International Immunology, Vol. 14, No. 6, pp. 637-645,
June 2002
© 2002 Japanese Society for Immunology
Inducible gene knockout of transcription factor recombination signal binding protein-J reveals its essential role in T versus B lineage decision
Departments of 1 Medical Chemistry and 2 Pediatrics, Graduate School of Medicine, Kyoto University, Kyoto 606-8501, Japan
Correspondence to: T Honjo; E-mail: honjo{at}mfour.med.kyoto-u.ac.jp
Transmitting editor: K. Sugamura
The transcription factor recombination signal binding protein-J (RBP-J) functions immediately downstream of the cell surface receptor Notch and mediates transcriptional activation by the intracellular domain of all four kinds of Notch receptors. To investigate the function of RBP-J, we introduced loxP sites on both sides of the RBP-J exons encoding its DNA binding domain. Mice bearing the loxP-flanked RBP-J alleles, RBP-Jf/f, were mated with Mx-Cre transgenic mice and deletional mutation of the RBP-J gene in adult mice was induced by injection of the IFN-
inducer poly(I)–poly(C). Here we show that inactivation of RBP-J in bone marrow resulted in a block of T cell development at the earliest stage and increase of B cell development in the thymus. Lymphoid progenitors deficient in RBP-J differentiate into B but not T cells when cultured in 2'-deoxyguanosine-treated fetal thymic lobes by hanging-drop fetal thymus organ culture. Competitive repopulation assay also revealed cell autonomous deficiency of T cell development from bone marrow of RBP-J knockout mouse. Myeloid and B lineage differentiation appears normal in the bone marrow of RBP-J-inactivated mice. These results suggest that RBP-J, probably by mediating Notch signaling, controls T versus B cell fate decision in lymphoid progenitors.
Keywords: gene targeting, Notch, RBP-J, T lymphocyte
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  A. N. Riesenberg, Z. Liu, R. Kopan, and N. L. Brown Rbpj Cell Autonomous Regulation of Retinal Ganglion Cell and Cone Photoreceptor Fates in the Mouse Retina J. Neurosci., October 14, 2009; 29(41): 12865 - 12877. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H.-C. Wang, S. S. Perry, and X.-H. Sun Id1 Attenuates Notch Signaling and Impairs T-Cell Commitment by Elevating Deltex1 Expression Mol. Cell. Biol., September 1, 2009; 29(17): 4640 - 4652. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. J. Mead and K. E. Yutzey Notch pathway regulation of chondrocyte differentiation and proliferation during appendicular and axial skeleton development PNAS, August 25, 2009; 106(34): 14420 - 14425. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P.-N. Tsao, M. Vasconcelos, K. I. Izvolsky, J. Qian, J. Lu, and W. V. Cardoso Notch signaling controls the balance of ciliated and secretory cell fates in developing airways Development, July 1, 2009; 136(13): 2297 - 2307. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y.-C. Wang, X.-B. Hu, F. He, F. Feng, L. Wang, W. Li, P. Zhang, D. Li, Z.-S. Jia, Y.-M. Liang, et al. Lipopolysaccharide-induced Maturation of Bone Marrow-derived Dendritic Cells Is Regulated by Notch Signaling through the Up-regulation of CXCR4 J. Biol. Chem., June 5, 2009; 284(23): 15993 - 16003. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Zong, A. Panikkar, J. Xu, A. Antoniou, P. Raynaud, F. Lemaigre, and B. Z. Stanger Notch signaling controls liver development by regulating biliary differentiation Development, May 15, 2009; 136(10): 1727 - 1739. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Dai Notch Signaling and Cancer Am. Assoc. Cancer Res. Educ. Book, April 18, 2009; 2009(1): 71 - 79. [Full Text] [PDF]
|
|
|
|
 |
|
