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.
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− singlepositive
(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)doi: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
Permalink -

https://repository.uel.ac.uk/item/84908

  • 3
    total views
  • 20
    total downloads
  • 1
    views this month
  • 6
    downloads this month

Related outputs

Foxa1 and Foxa2 in thymic epithelial cells (TEC) regulate medullary TEC and regulatory T-cell maturation
Lau, Ching-In, Yánez, Diana C., Solanki, Anisha, Papaioannou, Eleftheria, Saldaña, J. and Crompton, Tessa 2018. Foxa1 and Foxa2 in thymic epithelial cells (TEC) regulate medullary TEC and regulatory T-cell maturation. Journal of Autoimmunity. 93, pp. 131-138.
The kinesin motor protein Kif7 is required for T-cell development and normal MHC expression on thymic epithelial cells (TEC) in the thymus
Lau, Ching-In, Barbarulo, Alessandro, Solanki, Anisha, Saldaña, J. and Crompton, Tessa 2017. The kinesin motor protein Kif7 is required for T-cell development and normal MHC expression on thymic epithelial cells (TEC) in the thymus. Oncotarget. 8 (15), pp. 24163-24176.
A genome wide transcriptional model of the complex response to pre-TCR signalling during thymocyte differentiation
Sahni, Hemant, Susan, Ross, Barbarulo, Alessandro, Solanki, Anisha, Lau, Ching-In, Furmanski, Anna, Saldaña, J., Ono, Masahiro, Hubank, Mike, Barenco, Martino and Crompton, Tessa 2015. A genome wide transcriptional model of the complex response to pre-TCR signalling during thymocyte differentiation. Oncotarget. 6 (30), pp. 28646-28660.
Sonic Hedgehog regulates thymic epithelial cell differentiation
Saldaña, J., Solanki, Anisha, Lau, Ching-In, Sahni, Hemant, Ross, Susan, Furmanski, Anna L., Ono, Masahiro, Holländer, Georg and Crompton, Tessa 2016. Sonic Hedgehog regulates thymic epithelial cell differentiation. Journal of Autoimmunity. 68 (April), pp. 86-97.
Hedgehog Signalling in the Embryonic Mouse Thymus
Barbarulo, Alessandro, Lau, Ching-In, Mengrelis, Konstantinos, Ross, Susan, Solanki, Anisha, Saldaña, J. and Crompton, Tessa 2016. Hedgehog Signalling in the Embryonic Mouse Thymus. Journal of Developmental Biology. 4 (3).
The transcription factor Gli3 promotes B cell development in fetal liver through repression of Shh
Solanki, Anisha, Lau, Ching-In, Saldaña, J., Ross, Susan and Crompton, Tessa 2017. The transcription factor Gli3 promotes B cell development in fetal liver through repression of Shh. The Journal of Experimental Medicine. 214 (7), pp. 2041 -2058.