Gli3 in fetal thymic epithelial cells promotes thymocyte positive selection and differentiation by repression of Shh
| العنوان: | Gli3 in fetal thymic epithelial cells promotes thymocyte positive selection and differentiation by repression of Shh |
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| المؤلفون: | Solanki, Anisha, Yanez, Diana C., Ross, Susan, Lau, Ching-In, Papaioannou, Eleftheria, Li, Jiawei, Saldaña, José Ignacio, Crompton, Tessa |
| المصدر: | Development (Cambridge, England) |
| بيانات النشر: | The Company of Biologists Ltd, 2018. |
| سنة النشر: | 2018 |
| مصطلحات موضوعية: | musculoskeletal diseases, Male, congenital, hereditary, and neonatal diseases and abnormalities, animal structures, Mouse, T-Lymphocytes, Mice, Transgenic, Nerve Tissue Proteins, Thymus Gland, Gli3, T-cell development, Shh, Mice, Pregnancy, Zinc Finger Protein Gli3, Animals, Hedgehog Proteins, Mice, Knockout, Thymocytes, Gene Expression Profiling, fungi, Cell Differentiation, Epithelial Cells, CD4, Fetal thymus, Positive selection, Mice, Inbred C57BL, Repressor Proteins, embryonic structures, Female, Thymocyte, Thymic epithelial cell (TEC), Research Article |
| الوصف: | 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. Summary: Gli3 activity in thymic epithelial cells promotes maturation from CD4+ CD8+ to CD4+ CD8− thymocyte by reducing Shh, which signals to reduce T-cell receptor-mediated transcription during repertoire selection in mouse fetal thymus. |
| اللغة: | English |
| تدمد: | 1477-9129 0950-1991 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=pmid________::d3ae17e98578534e676af701bf90f91cTest http://europepmc.org/articles/PMC5817998Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.pmid..........d3ae17e98578534e676af701bf90f91c |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 14779129 09501991 |
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