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Blood, 15 October 2008, Vol. 112, No. 8, pp. 3164-3174. Prepublished online as a Blood First Edition Paper on August 6, 2008; DOI 10.1182/blood-2008-03-144956. This Article Full Text Full Text (PDF) Supplemental Methods, Figures, and Videos All Versions of this Article: blood-2008-03-144956v1 112/8/3164    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 Lordier, L. Articles by Chang, Y. Search for Related Content PubMed PubMed Citation Articles by Lordier, L. Articles by Chang, Y. Related Collections Hematopoiesis and Stem Cells Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  HEMATOPOIESIS AND STEM CELLS Megakaryocyte endomitosis is a failure of late cytokinesis related to defects in the contractile ring and Rho/Rock signaling Larissa Lordier13, Abdelali Jalil3, Fréderic Aurade14, Fréderic Larbret1,3, Jerôme Larghero5, Najet Debili13, William Vainchenker13, and Yunhua Chang13 1 Inserm, U790, Villejuif; 2 Université Paris XI, Villejuif; 3 Institut Gustave Roussy, IFR54, Villejuif; 4 Centre National de la Recherche Scientifique (CNRS), UPMC University Paris 06, Unité Mixte de Recherche (UMRS) 787, Paris; and 5 Inserm, EMI00-03, Laboratoire de Biologie Cellulaire Hématopoïétique, Hôpital Saint-Louis, Paris, France Megakaryocyte (MK) is the naturally polyploid cell that gives rise to platelets. Polyploidization occurs by endomitosis, which was a process considered to be an incomplete mitosis aborted in anaphase. Here, we used time-lapse confocal video microscopy to visualize the endomitotic process of primary human megakaryocytes. Our results show that the switch from mitosis to endomitosis corresponds to a late failure of cytokinesis accompanied by a backward movement of the 2 daughter cells. No abnormality was observed in the central spindle of endomitotic MKs. A furrow formation was present, but the contractile ring was abnormal because accumulation of nonmuscle myosin IIA was lacking. In addition, a defect in cell elongation was observed in dipolar endomitotic MKs during telophase. RhoA and F-actin were partially concentrated at the site of furrowing. Inhibition of the Rho/Rock pathway caused the disappearance of F-actin at midzone and increased MK ploidy level. This inhibition was associated with a more pronounced defect in furrow formation as well as in spindle elongation. Our results suggest that the late failure of cytokinesis responsible for the endomitotic process is related to a partial defect in the Rho/Rock pathway activation. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: L. Gilles, D. Bluteau, S. Boukour, Y. Chang, Y. Zhang, T. Robert, P. Dessen, N. Debili, O. A. Bernard, W. Vainchenker, et al. MAL/SRF complex is involved in platelet formation and megakaryocyte migration by regulating MYL9 (MLC2) and MMP9 Blood, November 5, 2009; 114(19): 4221 - 4232. [Abstract] [Full Text] [PDF] K. Ravid Megakaryocytes survive without survivin Blood, July 2, 2009; 114(1): 4 - 4. [Abstract] [Full Text] [PDF] Q. Wen, C. Leung, Z. Huang, S. Small, A. L. Reddi, J. D. Licht, and J. D. Crispino Survivin is not required for the endomitotic cell cycle of megakaryocytes Blood, July 2, 2009; 114(1): 153 - 156. [Abstract] [Full Text] [PDF] E.-c. Cheng, Q. Luo, E. M. Bruscia, M. J. Renda, J. A. Troy, S. A. Massaro, D. Tuck, V. Schulz, S. M. Mane, N. Berliner, et al. Role for MKL1 in megakaryocytic maturation Blood, March 19, 2009; 113(12): 2826 - 2834. [Abstract] [Full Text] [PDF]

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