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Publication : Casein kinase 1 alpha regulates chromosome congression and separation during mouse oocyte meiotic maturation and early embryo development.

First Author  Wang L Year  2013
Journal  PLoS One Volume  8
Issue  5 Pages  e63173
PubMed ID  23690993 Mgi Jnum  J:202172
Mgi Id  MGI:5517620 Doi  10.1371/journal.pone.0063173
Citation  Wang L, et al. (2013) Casein kinase 1 alpha regulates chromosome congression and separation during mouse oocyte meiotic maturation and early embryo development. PLoS One 8(5):e63173
abstractText  Casein kinase I alpha (CK1alpha) is a member of serine/threonine protein kinase, generally present in all eukaryotes. In mammals, CK1alpha regulates the transition from interphase to metaphase in mitosis. However, little is known about its role in meiosis. Here we examined Ck1alpha mRNA and protein expression, as well as its subcellular localization in mouse oocytes from germinal vesicle to the late 1-cell stage. Our results showed that the expression level of CK1alpha was increased in metaphase. Immunostaining results showed that CK1alpha colocalized with condensed chromosomes during oocyte meiotic maturation and early embryo development. We used the loss-of-function approach by employing CK1alpha specific morpholino injection to block the function of CK1alpha. This functional blocking leads to failure of polar body 1 (PB1) extrusion, chromosome misalignment and MII plate incrassation. We further found that D4476, a specific and efficient CK1 inhibitor, decreased the rate of PB1 extrusion. Moreover, D4476 resulted in giant polar body extrusion, oocyte pro-MI arrest, chromosome congression failure and impairment of embryo developmental potential. In addition, we employed pyrvinium pamoate (PP), an allosteric activator of CK1alpha, to enhance CK1alpha activity in oocytes. Supplementation of PP induced oocyte meiotic maturation failure, severe congression abnormalities and misalignment of chromosomes. Taken together, our study for the first time demonstrates that CK1alpha is required for chromosome alignment and segregation during oocyte meiotic maturation and early embryo development.
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