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

Anisha Solanki, Diana C. Yanez, Susan Ross, Ching In Lau, Eleftheria Papaioannou, Jiawei Li, José Ignacio Saldaña, Tessa Crompton

Producción científica: Contribución a una revistaArtículorevisión exhaustiva

21 Citas (Scopus)

Resumen

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.

Idioma originalInglés
Número de artículodev146910
PublicaciónDevelopment (Cambridge)
Volumen145
N.º3
DOI
EstadoPublicada - feb. 2018
Publicado de forma externa

Huella

Profundice en los temas de investigación de 'Gli3 in fetal thymic epithelial cells promotes thymocyte positive selection and differentiation by repression of Shh'. En conjunto forman una huella única.

Citar esto