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Foxn1 maintains thymic epithelial cells to support T-cell development via mcm2 in zebrafish
- Source :
- Proceedings of the National Academy of Sciences. 109:21040-21045
- Publication Year :
- 2012
- Publisher :
- Proceedings of the National Academy of Sciences, 2012.
-
Abstract
- The thymus is mainly comprised of thymic epithelial cells (TECs), which form the unique thymic epithelial microenvironment essential for intrathymic T-cell development. Foxn1, a member of the forkhead transcription factor family, is required for establishing a functional thymic rudiment. However, the molecular mechanisms underlying the function of Foxn1 are still largely unclear. Here, we show that Foxn1 functions in thymus development through Mcm2 in the zebrafish. We demonstrate that, in foxn1 knockdown embryos, the thymic rudiment is reduced and T-cell development is impaired. Genome-wide expression profiling shows that a number of genes, including some known thymopoiesis genes, are dysregulated during the initiation of the thymus primordium and immigration of T-cell progenitors to the thymus. Functional and epistatic studies show that mcm2 and cdca7 are downstream of Foxn1, and mcm2 is a direct target gene of Foxn1 in TECs. Finally, we find that the thymus defects in foxn1 and mcm2 morphants might be attributed to reduced cell proliferation rather than apoptosis. Our results reveal that the foxn1 - mcm2 axis plays a central role in the genetic regulatory network controlling thymus development in zebrafish.
- Subjects :
- Chromatin Immunoprecipitation
T-Lymphocytes
T cell
Green Fluorescent Proteins
Cell Cycle Proteins
Thymus Gland
Biology
Models, Biological
Microscopy, Electron, Transmission
medicine
Animals
RNA, Messenger
Progenitor cell
Transcription factor
Zebrafish
Cell Proliferation
Regulation of gene expression
Gene knockdown
Binding Sites
Multidisciplinary
integumentary system
FOXN1
Epithelial Cells
Forkhead Transcription Factors
Zebrafish Proteins
Biological Sciences
biology.organism_classification
Molecular biology
Cell biology
Gene expression profiling
medicine.anatomical_structure
Gene Expression Regulation
Subjects
Details
- ISSN :
- 10916490 and 00278424
- Volume :
- 109
- Database :
- OpenAIRE
- Journal :
- Proceedings of the National Academy of Sciences
- Accession number :
- edsair.doi.dedup.....30ae61193ef0df2480ac04ae776d7dc6