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Publication : E proteins and Notch signaling cooperate to promote T cell lineage specification and commitment.

First Author  Ikawa T Year  2006
Journal  J Exp Med Volume  203
Issue  5 Pages  1329-42
PubMed ID  16682500 Mgi Jnum  J:124090
Mgi Id  MGI:3720511 Doi  10.1084/jem.20060268
Citation  Ikawa T, et al. (2006) E proteins and Notch signaling cooperate to promote T cell lineage specification and commitment. J Exp Med 203(5):1329-42
abstractText  The helix-loop-helix protein, E47, is essential for both B- and T-lineage development. Here we demonstrate that in vitro E47 and Notch signaling act in concert to promote T cell development from fetal hematopoietic progenitors and to restrain development into the natural killer and myeloid cell lineages. The expression of an ensemble of genes associated with Notch signaling is activated by E47, and additionally, Notch signaling and E47 act in parallel pathways to induce a T lineage-specific program of gene expression. Enforced expression of the intracellular domain of Notch rescues the developmental arrest at the T cell commitment stage in E2A-deficient fetal thymocytes. Finally, we demonstrate that regulation of Hes1 expression by Notch signaling and E47 is strikingly similar to that observed during Drosophila melanogaster sensory development. Based on these observations, we propose that in developing fetal thymocytes E47 acts to induce the expression of an ensemble of genes involved in Notch signaling, and that subsequently E47 acts in parallel with Notch signaling to promote T-lineage maturation.
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