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Asymmetric Positioning and Organization of the Meiotic Spindle of Mouse Oocytes Requires CDC42 Function

Na, Jie and Zernicka-Goetz, Magdalena (2006) Asymmetric Positioning and Organization of the Meiotic Spindle of Mouse Oocytes Requires CDC42 Function. Current Biology, 16 (12). pp. 1249-1254. ISSN 0960-9822. https://resolver.caltech.edu/CaltechAUTHORS:20190419-105736846

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[img] Video (QuickTime) (Movie S1.. Mouse GV stage oocytes were injected with tubulin-GFP mRNA and allowed to undergo meiotic maturation) - Supplemental Material
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[img] Video (QuickTime) (Movie S2.. Mouse GV stage oocytes were injected with a mixture of mRNA encoding MycN17CDC42 and tubulin-GFP, respectively, and underwent meiotic maturation) - Supplemental Material
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[img] Video (QuickTime) (Movie S3.. Mouse GV stage oocytes were injected with a mixture of mRNA encoding MycL61CDC42 and tubulin-GFP, respectively, and underwent meiotic maturation) - Supplemental Material
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[img] Video (QuickTime) (Movie S4.. Mouse GV stage oocyte expressing Myc-tagged wtCDC42 and tubulin-GFP does not have long spindle and complete meiosis I successfully) - Supplemental Material
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Abstract

The mature mammalian oocyte is highly polarized because asymmetrical spindle migration to the oocyte cortex ensures extrusion of small polar bodies in the two meiotic divisions, essential for generation of the large egg. Actin filaments, myosin motors, and formin-2, but not microtubules, are required for spindle migration 1, 2, 3. Here, we show that Cdc42, a key regulator of cytoskeleton and cell polarity in other systems 4, 5, 6, 7, 8, 9, 10, is essential for meiotic maturation and oocyte asymmetry. Disrupting CDC42 function by ectopic expression of its GTPase-defective mutants causes both halves of the first meiotic spindle to extend symmetrically toward opposing cortical regions and prevents an asymmetrical division. The elongated spindle has numerous astral-like microtubules, and aPKCζ, normally associated with the spindle poles, is distributed along its length. Dynactin is displaced from kinetochores, consistently homologous chromosomes do not segregate, and polar body extrusion is prevented. Perturbing the function of aPKCζ also causes elongation of the meiotic spindle but still permits spindle migration and polar body extrusion. Thus, at least two pathways appear to be downstream of CDC42: one affecting the actin cytoskeleton and required for migration of the meiotic spindle, and a second affecting the spindle microtubules in which aPKCζ plays a role.


Item Type:Article
Related URLs:
URLURL TypeDescription
https://doi.org/10.1016/j.cub.2006.05.023DOIArticle
ORCID:
AuthorORCID
Zernicka-Goetz, Magdalena0000-0002-7004-2471
Additional Information:© 2006 Elsevier, Under an Elsevier user license. Received 1 February 2006, Revised 3 May 2006, Accepted 3 May 2006, Available online 19 June 2006. We are grateful to the Wellcome Trust for a Senior Research Fellowship to M.Z.-G., which funded this work. J.N. is supported by the Royal Society Relocation Fellowship in 2006. We thank A. Hall for N17CDC42, L61CDC42, and V14Rho constructs; M.H. Verlhac for pRN3-tubulin-GFP cDNA; and I. Macara for HA-Par6A construct. We also thank D. Glover, M. Savoian, J. Pines, A. Sossick, and S. Barton for discussions.
Funders:
Funding AgencyGrant Number
Wellcome TrustUNSPECIFIED
Royal SocietyUNSPECIFIED
Subject Keywords:CELLBIO; DEVBIO
Issue or Number:12
Record Number:CaltechAUTHORS:20190419-105736846
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20190419-105736846
Official Citation:Jie Na, Magdalena Zernicka-Goetz, Asymmetric Positioning and Organization of the Meiotic Spindle of Mouse Oocytes Requires CDC42 Function, Current Biology, Volume 16, Issue 12, 2006, Pages 1249-1254, ISSN 0960-9822, https://doi.org/10.1016/j.cub.2006.05.023. (http://www.sciencedirect.com/science/article/pii/S096098220601606X)
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:94811
Collection:CaltechAUTHORS
Deposited By: George Porter
Deposited On:23 Apr 2019 16:23
Last Modified:03 Oct 2019 21:07

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