Submitted February 13, 2008
Accepted July 19, 2008
Cell signaling directing the formation and function of hemogenic endothelium during murine embryogenesis
Lauren C. Goldie, Jennifer L. Lucitti, Mary E. Dickinson, and Karen K. Hirschi*
Center for Cell and Gene Therapy, Baylor College of Medicine, Houston, TX, United States
Dept. Molecular Physiology and Biophysics, Baylor College of Medicine, Houston, TX, United States
Dept. Medicine, Baylor College of Medicine, Houston, TX, United States
ARDS Children's Nutrition Research Center, Houston, TX, United States
* Corresponding author; email: khirschi{at}bcm.tmc.edu.
During developmental hematopoiesis, multi-lineage hematopoietic progenitors are thought to derive from a subset of vascular endothelium. Herein, we define the phenotype of such hemogenic endothelial cells and demonstrate, on a clonal level, that they exhibit multi-lineage hematopoietic potential. Furthermore, we have begun to define the molecular signals that regulate their development. We found that the formation of yolk sac hemogenic endothelium and its hematopoietic potential were significantly impaired in the absence of RA signaling, and could be restored in RA-deficient (Raldh2-/-) embryos by provision of exogenous RA in utero. Thus, we identify a novel, critical role for retinoic acid (RA) signaling in the development of hemogenic endothelium that contributes to definitive hematopoiesis.
