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.
| 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 |
| De Vries, Wilhelmine N; Evsikov, Alexei V; Haac, Bryce E et al. (2004) Maternal beta-catenin and E-cadherin in mouse development. Development 131:4435-45 |
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