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Blood, 2 April 2009, Vol. 113, No. 14, pp. 3182-3189. Prepublished online as a Blood First Edition Paper on November 4, 2008; DOI 10.1182/blood-2008-06-164061. This Article Full Text (PDF) Supplemental Figures All Versions of this Article: blood-2008-06-164061v1 113/14/3182    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 Eckly, A. Articles by Leon, C. Search for Related Content PubMed PubMed Citation Articles by Eckly, A. Articles by Leon, C. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted June 23, 2008 Accepted October 28, 2008 Abnormal megakaryocyte morphology and proplatelet formation in mice with megakaryocyte-restricted MYH9 inactivation Anita Eckly, Catherine Strassel, Monique Freund, Jean-Pierre Cazenave, Francois Lanza, Christian Gachet*, and Catherine Leon EFS-Alsace, INSERM UMR-S311, Universite Louis Pasteur, Strasbourg, France * Corresponding author; email: christian.gachet{at}efs-alsace.fr. Mutations in the MYH9 gene encoding non-muscle myosin IIA lead to macrothrombocytopenia as observed in MYH9-related disorders. We used mice with megakaryocyte-restricted MYH9 inactivation to explore the role of myosin in thrombopoiesis. In situ, bone marrow MYH9 megakaryocytes were irregularly shaped, appearing leaky with poorly defined limits. The demarcation membranes were abnormally organized and poorly developed, pointing to an insufficient reservoir for the future formation of platelets. The cytoskeletal-rich peripheral zone was lacking due to the absence of the myosin filament network which normally surrounds the granular zone in wild-type cells. In vitro studies of cultured cells showed that MYH9 megakaryocytes were unable to form stress fibers upon adhesion to collagen, suggesting that the leaky shape results from defects in internal tension and anchorage to the extracellular environment. Surprisingly, the proportion of cells extending proplatelets was increased in MYH9 megakaryocytes and the proplatelet buds were larger. Overall, this study provides evidence for a role of myosin in different steps of megakaryocyte development through its participation in the maintenance of cell shape, formation and organization of the demarcation membranes and the peripheral zone, anchorage the extracellular matrix and proplatelet formation. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: C. Strassel, A. Eckly, C. Leon, C. Petitjean, M. Freund, J.-P. Cazenave, C. Gachet, and F. Lanza Intrinsic impaired proplatelet formation and microtubule coil assembly of megakaryocytes in a mouse model of Bernard-Soulier syndrome Haematologica, June 1, 2009; 94(6): 800 - 810. [Abstract] [Full Text] [PDF]

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