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Blood, 1 April 2008, Vol. 111, No. 7, pp. 3313-3321. Prepublished online as a Blood First Edition Paper on December 14, 2007; DOI 10.1182/blood-2007-08-110114. This Article Full Text Full Text (PDF) Supplemental Figures All Versions of this Article: blood-2007-08-110114v1 111/7/3313    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Ghiaur, G. Articles by Williams, D. A. Search for Related Content PubMed PubMed Citation Articles by Ghiaur, G. Articles by Williams, D. A. Related Collections Hematopoiesis and Stem Cells Plenary Papers Cytoskeleton Free Research Articles Related Articles in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  PLENARY PAPER Rac1 is essential for intraembryonic hematopoiesis and for the initial seeding of fetal liver with definitive hematopoietic progenitor cells Gabriel Ghiaur1, Michael J. Ferkowicz2, Michael D. Milsom1, Jeff Bailey1, David Witte3, Jose A. Cancelas1,4, Mervin C. Yoder2, and David A. Williams1 1 Division of Experimental Hematology, Department of Pediatrics, Cincinnati Children's Research Foundation and Cincinnati Children's Hospital Medical Center, OH; 2 Herman B Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis; 3 Division of Pathology, Department of Pediatrics, Cincinnati Children's Research Foundation and Cincinnati Children's Hospital Medical Center, OH; and 4 Hoxworth Blood Center, University of Cincinnati College of Medicine, OH Definitive hematopoietic stem and progenitor cells (HSCs/Ps) originating from the yolk sac and/or para-aorta-splanchno-pleura/aorta-gonad-mesonephros are hypothesized to colonize the fetal liver, but mechanisms involved are poorly defined. The Rac subfamily of Rho GTPases has been shown to play essential roles in HSC/P localization to the bone marrow following transplantation. Here, we study the role of Rac1 in HSC/P migration during ontogeny and seeding of fetal liver. Using a triple-transgenic approach, we have deleted Rac1 in HSCs/Ps during very early embryonic development. Without Rac1, there was a decrease in circulating HSCs/Ps in the blood of embryonic day (E) 10.5 embryos, while yolk sac definitive hematopoiesis was quantitatively normal. Intraembryonic hematopoiesis was significantly impaired in Rac1-deficient embryos, culminating with absence of intra-aortic clusters and fetal liver hematopoiesis. At E10.5, Rac1-deficient HSCs/Ps displayed decreased transwell migration and impaired inter-action with the microenvironment in migration-dependent assays. These data suggest that Rac1 plays an important role in HSC/P migration during embryonic development and is essential for the emergence of intraembryonic hematopoiesis. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Articles in Blood Online: AGM: maternity ward or finishing school? Donald Metcalf Blood 2008 111: 3305-3306. [Full Text] [PDF] The wanderings of hematopoietic stem cells Margaret H. Baron Blood 2008 111: 3307-3308. [Full Text] [PDF] This article has been cited by other articles: E. Yi Ni Lam, J. Y. M. Chau, M. L. Kalev-Zylinska, T. M. Fountaine, R. S. Mead, C. J. Hall, P. S. Crosier, K. E. Crosier, and M. Vega Flores Zebrafish runx1 promoter-EGFP transgenics mark discrete sites of definitive blood progenitors Blood, February 5, 2009; 113(6): 1241 - 1249. [Abstract] [Full Text] [PDF] E. Dzierzak and A. Medvinsky The discovery of a source of adult hematopoietic cells in the embryo Development, July 15, 2008; 135(14): 2343 - 2346. [Abstract] [Full Text] [PDF]

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