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Published December 9, 2013 | Supplemental Material + Published
Journal Article Open

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.

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.

Attached Files

Published - 1-s2.0-S1534580713005777-main.pdf

Supplemental Material - 1-s2.0-S1534580713005777-mmc1.pdf

Supplemental Material - 1-s2.0-S1534580713005777-mmc2.mp4

Supplemental Material - 1-s2.0-S1534580713005777-mmc3.mp4

Supplemental Material - 1-s2.0-S1534580713005777-mmc4.mp4

Supplemental Material - 1-s2.0-S1534580713005777-mmc5.mp4

Supplemental Material - 1-s2.0-S1534580713005777-mmc6.mp4

Supplemental Material - 1-s2.0-S1534580713005777-mmc7.mp4

Supplemental Material - 1-s2.0-S1534580713005777-mmc8.mp4

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Additional details

Created:
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