Ontogenetic expression of thyroid hormone signaling genes: An in vitro and in vivo species comparison

Abstract

Thyroid hormone (TH) is essential for brain development. While disruption of TH signaling by environmental chemicals has been discussed as a mechanism of developmental neurotoxicity (DNT) for more than a decade, there remains a paucity of information linking specific TH disrupting chemicals to adverse neurodevelopmental outcomes. This data gap reflects, in part, the fact that the molecular machinery of TH signaling is complex and varies according to cell type and developmental time. Thus, establishing a baseline of the ontogenetic profile of expression of TH signaling molecules in relevant cell types is critical for developing in vitro and alternative systems-based models for screening TH disrupting chemicals for DNT. Here, we characterize the transcriptomic profile of molecules critical to TH signaling across three species–human, rat, and zebrafish–in vitro and in vivo across different stages of neurodevelopment. Our data indicate that while cultured human and rat neural progenitor cells, primary cultures of rat cortical cells, and larval zebrafish all express a fairly comprehensive transcriptome of TH signaling molecules, the spatiotemporal expression profiles as well as the responses to TH vary across species and developmental stages. The data presented here provides a roadmap for identifying appropriate in vitro and in simpler systems-based models for mechanistic studies and screening of chemicals that alter neurodevelopment via interference with TH action.

Risk Factors from Pregnancy to Adulthood in Multiple Sclerosis Outcome

“…There are two main THs synthesized by the thyroid gland, L-3,5,3 ,5 -tetraiodothyronine, or thyroxine (T 4 ), and 3,3 ,5-triiodo-L-thyronine, or triiodothyronine (T 3 ). T 4 is synthesized to a greater extent and converted to T 3 by specific iodothyronine deiodinases [188,189]. T 3 has been assumed to be the active form of THs and acts as the principal TH mediating metabolic activity [190].…”

Neurodevelopmental toxicity assessment of flame retardants using a human DNT in vitro testing battery

“…Analysis was performed using the software Rotor-Gene Q Series version 2.3.4 (Qiagen). Copy numbers (CN) of the genes of interest were calculated by using genespecific copy number standards as described previously in detail (Walter et al 2019) and normalized to the housekeeping gene beta-actin. Gene CN of solvent control and FR treated differentiated spheres were normalized to proliferative spheres, which are thought to express very low numbers of oligodendrocyte-specific mRNA.…”

The presynaptic glycine transporter GlyT2 is regulated by the Hedgehog pathway in vitro and in vivo

“…2a, b ) and suggest that theHedgehog signaling pathway physiologically modulates GlyT2 levels during development. In zebrafish, key neurodevelopmental events occur during the first 120 hpf (5 dpf): neural tube closure takes place approximately at 16 hpf, neural proliferation between 12 and 84 hpf, and neural migration between 18 and 96 hpf 98 , 99 . Regarding the expression of glycinergic neurotransmission elements, GlyT2 mRNA appears at 20 hpf 40 , 100 and GlyR α1 subunit at 24 hpf 101 .…”