Gonadogenesis: Female germ cells arrested at the prophase of the first meiotic division form follicles in which they are surrounded by somatic cells in the neonatal ovary. These follicles grow and asymmetrical cell division during meiosis ensures that ovulated eggs contain maternal factors necessary for successful development. Post-natal male germ cells maintain a spermatogonia stem cell niche within the testis from which cohorts are selected to undergo meiosis and are transmogrified into mature spermatozoa during spermiogenesis. Current studies investigate the roles of: 1) FIGLA, a germ cell specific transcription factor required for follicle formation in female mice; 2) SSNP1, a germ cell nuclear protein required for maintenance of spermatogonia stem cells; and 3) BTBD18, a nuclear protein that ensures pachytene piRNA expression necessary for spermiogenesis. Fertilization: The taxon-specificity of sperm-egg recognition in mammals that results in monospermic 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) molecular requirements to support taxon-specific sperm-egg recognition on the surface of the zona pellucida; 2) mechanism that result in acrosome exocytosis necessary for gamete fusion; and 3) the processes by which post-fertilization polyspermy is prevented. Early Development: 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. Using mouse transgenesis, the role of individual or complexes of maternal factors is studied in these processes. Current research investigates: 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 degradation of maternal components in activation of the embryonic genome.

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Support Year
11
Fiscal Year
2017
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Indirect Cost
Name
U.S. National Inst Diabetes/Digst/Kidney
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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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