Development, Vol 122, Issue 1 23-30, Copyright © 1996 by Company of Biologists

JOURNAL ARTICLES

Pax1 is expressed during development of the thymus epithelium and is required for normal T-cell maturation

J Wallin, H Eibel, A Neubuser, J Wilting, H Koseki and R Balling
Department of Developmental Biology, Max-Planck Institute of Immunobiology, Freiburg, Germany.

Pax1 is a transcriptional regulatory protein expressed during mouse embryogenesis and has been shown to have an important function in vertebral column development. Expression of Pax1 mRNA in the embryonic thymus has been reported previously. Here we show that Pax1 protein expression in thymic epithelial cells can be detected throughout thymic development and in the adult. Expression starts in the early endodermal epithelium lining the foregut region and includes the epithelium of the third pharyngeal pouch, a structure giving rise to part of the thymus epithelium. In early stages of thymus development a large proportion of thymus cells expresses Pax1. With increasing age, the proportion of Pax1-expressing cells is reduced and in the adult mouse only a small fraction of cortical thymic stromal cells retains strong Pax1 expression. Expression of Pax1 in thymus epithelium is necessary for establishing the thymus microenvironment required for normal T cell maturation. Mutations in the Pax-1 gene in undulated mice affect not only the total size of the thymus but also the maturation of thymocytes. The number of thymocytes is reduced about 2- to 5-fold, affecting mainly the CD4+8+ immature and CD4+ mature thymocyte subsets. The expression levels of major thymocyte surface markers remains unchanged with the exception of Thy-1 which was found to be expressed at 3- to 4-fold higher levels.

This article has been cited by other articles:

				K.-Q. Gong, A. R. Yallowitz, H. Sun, G. R. Dressler, and D. M. Wellik A Hox-Eya-Pax Complex Regulates Early Kidney Developmental Gene Expression Mol. Cell. Biol., November 1, 2007; 27(21): 7661 - 7668. [Abstract] [Full Text] [PDF]

				E. Assarsson, B. J. Chambers, K. Hogstrand, E. Berntman, C. Lundmark, L. Fedorova, S. Imreh, A. Grandien, S. Cardell, B. Rozell, et al. Severe Defect in Thymic Development in an Insertional Mutant Mouse Model J. Immunol., April 15, 2007; 178(8): 5018 - 5027. [Abstract] [Full Text] [PDF]

				S. Miura, S. Davis, J. Klingensmith, and Y. Mishina BMP signaling in the epiblast is required for proper recruitment of the prospective paraxial mesoderm and development of the somites Development, October 1, 2006; 133(19): 3767 - 3775. [Abstract] [Full Text] [PDF]

				A. L. Rychel, S. E. Smith, H. T. Shimamoto, and B. J. Swalla Evolution and Development of the Chordates: Collagen and Pharyngeal Cartilage Mol. Biol. Evol., March 1, 2006; 23(3): 541 - 549. [Abstract] [Full Text] [PDF]

				C. C. Bleul and T. Boehm BMP Signaling Is Required for Normal Thymus Development J. Immunol., October 15, 2005; 175(8): 5213 - 5221. [Abstract] [Full Text] [PDF]

				J. Dooley, M. Erickson, and A. G. Farr An Organized Medullary Epithelial Structure in the Normal Thymus Expresses Molecules of Respiratory Epithelium and Resembles the Epithelial Thymic Rudiment of Nude Mice J. Immunol., October 1, 2005; 175(7): 4331 - 4337. [Abstract] [Full Text] [PDF]

				V. Selvaraj, D. Bunick, C. Finnigan-Bunick, R. W. Johnson, H. Wang, L. Liu, and P. S. Cooke Gene Expression Profiling of 17{beta}-Estradiol and Genistein Effects on Mouse Thymus Toxicol. Sci., September 1, 2005; 87(1): 97 - 112. [Abstract] [Full Text] [PDF]

				M. Schubert, J.-K. Yu, N. D. Holland, H. Escriva, V. Laudet, and L. Z. Holland Retinoic acid signaling acts via Hox1 to establish the posterior limit of the pharynx in the chordate amphioxus Development, January 1, 2005; 132(1): 61 - 73. [Abstract] [Full Text] [PDF]

				Y. Kameda, Y. Arai, T. Nishimaki, and O. Chisaka The Role of Hoxa3 Gene in Parathyroid Gland Organogenesis of the Mouse J. Histochem. Cytochem., May 1, 2004; 52(5): 641 - 652. [Abstract] [Full Text] [PDF]

				E. Levantini, A. Giorgetti, F. Cerisoli, E. Traggiai, A. Guidi, R. Martin, D. Acampora, P. D. Aplan, G. Keller, A. Simeone, et al. Unsuspected role of the brain morphogenetic gene Otx1 in hematopoiesis PNAS, September 2, 2003; 100(18): 10299 - 10303. [Abstract] [Full Text] [PDF]

