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Clinical and Developmental Immunology
Volume 2012, Article ID 678705, 15 pages
Review Article

HEB in the Spotlight: Transcriptional Regulation of T-Cell Specification, Commitment, and Developmental Plasticity

Sunnybrook Research Institute, University of Toronto, 2075 Bayview Avenue, Toronto, ON, Canada M4N 3M5

Received 16 October 2011; Accepted 12 December 2011

Academic Editor: Alexandre S. Basso

Copyright © 2012 Marsela Braunstein and Michele K. Anderson. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


The development of T cells from multipotent progenitors in the thymus occurs by cascades of interactions between signaling molecules and transcription factors, resulting in the loss of alternative lineage potential and the acquisition of the T-cell functional identity. These processes require Notch signaling and the activity of GATA3, TCF1, Bcl11b, and the E-proteins HEB and E2A. We have shown that HEB factors are required to inhibit the thymic NK cell fate and that HEBAlt allows the passage of T-cell precursors from the DN to DP stage but is insufficient for suppression of the NK cell lineage choice. HEB factors are also required to enforce the death of cells that have not rearranged their TCR genes. The synergistic interactions between Notch1, HEBAlt, HEBCan, GATA3, and TCF1 are presented in a gene network model, and the influence of thymic stromal architecture on lineage choice in the thymus is discussed.