Inactivation of Notch1 impairs VDJbeta rearrangement and allows pre-TCR-independent survival of early alpha beta Lineage Thymocytes - PubMed (original) (raw)
Inactivation of Notch1 impairs VDJbeta rearrangement and allows pre-TCR-independent survival of early alpha beta Lineage Thymocytes
Anita Wolfer et al. Immunity. 2002 Jun.
Free article
Abstract
Notch proteins influence cell fate decisions in many developmental systems. During lymphoid development, Notch1 signaling is essential to direct a bipotent T/B precursor toward the T cell fate, but the role of Notch1 at later stages of T cell development remains controversial. We have recently reported that tissue-specific inactivation of Notch1 in immature (CD44(-) CD25(+)) thymocytes does not affect subsequent T cell development. Here, we demonstrate that loss of Notch1 signaling at an earlier (CD44(+)CD25(+)) developmental stage results in severe perturbation of alpha beta but not gamma delta lineage development. Immature Notch1(-/-) thymocytes show impaired VDJ beta rearrangement and aberrant pre-TCR-independent survival. Collectively, our data demonstrate that Notch1 controls several nonredundant functions necessary for alpha beta lineage development.
Similar articles
- Lunatic Fringe prolongs Delta/Notch-induced self-renewal of committed αβ T-cell progenitors.
Yuan JS, Tan JB, Visan I, Matei IR, Urbanellis P, Xu K, Danska JS, Egan SE, Guidos CJ. Yuan JS, et al. Blood. 2011 Jan 27;117(4):1184-95. doi: 10.1182/blood-2010-07-296616. Epub 2010 Nov 19. Blood. 2011. PMID: 21097675 - Separation of Notch1 promoted lineage commitment and expansion/transformation in developing T cells.
Allman D, Karnell FG, Punt JA, Bakkour S, Xu L, Myung P, Koretzky GA, Pui JC, Aster JC, Pear WS. Allman D, et al. J Exp Med. 2001 Jul 2;194(1):99-106. doi: 10.1084/jem.194.1.99. J Exp Med. 2001. PMID: 11435476 Free PMC article. - A novel role for HEB downstream or parallel to the pre-TCR signaling pathway during alpha beta thymopoiesis.
Barndt R, Dai MF, Zhuang Y. Barndt R, et al. J Immunol. 1999 Sep 15;163(6):3331-43. J Immunol. 1999. PMID: 10477603 - Notch1 and T-cell development: insights from conditional knockout mice.
MacDonald HR, Wilson A, Radtke F. MacDonald HR, et al. Trends Immunol. 2001 Mar;22(3):155-60. doi: 10.1016/s1471-4906(00)01828-7. Trends Immunol. 2001. PMID: 11286731 Review. - On the brink of becoming a T cell.
Borowski C, Martin C, Gounari F, Haughn L, Aifantis I, Grassi F, von Boehmer H. Borowski C, et al. Curr Opin Immunol. 2002 Apr;14(2):200-6. doi: 10.1016/s0952-7915(02)00322-9. Curr Opin Immunol. 2002. PMID: 11869893 Review.
Cited by
- GATA-3 deficiency abrogates the development and maintenance of T helper type 2 cells.
Pai SY, Truitt ML, Ho IC. Pai SY, et al. Proc Natl Acad Sci U S A. 2004 Feb 17;101(7):1993-8. doi: 10.1073/pnas.0308697100. Epub 2004 Feb 9. Proc Natl Acad Sci U S A. 2004. PMID: 14769923 Free PMC article. - E proteins and the regulation of early lymphocyte development.
de Pooter RF, Kee BL. de Pooter RF, et al. Immunol Rev. 2010 Nov;238(1):93-109. doi: 10.1111/j.1600-065X.2010.00957.x. Immunol Rev. 2010. PMID: 20969587 Free PMC article. Review. - Essential role of survivin, an inhibitor of apoptosis protein, in T cell development, maturation, and homeostasis.
Xing Z, Conway EM, Kang C, Winoto A. Xing Z, et al. J Exp Med. 2004 Jan 5;199(1):69-80. doi: 10.1084/jem.20031588. Epub 2003 Dec 29. J Exp Med. 2004. PMID: 14699085 Free PMC article. - The essential role of LAT in thymocyte development during transition from the double-positive to single-positive stage.
Shen S, Zhu M, Lau J, Chuck M, Zhang W. Shen S, et al. J Immunol. 2009 May 1;182(9):5596-604. doi: 10.4049/jimmunol.0803170. J Immunol. 2009. PMID: 19380807 Free PMC article. - Notch signaling in hematopoietic cell transplantation and T cell alloimmunity.
Ebens CL, Maillard I. Ebens CL, et al. Blood Rev. 2013 Nov;27(6):269-77. doi: 10.1016/j.blre.2013.08.001. Epub 2013 Aug 31. Blood Rev. 2013. PMID: 24050990 Free PMC article. Review.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Molecular Biology Databases
Miscellaneous