title: Polarized Cdc42 activation promotes polar body protrusion and asymmetric division in mouse oocytes.
abstract: Asymmetric meiotic divisions in mammalian oocytes rely on the eccentric positioning of the spindle and the remodeling of the overlying cortex, resulting in the formation of small polar bodies. The mechanism of this cortical polarization, exemplified by the formation of a thick F-actin cap, is poorly understood. Cdc42 is a major player in cell polarization in many systems; however, the spatio-temporal dynamics of Cdc42 activation during oocyte meiosis, and its contribution to mammalian oocyte polarization, have remained elusive. In this study, we investigated Cdc42 activation (Cdc42-GTP), dynamics and role during mouse oocyte meiotic divisions. We show that Cdc42-GTP accumulates in restricted cortical regions overlying meiotic chromosomes or chromatids, in a Ran-GTP-dependent manner. This polarized activation of Cdc42 is required for the recruitment of N-WASP and the formation of F-actin-rich protrusions during polar body formation. Cdc42 inhibition in MII oocytes resulted in the release of N-WASP into the cytosol, a loss of the polarized F-actin cap, and a failure to protrude the second polar body. Cdc42 inhibition also resulted in central spindle defects in activated MII oocytes. In contrast, emission of the first polar body during oocyte maturation could occur in the absence of a functional Cdc42/N-WASP pathway. Therefore, Cdc42 is a new protagonist in chromatin-induced cortical polarization in mammalian oocytes, with an essential role in meiosis II completion, through the recruitment and activation of N-WASP, downstream of the chromatin-centered Ran-GTP gradient.
authors: CNRS, UMR 6290, Institut de Génétique et Développement de Rennes, F-35043 Rennes, France.
authors: Benoit
authors: B
authors: Dehapiot
authors: Virginie
authors: V
authors: Carrière
authors: John
authors: J
authors: Carroll
authors: Guillaume
authors: G
authors: Halet
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D060049:Asymmetric Cell Division; D033481:Chromosomes, Mammalian / Q000378:metabolism; D048749:Cytokinesis; D004789:Enzyme Activation; D005260:Female; D006160:Guanosine Triphosphate / Q000378:metabolism; D008540:Meiosis; D051379:Mice; D009865:Oocytes / Q000166:cytology* / Q000201:enzymology*; D059705:Polar Bodies / Q000166:cytology*; D021381:Protein Transport; D015398:Signal Transduction; D008941:Spindle Apparatus / Q000378:metabolism; D051316:Wiskott-Aldrich Syndrome Protein / Q000378:metabolism; D020764:cdc42 GTP-Binding Protein / Q000037:antagonists & inhibitors / Q000378:metabolism*; D020931:ran GTP-Binding Protein / Q000378:metabolism
chemical_list: D000199:Actins; C581598:Cdc42 protein, mouse; D051316:Wiskott-Aldrich Syndrome Protein; D006160:Guanosine Triphosphate; D020764:cdc42 GTP-Binding Protein; D020931:ran GTP-Binding Protein
references: Dev Cell. 2008 Sep;15(3):386-400
references: 18804436
references: Dev Cell. 2007 Feb;12(2):309-17
references: 17276347
references: Cell. 1999 Apr 16;97(2):221-31
references: 10219243
references: Nature. 2004 Apr 15;428(6984):767-71
references: 15085137
references: Mol Biol Cell. 1998 Sep;9(9):2509-25
references: 9725909
references: EMBO J. 1994 Dec 1;13(23):5732-44
references: 7988569
references: Curr Biol. 2011 Jun 7;21(11):955-60
references: 21620703
references: PLoS One. 2009 Sep 29;4(9):e7171
references: 19787051
references: Mol Biol Cell. 2010 Sep 15;21(18):3182-92
references: 20660156
references: Science. 2000 Oct 27;290(5492):801-6
references: 11052943
references: Cell. 1996 Mar 8;84(5):723-34
references: 8625410
references: Nat Cell Biol. 2011 Aug 28;13(10):1252-8
references: 21874009
references: Nat Cell Biol. 2011 Oct 03;13(10):1183-5
references: 21968992
references: Curr Biol. 2000 Oct 19;10(20):1303-6
references: 11069114
references: Nat Rev Mol Cell Biol. 2008 Sep;9(9):690-701
references: 18719708
references: Langmuir. 2008 Feb 19;24(4):1451-8
references: 18027975
references: Curr Biol. 2004 Mar 23;14(6):520-5
references: 15043819
references: Nature. 2005 May 19;435(7040):365-9
references: 15902261
references: Curr Biol. 2006 Jun 20;16(12):1249-54
references: 16782018
references: Annu Rev Biochem. 2010;79:707-35
references: 20533885
references: Nat Cell Biol. 2008 Nov;10(11):1301-8
references: 18836438
references: Curr Biol. 2006 Jan 24;16(2):214-20
references: 16431375
references: PLoS One. 2011 Apr 08;6(4):e18392
references: 21494665
references: Development. 2011 Jul;138(14):2903-8
references: 21653611
references: Mol Reprod Dev. 2007 Jun;74(6):785-94
references: 17154294
references: J Cell Biol. 2007 Jan 29;176(3):295-305
references: 17261848
references: Curr Biol. 2008 Dec 23;18(24):1986-92
references: 19062278
references: Dev Biol. 2008 Oct 1;322(1):21-32
references: 18662680
references: J Cell Biol. 2005 Jan 31;168(3):429-39
references: 15684032
references: EMBO Rep. 2008 Mar;9(3):246-51
references: 18311174
references: Curr Biol. 2008 Oct 14;18(19):1514-9
references: 18848445
references: J Embryol Exp Morphol. 1986 Mar;92:11-32
references: 3723057
references: Cell. 2003 Feb 21;112(4):453-65
references: 12600310
references: J Biol Chem. 2000 Nov 24;275(47):36999-7005
references: 10950951
references: Dev Biol. 2005 Apr 1;280(1):38-47
references: 15766746
references: Reproduction. 2006 Jul;132(1):45-57
references: 16816332
references: Immunity. 2001 Aug;15(2):249-59
references: 11520460
references: EMBO J. 1996 Oct 1;15(19):5326-35
references: 8895577
references: J Cell Biol. 2005 Jan 17;168(2):221-32
references: 15642749
references: J Cell Biol. 2000 Sep 18;150(6):1299-310
references: 10995436
references: J Cell Sci. 2002 May 15;115(Pt 10):2139-49
references: 11973355
references: Development. 1992 May;115(1):221-37
references: 1638982
references: Mol Hum Reprod. 2009 Mar;15(3):139-47
references: 19179408
references: Dev Biol. 1985 Feb;107(2):382-94
references: 4038667
references: Dev Cell. 2007 Feb;12(2):301-8
references: 17276346
references: Annu Rev Cell Biol. 1993;9:411-44
references: 8280467