Transcriptomics reveal an integrative role for maternal thyroid hormones during zebrafish embryogenesis

Abstract

Thyroid hormones (THs) are essential for embryonic brain development but the genetic mechanisms involved in the action of maternal THs (MTHs) are still largely unknown. As the basis for understanding the underlying genetic mechanisms of MTHs regulation we used an established zebrafish monocarboxylic acid transporter 8 (MCT8) knock-down model and characterised the transcriptome in 25hpf zebrafish embryos. Subsequent mapping of differentially expressed genes using Reactome pathway analysis together with in situ expression analysis and immunohistochemistry revealed the genetic networks and cells under MTHs regulation during zebrafish embryogenesis. We found 4,343 differentially expressed genes and the Reactome pathway analysis revealed that TH is involved in 1681 of these pathways. MTHs regulated the expression of core developmental pathways, such as NOTCH and WNT in a cell specific context. The cellular distribution of neural MTH-target genes demonstrated their cell specific action on neural stem cells and differentiated neuron classes. Taken together our data show that MTHs have a role in zebrafish neurogenesis and suggest they may be involved in cross talk between key pathways in neural development. Given that the observed MCT8 zebrafish knockdown phenotype resembles the symptoms in human patients with Allan-Herndon-Dudley syndrome our data open a window into understanding the genetics of this human congenital condition.

Natural toxic impact and thyroid signaling interplay orchestrates riverine adaptive divergence of Dolly Varden.

“…Such SC pigmentation does not seem to be a simple reaction to the dark water and bottom, as DV always have silvery flanks at the same stream spots. In trout, the development of the pigment pattern is determined by the Wnt gene cascade(Sivka et al, 2013), whose activity is under control of the thyroid axis(Silva et al, 2017;Skah et al, 2017). This fact combined with our experimental and field data allows us to propose that thyroid axis contributes to the pigment pattern diversification of S. malma morphs since they reach the parr life stage…”

Thyroid hormone regulation of neural stem cell fate: From development to ageing

“…Her2 is normally required to maintain neural progenitor proliferation and to postpone neuronal differentiation during the neurogenic wave, while stimulating glial differentiation later in development, supporting a time‐dependent balance between neuro‐ and gliogenesis . Downregulation of Notch signalling also increased the expression of the cell cycle inhibitor genes pax6a and neurod6a , resulting in a premature depletion of the NSC population . Correspondingly, the neural progenitor pool was smaller in the 48 hpf mct8 mutant zebrafish brain .…”

“…In humans, inactivating mutations in the MCT8 gene are responsible for the Allan‐Herndon‐Dudley Syndrome (AHDS), an X‐linked psychomotor retardation syndrome . In zebrafish, a transcriptome analysis at 25 hpf following KO of mct8 showed dysregulation of the Wnt/Notch signalling pathways . This downregulated the expression of her2 , an important target of Notch and a homologue of the well‐known TH‐responsive Hairless gene in mammals.…”

Composition and endocrine effects of water collected in the Kibale national park in Uganda

“…Furthermore, due to the existence of a comprehensive genetic toolbox, characterization of knock-downs or knock-out of key TH signalling genes in zebrafish have resulted in fruitful modelling and have contributed to our understanding of thyroid-related human diseases, e.g., Allan-Herndon-Dudley syndrome and TH resistance syndrome due to loss-of-function of the gene encoding Mct8 and TRs, respectively (Campinho et al, 2014;Heijlen et al, 2013;Marelli and Persani, 2017;Silva et al, 2017;Trubiroha et al, 2018;Vancamp et al, 2018;Zada et al, 2017). Finally, expression profiles of genes involved in TH signalling during multiple time points encompassed by a validated teleost toxicity assay (Fish, Early-Life Stage Toxicity Test" (OECD TG210, 2018a)) have recently been obtained and have shown to be relatively similar in both the zebrafish and the fathead minnow (Vergauwen et al, 2018).…”