Folliculogenesis: Ovarian folliculogenesis in mammals is a complex process involving interactions between germ and somatic cells. Carefully orchestrated expression of transcription factors, cell adhesion molecules and growth factors are required for success. We have identified a germ-cell specific, basic helix-loop-helix transcription factor, FIGLA (Factor In the GermLine, Alpha). FIGLA is first detected at embryonic day 13.5 (E13.5) and persists in adult female mice. Initially investigated as an activator of female genes, it also represses male germline genes to prevent inappropriate expression during oogenesis. Current studies have identified potential oocyte-specific targets of FIGLA important for: 1) folliculogenesis;2) fertilization;and 3) pre-implantation development. Fertilization: The specificity of sperm-egg recognition in mammals is mediated primarily by the zona pellucida. However, despite extensive investigation, there is no unifying model for the molecular basis of sperm interactions with the zona matrix that result in mammalian fertilization. Current studies investigate: 1) the molecular biology of the formation of the extracellular zona pellucida;2) the molecular requirements of the zona pellucida matrix to support taxon-specific sperm-egg recognition;and 3) the mechanism 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. In simpler model organisms, there is compelling evidence that persistent gene products from the egg are required for successful embryogenesis. However, in mice such effects have been documented only more recently and constitute a rapidly evolving area of investigation. 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.

Project Start
Project End
Budget Start
Budget End
Support Year
4
Fiscal Year
2010
Total Cost
$1,733,176
Indirect Cost
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State
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Tokuhiro, Keizo; Dean, Jurrien (2018) Glycan-Independent Gamete Recognition Triggers Egg Zinc Sparks and ZP2 Cleavage to Prevent Polyspermy. Dev Cell :
Zhou, Liquan; Baibakov, Boris; Canagarajah, Bertram et al. (2017) Genetic mosaics and time-lapse imaging identify functions of histone H3.3 residues in mouse oocytes and embryos. Development 144:519-528
Shin, Seung-Wook; Vogt, Edgar John; Jimenez-Movilla, Maria et al. (2017) Cytoplasmic cleavage of DPPA3 is required for intracellular trafficking and cleavage-stage development in mice. Nat Commun 8:1643
Xiong, Bo; Zhao, Yangu; Beall, Stephanie et al. (2017) A Unique Egg Cortical Granule Localization Motif Is Required for Ovastacin Sequestration to Prevent Premature ZP2 Cleavage and Ensure Female Fertility in Mice. PLoS Genet 13:e1006580
Zhou, Liquan; Canagarajah, Bertram; Zhao, Yangu et al. (2017) BTBD18 Regulates a Subset of piRNA-Generating Loci through Transcription Elongation in Mice. Dev Cell 40:453-466.e5
Avella, Matteo A; Baibakov, Boris A; Jimenez-Movilla, Maria et al. (2016) ZP2 peptide beads select human sperm in vitro, decoy mouse sperm in vivo, and provide reversible contraception. Sci Transl Med 8:336ra60
Wu, Di; Dean, Jurrien (2016) BTG4, a maternal mRNA cleaner. J Mol Cell Biol 8:369-70
Dean, Jurrien (2016) Exacting Requirements for Development of the Egg. N Engl J Med 374:279-80
Zhou, Li-quan; Dean, Jurrien (2015) Reprogramming the genome to totipotency in mouse embryos. Trends Cell Biol 25:82-91
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

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