 K. Hozumi, C. Mailhos, N. Negishi, K.-i. Hirano, T. Yahata, K. Ando, S. Zuklys, G. A. Hollander, D. T. Shima, and S. Habu Delta-like 4 is indispensable in thymic environment specific for T cell development J. Exp. Med., October 27, 2008; 205(11): 2507 - 2513. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
U. Koch, E. Fiorini, R. Benedito, V. Besseyrias, K. Schuster-Gossler, M. Pierres, N. R. Manley, A. Duarte, H. R. MacDonald, and F. Radtke Delta-like 4 is the essential, nonredundant ligand for Notch1 during thymic T cell lineage commitment J. Exp. Med., October 27, 2008; 205(11): 2515 - 2523. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Song, Y.-W. Kim, B.-K. Koo, H.-W. Jeong, M.-J. Yoon, K.-J. Yoon, D.-J. Jun, S.-K. Im, J. Shin, M.-P. Kong, et al. Mind bomb 1 in the lymphopoietic niches is essential for T and marginal zone B cell development J. Exp. Med., October 27, 2008; 205(11): 2525 - 2536. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Fukushima, A. Nakao, F. Okamoto, M. Shin, H. Kajiya, S. Sakano, A. Bigas, E. Jimi, and K. Okabe The Association of Notch2 and NF-{kappa}B Accelerates RANKL-Induced Osteoclastogenesis Mol. Cell. Biol., October 15, 2008; 28(20): 6402 - 6412. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
I. Imayoshi, T. Shimogori, T. Ohtsuka, and R. Kageyama Hes genes and neurogenin regulate non-neural versus neural fate specification in the dorsal telencephalic midline Development, August 1, 2008; 135(15): 2531 - 2541. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Guo, I. Maillard, S. Chakraborti, E. V. Rothenberg, and N. A. Speck Core binding factors are necessary for natural killer cell development and cooperate with Notch signaling during T-cell specification Blood, August 1, 2008; 112(3): 480 - 492. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. J. Thompson, V. Jankovic, J. Gao, S. Buonamici, A. Vest, J. M. Lee, J. Zavadil, S. D. Nimer, and I. Aifantis Control of hematopoietic stem cell quiescence by the E3 ubiquitin ligase Fbw7 J. Exp. Med., June 9, 2008; 205(6): 1395 - 1408. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G.-R. Dou, Y.-C. Wang, X.-B. Hu, L.-H. Hou, C.-M. Wang, J.-F. Xu, Y.-S. Wang, Y.-M. Liang, L.-B. Yao, A.-G. Yang, et al. RBP-J, the transcription factor downstream of Notch receptors, is essential for the maintenance of vascular homeostasis in adult mice FASEB J, May 1, 2008; 22(5): 1606 - 1617. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Zhang and L. Li Stem Cell Niche: Microenvironment and Beyond J. Biol. Chem., April 11, 2008; 283(15): 9499 - 9503. [Full Text] [PDF]
|
|
|
|
|
|
P. Hayward, T. Kalmar, and A. Martinez Arias Wnt/Notch signalling and information processing during development Development, February 1, 2008; 135(3): 411 - 424. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. M. Michie, A. C. Chan, M. Ciofani, M. Carleton, J. M. Lefebvre, Y. He, D. M. Allman, D. L. Wiest, J. C. Zuniga-Pflucker, and D. J. Izon Constitutive Notch signalling promotes CD4 CD8 thymocyte differentiation in the absence of the pre-TCR complex, by mimicking pre-TCR signals Int. Immunol., December 1, 2007; 19(12): 1421 - 1430. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Wu, I. Maillard, M. Nakamura, W. S. Pear, and J. D. Griffin The transcriptional coactivator Maml1 is required for Notch2-mediated marginal zone B-cell development Blood, November 15, 2007; 110(10): 3618 - 3623. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Laky and B.J. Fowlkes Presenilins regulate {alpha}{beta} T cell development by modulating TCR signaling J. Exp. Med., September 3, 2007; 204(9): 2115 - 2129. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. L. Caton, M. R. Smith-Raska, and B. Reizis Notch-RBP-J signaling controls the homeostasis of CD8- dendritic cells in the spleen J. Exp. Med., July 9, 2007; 204(7): 1653 - 1664. