|
 |
|
|
| Subject Categories: Signal Transduction | Immunology |
|
| The EMBO Journal
(2007) 26, 3629–3640, doi:10.1038/sj.emboj.7601801 Published online 19 July 2007 |
|
| c-Myb regulates lineage choice in developing thymocytes via its target gene Gata3 |
|
|
| Diane Maurice, Joel Hooper, Georgina Lang and Kathleen Weston |
|
|
Institute of Cancer Research, Cancer Research UK Centre for Cell and Molecular Biology, London, UK To whom correspondence should be addressed Kathleen Weston, Institute of Cancer Research, Cancer Research UK Centre for Cell and Molecular Biology, 237 Fulham Road, London SW3 6JB, UK. Tel.: +44 207 153 5253; Fax: +44 207 352 3299; E-mail: kathy.weston@icr.ac.uk Received 1 December 2006; Accepted 26 June 2007; Published online 19 July 2007. |
|
|
|
| Abstract |
|
| During T-cell development, thymocytes with intermediate avidity for antigen–MHC complexes are positively selected and then differentiate into functional cytotoxic and helper T cells. This process is controlled by signalling from the T-cell receptor (TCR). Here, we show that the c-Myb transcription factor is a critical downstream regulator of positive selection, promoting the development of helper T cells and blocking the development of cytotoxic T cells. A gain-of-function c-Myb transgene stops development of cytotoxic T cells, instead causing accumulation of a precursor population. Conversely, loss of c-Myb in selecting cells results in significantly fewer helper T cells. In c-Myb-null thymocytes, Gata3, a critical inducer of T-helper cell fate, is not upregulated in response to T-cell receptor signaling, following selection. We show that Gata3 is a direct target of c-Myb, and propose that c-Myb is an important regulator of Gata3, required for transduction of the T-cell receptor signal for subsequent helper cell lineage differentiation. |
|
| Keywords: CD4, Gata3, Myb, T cell, transcription |
|
|
|
Top of page MORE ARTICLES LIKE THISThese links to content published by NPG are automatically generated NEWS AND VIEWSSwitching sides: transcriptional control of CD4 thymocyte lineage commitment Nature Immunology News and Views (01 Apr 2005) Immunology Guide for a cell-fate decision Nature News and Views (24 Feb 2005) RESEARCHJournal of Cerebral Blood Flow & Metabolism Original Article Journal of Cerebral Blood Flow & Metabolism Original Article |
|
|
| |
| |
| |
 | Email link to a friend |
| |
 | Download PDF |
| |
 | Full text |
| |
| |
| |
 | Next article |
| |
 | Previous article |
| |
 | Table of contents |
| |
| |
 | Rights and permissions |
| |
 | Reprints |
| |
| |
| |
 Register for table of contents by email | |
| |
| |
| |