The concept that maternal transcripts govern the physiology of the newly formed embryo is derived from studying non-mammalian organisms with readily accessible oocytes and embryos. The eggs of these organisms usually contain spatially localized proteins and mRNAs, and their embryos become motile and transcriptionally active within hours of fertilization. In contrast, full-grown mammalian oocytes are nonpolar, mammalian embryos do not implant into the uterus until several days after fertilization, and embryonic genome activation occurs a day or more after fertilization. Genomic reprogramming takes place during the oocyte to embryo transition, a process that until now has not been possible to study at a large-scale molecular level in mammals. Our goal is to use the information we derived from the large, representative EST libraries we prepared from mouse oocytes and embryos to explore the mechanisms driving nuclear reprogramming. Timely translation of stored maternal mRNAs provides one mechanism for molecular change in a transcriptionally silent cell. We propose combined computational and molecular approaches to identify cis-elements and their protein partners, which delay translation of maternal mRNAs until oocyte maturation or after fertilization. Retrotransposons may shape and/or inform about the processes that modulate the transcriptional activity of the oocyte and 2-cell embryo. We propose in silico and experimental approaches to explore the effects of retrotransposons on the changing architecture of the embryonic genome.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Project (R01)
Project #
5R01HD037102-10
Application #
7337392
Study Section
Reproductive Biology Study Section (REB)
Program Officer
Tasca, Richard J
Project Start
1999-01-01
Project End
2009-12-31
Budget Start
2008-01-01
Budget End
2009-12-31
Support Year
10
Fiscal Year
2008
Total Cost
$318,002
Indirect Cost
Name
Jackson Laboratory
Department
Type
DUNS #
042140483
City
Bar Harbor
State
ME
Country
United States
Zip Code
04609
Varlakhanova, Natalia V; Cotterman, Rebecca F; deVries, Wilhelmine N et al. (2010) myc maintains embryonic stem cell pluripotency and self-renewal. Differentiation 80:9-19
de Vries, W N; Evsikov, A V; Brogan, L J et al. (2008) Reprogramming and differentiation in mammals: motifs and mechanisms. Cold Spring Harb Symp Quant Biol 73:33-8
Harwood, Benjamin N; Cross, Sophia K; Radford, Emily E et al. (2008) Members of the WNT signaling pathways are widely expressed in mouse ovaries, oocytes, and cleavage stage embryos. Dev Dyn 237:1099-111
Graber, Joel H; Salisbury, Jesse; Hutchins, Lucie N et al. (2007) C. elegans sequences that control trans-splicing and operon pre-mRNA processing. RNA 13:1409-26
Liu, Donglin; Brockman, J Michael; Dass, Brinda et al. (2007) Systematic variation in mRNA 3'-processing signals during mouse spermatogenesis. Nucleic Acids Res 35:234-46
Peaston, A E; Knowles, B B; Hutchison, K W (2007) Genome plasticity in the mouse oocyte and early embryo. Biochem Soc Trans 35:618-22
Evsikov, Alexei V; Graber, Joel H; Brockman, J Michael et al. (2006) Cracking the egg: molecular dynamics and evolutionary aspects of the transition from the fully grown oocyte to embryo. Genes Dev 20:2713-27
Liu, Donglin; Graber, Joel H (2006) Quantitative comparison of EST libraries requires compensation for systematic biases in cDNA generation. BMC Bioinformatics 7:77
Salisbury, Jesse; Hutchison, Keith W; Graber, Joel H (2006) A multispecies comparison of the metazoan 3'-processing downstream elements and the CstF-64 RNA recognition motif. BMC Genomics 7:55
Solter, D; Hiiragi, T; Evsikov, A V et al. (2004) Epigenetic mechanisms in early mammalian development. Cold Spring Harb Symp Quant Biol 69:11-7

Showing the most recent 10 out of 20 publications