ORCID Profile
0000-0002-9765-4021
Current Organisation
Monash University
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Developmental Genetics (incl. Sex Determination) | Evolution of Developmental Systems | Animal Physiology - Systems | Receptors and Membrane Biology | Population, Ecological and Evolutionary Genetics | Genetics | Evolutionary Biology | Biological Adaptation
Publisher: Oxford University Press (OUP)
Date: 09-2020
DOI: 10.1534/GENETICS.120.303475
Abstract: As juvenile animals grow, their behavior, physiology, and development need to be matched to environmental conditions to ensure they survive to adulthood. However, we know little about how behavior and physiology are integrated with development to achieve this outcome. Neuropeptides are prime candidates for achieving this due to their well-known signaling functions in controlling many aspects of behavior, physiology, and development in response to environmental cues. In the growing Drosophila larva, while several neuropeptides have been shown to regulate feeding behavior, and a handful to regulate growth, it is unclear if any of these play a global role in coordinating feeding behavior with developmental programs. Here, we demonstrate that Neuropeptide F Receptor (NPFR), best studied as a conserved regulator of feeding behavior from insects to mammals, also regulates development in Drosophila. Knocking down NPFR in the prothoracic gland, which produces the steroid hormone ecdysone, generates developmental delay and an extended feeding period, resulting in increased body size. We show that these effects are due to decreased ecdysone production, as these animals have reduced expression of ecdysone biosynthesis genes and lower ecdysone titers. Moreover, these phenotypes can be rescued by feeding larvae food supplemented with ecdysone. Further, we show that NPFR negatively regulates the insulin signaling pathway in the prothoracic gland to achieve these effects. Taken together, our data demonstrate that NPFR signaling plays a key role in regulating animal development, and may, thus, play a global role in integrating feeding behavior and development in Drosophila.
Publisher: Wiley
Date: 08-06-2022
DOI: 10.1002/JEZ.B.23165
Abstract: For centuries, it has been understood that the final size of adult holometabolous insects is determined by the end of the larval stage, and that once they transform to adults, holometabolous insects do not grow. Despite this, no previous study has directly tested these “old truths” across holometabolous insects. Here, we demonstrate that final adult size is set at the end of the last larval stage in species representing each of the four orders of holometabolous insects: the fruit fly Drosophila melanogaster (Diptera), the tobacco hornworm Manduca sexta (Lepidoptera), the dung beetle Onthophagus taurus (Coleoptera), and the Florida carpenter ant C onotus floridanus (Hymenoptera). Furthermore, in both D. melanogaster and C. floridanus , we show that the size of adult in iduals fluctuates but does not significantly change. Therefore, our study finally confirms these two basic assumptions in the biology of insects, which have for centuries served as the foundation for studies of insect growth, size, and allometry.
Publisher: Wiley
Date: 05-08-2019
Publisher: Cold Spring Harbor Laboratory
Date: 03-11-2021
DOI: 10.1101/2021.11.03.467051
Abstract: Dietary interventions that restrict protein intake have repeatedly been shown to offer beneficial health outcomes to the consumer. Benefits such as increased stress tolerance can be observed in response to restricting in idual amino acids, thus mimicking dietary protein restriction. Here, we sought to further understand the relationship between dietary amino acids and stress tolerance using Drosophila melanogaster . Utilising a chemically defined medium for Drosophila , we found that transiently restricting adult flies of a single essential amino acid generally protects against a lethal dose of the naturally occurring insecticide, nicotine. This protection was conferred during the pre-treatment window, was specific for in idual amino acids and depended on the identity of the focal amino acid, as well as the duration and intensity of its restriction. For instance, complete isoleucine deprivation for 7 days maximised its protective effect - increasing survival during nicotine exposure by 100%. However, a dose of 25% threonine was required to maximise its protective effect (53% enhanced survival). To understand the molecular basis of these effects, we modified the signalling of two cellular sensors of amino acids, GCN2 (General control non-derepressible) and mTORC1 (mechanistic Target of Rapamycin Complex 1) in combination with amino acid restriction. We found that GCN2 was necessary for diets to protect against nicotine, whereas suppression of mTORC1 was sufficient to induce nicotine resistance. This finding implies that amino acid restriction acts via amino acid signalling to cross-protect against seemingly unrelated stressors. Altogether, our study offers new insights into the physiological responses to restriction of in idual amino acids that confer stress tolerance. This has broad potential for application in animal and human health.
