title: Spindle formation in the mouse embryo requires Plk4 in the absence of centrioles.
abstract: During the first five rounds of cell division in the mouse embryo, spindles assemble in the absence of centrioles. Spindle formation initiates around chromosomes, but the microtubule nucleating process remains unclear. Here we demonstrate that Plk4, a protein kinase known as a master regulator of centriole formation, is also essential for spindle assembly in the absence of centrioles. Depletion of maternal Plk4 prevents nucleation and growth of microtubules and results in monopolar spindle formation. This leads to cytokinesis failure and, consequently, developmental arrest. We show that Plk4 function depends on its kinase activity and its partner protein, Cep152. Moreover, tethering Cep152 to cellular membranes sequesters Plk4 and is sufficient to trigger spindle assembly from ectopic membranous sites. Thus, the Plk4-Cep152 complex has an unexpected role in promoting microtubule nucleation in the vicinity of chromosomes to mediate bipolar spindle formation in the absence of centrioles.
authors.affiliation: Cancer Research UK Cell Cycle Genetics Group, Department of Genetics, University of Cambridge, Cambridge CB2 3EH, UK; Pluripotency and Differentiation in Early Mouse Development Group, Gurdon Institute and Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge CB2 1QN, UK.
authors.forename: Paula A
authors.initials: PA
authors.lastname: Coelho
authors.affiliation: Cancer Research UK Cell Cycle Genetics Group, Department of Genetics, University of Cambridge, Cambridge CB2 3EH, UK; Pluripotency and Differentiation in Early Mouse Development Group, Gurdon Institute and Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge CB2 1QN, UK.
authors.forename: Leah
authors.initials: L
authors.lastname: Bury
authors.affiliation: Cancer Research UK Cell Cycle Genetics Group, Department of Genetics, University of Cambridge, Cambridge CB2 3EH, UK; Pluripotency and Differentiation in Early Mouse Development Group, Gurdon Institute and Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge CB2 1QN, UK.
authors.forename: Bedra
authors.initials: B
authors.lastname: Sharif
authors.affiliation: Department of Evolutionary Biology, University of Siena, Via A. Moro 41-53100, Siena, Italy.
authors.forename: Maria G
authors.initials: MG
authors.lastname: Riparbelli
authors.affiliation: Cancer Research UK Cell Cycle Genetics Group, Department of Genetics, University of Cambridge, Cambridge CB2 3EH, UK.
authors.forename: Jingyan
authors.initials: J
authors.lastname: Fu
authors.affiliation: Department of Evolutionary Biology, University of Siena, Via A. Moro 41-53100, Siena, Italy.
authors.forename: Giuliano
authors.initials: G
authors.lastname: Callaini
authors.affiliation: Cancer Research UK Cell Cycle Genetics Group, Department of Genetics, University of Cambridge, Cambridge CB2 3EH, UK. Electronic address: dmg25@mole.bio.cam.ac.uk.
authors.forename: David M
authors.initials: DM
authors.lastname: Glover
authors.affiliation: Pluripotency and Differentiation in Early Mouse Development Group, Gurdon Institute and Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge CB2 1QN, UK. Electronic address: mz205@cam.ac.uk.
authors.forename: Magdalena
authors.initials: M
authors.lastname: Zernicka-Goetz
mesh_terms: D000818:Animals; D018797:Cell Cycle Proteins / Q000378:metabolism; D002455:Cell Division / Q000502:physiology; D002502:Centrioles / Q000378:metabolism*; D005260:Female; D005333:Fetus / Q000166:cytology; D008297:Male; D008540:Meiosis / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D008870:Microtubules / Q000378:metabolism*; D008938:Mitosis / Q000502:physiology; D011247:Pregnancy; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D008941:Spindle Apparatus / Q000378:metabolism*
chemical_list: D018797:Cell Cycle Proteins; D012333:RNA, Messenger; C088051:Plk4 protein, mouse; D017346:Protein Serine-Threonine Kinases