Molecular Biology of the Oocyte

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Maternal Effect Genes: Transcription that terminates during meiotic maturation of mouse eggs, resumes only after robust activation of the embryonic genome of the two-cell embryo. This interregnum between oocyte and embryonic gene transcription dictates a role for stored maternal factors in early mammalian development. Encoded by maternal effect genes, these components accumulate during oogenesis and provide pathways essential for fertilization, activation of the embryonic genome and cleavage stage embryogenesis. Using mouse transgenesis, the role of individual or complexes of maternal factors is investigated in these processes. Fertilization: The taxon-specificity of sperm-egg recognition in mammals that results in fertilization is mediated primarily by the zona pellucida, an extracellular matrix surrounding ovulated eggs. Although a simple structure of 3-4 glycoproteins, the molecular basis of this sperm binding to the zona pellucida has been controversial. Current studies investigate: 1) the molecular biology of the formation of the extracellular zona pellucida; 2) molecular requirements of the zona pellucida matrix to support taxon-specific sperm-egg recognition; 3) mechanism that result in acrosome exocytosis necessary for gamete fusion; and 4) the processes by which post-fertilization polyspermy is prevented. Early Development: Activation of the embryonic genome in mice begins late in the one-cell zygote and is fully underway by the two-cell cleavage stage. Initial cell lineages that presage the inner cell mass and extra-embryonic trophectoderm are established when eight blastomeres compact to form polarized morulae in pre-implantation mouse development. The role of maternal effect genes in these processes in mammals constitute a rapidly evolving area of inquiry. Current studies investigate: 1) novel maternal effect genes that affect early mouse development; 2) components of a recently described maternally encoded subcortical complex; and 3) mechanisms by which the loss of the complex affects cleavage stage embryogenesis.