Publisher: Cold Spring Harbor Laboratory
Date: 06-08-2022
DOI: 10.1101/2022.08.05.502931
Abstract: Modifying the relative proportions of macronutrients in an animal’s diet has noteworthy effects on its reproduction, lifelong health, and lifespan. Because of this, a wide range of animals carefully regulate their nutrient intake toward species and stage-specific targets. However, when animals are unable to reach their nutrient target from their existing food resources, they will compromise between overconsuming one nutrient and under-consuming the deficit nutrient. In this study, we used capillary feeding (CAFE) assays to understand the rules of compromise of adult fruit flies ( Drosophila melanogaster ) of different sex, mating status, and age when constrained to single diets. We found that young male and female D. melanogaster compromised by consuming more food on diets with low protein to carbohydrate (P:C) ratios compared to diets with high P:C ratios. Further, young male and female flies varied their carbohydrate intake significantly more than their protein intake, and female flies varied their carbohydrate intake significantly more than males. To test for effects of mating status on nutrient intake, we compared food intake of young mated and virgin females. We found that both virgin and mated females compromised by consuming more food on the low P:C diet compared to high P:C diets however, mated females consumed more food than virgin females. As flies aged, they decreased their overall food intake and showed more modest alterations in their food intake across varying P:C diets. Further, mated females ceased to compromise for the protein deficit at a younger age than males. These findings provide new understanding about differences in protein leveraging behaviour across sexes, and how these behaviours change with age. Young fruit flies exhibit protein leveraging behaviour, varying their carbohydrate consumption more than protein Young mated female flies vary their carbohydrate consumption significantly more than young males Both virgin and mated female flies balance their nutrient intake similarly As flies age, their ability to protein leverage declines, and this occurs faster in female flies
Publisher: eLife Sciences Publications, Ltd
Date: 26-01-2021
DOI: 10.7554/ELIFE.62335
Abstract: Diet plays a significant role in maintaining lifelong health. In particular, lowering the dietary protein: carbohydrate ratio can improve lifespan. This has been interpreted as a direct effect of these macronutrients on physiology. Using Drosophila melanogaster , we show that the role of protein and carbohydrate on lifespan is indirect, acting by altering the partitioning of limiting amounts of dietary sterols between reproduction and lifespan. Shorter lifespans in flies fed on high protein: carbohydrate diets can be rescued by supplementing their food with cholesterol. Not only does this fundamentally alter the way we interpret the mechanisms of lifespan extension by dietary restriction, these data highlight the important principle that life histories can be affected by nutrient-dependent trade-offs that are indirect and independent of the nutrients (often macronutrients) that are the focus of study. This brings us closer to understanding the mechanistic basis of dietary restriction.
Publisher: Elsevier BV
Date: 2023
Publisher: Elsevier BV
Date: 11-2015
DOI: 10.1016/J.JINSPHYS.2015.09.003
Abstract: Species coexist using the same nutritional resource by partitioning it either in space or time, but few studies explore how species-specific nutritional requirements allow partitioning. Zaprionus indianus and Drosophila simulans co-exist in figs by invading the fruit at different stages Z. indianus colonizes ripe figs, whereas D. simulans oviposits in decaying fruit. Larvae feed on yeast growing on the fruit, which serves as their primary protein source. Because yeast populations increase as fruit decays, we find that ripe fruit has lower protein content than rotting fruit. Therefore, we hypothesized that Z. indianus and D. simulans larvae differ in their dietary requirements for protein. We used nutritional geometry to assess the effects of protein and carbohydrate concentration in the larval diet on life history characters in both species. Survival, development time, and ovariole number respond differently to the composition of the larval diet, with Z. indianus generally performing better across a wider range of protein concentrations. Correspondingly, we found that Z. indianus females preferred to lay eggs on low protein foods, while D. simulans females chose higher protein foods for oviposition when competing with Z. indianus. We propose the different nutritional requirements and oviposition preference of these two species allows them to temporally partition their habitat.
Publisher: Cold Spring Harbor Laboratory
Date: 04-11-2021
DOI: 10.1101/2021.11.03.467059
Abstract: Dietary nutrient composition is essential for shaping important fitness traits and behaviours. Many organisms are protein limited and for Drosophila melanogaster , this limitation manifests at the level of the single most limiting essential Amino Acid (AA) in the diet. The identity of this AA and its effects on female fecundity is readily predictable by a procedure called exome matching in which the sum of AAs encoded by a consumer’s exome is used to predict the relative proportion of AAs required in its diet. However, the exome matching calculation does not weight AA contributions to the overall profile by protein size or expression. Here we update the exome matching calculation to include these weightings. Surprisingly, although nearly half of the transcriptome is differentially expressed when comparing male and female flies, we found that creating transcriptome-weighted exome matched diets for each sex did not enhance their fecundity over that supported by exome matching alone. These data indicate that while organisms may require different amounts of dietary protein across conditions, the relative proportion of the constituent AAs remains constant. Interestingly, we also found remarkable conservation of exome matched AA profiles across taxa and that the composition of these profiles could be explained by the metabolic costs of microbial AA synthesis. Thus, it appears that bioenergetic constraints amongst autotrophs shape the relative proportion of AAs that are available across trophic levels and that that this constrains biomass composition.
