Glycogen synthase kinase-3 regulation of chromatin segregation and cytokinesis in mouse preimplantation embryos
Acevedo, Nicole; Wang, Xia; Dunn, Rodney L.; Smith, Gary D.
2007-02
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>
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.Publisher
Wiley Subscription Services, Inc., A Wiley Company
ISSN
1040-452X 1098-2795
Other DOIs
PMID
16941690
Types
Article
URI
http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=retrieve&db=pubmed&list_uids=16941690&dopt=citationMetadata
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