title: Casein kinase 1 alpha regulates chromosome congression and separation during mouse oocyte meiotic maturation and early embryo development.
abstract: Casein kinase I alpha (CK1α) is a member of serine/threonine protein kinase, generally present in all eukaryotes. In mammals, CK1α regulates the transition from interphase to metaphase in mitosis. However, little is known about its role in meiosis. Here we examined Ck1α 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 CK1α was increased in metaphase. Immunostaining results showed that CK1α colocalized with condensed chromosomes during oocyte meiotic maturation and early embryo development. We used the loss-of-function approach by employing CK1α specific morpholino injection to block the function of CK1α. 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 CK1α, to enhance CK1α 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 CK1α is required for chromosome alignment and segregation during oocyte meiotic maturation and early embryo development.
authors.affiliation: The Key Laboratory of National Education Ministry for Mammalian Reproductive Biology and Biotechnology, Inner Mongolia University, Hohhot, Inner Mongolia, People's Republic of China.
authors.forename: Lu
authors.initials: L
authors.lastname: Wang
authors.forename: Angeleem
authors.initials: A
authors.lastname: Lu
authors.forename: Hong-Xia
authors.initials: HX
authors.lastname: Zhou
authors.forename: Ran
authors.initials: R
authors.lastname: Sun
authors.forename: Jie
authors.initials: J
authors.lastname: Zhao
authors.forename: Cheng-Jie
authors.initials: CJ
authors.lastname: Zhou
authors.forename: Jiang-Peng
authors.initials: JP
authors.lastname: Shen
authors.forename: Sha-Na
authors.initials: SN
authors.lastname: Wu
authors.forename: Cheng-Guang
authors.initials: CG
authors.lastname: Liang
mesh_terms: D000494:Allosteric Regulation; D000818:Animals; D001549:Benzamides / Q000494:pharmacology; D015153:Blotting, Western; D048128:Casein Kinase Ialpha / Q000037:antagonists & inhibitors / Q000378:metabolism*; D020090:Chromosome Segregation; D047108:Embryonic Development; D005260:Female; D005455:Fluorescent Antibody Technique; D007093:Imidazoles / Q000494:pharmacology; D008540:Meiosis; D051379:Mice; D009865:Oocytes / Q000166:cytology*; D011774:Pyrvinium Compounds / Q000494:pharmacology; D060888:Real-Time Polymerase Chain Reaction
chemical_list: C493177:4-(4-(2,3-dihydrobenzo(1,4)dioxin-6-yl)-5-pyridin-2-yl-1H-imidazol-2-yl)benzamide; D001549:Benzamides; D007093:Imidazoles; D011774:Pyrvinium Compounds; C024631:pyrvinium; D048128:Casein Kinase Ialpha