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Blood, 30 July 2009, Vol. 114, No. 5, pp. 995-1004. Prepublished online as a Blood First Edition Paper on May 29, 2009; DOI 10.1182/blood-2009-03-208330. This Article Full Text Full Text (PDF) Supplemental Table and Figures All Versions of this Article: blood-2009-03-208330v1 114/5/995    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 CrossRef Google Scholar Articles by Siggins, S. L. Articles by Curtis, D. J. PubMed PubMed Citation Articles by Siggins, S. L. Articles by Curtis, D. J. Related Collections Hematopoiesis and Stem Cells Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  HEMATOPOIESIS AND STEM CELLS The Hedgehog receptor Patched1 regulates myeloid and lymphoid progenitors by distinct cell-extrinsic mechanisms Sarah L. Siggins1, Nhu-Y N. Nguyen1, Matthew P. McCormack1,2, Sumitha Vasudevan1, Rehan Villani3, Stephen M. Jane1,2, Brandon J. Wainwright3, and David J. Curtis1,2 1 Rotary Bone Marrow Research Laboratories, Royal Melbourne Hospital, Parkville; 2 Department of Medicine, University of Melbourne, Parkville; and 3 Institute for Molecular Bioscience, The University of Queensland, Brisbane, Australia Hedgehog (Hh) ligands bind to the Patched1 (Ptch1) receptor, relieving repression of Smoothened, which leads to activation of the Hh signaling pathway. Using conditional Ptch1 knockout mice, the aim of this study was to determine the effects of activating the Hh signaling pathway in hematopoiesis. Surprisingly, hematopoietic-specific deletion of Ptch1 did not lead to activation of the Hh signaling pathway and, consequently, had no phenotypic effect. In contrast, deletion of Ptch1 in nonhematopoietic cells produced 2 distinct hematopoietic phenotypes. First, activation of Hh signaling in epithelial cells led to apoptosis of lymphoid progenitors associated with markedly elevated levels of circulating thymic stromal lymphopoietin. Second, activation of Hh signaling in the bone marrow cell niche led to increased numbers of lineage-negative c-kit+ Sca-1+ bone marrow cells and mobilization of myeloid progenitors associated with a marked loss of osteoblasts. Thus, deletion of Ptch1 leads to hematopoietic effects by distinct cell-extrinsic mechanisms rather than by direct activation of the Hh signaling pathway in hematopoietic cells. These findings have important implications for therapeutics designed to activate the Hh signaling pathway in hematopoietic cells including hematopoietic stem cells. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

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