title: Megakaryocyte endomitosis is a failure of late cytokinesis related to defects in the contractile ring and Rho/Rock signaling.
abstract: 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.
authors.affiliation: Inserm, U790, Villejuif, France.
authors.forename: Larissa
authors.initials: L
authors.lastname: Lordier
authors.forename: Abdelali
authors.initials: A
authors.lastname: Jalil
authors.forename: Fréderic
authors.initials: F
authors.lastname: Aurade
authors.forename: Fréderic
authors.initials: F
authors.lastname: Larbret
authors.forename: Jerôme
authors.initials: J
authors.lastname: Larghero
authors.forename: Najet
authors.initials: N
authors.lastname: Debili
authors.forename: William
authors.initials: W
authors.lastname: Vainchenker
authors.forename: Yunhua
authors.initials: Y
authors.lastname: Chang
mesh_terms: D000199:Actins / Q000378:metabolism; D018952:Antigens, CD34 / Q000096:biosynthesis; D002469:Cell Separation; D048749:Cytokinesis; D006801:Humans; D016086:Lentivirus / Q000378:metabolism; D008533:Megakaryocytes / Q000166:cytology*; D018613:Microscopy, Confocal; D018715:Microscopy, Video; D008938:Mitosis; D011003:Ploidies; D015398:Signal Transduction; D013692:Telophase; D054460:rho-Associated Kinases / Q000378:metabolism*
chemical_list: D000199:Actins; D018952:Antigens, CD34; D054460:rho-Associated Kinases