The Role Of Casein Kinase1Alpha On Mouse Oocyte Meiotic Maturation And Early Embryo Development

Casein kinase1alpha (CK1α) is a member of the serine/threonine protein kinase family and is generally considered ubiquitous among eukaryotes. In mammals, CK1α regulates the transition from interphase to metaphase in mitosis, but less is known about its role in meiosis. Here, we examined CK1α mRNA and protein expression, as well as subcellular localization of the protein in mouse oocytes from germinal vesicle to late1-cell stage. The expression level of CKla increased in metaphase. Immunostaining results showed that CK1α colocalized with condensed chromosome during oocyte meiotic maturation and early embryonic development. We used a loss-of-function approach, knockdown by injection of CK1α-specific morpholinos, to block CK1α function. This functional blocking led to failure of extrusion of the first polar body (PB1), chromosome misalignment, and MII plate thickening. We further found that D4476, a specific and efficient CK1inhibitor, decreased the rate of PB1extrusion. Moreover, D4476treatment resulted in extrusion of giant polar bodies, arrest of oocytes in prometaphase I, failure of chromosome congression, and impairment of embryo developmental potential. We also employed pyrvinium pamoate (PP), an allosteric activator of CK1α, to enhance CK1α activity in oocytes. Supplementation with PP induced oocyte meiotic maturation failure and severe over-congression and misalignment of chromosomes. Taken together, our data demonstrate, for the first time, that CK1α is required for chromosome alignment and segregation during oocyte meiotic maturation and early embryo development.