Abstract
Recent studies have indicated that the insulin-signaling pathway controls body and organ size in Drosophila, and most metazoans, by signaling nutritional conditions to the growing organs. The temporal requirements for insulin signaling during development are, however, unknown. Using a temperature-sensitive insulin receptor (Inr) mutation in Drosophila, we show that the developmental requirements for Inr activity are organ specific and vary in time. Early in development, before larvae reach the “critical size” (the size at which they commit to metamorphosis and can complete development without further feeding), Inr activity influences total development time but not final body and organ size. After critical size, Inr activity no longer affects total development time but does influence final body and organ size. Final body size is affected by Inr activity from critical size until pupariation, whereas final organ size is sensitive to Inr activity from critical size until early pupal development. In addition, different organs show different sensitivities to changes in Inr activity for different periods of development, implicating the insulin pathway in the control of organ allometry. The reduction in Inr activity is accompanied by a two-fold increase in free-sugar levels, similar to the effect of reduced insulin signaling in mammals. Finally, we find that varying the magnitude of Inr activity has different effects on cell size and cell number in the fly wing, providing a potential linkage between the mode of action of insulin signaling and the distinct downstream controls of cell size and number. We present a model that incorporates the effects of the insulin-signaling pathway into the Drosophila life cycle. We hypothesize that the insulin-signaling pathway controls such diverse effects as total developmental time, total body size and organ size through its effects on the rate of cell growth, and proliferation in different organs.
Highlights
Development in multicellular animals is a process that involves both tight control and flexibility in the regulation of cell size and cell number
During a study of the interaction of environmental factors and the insulin-signaling pathway, we discovered that flies trans-heteroallelic for insulin receptor mutations Inr E19 and Inr GC25 show a temperature-sensitive suppression of the insulin pathway
We measured the timing of critical size in Inr E19/Inr GC25 flies reared at 17 8C under our experimental conditions and found that it is attained at approximately day 9, coinciding with the time at which Inr activity switches from affecting developmental time to body size
Summary
Development in multicellular animals is a process that involves both tight control and flexibility in the regulation of cell size and cell number. Flies carrying mutations of the insulin receptor (Inr) and mice carrying mutations of the IGF1 receptor show delayed development and growth deficiency with a reduction in body and organ size [3,4,5,6]. These and similar ‘‘knock out’’ experiments have demonstrated the gross effects of the insulin-signaling pathway on adult phenotype. Final body and organ size are affected by changes in insulin signaling only if those changes occur late in development, once a larva has passed critical size. We find that the genitals show a limited response to suppression of insulin signaling in Inr E19/ Inr GC25 flies, implicating insulin signaling in the control of allometries
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
