The thyroid hormone nuclear receptor TRα1 controls the Notch signaling pathway and cell fate in murine intestine

Sirakov, M; Tortereau, Antonin; Kress, Elsa; Frau, Carla; Lone, Imtiaz Nisar; Nadjar, Julien; Angelov, Dimitar; Plateroti, Michelina

doi:10.1242/dev.121962

Cited by 33 publications

(19 citation statements)

References 61 publications

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“…In particular, Hairy1, but not the other genes analyzed, was significantly up‐regulated even after 1 day of T3 treatment. However, Hairy1 may still be indirectly regulated by T3 as reported in the mouse intestine , because its up‐regulation by T3 was impaired by Notch inhibition. Hairy2b is also considered to be a TH‐indirect response gene, since its expression was not up‐regulated until 4 days after T3 treatment.…”

Section: Discussionmentioning

confidence: 91%

Thyroid Hormone-Induced Activation of Notch Signaling is Required for Adult Intestinal Stem Cell Development During Xenopus Laevis Metamorphosis

et al. 2016

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In Xenopus laevis intestine during metamorphosis, the larval epithelial cells are removed by apoptosis, and the adult epithelial stem (AE) cells appear concomitantly. They proliferate and differentiate to form the adult epithelium (Ep). Thyroid hormone (TH) is well established to trigger this remodeling by regulating the expression of various genes including Notch receptor. To study the role of Notch signaling, we have analyzed the expression of its components, including the ligands (DLL and Jag), receptor (Notch), and targets (Hairy), in the metamorphosing intestine by real‐time reverse transcription‐polymerase chain reaction and in situ hybridization or immunohistochemistry. We show that they are up‐regulated during both natural and TH‐induced metamorphosis in a tissue‐specific manner. Particularly, Hairy1 is specifically expressed in the AE cells. Moreover, up‐regulation of Hairy1 and Hairy2b by TH was prevented by treating tadpoles with a γ‐secretase inhibitor (GSI), which inhibits Notch signaling. More importantly, TH‐induced up‐regulation of LGR5, an adult intestinal stem cell marker, was suppressed by GSI treatment. Our results suggest that Notch signaling plays a role in stem cell development by regulating the expression of Hairy genes during intestinal remodeling. Furthermore, we show with organ culture experiments that prolonged exposure of tadpole intestine to TH plus GSI leads to hyperplasia of secretory cells and reduction of absorptive cells. Our findings here thus provide evidence for evolutionarily conserved role of Notch signaling in intestinal cell fate determination but more importantly reveal, for the first time, an important role of Notch pathway in the formation of adult intestinal stem cells during vertebrate development. Stem Cells 2017;35:1028–1039

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Section: Discussionmentioning

confidence: 91%

Thyroid Hormone-Induced Activation of Notch Signaling is Required for Adult Intestinal Stem Cell Development During Xenopus Laevis Metamorphosis

et al. 2016

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“…As mentioned above, the Notch pathway maintains the NSC pool in the adult SVZ and is also required for OPC generation in the embryo . Moreover, Notch signalling responds to THs . Thus, in the adult, Notch‐induced inhibition of fission might be involved in the reduced activation of DRP1 in SVZ‐OPCs .…”

Section: Implications Of Cell Metabolism On Neurogenesis and Th‐inducmentioning

confidence: 92%

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

et al. 2019

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In the vertebrate brain, neural stem cells (NSCs) generate both neuronal and glial cells throughout life. However, their neuro-and gliogenic capacity changes as a function of the developmental context. Despite the growing body of evidence on the variety of intrinsic and extrinsic factors regulating NSC physiology, their precise cellular and molecular actions are not fully determined. Our review focuses on thyroid hormone (TH), a vital component for both development and adult brain function that regulates NSC biology at all stages. First, we review comparative data to analyse how TH modulates neuro-and gliogenesis during vertebrate brain development. Second, as the mammalian brain is the most studied, we highlight the molecular mechanisms underlying TH action in this context. Lastly, we explore how the interplay between TH signalling and cell metabolism governs both neurodevelopmental and adult neurogenesis. We conclude that, together, TH and cellular metabolism regulate optimal brain formation, maturation and function from early foetal life to adult in vertebrate species. cell fate, development, evo-devo, metabolism, mitochondria, neural stem cell, thyroid hormone This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made. K E Y W O R D S

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“…It is worth to underline that complex cross-regulations between T 3 /TRα and key signalling pathways including Wnt, Notch and BMP have been largely described in the intestinal epithelium, where T 3 /TRα controls the balance between cell proliferation and cell differentiation of the crypt precursor cells (Plateroti et al 2006, Sirakov et al 2015. Interestingly, studies in human HCC showed that KLF9 expression is downregulated compared with the normal liver counterpart, and that exogenous KLF9 expression inhibits proliferation of HCC cell lines and their tumourigenic capacity when xenografted in immunodepressed mice (Sun et al 2014).…”

Section: T 3 /Trs Axis and Cell Differentiationmentioning

confidence: 99%

T3/TRs axis in hepatocellular carcinoma: new concepts for an old pair

Perra

Plateroti

Columbano

2016

Endocrine-Related Cancer

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Hepatocellular carcinoma (HCC) is a leading cause of cancer-related death worldwide, and its burden is expected to further increase in the next years. Chronic inflammation, induced by multiple viruses or metabolic alterations, and epigenetic and genetic modifications, cooperate in cancer development via a combination of common and distinct aetiology-specific pathways. In spite of the advances of classical therapies, the prognosis of this neoplasm has not considerably improved over the past few years. The advent of targeted therapies and the approval of the systemic treatment of advanced HCC with the kinase inhibitor sorafenib have provided some hope for the future. However, the benefits obtained from this treatment are still disappointing, as it extends the median life expectancy of patients by only few months. It is thus mandatory to find alternative effective treatments. Although the role played by thyroid hormones (THs) and their nuclear receptors (TRs) in human cancer is still unclear, mounting evidence indicates that they behave as oncosuppressors in HCC. However, the molecular mechanisms by which they exert this effect and the consequence of their activation following ligand binding on HCC progression remain elusive. In this review, we re-evaluate the existing evidence of the role of TH/TRs in HCC development; we will also discuss how TR alterations could affect fundamental biological processes, such as hepatocyte proliferation and differentiation, and consequently HCC progression. Finally, we will discuss if and how TRs can be foreseen as therapeutic targets in HCC and whether selective TR modulation by TH analogues may hold promise for HCC treatment.

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The thyroid hormone nuclear receptor TRα1 controls the Notch signaling pathway and cell fate in murine intestine

Cited by 33 publications

References 61 publications

Thyroid Hormone-Induced Activation of Notch Signaling is Required for Adult Intestinal Stem Cell Development During Xenopus Laevis Metamorphosis

Thyroid Hormone-Induced Activation of Notch Signaling is Required for Adult Intestinal Stem Cell Development During Xenopus Laevis Metamorphosis

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

T3/TRs axis in hepatocellular carcinoma: new concepts for an old pair

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