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

Kyla M. Walter, Katharina Dach, Keri Hayakawa, Susanne Giersiefer, Heike Heuer, Pamela J Lein, Ellen Fritsche

Research output: Contribution to journalArticle

2 Scopus citations

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 systemsbased models for mechanistic studies and screening of chemicals that alter neurodevelopment via interference with TH action.

Original languageEnglish (US)
Article numbere0221230
JournalPloS one
Volume14
Issue number9
DOIs
StatePublished - Jan 1 2019

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

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    Walter, K. M., Dach, K., Hayakawa, K., Giersiefer, S., Heuer, H., Lein, P. J., & Fritsche, E. (2019). Ontogenetic expression of thyroid hormone signaling genes: An in vitro and in vivo species comparison. PloS one, 14(9), [e0221230]. https://doi.org/10.1371/journal.pone.0221230