PUBLICATION

Foxn1 maintains thymic epithelial cells to support T-cell development via mcm2 in zebrafish

Authors
Ma, D., Wang, L., Wang, S., Gao, Y., Wei, Y., and Liu, F.
ID
ZDB-PUB-121210-2
Date
2012
Source
Proceedings of the National Academy of Sciences of the United States of America   109(51): 21040-21045 (Journal)
Registered Authors
Gao, Ya, Liu, Feng, Ma, Dongyuan, Wang, Lu, Wang, Shifeng, Wei, Yonglong
Keywords
none
MeSH Terms
  • Animals
  • Binding Sites
  • Cell Cycle Proteins/metabolism*
  • Cell Proliferation
  • Chromatin Immunoprecipitation
  • Epithelial Cells/cytology*
  • Forkhead Transcription Factors/metabolism*
  • Gene Expression Regulation*
  • Green Fluorescent Proteins/metabolism
  • Microscopy, Electron, Transmission/methods
  • Models, Biological
  • RNA, Messenger/metabolism
  • T-Lymphocytes/cytology*
  • Thymus Gland/cytology*
  • Thymus Gland/metabolism
  • Zebrafish/physiology*
  • Zebrafish Proteins/metabolism*
PubMed
23213226 Full text @ Proc. Natl. Acad. Sci. USA
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.

Genes / Markers
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Mutation and Transgenics
Human Disease / Model Data
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping
Errata and Notes