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Spindle Formation in the Mouse Embryo Requires Plk4 in the Absence of Centrioles

Coelho, Paula A. and Bury, Leah and Sharif, Bedra and Riparbelli, Maria G. and Fu, Jingyan and Callaini, Giuliano and Glover, David M. and Zernicka-Goetz, Magdalena (2013) Spindle Formation in the Mouse Embryo Requires Plk4 in the Absence of Centrioles. Developmental Cell, 27 (5). pp. 586-597. ISSN 1534-5807. PMCID PMC3898710. doi:10.1016/j.devcel.2013.09.029. https://resolver.caltech.edu/CaltechAUTHORS:20190405-170316524

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[img] PDF (Document S1. Figures S1–S4 and Table S1) - Supplemental Material
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[img] Video (MPEG) (Movie S1. Plk4 Associates with Acentriolar MTOCs of the Early Mouse Embryo, Related to Figure 1) - Supplemental Material
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[img] Video (MPEG) (Movie S2. Plk4 Depletion Results in Monopolar Spindle Formation in the Early Mouse Embryo, Related to Figure 2. Time-lapse imaging of 2- to 4-cell stage transition.) - Supplemental Material
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[img] Video (MPEG) (Movie S3. Plk4 Depletion Dramatically Reduces Kinetics of Microtubule Regrowth, Related to Figure 3) - Supplemental Material
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[img] Video (MPEG) (Movie S4. Expression of Kinase-Defective Plk4 Results in Monopolar Spindle Formation in the Early Mouse Embryo, Related to Figure 4) - Supplemental Material
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[img] Video (MPEG) (Movie S5. Constitutively Active or Degron Mutants of Plk4 Do Not Affect Spindle Formation in the Early Mouse Embryo, Related to Figure 4) - Supplemental Material
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[img] Video (MPEG) (Movie S6. Depletion of Cep152 Results in Monopolar Spindle Formation in the Early Mouse Embryo, Related to Figure 5) - Supplemental Material
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[img] Video (MPEG) (Movie S7. Membrane-Targeted Cep152 Directs Active, but Not Inactive, Plk4 to This Ectopic Site to Rescue Double Depletion of Endogenous Plk4 and Cep152, Related to Figure 6) - Supplemental Material
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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.


Item Type:Article
Related URLs:
URLURL TypeDescription
https://doi.org/10.1016/j.devcel.2013.09.029DOIArticle
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3898710/PubMed CentralArticle
ORCID:
AuthorORCID
Coelho, Paula A.0000-0003-0614-7575
Bury, Leah0000-0002-6218-2837
Glover, David M.0000-0003-0956-0103
Zernicka-Goetz, Magdalena0000-0002-7004-2471
Additional Information:© 2013 The Authors. Published by Elsevier. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Received 12 June 2013, Revised 7 August 2013, Accepted 30 September 2013, Available online 21 November 2013. P.A.C. and J.F. are supported by a Program Grant from Cancer Research UK to D.M.G. L.B. is the recipient of a Cancer Research UK research studentship from Cambridge Cancer Centre. We thank the Wellcome Trust for Senior Research Fellowship and Programme support to M.Z.-G. We are grateful to Ingrid Hoffmann, Paolo D’Avino, and Luisa Capalbo for constructs and Tamara Advedissian, Tharshana Stephen, and Natalie Caterwood for valuable assistance.
Funders:
Funding AgencyGrant Number
Cancer Research UKUNSPECIFIED
Wellcome TrustUNSPECIFIED
Issue or Number:5
PubMed Central ID:PMC3898710
DOI:10.1016/j.devcel.2013.09.029
Record Number:CaltechAUTHORS:20190405-170316524
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20190405-170316524
Official Citation:Paula A. Coelho, Leah Bury, Bedra Sharif, Maria G. Riparbelli, Jingyan Fu, Giuliano Callaini, David M. Glover, Magdalena Zernicka-Goetz, Spindle Formation in the Mouse Embryo Requires Plk4 in the Absence of Centrioles, Developmental Cell, Volume 27, Issue 5, 2013, Pages 586-597, ISSN 1534-5807, https://doi.org/10.1016/j.devcel.2013.09.029. (http://www.sciencedirect.com/science/article/pii/S1534580713005777)
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:94552
Collection:CaltechAUTHORS
Deposited By: George Porter
Deposited On:11 Apr 2019 19:54
Last Modified:16 Nov 2021 17:05

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