Filia, a Maternal Effect Gene that Regulates Cleavage Embryogenesis in Mice.

Abstract

During oogenesis, mammalian eggs accumulate and store proteins required for early embryonic development. Mater (Maternal Antigen that Embryos Require) is a maternal effect gene and mouse embryos derived from Mater tm/tm eggs arrest at the two-cell stage. Recently, FILIA has been described as a binding partner that co-localizes with MATER in the subcortex of ovulated eggs and persists until the early blastocyst. Filia tm/tm mouse line that lack the cognate protein has been established and female, but not male mice, have reduced fertility. Although equivalent numbers of two-cell embryos are recovered from normal and Filia tm/tm female mice, impaired progression of cleavage stage development results in a 50% decrease in fecundity in the mutant embryos. Defects observed in mitotic entry and spindle assembly correlate with abnormalities of aurora kinase A and polo-like kinase 1 (PLK1), two kinases known to regulate mitosis and spindle assembly. These data suggested that FILIA is encoded by a maternal effect gene and regulates cell cycle progression of early cleavage embryos through modulations of aurora A and PLK1.