The Journal of Experimental Medicine
StemCell Technologies
  Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents
Published online 8 May 2006 doi:10.1084/jem.20060268
Rockefeller University Press, 0022-1007 $8.00
JEM, Volume 203, Number 5, 1329-1342
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow PPT slides of all figures
Right arrow Alert me when this article is cited
Right arrow Citation Map
Services
Right arrow Email this article
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new content in the JEM
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via CrossRef
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Ikawa, T.
Right arrow Articles by Murre, C.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Ikawa, T.
Right arrow Articles by Murre, C.
Social Bookmarking
Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati  
What's this?

ARTICLE

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

Tomokatsu Ikawa1, Hiroshi Kawamoto2, Ananda W. Goldrath1, and Cornelis Murre1

1 Division of Biological Sciences, University of California, San Diego, La Jolla, CA 92093
2 Laboratory for Lymphocyte Development, Riken Research Center for Allergy and Immunology, Yokohama, Kanagawa 230-0045, Japan

CORRESPONDENCE Cornelis Muree: murre{at}biomail.ucsd.edu

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.

Abbreviations used: 4-OHT, 4-hydroxytamoxifen; ARP, acidic ribosomal protein; bHLH, basic HLH; ChIP, chromatin immunoprecipitation; CLP, common lymphoid progenitor cells; CHX, cycloheximide; DL1, delta-like 1; DN, double negative; DP, double positive; HLH, helix loop helix; HPC, hematopoietic progenitor cell; HSC, hematopoietic stem cell; MAP, mitogen-activated protein.


Add to CiteULike CiteULike   Add to Complore Complore   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Reddit Reddit   Add to Technorati Technorati    What's this?


This article has been cited by other articles:



  Home | Help | Feedback | Subscriptions | Archive | Search
TABLE OF CONTENTS