In the fetal thymus, Gli3 in thymic epithelial cells promotes thymocyte positive selection and differentiation by repression of<i>Shh</i>

Solanki, Anisha; Yánez, Diana C.; Ross, Scott R.; Lau, Ching‐In; Papaioannou, Eleftheria; Li, Jiawei; Saldaña, José Ignacio; Crompton, Tessa

doi:10.1242/dev.146910

Cited by 24 publications

(27 citation statements)

References 76 publications

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“…Gli3T is a constitutive repressor form of Gli3 that antagonizes, in a dominant fashion, the transcription of Gli factors, including Gli1 and Gli2. Overexpression of Gli3T leading to elevation of TGF␤2 expression has also been reported for pancreatic cancer cells (32) or with activation of Smoothened (24). On the other hand, microarray analysis suggests that Gli3 alone regulates TGF␤1 expression levels in thymocytes at the embryonic day 18.5 (E18.5) (33).…”

Section: Discussionmentioning

confidence: 93%

Stromal Gli signaling regulates the activity and differentiation of prostate stem and progenitor cells

Alsaidan

Rai

et al. 2018

Journal of Biological Chemistry

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Interactions between cells in the stroma and epithelium facilitate prostate stem cell activity and tissue regeneration capacity. Numerous molecular signal transduction pathways, including the induction of sonic hedgehog (Shh) to activate the Gli transcription factors, are known to mediate the cross-talk of these two cellular compartments. However, the details of how these signaling pathways regulate prostate stem and progenitor cell activity remain elusive. Here we demonstrate that, although cell-autonomous epithelial Shh-Gli signaling is essential to determine the expression levels of basal cell markers and the renewal potential of epithelial stem and progenitor cells, stromal Gli signaling regulates prostate stem and progenitor cell activity by increasing the number and size of prostate spheroids Blockade of stromal Gli signaling also inhibited prostate tissue regeneration The inhibition of stromal Gli signaling suppressed the differentiation of basal and progenitor cells to luminal cells and limited prostate tubule secretory capability. Additionally, stromal cells were able to compensate for the deficiency of epithelial Shh signaling in prostate tissue regeneration. Mechanistically, suppression of Gli signaling increased the signaling factor transforming growth factor β (TGFβ) in stromal cells. Elevation of exogenous TGFβ1 levels inhibited prostate spheroid formation, suggesting that a stromal Gli-TGFβ signaling axis regulates the activity of epithelial progenitor cells. Our study illustrates that Gli signaling regulates epithelial stem cell activity and renewal potential in both epithelial and stromal compartments.

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Section: Discussionmentioning

confidence: 93%

Stromal Gli signaling regulates the activity and differentiation of prostate stem and progenitor cells

Alsaidan

Rai

et al. 2018

Journal of Biological Chemistry

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“…Loss of Gli2 causes growth arrest in the hair follicle [286]. Gli1, Gli2, and Gli3 play non-redundant roles in T-cell maturation in the thymus and B-cell development in the liver [236,287,288,289]. Gli2, and to a lesser degree Gli1, are involved in pituitary gland formation, and deletion of both genes results in complete loss of the pituitary gland [237].…”

Section: Gli Proteins In Development and Tissue Regenerationmentioning

confidence: 99%

Gli Proteins: Regulation in Development and Cancer

Niewiadomski

Niedziółka

Markiewicz

et al. 2019

Cells

141

124

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Gli proteins are transcriptional effectors of the Hedgehog signaling pathway. They play key roles in the development of many organs and tissues, and are deregulated in birth defects and cancer. We review the molecular mechanisms of Gli protein regulation in mammals, with special emphasis on posttranslational modifications and intracellular transport. We also discuss how Gli proteins interact with co-activators and co-repressors to fine-tune the expression of Hedgehog target genes. Finally, we provide an overview of the regulation of developmental processes and tissue regeneration by Gli proteins and discuss how these proteins are involved in cancer progression, both through canonical regulation via the Hedgehog pathway and through cross-talk with other signaling pathways.

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“…Principal Component Analysis used CRAN package ade4. Canonical Correspondence analysis (Ono et al, 2014) used CCA function of CRAN package 'vegan' as described (Solanki et al, 2018).…”

Section: Rna-sequencingmentioning

confidence: 99%

The transcriptional repressor Bcl6 promotes pre-TCR induced differentiation to CD4+CD8+ thymocyte and attenuates Notch1 activation

et al. 2020

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Pre-TCR signal transduction is required for developing thymocytes to differentiate from CD4-CD8- double negative (DN) to CD4+CD8+ double positive (DP) cell. Notch signalling is required for T-cell fate specification and must be maintained throughout β-selection, but inappropriate Notch activation in DN4 and DP cells is oncogenic. Here, we show that pre-TCR signalling leads to increased expression of the transcriptional repressor Bcl6 and that Bcl6 is required for differentiation to DP. Conditional deletion of Bcl6 from thymocytes reduced pre-TCR-induced differentiation to DP cell, disrupted expansion and enrichment of icTCRβ+ cells within the DN population and increased DN4 cell death. It also increased Notch1 activation and Notch-mediated transcription in the DP population. Thus, Bcl6 is required in thymocyte development for efficient differentiation from DN3 to DP cell and to attenuate Notch1 activation in DP cells. Given the importance of inappropriate NOTCH1 signalling in T-ALL, and the involvement of Bcl6 in other types of leukaemia, this study is important to our understanding of T-ALL.

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In the fetal thymus, Gli3 in thymic epithelial cells promotes thymocyte positive selection and differentiation by repression ofShh

Cited by 24 publications

References 76 publications

Stromal Gli signaling regulates the activity and differentiation of prostate stem and progenitor cells

Stromal Gli signaling regulates the activity and differentiation of prostate stem and progenitor cells

Gli Proteins: Regulation in Development and Cancer

The transcriptional repressor Bcl6 promotes pre-TCR induced differentiation to CD4+CD8+ thymocyte and attenuates Notch1 activation

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