Studying the emerging contributions of long non-coding RNAs as drivers of early embryogenesis.

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The first week of mammalian life involves a succession of key events that include the formation of a developmentally competent oocyte, fertilization, embryonic genome activation and initiation of cell lineage differentiation. This developmental time frame is also of financial significance since most assisted reproductive technologies, such as in vitro embryo production, are applied within it. To date, very little is known about the mechanisms driving embryogenesis. My research program will significantly contribute by studying a new population of transcribed elements that was recently discovered. Transcriptomic surveys of bovine oocytes and early embryos indicate that these cells harbor a large contingent of novel transcripts, many of them being long non-coding RNAs. It was also shown that this RNA population is profoundly influenced by environmental stresses. Their contribution to embryogenesis is still mostly unknown. It is hypothesized that they play a pivotal role during embryogenesis and are important factors in gene expression regulation and cellular differentiation. The objectives are to further characterize these novel transcripts by sorting them according to their genomic location and known functional features. Whether any of them are actually novel protein encoding transcripts will be determined. Their abundance in other tissues and during early embryo development will be measured. Functional assessments will be conducted by determining the cellular localization of candidates as well as the physiological impacts of their depletion from the cells. To assess whether they play a role in gene expression, their expression will be paralleled with the state of DNA methylation and abundance of other transcripts. These efforts will develop Canadian leadership in the field studying the making of a mammalian early embryo but also provide a stepping stone to the emerging field linking living conditions such as maternal nutrition and reproductive performances. It will also generate important knowledge relevant to many key sectors dealing with differentiating cells such as cancer, stem cells and regenerative research.