Biology subjects

Baugh, L. R.

Publications and source records attributed to Baugh, L. R..

4 recordsLinked to original sources

bioRxiv2018

Dauer diapause has transgenerational effects on starvation survival and gene expression plasticity

Phenotypic plasticity is facilitated by epigenetic regulation, and remnants of such regulation may persist after plasticity-inducing cues are gone. However, the relationship between plasticity and transgenerational epigenetic memory is not understood. Dauer diapause in Caenorhabditis elegans provides an opportunity to determine how a plastic response to the early-life environment affects traits later in life and in subsequent generations. We report that after extended diapause, post-dauer worms initially exhibit reduced reproductive success and greater inter-individual variation. In contrast, F3 progeny of post-dauers display increased starvation resistance and lifespan, revealing potentially adaptive transgenerational effects. Transgenerational effects are dependent on the duration of diapause, indicating an effect of extended starvation. In agreement, RNA-seq demonstrates a transgenerational effect on nutrient-responsive genes. Further, post-dauer F3 progeny exhibit reduced gene expression plasticity, suggesting a trade-off between plasticity and epigenetic memory. This work reveals complex effects of nutrient stress over different time scales in an animal that evolved to thrive in feast and famine.

evolutionary biology↗

bioRxiv2018

Intergenerational effects of dietary restriction on insulin/IGF signaling and reproductive development

The roundworm C. elegans transiently arrests larval development to survive extended starvation (1), but such early-life starvation reduces reproductive success (2, 3). Maternal dietary restriction (DR) buffers progeny from starvation, increasing reproductive success (4). It is unknown why early-life starvation decreases reproductive success and how maternal diet modifies this process. We show here that extended starvation in first-stage (L1) larvae followed by unrestricted feeding results in a variety of abnormalities in the reproductive system, including glp-1/Notch-sensitive germ-cell tumors and uterine masses that express neuronal and epidermal markers. We found that maternal DR reduces the penetrance of starvation-induced abnormalities, including tumors. Furthermore, we show that maternal DR reduces insulin/IGF signaling (IIS) in progeny, and that daf-16/FoxO and skn-1/Nrf, transcriptional effectors of IIS, are required in progeny for maternal DR to suppress abnormalities. daf-16/FoxO activity in somatic tissues is sufficient to suppress starvation-induced abnormalities, suggesting cell-nonautonomous regulation of reproductive system development. This work reveals complex inter- and intra-generational effects of nutrient availability mediated by IIS with consequences on developmental integrity and reproductive success.\n\nOne Sentence SummaryIntergenerational effects of diet on IIS

developmental biology↗

bioRxiv2018

Pervasive positive and negative feedback regulation of insulin like signaling in Caenorhabditis elegans

The C. elegans insulin-like signaling network supports homeostasis and developmental plasticity. The genome encodes 40 insulin-like peptides and one receptor. Feedback regulation has been reported, but the extent of feedback and its effect on signaling dynamics during a state transition has not been determined. We measured mRNA expression for each insulin-like peptide, the receptor daf-2, components of the PI3K pathway, and its transcriptional effectors daf-16/FoxO and skn-1/Nrf at high temporal resolution during transition from a starved, quiescent state to a fed, growing state in wild type and mutants affecting daf-2/InsR and daf-16/FoxO. We also analyzed the effect of temperature on insulin-like gene expression. We found that numerous PI3K pathway components and insulin-like peptides are affected by signaling activity, revealing pervasive positive and negative feedback regulation. Reporter gene analysis demonstrated that the daf-2/InsR agonist daf-28 positively regulates its own expression and that other agonists cross-regulate daf-28 transcription through feedback. Our results show that feedback regulation of insulin-like signaling is widespread, suggesting a critical role of feedback in signaling dynamics in this endocrine network and likely others.

genetics↗

bioRxiv2018

Perception of environmental polypeptides in C. elegans activates insulin/IGF signaling and alters lipid metabolism

Food perception affects animal physiology in complex ways. We uncoupled the effects of food perception and ingestion in the roundworm C. elegans. Perception was not sufficient to promote development, but larvae exposed to food without ingestion failed to develop upon return to normal culture conditions. Inhibition of gene expression during perception rescued subsequent development, demonstrating the response to perception without feeding is deleterious. Perception altered DAF-16/FOXO localization, reflecting activation of insulin/IGF signaling (IIS). The insulin-like peptide daf-28 was specifically required, suggesting perception in chemosensory neurons directly regulates peptide secretion. Gene expression and Nile Red staining suggest that perception alters lipid metabolism. Environmental polypeptides are sensed by starved larvae and promote dauer diapause recovery. We conclude that polypeptides are perceived as a food-associated cue, initiating a signaling and gene regulatory cascade that alters metabolism in anticipation of feeding and development, but that this response is detrimental if feeding does not occur.

developmental biology↗