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

Solanki, A; Yanez, DC; Ross, S; Lau, C-I; Papaioannou, E; Li, J; Saldaña, JI; (2018) In the fetal thymus, Gli3 in thymic epithelial cells promotes thymocyte positive selection and differentiation by repression of Shh. Development , 145 (3) , Article dev146910. 10.1242/dev.146910. Green open access

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Abstract

Gli3 is a Hedgehog (Hh) responsive transcription factor that can function as a transcriptional repressor or activator. We show that Gli3 activity in thymic epithelial cells (TEC) promotes positive selection and differentiation from CD4+CD8+ to CD4+CD8- single positive (SP4) cell in the fetal thymus and that Gli3 represses Shh Constitutive deletion of Gli3, and conditional deletion of Gli3 from TEC, reduced differentiation to SP4, whereas conditional deletion of Gli3 from thymocytes did not. Conditional deletion of Shh from TEC increased differentiation to SP4, and expression of Shh was upregulated in the Gli3-deficient thymus. Use of a transgenic Hh-reporter showed that the Hh pathway was active in thymocytes, and increased in the Gli3-deficient fetal thymus. Neutralisation of endogenous Hh proteins in the Gli3-/- thymus restored SP4 differentiation, indicating that Gli3 in TEC promotes SP4 differentiation by repression of Shh Transcriptome analysis showed that Hh-mediated transcription was increased but TCR-mediated transcription decreased in Gli3-/- thymocytes compared to WT.

Type: Article
Title: In the fetal thymus, Gli3 in thymic epithelial cells promotes thymocyte positive selection and differentiation by repression of Shh
Location: England
Open access status: An open access version is available from UCL Discovery
DOI: 10.1242/dev.146910
Publisher version: https://doi.org/10.1242/dev.146910
Language: English
Additional information: This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed.
Keywords: Shh, Gli3, Fetal thymus, Positive selection, CD4, T-cell development, Thymocyte, Thymic epithelial cell (TEC), Mouse
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health > Infection, Immunity and Inflammation Dept
URI: https://discovery.ucl.ac.uk/id/eprint/10042367
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