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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 (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 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. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted March 14, 2008 Accepted July 12, 2008 Megakaryocyte endomitosis is a failure of late cytokinesis related to defects in the contractile ring and Rho/Rock signaling Larissa Lordier, Abdelali Jalil, Frederic Aurade, Frederic Larbret, Jerome Larghero, Najet Debili, William Vainchenker*, and Yunhua Chang Unit 790, Institut National de la Sante et de la Recherche Medicale, Villejuif, France IFR54, Institut National de la Sante et de la Recherche Medicale, Villejuif, France UMRS 787, UPMC University Paris 06, Centre National de la Recherche Scientifique, Paris, France EMI00-03, Institut National de la Sante et de la Recherche Medicale, Paris, France Universite Paris XI, Villejuif, France * Corresponding author; email: verpre{at}igr.fr. Megakaryocyte is the naturally polyploid cell that gives rise to platelets. Polyploidization occurs by endomitosis, which was a process considered as 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 two daughter cells. No abnormality was observed in the central spindle of endomitotic MKs. A furrow formation was present, but the contractile ring was abnormal since accumulation of non muscle 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 disappearing 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 of 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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