ZFIN ID: ZDB-PUB-121210-2
Foxn1 maintains thymic epithelial cells to support T-cell development via mcm2 in zebrafish
Ma, D., Wang, L., Wang, S., Gao, Y., Wei, Y., and Liu, F.
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

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.