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Prepublished online as a Blood First Edition Paper on June 5, 2003July 17, 2003; DOI 10.1182/blood-2003-02-0634.
Submitted February 28, 2003
Accepted May 26, 2003
The homeoprotein Hex is required for hemangioblast differentiation
Ying Guo, Rebecca Chan, Heather Ramsey, Weimin Li, Xiaodong Xie, William C Shelley, Juan Pedro Martinez-Barbera, Bernardo Bort, Kenneth Zaret, Mervin Yoder, and Robert Hromas*
Medicine and the Walther Oncology Center, Indiana University Cancer Center, Indianapolis, IN, USA
Pediatrics and the Wells Center for Pediatric Research, Indiana University Medical Center, Indianapolis, IN, USA
Cancer Reserch and Treatment Center, University of New Mexico, Albuquerque, NM, USA
Neural Development Unit, Institute of Child Health, London, United Kingdom
Cell and Developmental Biology Program, Fox Chase Cancer Center, Philadelphia, PA, USA
* Corresponding author; email: rhromas{at}salud.unm.edu.
The first hematopoietic and endothelial progenitors are derived from a common embryonic precursor termed the hemangioblast. The genetic cascades that regulate the differentiation of the hemangioblast to hematopoietic and endothelial cells are largely unknown. In general, much of embryonic development is coordinately regulated by temporal and spatial expression of transcription factors, such as the Homeobox (Hox) gene family. We and others isolated a divergent homeobox gene termed Hex (or Prh) that is preferentially expressed in hematopoietic and endothelial cells. Using in vitro Hex -/- embryonic stem (ES) cell differentiation, in vivo yolk sac hematopoietic progenitor assays, and chimeric mouse analysis, we found that Hex is required for differentiation of the hemangioblast to definitive embryonic hematopoietic progenitors and to a lesser extent endothelial cells. Therefore, Hex is a novel regulator of hemangioblast differentiation to hematopoietic and endothelial cells.
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