Evolution of non-genomic nuclear receptor function

Taylor, Elias; Heyland, Andreas

doi:10.1016/j.mce.2021.111468

Cited by 12 publications

(12 citation statements)

References 103 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Both the differential effects of THs on arm retraction and apoptosis markers, and the responses of different cell types indicate that THs may be signalling via non-genomic pathways. Previous work from our lab also indicates that T4 can bind to specific integrin subunits in the membrane and regulate skeletogenesis via phosphorylation of MAPK (ERK1/2) in PMCs ( Taylor and Heyland, 2017 , 2018 , 2022 ). Therefore, our results support skeletogenesis in post-ingression larvae being at least partially regulated by non-genomic actions, rather than genomic action alone.…”

Section: Discussionmentioning

confidence: 72%

“…The detailed mechanisms of TH action in sea urchins remain unknown. However, new evidence suggests that TH treatment affects the expression of skeletogenic genes and activates MAPK via a homologue of integrin αvβ3, a non-genomic TH transduction pathway that has been previously described in mammals ( Taylor and Heyland, 2017 , 2018 , 2022 ; Brent, 2012 ; Davis et al, 2008 ; Lin et al, 2015 ; Martin et al, 2014 ; Yang et al, 2021 ).…”

Section: Introductionmentioning

confidence: 93%

See 1 more Smart Citation

Thyroid hormone-induced cell death in sea urchin metamorphic development

Wynen

Taylor

Heyland

2022

Journal of Experimental Biology

Self Cite

View full text Add to dashboard Cite

Thyroid hormones (THs) are important regulators of development, metabolism, and homeostasis in metazoans. Specifically, they have been shown to regulate the metamorphic transitions of vertebrates and invertebrates alike. Indirectly developing sea urchin larvae accelerate the formation of juvenile structures in response to thyroxine (T4) treatment, while reducing their larval arm length. The mechanisms underlying larval arm reduction are unknown and we hypothesized that programmed cell death (PCD) is linked to this process. To test this hypothesis, we measured larval arm retraction in response to different THs (T4, T3, rT3, Tetrac) and assessed cell death in larvae using three different methods (TUNEL, YO-PRO-1 and Caspase-3 activity) in the sea urchin Strongylocentrotus purpuratus. We also compared the extent of PCD in response to TH treatment before and after the invagination of the larval ectoderm, which marks the initiation of juvenile development in larval sea urchin species. We found that T4 treatment results in the strongest reduction of larval arms but detected a significant increase of PCD in response to T4, T3 and Tetrac in post-ingression but not pre-ingression larvae. As post-ingression larvae have initiated metamorphic development and therefore allocate resources to both, larval and the juvenile structures, these results provide evidence that THs regulate larval development differentially via PCD. PCD in combination with cell proliferation likely has a key function in sea urchin development.

show abstract

Section: Discussionmentioning

confidence: 72%

Section: Introductionmentioning

confidence: 93%

Thyroid hormone-induced cell death in sea urchin metamorphic development

Wynen

Taylor

Heyland

2022

Journal of Experimental Biology

Self Cite

View full text Add to dashboard Cite

show abstract

“…Our data suggest that actions of THs on older sea urchin larvae can be attributed at least in part to genomic signaling via a nuclear hormone receptor, likely THRb. Along with previous evidence linking THRb to regulation of metamorphosis by THs in molluscs and annelids (62,135) and the fact the THR signaling is likely a bilaterian innovation (37), it is plausible that TH signaling is widespread among bilaterians.…”

Section: Evolution Of Thyroid Hormone Regulation Of Developmentmentioning

confidence: 73%

“…A number of additional non-genomic pathways wherein THs bind to an extranuclear TR have also been described (14,(33)(34)(35); N. P. 36) and these pathways may also result in regulation of gene transcription (14,30). There is evidence that some of these pathways may be conserved among bilaterians (37).…”

mentioning

confidence: 99%

Thyroid hormone membrane receptor binding and transcriptional regulation in the sea urchin Strongylocentrotus purpuratus

