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

Article


Solanki, Anisha, Yanez, Diana C., Ross, Susan, Lau, Ching-In, Papaioannou, Eleftheria, Li, Jiawei, Saldaña, J. and Crompton, Tessa 2018. Gli3 in fetal thymic epithelial cells promotes thymocyte positive selection and differentiation by repression of Shh. Development. 145 (3), p. dev146910. https://doi.org/10.1242/dev.146910
AuthorsSolanki, Anisha, Yanez, Diana C., Ross, Susan, Lau, Ching-In, Papaioannou, Eleftheria, Li, Jiawei, Saldaña, J. and Crompton, Tessa
Abstract

Gli3 is a Hedgehog (Hh)-responsive transcription factor that can function as a transcriptional repressor or activator. We show that Gli3 activity in mouse thymic epithelial cells (TECs) promotes positive selection and differentiation from CD4+ CD8+ to CD4+ CD8− single positive (SP4) cells in the fetal thymus and that Gli3 represses Shh. Constitutive deletion of Gli3, and conditional deletion of Gli3 from TECs, reduced differentiation to SP4, whereas conditional deletion of Gli3 from thymocytes did not. Conditional deletion of Shh from TECs 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 TECs promotes SP4 differentiation by repression of Shh. Transcriptome analysis showed that Hh-mediated transcription was
increased whereas TCR-mediated transcription was decreased in Gli3−/− thymocytes compared with wild type.

JournalDevelopment
Journal citation145 (3), p. dev146910
ISSN0950-1991
Year2018
PublisherThe Company of Biologists
Publisher's version
License
CC BY
Digital Object Identifier (DOI)https://doi.org/10.1242/dev.146910
Web address (URL)https://doi.org/10.1242/dev.146910
Publication dates
Print31 Jan 2018
Publication process dates
Deposited11 Apr 2018
Accepted03 Jan 2018
Accepted03 Jan 2018
FunderMedical Research Council
Biotechnology and Biological Sciences Research Council
Wellcome Trust
Great Ormond Street Hospital
National Secretariat for Higher Education, Science, Technology and Innovation of Ecuador
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