Localization and pollutant-induced responses of nuclear receptors during sea urchin development
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Localization and pollutant-induced responses of nuclear receptors during sea urchin development

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Abstract

Gene regulation during embryogenesis is required for executing the program fordevelopment, as well as responding to the environment in a context-specific manner. Nuclear receptors (NRs) are transcription factors that modulate gene expression, often in response to xenobiotics. However, NRs role in early development remains less understood. To address this gap, a marine model organism like the sea urchin, Strongylocentrotus purpuratus, is ideal for studying NRs during embryogenesis. This study screened 10 NRs important for cellular defense and localized mRNA through colorimetric and fluorescence whole mount in-situ hybridization at key developmental stages. With this initial screen, we found two NRs with localized expression patterns. These include: hnf1a, expressed primarily in the developing hindgut and later in larval gut and ciliary band and ppara1, which localized to the larval foregut and midgut. With hybridization chain reaction in-situ, ppara1 is confirmed to be localized in the gut along with ppargc1, a coactivator for ppara1. Coactivators are recruited after a NR is ligand bound and facilitates transactivation. NRs were further characterized with scRNA-seq data in the 72 hpf embryo and AlphaFold protein modeling to predict structure and binding. With scRNA-seq, rxr, a NR that heterodimerizes with ppara1, was found expressed in the larval gut. AlphaFold models the ligand binding domain helices and residues responsible for ligand binding and predicts Sp-PPAR:RXR heterodimer functions in binding to the pollutant tributyltin chloride. This study lays the conceptual framework for researching PPAR:RXR function to understand gene regulation by both endogenous and xenobiotic ligands.

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This item is under embargo until October 9, 2025.