Mammalian female germ cells must successfully complete developmental programs to initiate folliculogenesis that lead to mature gametes capable of fertilization and the transfer of genetic material to the next generation. At birth, the ovary contains a full complement of germ cells, each surrounded by a single layer of granulosa cells which together form the primordial follicle. We have identified a basic helix-loop-helix transcription factor, FIGLA (Factor In the GermLine, alpha), that plays a central role in oocyte-specific gene expression. Using microarrays and SAGE, we have identified potential downstream targets of FIGLA and are investigating their effects on folliculogenesis, fertilization and early development. ? ? During oocyte growth, FIGLA activates the single-copy genes encoding ZP1, ZP2 and ZP3 that form a zona pellucida surrounding ovulated eggs. Using mouse genetics we have established mouse lines in which endogenous mouse genes are replaced with human homologues or mutant forms of mouse zona proteins. Based on our investigations, we propose a ?zona scaffold? model for sperm-egg recognition in which the cleavage status of ZP2 determines whether the zona matrix is permissive (ZP2 intact) or non-permissive (ZP2 cleaved), independent of fertilization and cortical granule exocytosis. We further propose that the subsequent induction of sperm acrosome exocytosis is induced by mechanosensory signaling transmitted during sperm penetration of the zona pellucida. Taken together, these observations prompt re-evaluation of current model of mouse fertilization. ? ? FIGLA also regulates oocyte-specific maternal effect genes that are critical for normal embryogenesis. During oocyte growth, FIGLA activates Mater (Maternal antigen that embryos require), a single copy gene that encodes a cytoplasmic protein that is required for embryonic progression beyond the two-cells. We have identified a binding partner, FILIA, that co-localizes with MATER in the cortical regions of the mature egg and pre-implantation embryos. Genetically altered mice, lacking FILIA and MATER are being evaluated to determine the mechanisms by which they affect mouse embryogenesis.
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