2023

Self Cite

View full text Add to dashboard Cite

Thyroid hormones (THs) are small amino acid derived signaling molecules with broad physiological and developmental functions in animals. Specifically, their function in metamorphic development, ion regulation, angiogenesis and many others have been studied in detail in mammals and some other vertebrates. Despite extensive reports showing pharmacological responses of invertebrate species to THs, little is known about TH signaling mechanisms outside of vertebrates. Previous work in sea urchins suggests that non-genomic mechanisms are activated by TH ligands. Here we show that several THs bind to sea urchin (Strongylocentrotus purpuratus) cell membrane extracts and are displaced by ligands of RGD-binding integrins. A transcriptional analysis across sea urchin developmental stages shows activation of genomic and non-genomic pathways in response to TH exposure, suggesting that both pathways are activated by THs in sea urchin embryos and larvae. We also provide evidence associating TH regulation of gene expression with TH response elements in the genome. In ontogeny, we found more differentially expressed genes in older larvae compared to gastrula stages. In contrast to gastrula stages, the acceleration of skeletogenesis by thyroxine in older larvae is not fully inhibited by competitive ligands or inhibitors of the integrin membrane receptor pathway, suggesting that THs likely activate multiple pathways. Our data confirms a signaling function of THs in sea urchin development and suggests that both genomic and non-genomic mechanisms play a role, with genomic signaling being more prominent during later stages of larval development.

show abstract

“…This is achieved by a fine-tuned regulation of an intricate network of TH synthesis, feedback mechanisms, serum distribution, membrane transporters, metabolizing enzymes, receptors and more ( Zoeller et al, 2007 ; Ortiga-Carvalho et al, 2016 ). The different components all work in concert to deliver THs to target cells where they regulate gene expression through interactions with nuclear TH receptors (TRs) or through non-genomic mechanisms ( Ortiga-Carvalho et al, 2016 ; Taylor and Heyland, 2022 ).…”

Section: Introductionmentioning

confidence: 99%

New approach methods to improve human health risk assessment of thyroid hormone system disruption–a PARC project

Ramhøj,

Axelstad,

Baert

et al. 2023

Front. Toxicol.

View full text Add to dashboard Cite

Current test strategies to identify thyroid hormone (TH) system disruptors are inadequate for conducting robust chemical risk assessment required for regulation. The tests rely heavily on histopathological changes in rodent thyroid glands or measuring changes in systemic TH levels, but they lack specific new approach methodologies (NAMs) that can adequately detect TH-mediated effects. Such alternative test methods are needed to infer a causal relationship between molecular initiating events and adverse outcomes such as perturbed brain development. Although some NAMs that are relevant for TH system disruption are available–and are currently in the process of regulatory validation–there is still a need to develop more extensive alternative test batteries to cover the range of potential key events along the causal pathway between initial chemical disruption and adverse outcomes in humans. This project, funded under the Partnership for the Assessment of Risk from Chemicals (PARC) initiative, aims to facilitate the development of NAMs that are specific for TH system disruption by characterizing in vivo mechanisms of action that can be targeted by in embryo/in vitro/in silico/in chemico testing strategies. We will develop and improve human-relevant in vitro test systems to capture effects on important areas of the TH system. Furthermore, we will elaborate on important species differences in TH system disruption by incorporating non-mammalian vertebrate test species alongside classical laboratory rat species and human-derived in vitro assays.

show abstract

Evolution of non-genomic nuclear receptor function

Cited by 12 publications

References 103 publications

Thyroid hormone-induced cell death in sea urchin metamorphic development

Thyroid hormone-induced cell death in sea urchin metamorphic development

Thyroid hormone membrane receptor binding and transcriptional regulation in the sea urchin Strongylocentrotus purpuratus

New approach methods to improve human health risk assessment of thyroid hormone system disruption–a PARC project

Contact Info

Product

Resources

About