				C. Kokubu, B. Wilm, T. Kokubu, M. Wahl, I. Rodrigo, N. Sakai, F. Santagati, Y. Hayashizaki, M. Suzuki, K.-i. Yamamura, et al. Undulated short-tail Deletion Mutation in the Mouse Ablates Pax1 and Leads to Ectopic Activation of Neighboring Nkx2-2 in Domains That Normally Express Pax1 Genetics, September 1, 2003; 165(1): 299 - 307. [Abstract] [Full Text] [PDF]

				H. Escriva, N. D. Holland, H. Gronemeyer, V. Laudet, and L. Z. Holland The retinoic acid signaling pathway regulates anterior/posterior patterning in the nerve cord and pharynx of amphioxus, a chordate lacking neural crest Development, March 8, 2003; 129(12): 2905 - 2916. [Abstract] [Full Text] [PDF]

				P.-X. Xu, W. Zheng, C. Laclef, P. Maire, R. L. Maas, H. Peters, and X. Xu Eya1 is required for the morphogenesis of mammalian thymus, parathyroid and thyroid Development, January 7, 2002; 129(13): 3033 - 3044. [Abstract] [Full Text] [PDF]

				J.-M. Revest, R. K. Suniara, K. Kerr, J. J. T. Owen, and C. Dickson Development of the Thymus Requires Signaling Through the Fibroblast Growth Factor Receptor R2-IIIb J. Immunol., August 15, 2001; 167(4): 1954 - 1961. [Abstract] [Full Text] [PDF]

				E. F. Lind, S. E. Prockop, H. E. Porritt, and H. T. Petrie Mapping Precursor Movement through the Postnatal Thymus Reveals Specific Microenvironments Supporting Defined Stages of Early Lymphoid Development J. Exp. Med., July 9, 2001; 194(2): 127 - 134. [Abstract] [Full Text] [PDF]

				D.-m. Su and N. R. Manley Hoxa3 and Pax1 Transcription Factors Regulate the Ability of Fetal Thymic Epithelial Cells to Promote Thymocyte Development J. Immunol., June 1, 2000; 164(11): 5753 - 5760. [Abstract] [Full Text] [PDF]

				O Wendling, C Dennefeld, P Chambon, and M Mark Retinoid signaling is essential for patterning the endoderm of the third and fourth pharyngeal arches Development, January 4, 2000; 127(8): 1553 - 1562. [Abstract] [PDF]

				M Rossel and M. Capecchi Mice mutant for both Hoxa1 and Hoxb1 show extensive remodeling of the hindbrain and defects in craniofacial development Development, January 11, 1999; 126(22): 5027 - 5040. [Abstract] [PDF]

				M Ogasawara, H Wada, H Peters, and N Satoh Developmental expression of Pax1/9 genes in urochordate and hemichordate gills: insight into function and evolution of the pharyngeal epithelium Development, January 6, 1999; 126(11): 2539 - 2550. [Abstract] [PDF]

				B. Wilm, E. Dahl, H. Peters, R. Balling, and K. Imai Targeted disruption of Pax1 defines its null phenotype and proves haploinsufficiency PNAS, July 21, 1998; 95(15): 8692 - 8697. [Abstract] [Full Text] [PDF]

				W. Van Ewijk, J. de Kruif, W. T. V. Germeraad, P. Berendes, C. Ropke, P. P. Platenburg, and T. Logtenberg Subtractive isolation of phage-displayed single-chain antibodies to thymic stromal cells by using intact thymic fragments PNAS, April 15, 1997; 94(8): 3903 - 3908. [Abstract] [Full Text] [PDF]

				S L Nutt, P Urbanek, A Rolink, and M Busslinger Essential functions of Pax5 (BSAP) in pro-B cell development: difference between fetal and adult B lymphopoiesis and reduced V-to-DJ recombination at the IgH locus. Genes & Dev., February 15, 1997; 11(4): 476 - 491. [Abstract] [PDF]

				P. Xu, I Woo, H Her, D. Beier, and R. Maas Mouse Eya homologues of the Drosophila eyes absent gene require Pax6 for expression in lens and nasal placode Development, January 1, 1997; 124(1): 219 - 231. [Abstract] [PDF]

				D Fitzsimmons, W Hodsdon, W Wheat, S M Maira, B Wasylyk, and J Hagman Pax-5 (BSAP) recruits Ets proto-oncogene family proteins to form functional ternary complexes on a B-cell-specific promoter. Genes & Dev., September 1, 1996; 10(17): 2198 - 2211. [Abstract] [PDF]

				M Torres, E Gomez-Pardo, and P Gruss Pax2 contributes to inner ear patterning and optic nerve trajectory Development, January 11, 1996; 122(11): 3381 - 3391. [Abstract] [PDF]