Glycogen synthase kinase-3 regulation of chromatin segregation and cytokinesis in mouse preimplantation embryos
dc.contributor.author | Acevedo, Nicole | en_US |
dc.contributor.author | Wang, Xia | en_US |
dc.contributor.author | Dunn, Rodney L. | en_US |
dc.contributor.author | Smith, Gary D. | en_US |
dc.date.accessioned | 2007-09-20T18:00:54Z | |
dc.date.available | 2008-04-03T18:46:39Z | en_US |
dc.date.issued | 2007-02 | en_US |
dc.identifier.citation | Acevedo, Nicole; Wang, Xia; Dunn, Rodney L.; Smith, Gary D. (2007). "Glycogen synthase kinase-3 regulation of chromatin segregation and cytokinesis in mouse preimplantation embryos." Molecular Reproduction and Development 74(2): 178-188. <http://hdl.handle.net/2027.42/55901> | en_US |
dc.identifier.issn | 1040-452X | en_US |
dc.identifier.issn | 1098-2795 | en_US |
dc.identifier.uri | https://hdl.handle.net/2027.42/55901 | |
dc.identifier.uri | http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=retrieve&db=pubmed&list_uids=16941690&dopt=citation | en_US |
dc.description.abstract | Glycogen synthase kinase-3 (GSK-3) is a highly conserved serine/threonine protein kinase implicated in diverse cellular processes. Activity of GSK-3 is essential for meiotic chromatin segregation in oocytes, yet expression and/or function of GSK-3 have not been reported in mammalian preimplantation embryos. Objectives of this study were to characterize GSK-3 protein expression/phosphorylation in mouse preimplantation embryos, to assess the effect of GSK-3 activity inhibition on early mitotic events, and to differentiate nuclear and cytoplasmic anomalies in GSK-3 inhibited embryos. Both GSK-3 isoforms were expressed during embryo development, with a differential expression of Α versus Β. Phosphorylation of GSK-3Α/Β at residues Y279/Y216 indicated constitutive activation throughout preimplantation development. Phosphorylation at N-terminal residues S21/S9 indicated inhibition of GSK-3Α/Β activity that was differentially regulated during early development; both Α and Β isoforms were phosphorylated during early divisions, whereas at the blastocyst stage, only Β was phosphorylated. Cytoplasmic microinjection of zygotes with anti-GSK-3Α/Β antibody significantly compromised embryonic development past the two-cell stage compared to controls. Reversibility of developmental block was tested via pharmacological inhibitors of GSK-3, lithium chloride (LiCl) and alsterpaullone. Similar to immunoneutralization, significantly fewer zygotes cultured with either LiCl or alsterpaullone developed past the two-cell stage compared to controls and this mitotic block was not reversible. Inhibition of GSK-3 activity significantly compromised timing of pronuclear membrane breakdown and mitosis initiation, nuclear development, and cytokinesis. Inhibition of GSK-3 also resulted in abnormal chromatin segregation, evidenced by incomplete karyokinesis and micronuclei formation. These results suggest that GSK-3 activity is critical for early preimplantation embryonic development. Mol. Reprod. Dev. © 2006 Wiley-Liss, Inc. | en_US |
dc.format.extent | 333234 bytes | |
dc.format.extent | 3118 bytes | |
dc.format.mimetype | application/pdf | |
dc.format.mimetype | text/plain | |
dc.publisher | Wiley Subscription Services, Inc., A Wiley Company | en_US |
dc.subject.other | Life and Medical Sciences | en_US |
dc.subject.other | Cell & Developmental Biology | en_US |
dc.title | Glycogen synthase kinase-3 regulation of chromatin segregation and cytokinesis in mouse preimplantation embryos | en_US |
dc.type | Article | en_US |
dc.rights.robots | IndexNoFollow | en_US |
dc.subject.hlbsecondlevel | Obstetrics and Gynecology | en_US |
dc.subject.hlbsecondlevel | Women's and Gender Studies | en_US |
dc.subject.hlbsecondlevel | Public Health | en_US |
dc.subject.hlbsecondlevel | Kinesiology and Sports | en_US |
dc.subject.hlbtoplevel | Health Sciences | en_US |
dc.subject.hlbtoplevel | Humanities | en_US |
dc.subject.hlbtoplevel | Social Sciences | en_US |
dc.description.peerreviewed | Peer Reviewed | en_US |
dc.contributor.affiliationum | Departments of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, Michigan ; Department of Reproductive Sciences Program, University of Michigan, Ann Arbor, Michigan | en_US |
dc.contributor.affiliationum | Departments of Obstetrics and Gynecology, University of Michigan, Ann Arbor, Michigan ; Department of Reproductive Sciences Program, University of Michigan, Ann Arbor, Michigan | en_US |
dc.contributor.affiliationum | Department of Urology, University of Michigan, Ann Arbor, Michigan | en_US |
dc.contributor.affiliationum | Departments of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, Michigan ; Department of Urology, University of Michigan, Ann Arbor, Michigan ; Departments of Obstetrics and Gynecology, University of Michigan, Ann Arbor, Michigan ; Department of Reproductive Sciences Program, University of Michigan, Ann Arbor, Michigan ; 6428 Medical Sciences I, 1301 E. Catherine St, Ann Arbor, MI 48109-0617. | en_US |
dc.identifier.pmid | 16941690 | en_US |
dc.description.bitstreamurl | http://deepblue.lib.umich.edu/bitstream/2027.42/55901/1/20495_ftp.pdf | en_US |
dc.identifier.doi | http://dx.doi.org/10.1002/mrd.20495 | en_US |
dc.identifier.source | Molecular Reproduction and Development | en_US |
dc.owningcollname | Interdisciplinary and Peer-Reviewed |
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