[
International Worm Meeting,
2015]
As women age, they experience both a decline in fertility and an increased risk of miscarriage and birth defects. In addition to purely genetic contributions, reproductive aging is thought to be regulated by the complex interactions of genetic signaling pathways and environmental conditions. However, the molecular mechanisms integrating environmental and genetic signals to regulate reproductive aging remain unknown. Caenorhabditis elegans experience their diet of bacteria as a source of both metabolic and sensory input. We took advantage of this relationship as a convenient method of introducing environmental variation by raising C. elegans on different bacterial diets to investigate the effect of environment on reproductive aging. We found that C. elegans exposed to different bacterial environments show significant differences in the duration of their reproductive span. To further dissect the molecular mechanisms underlying these reproductive span differences we chose to focus on two strains of Escherichia coli (OP50 and HB101) that gave drastically different effects on C. elegans reproduction. We found that worms raised on OP50 reproduce longer and maintain their fertility later than worms raised on HB101. This effect is mediated by a pair of olfactory neurons which perceive a volatile odorant signal from the HB101 E.coli. The presence or absence of this environmental cue affects germline proliferation and maintenance in C. elegans, ultimately contributing to the timing of reproductive senescence. We have identified a pair of olfactory neurons, the AWB neurons,that are specifically required for this olfaction-mediated reproductive adaptation as well as for chemotaxis of C. elegans to the smell of the HB101 bacterial diet. Optogenetic activation of the AWB neurons confirmed that AWB activation was sufficient to induce reproductive span shortening in the absence of HB101. Finally, we identified neuropeptide release as the mechanism of AWB neurotransmission in response to the HB101 odorant. Together, our results reveal a novel pathway for the regulation of reproductive aging in C. elegans, and suggest the relevance of environment-sensitive signaling mechanisms in regulating the onset and progression of reproductive aging.
[
International Worm Meeting,
2019]
Early embryonic cells are pluripotent, possessing the transient capacity to generate all the cells of an organism. A fundamental question in developmental biology concerns identifying the epigenetic factors that underlie this temporary developmental plasticity, as well as understanding how commitment to a specific cell lineage is achieved and maintained. How embryonic pluripotency is established, and whether development coordinates the restriction of cellular plasticity with the acquisition of cell fate is poorly understood. Recently, we have uncovered an unappreciated developmental regulation of the incorporation of key molecular carriers of epigenetic information, the replication-coupled histone H3 and histone variant, H3.3, during gametogenesis that influence the epigenetic organization in the early embryo, with a lasting effect on pluripotency and lineage commitment. To study the dynamics of endogenous histone genes throughout the C. elegans lineage, I have generated knock-in strains inserting protein-translational tags at the endogenous histone loci, as well as knock-out and point-mutations to study the developmental impact of the loss of tissue-specific histone incorporation. In doing so, I have uncovered a surprising difference in the epigenome established in the germline, and maintained during early embryogenesis, which incorporates low levels of canonical H3 incorporation in favor of the histone variant, H3.3. Furthermore, upon cellular differentiation, I have identified a 400-fold increase in canonical H3 incorporation in the somatic cell lineage. This onset of canonical H3 incorporation in late stage embryos correlates with a window of developmental plasticity which has been characterized in C. elegans embryonic blastomeres (Yuzyuk et al., 2009). Furthermore, as cells differentiate in late embryonic stages, transcriptionally silent heterochromatin begins to appear, this accumulation also correlates with a loss of both pluripotency and capacity to be reprogramed to alternative cell fates (Mutlu et al., 2018). I propose that global canonical H3 incorporation is developmentally programmed to restrict plasticity during embryogenesis, restricting cell fate choices.