title: Foxn1 maintains thymic epithelial cells to support T-cell development via mcm2 in zebrafish.
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.
authors.affiliation: State Key Laboratory of Biomembrane and Membrane Biotechnology, Institute of Zoology,  Chinese Academy of Sciences, Beijing 100101,  China.
authors.forename: Dongyuan
authors.initials: D
authors.lastname: Ma
authors.forename: Lu
authors.initials: L
authors.lastname: Wang
authors.forename: Sifeng
authors.initials: S
authors.lastname: Wang
authors.forename: Ya
authors.initials: Y
authors.lastname: Gao
authors.forename: Yonglong
authors.initials: Y
authors.lastname: Wei
authors.forename: Feng
authors.initials: F
authors.lastname: Liu
mesh_terms: D000818:Animals; D001665:Binding Sites; D018797:Cell Cycle Proteins / Q000378:metabolism*; D049109:Cell Proliferation; D047369:Chromatin Immunoprecipitation; D004847:Epithelial Cells / Q000166:cytology*; D051858:Forkhead Transcription Factors / Q000378:metabolism*; D005786:Gene Expression Regulation; D049452:Green Fluorescent Proteins / Q000378:metabolism; D046529:Microscopy, Electron, Transmission / Q000379:methods; D008954:Models, Biological; D012333:RNA, Messenger / Q000378:metabolism; D013601:T-Lymphocytes / Q000166:cytology*; D013950:Thymus Gland / Q000166:cytology* / Q000378:metabolism; D015027:Zebrafish / Q000502:physiology*; D029961:Zebrafish Proteins / Q000378:metabolism*
chemical_list: D018797:Cell Cycle Proteins; D051858:Forkhead Transcription Factors; C474191:Foxn1 protein, zebrafish; C578531:Mcm2 protein, zebrafish; D012333:RNA, Messenger; D029961:Zebrafish Proteins; D049452:Green Fluorescent Proteins