To Grow or Not to Grow: Nutritional Control of Development DuringCaenorhabditis elegansL1 Arrest

Abstract

It is widely appreciated that larvae of the nematode Caenorhabditis elegans arrest development by forming dauer larvae in response to multiple unfavorable environmental conditions. C. elegans larvae can also reversibly arrest development earlier, during the first larval stage (L1), in response to starvation. "L1 arrest" (also known as "L1 diapause") occurs without morphological modification but is accompanied by increased stress resistance. Caloric restriction and periodic fasting can extend adult lifespan, and developmental models are critical to understanding how the animal is buffered from fluctuations in nutrient availability, impacting lifespan. L1 arrest provides an opportunity to study nutritional control of development. Given its relevance to aging, diabetes, obesity and cancer, interest in L1 arrest is increasing, and signaling pathways and gene regulatory mechanisms controlling arrest and recovery have been characterized. Insulin-like signaling is a critical regulator, and it is modified by and acts through microRNAs. DAF-18/PTEN, AMP-activated kinase and fatty acid biosynthesis are also involved. The nervous system, epidermis, and intestine contribute systemically to regulation of arrest, but cell-autonomous signaling likely contributes to regulation in the germline. A relatively small number of genes affecting starvation survival during L1 arrest are known, and many of them also affect adult lifespan, reflecting a common genetic basis ripe for exploration. mRNA expression is well characterized during arrest, recovery, and normal L1 development, providing a metazoan model for nutritional control of gene expression. In particular, post-recruitment regulation of RNA polymerase II is under nutritional control, potentially contributing to a rapid and coordinated response to feeding. The phenomenology of L1 arrest will be reviewed, as well as regulation of developmental arrest and starvation survival by various signaling pathways and gene regulatory mechanisms.

A size threshold governsCaenorhabditis elegansdevelopmental progression

“…Consistent with this, interfering with the oscillatory expression of certain heterochronic genes uncouples moult timing from completion of stage-specific development, causing major growth abnormalities [9,10]. Moreover, in the absence of food, L1 larvae can completely arrest development and survive for weeks without moulting or any other morphological changes [11]; L2 worms can also undergo a transition to a quiescent dauer form [12]. Despite the strong dependence of C. elegans growth and development on nutrition, we lack a mechanistic understanding of the cues that trigger moulting and developmental progression.…”

RNA Polymerase II transcription elongation and Pol II CTD Ser2 phosphorylation

“…Under these conditions, Baugh and colleagues identified an accumulation of Pol II at the 5′ end of a substantial fraction of genes 160 (for a review of larval starvation arrest see ref. 161). Most recently, two studies have confirmed that some of these genes with 5′ Pol II accumulation do indeed harbor paused Pol II.…”

Reversible developmental stasis in response to nutrient availability in theXenopus laevisCNS

“…Insects enter diapause when food supplies are low, with the most well studied being the fruit fly, Drosophila melanogaster, which undergoes a specific developmental starvation response. When faced with food scarcity, the nematode Caenorhabditis elegans undergoes a developmental arrest at the L1 larval stage and can remain in this arrested state for up to 10 days until food becomes available (Baugh, 2013;Johnson et al, 1984). Each of these responses to nutrient scarcity is coupled with decreased metabolism and long periods of inactivity in mature organisms.…”