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

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 lin...

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Detalles Bibliográficos
Autores principales: Ikawa, Tomokatsu, Kawamoto, Hiroshi, Goldrath, Ananda W., Murre, Cornelis
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2006
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2121213/
https://www.ncbi.nlm.nih.gov/pubmed/16682500
http://dx.doi.org/10.1084/jem.20060268
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author Ikawa, Tomokatsu
Kawamoto, Hiroshi
Goldrath, Ananda W.
Murre, Cornelis
author_facet Ikawa, Tomokatsu
Kawamoto, Hiroshi
Goldrath, Ananda W.
Murre, Cornelis
author_sort Ikawa, Tomokatsu
collection PubMed
description 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.
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spelling pubmed-21212132007-12-13 E proteins and Notch signaling cooperate to promote T cell lineage specification and commitment Ikawa, Tomokatsu Kawamoto, Hiroshi Goldrath, Ananda W. Murre, Cornelis J Exp Med Articles 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. The Rockefeller University Press 2006-05-15 /pmc/articles/PMC2121213/ /pubmed/16682500 http://dx.doi.org/10.1084/jem.20060268 Text en Copyright © 2006, The Rockefeller University Press This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/4.0/).
spellingShingle Articles
Ikawa, Tomokatsu
Kawamoto, Hiroshi
Goldrath, Ananda W.
Murre, Cornelis
E proteins and Notch signaling cooperate to promote T cell lineage specification and commitment
title E proteins and Notch signaling cooperate to promote T cell lineage specification and commitment
title_full E proteins and Notch signaling cooperate to promote T cell lineage specification and commitment
title_fullStr E proteins and Notch signaling cooperate to promote T cell lineage specification and commitment
title_full_unstemmed E proteins and Notch signaling cooperate to promote T cell lineage specification and commitment
title_short E proteins and Notch signaling cooperate to promote T cell lineage specification and commitment
title_sort e proteins and notch signaling cooperate to promote t cell lineage specification and commitment
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2121213/
https://www.ncbi.nlm.nih.gov/pubmed/16682500
http://dx.doi.org/10.1084/jem.20060268
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