MAP Kinase Signaling Involvement in Meiotic Progression and Oocyte Aging

The leading cause for infertility, naturally-occurring miscarriages and congenital defects (e.g. Down syndrome) is failed chromosome segregations during oogenesis. Finding the molecular base for this age related failures requires deciphering the genetic program that facilitates the meiotic cell divisions. High-throughput RNA sequencing allows for the quantification of mRNA dynamics through differentiation processes, but uncovering the genetic plan which underlies the transcriptome trends still pose a considerable challenge. We previously reported our success in producing a full spatial transcriptomic maps of C. elegans oogenesis and spermatogenesis. We uncovered a transcriptomal switch during gametogenesis, such as most genes are expressed during either early or late stages. We found this is partially achieved by silencing the X chromosomes throughout the first half of oogenesis. We hypothesized that the X chromosomes are silenced by a parallel mechanism to X chromosome inactivation in mammalian somatic female cells. Indeed, we identified that the Long Intergenic Non-Coding (LINC) RNA, xcs-1, is required for X chromosome silencing in early oogenesis. A worm strain with CRISPR deletion of xcs-1 have dramatic fertility defects and aberrations in meiotic double strand break repair. Immuno-fluorescence shows that unlike wild type worms, in Dxcs-1 gonads open chromatin markers and activate RNA Pol-II are present on the X chromosomes at early meiotic stages. Transcriptome analysis identified an increase in the level of transcripts from the X chromosome in Dxcs-1. We suggest that the LINC RNA xsc-1 is required for correct chromosome structure to facilitate the oogonial transcription program and enable successful chromosome segregations.