Submitted June 25, 2008
Accepted November 22, 2008
Gene expression profile of third pharyngeal pouch reveals role of mesenchymal MafB in embryonic thymus development
Dil Afroz Sultana, Shuhei Tomita, Michito Hamada, Yasuyuki Iwanaga, Yuki Kitahama, Nguyen Van Khang, Shuichi Hirai, Izumi Ohigashi, Sachiko Nitta, Takashi Amagai, Satoru Takahashi, and Yousuke Takahama*
Division of Experimental Immunology, Institute for Genome Research, University of Tokushima, Tokushima, Japan
Department of Anatomy and Embryology, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Ibaraki, Japan
Department of Anesthesiology and Emergency Medicine, Faculty of Medicine, Kagawa University, Kagawa, Japan
Department of Immunology and Microbiology, Meiji University of Oriental Medicine, Kyoto, Japan
* Corresponding author; email: takahama{at}genome.tokushima-u.ac.jp.
The thymus provides a microenvironment that induces the differentiation of T-progenitor cells into functional T cells and that establishes a diverse yet self-tolerant T-cell repertoire. However, the mechanisms that lead to the development of the thymus are incompletely understood. We report herein the results of screening for genes that are expressed in the third pharyngeal pouch that contains thymic primordium. PCR-based cDNA subtraction screening for genes expressed in microdissected tissues of the third pharyngeal pouch rather than the second pharyngeal arch yielded one transcription factor, MafB, which was predominantly expressed in CD45-IA-PDGFR
+ mesenchymal cells and was detectable even in the third pharyngeal pouch of FoxN1-deficient nude mice. Interestingly, the number of CD45+ cells that initially accumulated in embryonic thymus was significantly decreased in MafB-deficient mice. Alterations of gene expression in embryonic thymus of MafB-deficient mice included the reduced expression of Wnt3 and BMP4 in mesenchymal cells and of CCL21 and CCL25 in epithelial cells. These results suggest that MafB expressed in third pharyngeal pouch mesenchymal cells critically regulates lymphocyte accumulation in embryonic thymus.
