Integrating Body and Organ Size in Drosophila: Recent Advances and Outstanding Problems

Over the past two decades, fundamental strides in physiology and genetics have allowed us to finally grasp the developmental mechanisms regulating body size, primarily in one model organism: the fruit fly Drosophila melanogaster. In Drosophila, as in all animals, final body size is regulated by the rate and duration of growth. These studies have identified important roles for the insulin and the target of rapamycin (TOR) signaling pathways in regulating the growth rate of the larva, the stage most important in determining final adult size. Furthermore, they have shown that the insulin/TOR pathway interacts with hormonal systems, like ecdysone and juvenile hormone, to regulate the timing of development and hence the duration of growth. This interaction allows the growing larvae to integrate cues from the environment with environmentally sensitive developmental windows to ensure that optimal size and proportions are reached given the larval rearing conditions. Results from this work have opened up new avenues of studies, including how environmental cues are integrated to regulate developmental time and how organs maintain proportional growth. Other researchers interested in the evolution of body size are beginning to apply these results to studies of body size evolution and the generation of allometry. With these new findings, and with the developments to come, the field of size control finds itself in the fortunate position of finally being able to tackle century old questions of how organisms achieve final adult size and proportions. This review discusses the state of the art of size control from a Drosophila perspective, and outlines an approach to resolving outstanding issues

Temperature Size Rule is mediated by thermal plasticity of critical size in Drosophila melanogaster

Most ectotherms show an inverse relationship between developmental temperature and body size, a phenomenon known as the temperature size rule (TSR). Several competing hypotheses have been proposed to explain its occurrence. According to one set of views, the TSR results from inevitable biophysical effects of temperature on the rates of growth and differentiation, whereas other views suggest the TSR is an adaptation that can be achieved by a diversity of mechanisms in different taxa. Our data reveal that the fruit fly, Drosophila melanogaster, obeys the TSR using a novel mechanism: reduction of critical size at higher temperatures. In holometabolous insects, attainment of critical size initiates the hormonal cascade that terminates growth, and hence, Drosophila larvae appear to instigate the signal to stop growth at a smaller size at higher temperatures. This is in contrast to findings from another holometabolous insect, Manduca sexta, in which the TSR results from the effect of temperature on the rate and duration of growth. This contrast suggests that there is no single mechanism that accounts for the TSR. Instead, the TSR appears to be an adaptation that is achieved at a proximate level through different mechanisms in different taxa.Comment: Accepted in Proceedings of Royal Society B: Biological Science

Diapause in the pea aphid (Acyrthosiphon pisum) is a slowing but not a cessation of development

BACKGROUND: Many insects undergo a period of arrested development, called diapause, to avoid seasonally recurring adverse conditions. Whilst the phenology and endocrinology of insect diapause have been well studied, there has been comparatively little research into the developmental details of diapause. We investigated developmental aspects of diapause in sexually-produced embryos of the pea aphid, Acyrthosiphon pisum. RESULTS: We found that early stages of embryogenesis progressed at a temperature-independent rate, characteristic of diapause, whereas later stages of embryogenesis progressed at a temperature-dependent rate. However, embryos maintained at very high temperatures during the temperature-independent stage showed severe developmental abnormalities. Under no temperature regime did embryos display a distinct resting stage. Rather, morphological development progressed slowly but continuously throughout embryogenesis. CONCLUSION: Diapause in the pea aphid, and perhaps in many other insects, is a temperature-independent slowing but not a cessation of morphological development. This suggests that the mechanisms limiting developmental rate during diapause may be the same as those controlling developmental rate at other stages of growth

Coordinating Development: How Do Animals Integrate Plastic and Robust Developmental Processes?

Our developmental environment significantly affects myriad aspects of our biology, including key life history traits, morphology, physiology, and our susceptibility to disease. This environmentally-induced variation in phenotype is known as plasticity. In many cases, plasticity results from alterations in the rate of synthesis of important developmental hormones. However, while developmental processes like organ growth are sensitive to environmental conditions, others like patterning – the process that generates distinct cell identities – remain robust to perturbation. This is particularly surprising given that the same hormones that regulate organ growth also regulate organ patterning. In this review, we revisit the current approaches that address how organs coordinate their growth and pattern, and outline our hypotheses for understanding how organs achieve correct pattern across a range of sizes

Plasticity Through Canalization: The Contrasting Effect of Temperature on Trait Size and Growth in Drosophila

In most ectotherms, a reduction in developmental temperature leads to an increase in body size, a phenomenon known as the temperature size rule (TSR). In Drosophila melanogaster, temperature affects body size primarily by affecting critical size, the point in development when larvae initiate the hormonal cascade that stops growth and starts metamorphosis. However, while the thermal plasticity of critical size can explain the effect of temperature on overall body size, it cannot entirely account for the effect of temperature on the size of individual traits, which vary in their thermal sensitivity. Specifically, the legs and male genitalia show reduced thermal plasticity for size, while the wings show elevated thermal plasticity, relative to overall body size. Here, we show that these differences in thermal plasticity among traits reflect, in part, differences in the effect of temperature on the rates of cell proliferation during trait growth. Counterintuitively, the elevated thermal plasticity of the wings is due to canalization in the rate of cell proliferation across temperatures. The opposite is true for the legs. These data reveal that environmental canalization at one level of organization may explain plasticity at another, and vice versa

