HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 2008-0133v1 26/9/2237    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints/Permissions Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Coles, E. G. Articles by Bronner-Fraser, M. Search for Related Content PubMed PubMed Citation Articles by Coles, E. G. Articles by Bronner-Fraser, M.

EMBRYONIC STEM CELLS/INDUCED PLURIPOTENT STEM CELLS

EWS-FLI1 Causes Neuroepithelial Defects and Abrogates Emigration of Neural Crest Stem Cells

^aDivision of Biology, California Institute of Technology, Pasadena, California, USA;
^bDepartment of Pediatrics and Pathology, Keck School of Medicine, USC, Childrens Hospital Los Angeles, Los Angeles, California, USA

Key Words. Neural crest stem cell • Ewing's sarcoma • EWS-FLI1 • Chick embryo

Correspondence: Correspondence: Marianne Bronner-Fraser, Ph.D., Division of Biology M/C 139-74, California Institute of Technology, Pasadena, California 91125, USA. Telephone: 626-395-3355; Fax: 626-395-7717; e-mail: mbronner{at}caltech.edu

Received on February 12, 2008; accepted for publication on June 2, 2008.

First published online in STEM CELLS EXPRESS  June 12, 2008.

The most frequently occurring chromosomal translocation that gives rise to the Ewing's sarcoma family of tumors (ESFT) is the chimeric fusion gene EWS-FLI1 that encodes an oncogenic protein composed of the N terminus of EWS and the C terminus of FLI1. Although the genetic basis of ESFT is fairly well understood, its putative cellular origin remains to be determined. Previous work has proposed that neural crest progenitor cells may be the causative cell type responsible for ESFT. However, surprisingly little is known about the expression pattern or role of either wild-type EWS or wild-type FLI1 in this cell population during early embryonic development. Using the developing chick embryo as a model system, we identified EWS expression in emigrating and migratory neural crest stem cells, whereas FLI1 transcripts were found to be absent in these populations and were restricted to developing endothelial cells. By ectopically expressing EWS-FLI1 or wild-type FLI1 in the developing embryo, we have been able to study the cellular transformations that ensue in the context of an in vivo model system. Our results reveal that misexpression of the chimeric EWS-FLI1 fusion gene, or wild-type FLI1, in the developing neural crest stem cell population leads to significant aberrations in neural crest development. An intriguing possibility is that misexpression of the EWS-FLI1 oncogene in neural crest-derived stem cells may be an initiating event in ESFT genesis.

Disclosure of potential conflicts of interest is found at the end of this article.