Should I stay or should I go? Identification of novel nutritionally regulated developmental checkpoints inC. elegans

Abstract

A fter embryogenesis, developing organisms typically secure their own nutrients to enable further growth. The fitness of an organism depends on developing when food is abundant and slowing or stopping development during periods of scarcity. Although several key pathways that link nutrition with development have been identified, a mechanistic understanding of how these pathways coordinate growth with nutritional conditions is lacking. We took advantage of the stereotyped development and experimental accessibility of C. elegans to study nutritional control of late larval development. We discovered that C. elegans larval development is punctuated by precisely time checkpoints that globally arrest growth when nutritional conditions are unfavorable. Arrest at the checkpoints is regulated by insulin-and insulin-like signaling and steroid hormone signaling. These pathways are conserved in mammals, suggesting that similar mechanisms could regulate growth and development in humans. We highlight several implications of our research, including quiescence of diverse cellular behaviors as an adaptive response to unfavorable growth conditions, the existence of oscillatory checkpoints that coordinate development across tissues, and the connections between systemic and cell-autonomous regulators of nutritional response. Together, our findings describe a fascinating developmental strategy in C. elegans that we expect will not only provide insight into nutritional regulation of development, but also into poorly understood cellular processes such as quiescence and aging.

Plant-parasitic nematodes: towards understanding molecular players in stress responses

“…This finding supports the hypothesis that there are developmental checkpoints in C. elegans in accordance with the model ‘ should I stay/should I go ’ (Murphy and Hu, 2013; Schindler and Sherwood, 2014). A hypothesis would be that the IIS pathway comprising C. elegans DAF-16 orthologues in PPNs takes part in the ‘ go/no-go checkpoints ’ model during nematode parasitism and its exophytic stage (Goverse and Smant, 2014; Schindler and Sherwood, 2014). Therefore, it would be interesting to establish comparisons between the ‘ go/no-go checkpoint ’ model from plant–nematode interactions and the ‘ should I stay or should I go ’ model derived from the IIS established in C. elegans .…”

“…DAF-16 and SKN-1 share these features and can be considered as hub proteins (Schindler and Sherwood, 2014; Webb and Brunet, 2014). Such proteins are often identified as cellular targets by pathogens (Mukhtar et al , 2011; Schleker and Trilling, 2013).…”

“…Similarly, nematode J2s that have not yet entered the root (pre-parasitic plant nematodes) also provide pronounced resistance to oxidative stress, correlating with their degree of virulence (Dubreuil et al , 2011; Vicente et al , 2015; Li et al , 2016). In fact, previous findings have reported the insulin/IGF-1 signalling (IIS) pathway as a mediator between development and stress responses following the model ‘ should I stay or should I go ’ (Schindler and Sherwood, 2014). Specifically, the IIS pathway modulates oxidative stress responses in nematodes at several levels and acts more generally in animals (McElwee et al , 2004; Fielenbach and Antebi, 2008; Kenyon, 2010; Murphy and Hu, 2013).…”

“…DAF-16 and SKN-1 contribute to the orchestration of several adaptive cellular pathways in response to various environmental stimuli (Schindler and Sherwood, 2014; Blackwell et al , 2015). In C. elegans , the effects of aspirin and SA on stress responses have been assessed (Ayyadevara et al , 2013; Wan et al , 2013).…”

Microfluidic platform with spatiotemporally controlled micro-environment for studying long-term C. elegans developmental arrests

“…Using a small, experimentally mapped nervous system, they can sense, integrate and respond to a variety of environmental cues using both short-term behavior and long-term developmental trajectories 3–8 . For example, Jin et.…”