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 and organelles 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) the role of maternal organelles in the maternal to zygotic transition;and 3) the role of degradation of maternal components in activation of the embryonic genome.

Project Start
Project End
Budget Start
Budget End
Support Year
7
Fiscal Year
2013
Total Cost
$2,424,710
Indirect Cost
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State
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Lin, Ruei-Shiuan; Jimenez-Movilla, Maria; Dean, Jurrien (2014) Figla-Cre transgenic mice expressing myristoylated EGFP in germ cells provide a model for investigating perinatal oocyte dynamics. PLoS One 9:e84477
Avella, Matteo A; Baibakov, Boris; Dean, Jurrien (2014) A single domain of the ZP2 zona pellucida protein mediates gamete recognition in mice and humans. J Cell Biol 205:801-9
Lee, Geun-Shik; He, Yuanzheng; Dougherty, Edward J et al. (2013) Disruption of Ttll5/stamp gene (tubulin tyrosine ligase-like protein 5/SRC-1 and TIF2-associated modulatory protein gene) in male mice causes sperm malformation and infertility. J Biol Chem 288:15167-80
Avella, Matteo A; Xiong, Bo; Dean, Jurrien (2013) The molecular basis of gamete recognition in mice and humans. Mol Hum Reprod 19:279-89
Zheng, Ping; Baibakov, Boris; Wang, Xi-hong et al. (2013) PtdIns(3,4,5)P3 is constitutively synthesized and required for spindle translocation during meiosis in mouse oocytes. J Cell Sci 126:715-21
Zheng, Ping; Dean, Jurrien (2009) Role of Filia, a maternal effect gene, in maintaining euploidy during cleavage-stage mouse embryogenesis. Proc Natl Acad Sci U S A 106:7473-8
Li, Lei; Baibakov, Boris; Dean, Jurrien (2008) A subcortical maternal complex essential for preimplantation mouse embryogenesis. Dev Cell 15:416-25