The Temporal Requirements for Insulin Signaling During Development in Drosophila

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

The sex-specific effects of diet quality versus quantity on morphology in Drosophila melanogaster

This deposit is composed by the main article plus the supplementary materials of the publication.Variation in the quality and quantity of nutrition is a major contributor to phenotypic variation in animal populations. Although we know much of how dietary restriction impacts phenotype, and of the molecular-genetic and physiological mechanisms that underlie this response, we know much less of the effects of dietary imbalance. Specifically, although dietary imbalance and restriction both reduce overall body size, it is unclear whether both have the same effect on the size of individual traits. Here, we use the fruit fly Drosophila melanogaster to explore the effect of dietary food versus protein-to-carbohydrate ratio on body proportion and trait size. Our results indicate that body proportion and trait size respond differently to changes in diet quantity (food concentration) versus diet quality (protein-to-carbohydrate ratio), and that these effects are sex specific. While these differences suggest that Drosophila use at least partially distinct developmental mechanisms to respond to diet quality versus quantity, further analysis indicates that the responses can be largely explained by the independent and contrasting effects of protein and carbohydrate concentration on trait size. Our data highlight the importance of considering macronutrient composition when elucidating the effect of nutrition on trait size, at the levels of both morphology and developmental physiology.National Science Foundation grants: (IOS-1557638, IOS-0919855); Lake Forest College.info:eu-repo/semantics/publishedVersio

Size and shape: the developmental regulation of static allometry in insects

Among all organisms, the size of each body part or organ scales with overall body size, a phenomenon called allometry. The study of shape and form has attracted enormous interest from biologists, but the genetic, developmental and physiological mechanisms that control allometry and the proportional growth of parts have remained elusive. Recent progress in our understanding of body‐size regulation provides a new synthetic framework for thinking about the mechanisms and the evolution of allometric scaling. In particular, insulin/IGF signaling, which plays major roles in longevity, diabetes and the regulation of cell, organ and body size, might also be centrally involved in regulating organismal shape. Here we review recent advances in the fields of growth regulation and endocrinology and use them to construct a developmental model of static allometry expression in insects. This model serves as the foundation for a research program that will result in a deeper understanding of the relationship between growth and form, a question that has fascinated biologists for centuries

Ecdysone promotes growth of imaginal discs through the regulation of Thor in D. melanogaster

Animals have a determined species-specific body size that results from the combined action of hormones and signaling pathways regulating growth rate and duration. In Drosophila, the steroid hormone ecdysone controls developmental transitions, thereby regulating the duration of the growth period. Here we show that ecdysone promotes the growth of imaginal discs in mid-third instar larvae, since imaginal discs from larvae with reduced or no ecdysone synthesis are smaller than wild type due to smaller and fewer cells. We show that insulin-like peptides are produced and secreted normally in larvae with reduced ecdysone synthesis, and upstream components of insulin/insulin-like signaling are activated in their discs. Instead, ecdysone appears to regulate the growth of imaginal discs via Thor/4E-BP, a negative growth regulator downstream of the insulin/insulin-like growth factor/Tor pathways. Discs from larvae with reduced ecdysone synthesis have elevated levels of Thor, while mutations in Thor partially rescue their growth. The regulation of organ growth by ecdysone is evolutionarily conserved in hemimetabolous insects, as shown by our results obtained using Blattella germanica. In summary, our data provide new insights into the relationship between components of the insulin/insulin-like/Tor and ecdysone pathways in the control of organ growth.Spanish Ministry of Science and Consolider program grants: (BFU-2008-01884, BFU2011-25986, CSD2007-008-25120, BFU2009-10571 and BES-2009-016077); Departments of Education and Industry of the Basque Government grant: (PI2012/42); Bizkaia County; Instituto Gulbenkian de Ciência/Fundação Calouste Gulbenkian; Fundação Para a Ciência e a Tecnologia fellowship: (SFRH/BD/51181/2010)

The Effect of Genetic and Environmental Variation on Genital Size in Male Drosophila: Canalized but Developmentally Unstable

The genitalia of most male arthropods scale hypoallometrically with body size, that is they are more or less the same size across large and small individuals in a population. Such scaling is expected to arise when genital traits show less variation than somatic traits in response to factors that generate size variation among individuals in a population. Nevertheless, there have been few studies directly examining the relative sensitivity of genital and somatic traits to factors that affect their size. Such studies are key to understanding genital evolution and the evolution of morphological scaling relationships more generally. Previous studies indicate that the size of genital traits in male Drosophila melanogaster show a relatively low response to variation in environmental factors that affect trait size. Here we show that the size of genital traits in male fruit flies also exhibit a relatively low response to variation in genetic factors that affect trait size. Importantly, however, this low response is only to genetic factors that affect body and organ size systemically, not those that affect organ size autonomously. Further, we show that the genital traits do not show low levels of developmental instability, which is the response to stochastic developmental errors that also influence organ size autonomously. We discuss these results in the context of current hypotheses on the proximate and ultimate mechanisms that generate genital hypoallometry