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

Abstract

After 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.