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

Tomokatsu Ikawa, Hiroshi Kawamoto, Ananda W. Goldrath, Cornelis Murre

Research output: Contribution to journalArticlepeer-review

146 Citations (Scopus)

Abstract

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 hematopoieitic 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. JEM

Original languageEnglish
Pages (from-to)1329-1342
Number of pages14
JournalJournal of Experimental Medicine
Volume203
Issue number5
DOIs
Publication statusPublished - 15-05-2006
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

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