Polo-like kinase 1 is essential for the first mitotic division in the mouse embryo

• Published in: Molecular reproduction and development Vol. 80; no. 7; pp. 522 - 534
• Main Authors: Baran, V., Solc, P., Kovarikova, V., Rehak, P., Sutovsky, P.
• Format: Journal Article
• Language: English
• Published: United States Blackwell Publishing Ltd 01.07.2013; Wiley Subscription Services, Inc
• Subjects: Animals; Blastocyst - metabolism; Blastocyst - physiology; Blotting, Western; Cell Cycle Proteins - antagonists & inhibitors; Cell Cycle Proteins - metabolism; Female; Fluorescent Antibody Technique; Gene Expression Regulation, Developmental - genetics; Gene Expression Regulation, Developmental - physiology; Male; Mice; Microtubule-Organizing Center - metabolism; Mitosis - physiology; Polo-Like Kinase 1; Protein Serine-Threonine Kinases - antagonists & inhibitors; Protein Serine-Threonine Kinases - metabolism; Proto-Oncogene Proteins - antagonists & inhibitors; Proto-Oncogene Proteins - metabolism; Pteridines - pharmacology; Spindle Apparatus - drug effects; Spindle Apparatus - physiology; Time-Lapse Imaging
• ISSN: 1040-452X; 1098-2795
• DOI: 10.1002/mrd.22188

SUMMARY Polo‐like kinase 1 (PLK1), a member of the serine/threonine protein kinases family, is involved in multiple steps of mitotic progression. It regulates centrosome maturation, mitotic spindle formation, and cytokinesis. While studied extensively in somatic cells, little is known about PLK1 activities in the mammalian preimplantation embryo. We examined the role of PLK1 in the one‐cell mouse embryo. Western blotting showed that the PLK1 protein content increased significantly during the S‐phase of the one‐cell stage and declined during the first mitotic division. Activation of PLK1 preceded nuclear envelope breakdown (NEBD) in both pronuclei at the entry to first embryo mitosis. Immunofluorescence revealed the presence of phosphorylated, active PLK1 (pThr210‐PLK1) in both male and female pronuclei, and in the microtubule‐organizing centers (MTOCs) shortly before NEBD. During the first mitotic metaphase, pThr210‐PLK1 accumulated at the spindle poles and was also associated with condensed chromosomes. Inhibition of PLK1 activity with a specific PLK1 inhibitor, BI 2536, at the one‐cell stage induced the formation of a bipolar spindle that displayed disordered microtubular arrangements and dislocated, condensed chromosomes. Although such embryos entered mitosis, they did not complete mitosis and arrested at metaphase. Time‐lapse recording revealed progressive misalignment of condensed chromosomes during first mitotic metaphase. These data indicate that PLK1 activity is not essential for entry into first mitosis, but is required for the events leading up to metaphase‐anaphase transition in the one‐cell mouse embryo. Mol. Reprod. Dev. 80: ?–?, 2013. © 2013 Wiley Periodicals, Inc.