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. K. Taylor, K. Yeager, and S. J. Morrison Physiological Notch signaling promotes gliogenesis in the developing peripheral and central nervous systems Development, July 1, 2007; 134(13): 2435 - 2447. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Oyama, K. Harigaya, A. Muradil, K. Hozumi, S. Habu, H. Oguro, A. Iwama, K. Matsuno, R. Sakamoto, M. Sato, et al. Mastermind-1 is required for Notch signal-dependent steps in lymphocyte development in vivo PNAS, June 5, 2007; 104(23): 9764 - 9769. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Wilson, D.-L. Ardiet, C. Saner, N. Vilain, F. Beermann, M. Aguet, H. R. MacDonald, and O. Zilian Normal Hemopoiesis and Lymphopoiesis in the Combined Absence of Numb and Numblike J. Immunol., June 1, 2007; 178(11): 6746 - 6751. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. Besseyrias, E. Fiorini, L. J. Strobl, U. Zimber-Strobl, A. Dumortier, U. Koch, M.-L. Arcangeli, S. Ezine, H. R. MacDonald, and F. Radtke Hierarchy of Notch-Delta interactions promoting T cell lineage commitment and maturation J. Exp. Med., February 19, 2007; 204(2): 331 - 343. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Tsuji, R. Shinkura, K. Kuroda, D. Yabe, and T. Honjo Msx2-interacting nuclear target protein (Mint) deficiency reveals negative regulation of early thymocyte differentiation by Notch/RBP-J signaling PNAS, January 30, 2007; 104(5): 1610 - 1615. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S.-i. Tsukumo, K. Hirose, Y. Maekawa, K. Kishihara, and K. Yasutomo Lunatic Fringe Controls T Cell Differentiation through Modulating Notch Signaling J. Immunol., December 15, 2006; 177(12): 8365 - 8371. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Souilhol, S. Cormier, K. Tanigaki, C. Babinet, and M. Cohen-Tannoudji RBP-J{kappa}-Dependent Notch Signaling Is Dispensable for Mouse Early Embryonic Development. Mol. Cell. Biol., July 1, 2006; 26(13): 4769 - 4774. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Ikawa, H. Kawamoto, A. W. Goldrath, and C. Murre E proteins and Notch signaling cooperate to promote T cell lineage specification and commitment J. Exp. Med., May 15, 2006; 203(5): 1329 - 1342. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Moriyama, M. Osawa, S.-S. Mak, T. Ohtsuka, N. Yamamoto, H. Han, V. Delmas, R. Kageyama, F. Beermann, L. Larue, et al. Notch signaling via Hes1 transcription factor maintains survival of melanoblasts and melanocyte stem cells J. Cell Biol., May 8, 2006; 173(3): 333 - 339. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Olivier, E. Lauret, P. Gonin, and A. Galy The Notch ligand delta-1 is a hematopoietic development cofactor for plasmacytoid dendritic cells Blood, April 1, 2006; 107(7): 2694 - 2701. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Lu, R. Tayu, T. Ikawa, K. Masuda, I. Matsumoto, H. Mugishima, H. Kawamoto, and Y. Katsura The Earliest Thymic Progenitors in Adults Are Restricted to T, NK, and Dendritic Cell Lineage and Have a Potential to Form More Diverse TCR{beta} Chains than Fetal Progenitors J. Immunol., November 1, 2005; 175(9): 5848 - 5856. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. van den Brandt, S.-H. Kwon, T. Hunig, K. G. McPherson, and H. M. Reichardt Sustained Pre-TCR Expression in Notch1IC-Transgenic Rats Impairs T Cell Maturation and Selection J. Immunol., June 15, 2005; 174(12): 7845 - 7852. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Dias, H. Silva Jr., A. Cumano, and P. Vieira Interleukin-7 is necessary to maintain the B cell potential in common lymphoid progenitors J. Exp. Med., March 21, 2005; 201(6): 971 - 979. