Casein Kinase 1 Alpha Regulates Chromosome Congression and Separation during Mouse Oocyte Meiotic Maturation and Early Embryo Development

Casein kinase I alpha (CK1 alpha) is a member of serine/threonine protein kinase, generally present in all eukaryotes. In mammals, CK1a regulates the transition from interphase to metaphase in mitosis. However, little is known about its role in meiosis. Here we examined Ck1 alpha 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 CK1 alpha was increased in metaphase. Immunostaining results showed that CK1 alpha colocalized with condensed chromosomes during oocyte meiotic maturation and early embryo development. We used the loss-of-function approach by employing CK1 alpha specific morpholino injection to block the function of CK1 alpha. 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 CK1 alpha, to enhance CK1 alpha 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 CK1 alpha is required for chromosome alignment and segregation during oocyte meiotic maturation and early embryo development.