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Blood, 1 December 2007, Vol. 110, No. 12, pp. 3853-3861. Prepublished online as a Blood First Edition Paper on August 16, 2007; DOI 10.1182/blood-2007-03-079582. This Article Full Text Full Text (PDF) All Versions of this Article: blood-2007-03-079582v1 110/12/3853    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 Yang, L. Articles by Zheng, Y. Search for Related Content PubMed PubMed Citation Articles by Yang, L. Articles by Zheng, Y. Related Collections Hematopoiesis and Stem Cells Cell Adhesion and Motility Cytoskeleton Signal Transduction Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  HEMATOPOIESIS Cdc42 critically regulates the balance between myelopoiesis and erythropoiesis Linda Yang1,2, Lei Wang1,3, Theodosia A. Kalfa1, Jose A. Cancelas1, Xun Shang1, Suvarnamala Pushkaran1, Jun Mo2, David A. Williams1, and Yi Zheng1,3 Divisions of1 Experimental Hematology and 2 Pathology, Children's Hospital Medical Center, Cincinnati; and 3 Molecular Developmental Biology Graduate Program, University of Cincinnati, OH The Rho GTPase Cdc42 regulates adhesion, migration, and homing, as well as cell cycle progression, of hematopoietic stem cells, but its role in multilineage blood development remains unclear. We report here that inducible deletion of cdc42 in cdc42-floxed mouse bone marrow by the interferon-responsive, Mx1-Cre–mediated excision led to myeloid and erythroid developmental defects. Cdc42 deletion affected the number of early myeloid progenitors while suppressing erythroid differentiation. Cdc42-deficient mice developed a fatal myeloproliferative disorder manifested by significant leukocytosis with neutrophilia, myeloid hyperproliferation, and myeloid cell infiltration into distal organs. Concurrently, Cdc42 deficiency caused anemia and splenomegaly accompanied with decreased bone marrow erythroid burst-forming units (BFU-Es) and colony-forming units-erythroid (CFU-Es) activities and reduced immature erythroid progenitors, suggesting that Cdc42 deficiency causes a block in the early stage of erythropoiesis. Cdc42 activity is responsive to stimulation by SCF, IL3, SDF-1, and fibronectin. The increased myelopoiesis and decreased erythropoiesis of the knockout mice are associated with an altered gene transcription program in hematopoietic progenitors, including up-regulation of promyeloid genes such as PU.1, C/EBP1, and Gfi-1 in the common myeloid progenitors and granulocyte-macrophage progenitors and down-regulation of proerythroid gene such as GATA-2 in the megakaryocyte-erythroid progenitors. Thus, Cdc42 is an essential regulator of the balance between myelopoiesis and erythropoiesis. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: F. Guo, C. S. Velu, H. L. Grimes, and Y. Zheng Rho GTPase Cdc42 is essential for B-lymphocyte development and activation Blood, October 1, 2009; 114(14): 2909 - 2916. [Abstract] [Full Text] [PDF]

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