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.

Project Start
Project End
Budget Start
Budget End
Support Year
6
Fiscal Year
2012
Total Cost
$2,190,423
Indirect Cost
City
State
Country
Zip Code
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
Dean, Jurrien (2016) Exacting Requirements for Development of the Egg. N Engl J Med 374:279-80
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
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

Showing the most recent 10 out of 26 publications