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Masuda, M. Itoi, T. Amagai, N. Minato, Y. Katsura, and H. Kawamoto Thymic Anlage Is Colonized by Progenitors Restricted to T, NK, and Dendritic Cell Lineages J. Immunol., March 1, 2005; 174(5): 2525 - 2532. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Robert-Moreno, L. Espinosa, J. L. de la Pompa, and A. Bigas RBPj{kappa}-dependent Notch function regulates Gata2 and is essential for the formation of intra-embryonic hematopoietic cells Development, March 1, 2005; 132(5): 1117 - 1126. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. K. Hadland, S. S. Huppert, J. Kanungo, Y. Xue, R. Jiang, T. Gridley, R. A. Conlon, A. M. Cheng, R. Kopan, and G. D. Longmore A requirement for Notch1 distinguishes 2 phases of definitive hematopoiesis during development Blood, November 15, 2004; 104(10): 3097 - 3105. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Hock, E. Meade, S. Medeiros, J. W. Schindler, P. J.M. Valk, Y. Fujiwara, and S. H. Orkin Tel/Etv6 is an essential and selective regulator of adult hematopoietic stem cell survival Genes & Dev., October 1, 2004; 18(19): 2336 - 2341. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Hoflinger, K. Kesavan, M. Fuxa, C. Hutter, B. Heavey, F. Radtke, and M. Busslinger Analysis of Notch1 Function by In Vitro T Cell Differentiation of Pax5 Mutant Lymphoid Progenitors J. Immunol., September 15, 2004; 173(6): 3935 - 3944. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
I. Maillard, A. P. Weng, A. C. Carpenter, C. G. Rodriguez, H. Sai, L. Xu, D. Allman, J. C. Aster, and W. S. Pear Mastermind critically regulates Notch-mediated lymphoid cell fate decisions Blood, September 15, 2004; 104(6): 1696 - 1702. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Iwata, N. Awaya, L. Graf, C. Kahl, and B. Torok-Storb Human marrow stromal cells activate monocytes to secrete osteopontin, which down-regulates Notch1 gene expression in CD34+ cells Blood, June 15, 2004; 103(12): 4496 - 4502. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Qin, J. Wang, Y. Liang, Y. Taniguchi, K. Tanigaki, and H. Han RING1 inhibits transactivation of RBP-J by Notch through interaction with LIM protein KyoT2 Nucleic Acids Res., March 3, 2004; 32(4): 1492 - 1501. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Ikawa, K. Masuda, M. Lu, N. Minato, Y. Katsura, and H. Kawamoto Identification of the earliest prethymic T-cell progenitors in murine fetal blood Blood, January 15, 2004; 103(2): 530 - 537. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. F. Hoyne Notch signaling in the immune system J. Leukoc. Biol., December 1, 2003; 74(6): 971 - 981. [Abstract] [Full Text]
|
|
|
|
|
|
A. Bhandoola, A. Sambandam, D. Allman, A. Meraz, and B. Schwarz Early T Lineage Progenitors: New Insights, but Old Questions Remain J. Immunol., December 1, 2003; 171(11): 5653 - 5658. [Full Text] [PDF]
|
|
|
|
|
|
T. J. Yun and M. J. Bevan Notch-Regulated Ankyrin-Repeat Protein Inhibits Notch1 Signaling: Multiple Notch1 Signaling Pathways Involved In T Cell Development J. Immunol., June 15, 2003; 170(12): 5834 - 5841. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Schroeder, S. T. Fraser, M. Ogawa, S. Nishikawa, C. Oka, G. W. Bornkamm, S.-I. Nishikawa, T. Honjo, and U. Just Recombination signal sequence-binding protein Jkappa alters mesodermal cell fate decisions by suppressing cardiomyogenesis PNAS, April 1, 2003; 100(7): 4018 - 4023. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Hashimoto, E. Montecino-Rodriguez, H. Leathers, R. P. Stephan, and K. Dorshkind B-cell development in the thymus is limited by inhibitory signals from the thymic microenvironment Blood, November 15, 2002; 100(10): 3504 - 3511. [Abstract] [Full Text] [PDF]
|
|