and FRTL-5 cell lines

Thyroid disruption by triphenyl phosphate, an organophosphate flame retardant, in zebrafish (Danio rerio) embryos/larvae, and in GH3 and FRTL-5 cell lines

Deiodinases and thyroid metabolism disruption in teleost fish

Altered Behavioral Performance and Live Imaging of Circuit-Specific Neural Deficiencies in a Zebrafish Model for Psychomotor Retardation

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