Publisher: Bio-Protocol, LLC
Date: 2021
Publisher: Elsevier BV
Date: 05-2020
Publisher: Elsevier BV
Date: 02-2018
DOI: 10.1016/J.COIS.2017.11.002
Abstract: Insects show impressive ersity in adult body size across species, and within species adult body size is sensitive to numerous environmental conditions, particularly to changes in nutrition. Body size in adult insects correlates with a number of important fitness-related traits such as fecundity, longevity, stress resistance, and mating success. Over the past few decades, the field of insect body size regulation has made impressive progress towards understanding the signalling pathways that regulate body size in response to nutrition. These studies have shown that conserved nutrition-sensitive signalling pathways act in animals from insects to vertebrates to regulate growth. In particular, pathways like the insulin/insulin-like growth factor signalling (IIS) pathway and the Target of rapamycin (TOR) pathway respond to the levels of dietary nutrients to adjust both the rate of growth and the duration of the growth period. They do this not only by regulating organ growth, but also by modifying the rates of synthesis and circulating concentrations of key developmental hormones. Although the mechanisms through which this occurs have been well documented in one insect, the fruit fly Drosophila melanogaster, it is becoming increasingly clear that the downstream mechanisms through which IIS and TOR signalling alter size in response to nutrition differ between organs and across species. In this review, we highlight how understanding the organ-specific effects of IIS/TOR signalling are key to revealing the ersity of size control mechanisms across insects.
Publisher: Elsevier BV
Date: 05-2022
Publisher: Cold Spring Harbor Laboratory
Date: 27-03-2023
DOI: 10.1101/2023.03.26.534290
Abstract: Phenotypic plasticity helps animals to buffer the effects of increasing thermal and nutritional stress created by climate change. Studies have shown that plastic responses to single and combined stressors can vary among genetically erged populations. However, less is known about how plasticity in response to combined stress varies among in iduals within a population or whether such variation changes across life-history traits. This is important because in idual variation within populations shapes population level responses to environmental change. Here, we used isogenic lines of Drosophila melanogaster to assess plasticity of egg-adult viability and sex-specific body size for combinations of two temperatures (25°C or 28°C) and three diets (standard diet, low caloric diet, or low protein:carbohydrate ratio diet). Our results reveal substantial within-population genetic variation in plasticity for egg-to-adult viability and wing size in response to combined thermal-nutritional stress. This genetic variation in plasticity was a result of cross-environment genetic correlations that were generally 1 rather than changes in the expression of genetic variation across environments. Cross-sex genetic correlations for body size were weaker when the sexes were reared in different conditions, suggesting wing size has the potential to evolve independently across sexes. Further, our results suggest that plasticity in egg-adult viability is genetically independent from plasticity in body size. By quantifying plasticity in response to combined stress between sexes and across traits, our study aims to develop a more nuanced understanding of the potential for populations to adapt to ongoing climate change.
Publisher: Elsevier BV
Date: 06-2002
Publisher: Wiley
Date: 08-10-2022
DOI: 10.1111/JEB.14099
Abstract: Ongoing climate change has forced animals to face changing thermal and nutritional environments. Animals can adjust to such combinations of stressors via plasticity. Body size is a key trait influencing organismal fitness, and plasticity in this trait in response to nutritional and thermal conditions varies among genetically erse, locally adapted populations. The standing genetic variation within a population can also influence the extent of body size plasticity. We generated near-isogenic lines from a newly collected population of Drosophila melanogaster at the mid-point of east coast Australia and assayed body size for all lines in combinations of thermal and nutritional stress. We found that isogenic lines showed distinct underlying patterns of body size plasticity in response to temperature and nutrition that were often different from the overall population response. We then tested whether plasticity in development time could explain, and therefore regulate, variation in body size to these combinations of environmental conditions. We selected five genotypes that showed the greatest variation in response to combined thermal and nutritional stress and assessed the correlation between response of developmental time and body size. While we found significant genetic variation in development time plasticity, it was a poor predictor of body size among genotypes. Our results therefore suggest that multiple developmental pathways could generate genetic variation in body size plasticity. Our study emphasizes the need to better understand genetic variation in plasticity within a population, which will help determine the potential for populations to adapt to ongoing environmental change.
Publisher: Elsevier BV
Date: 10-2015
DOI: 10.1016/J.JINSPHYS.2015.07.002
Abstract: Organisms from slime moulds to humans carefully regulate their macronutrient intake to optimize a wide range of life history characters including survival, stress resistance, and reproductive success. However, life history characters often differ in their response to nutrition, forcing organisms to make foraging decisions while balancing the trade-offs between these effects. To date, we have a limited understanding of how the nutritional environment shapes the relationship between life history characters and foraging decisions. To gain insight into the problem, we used a geometric framework for nutrition to assess how the protein and carbohydrate content of the larval diet affected key life history traits in the fruit fly, Drosophila melanogaster. In no-choice assays, survival from egg to pupae, female and male body size, and ovariole number - a proxy for female fecundity - were maximized at the highest protein to carbohydrate (P:C) ratio (1.5:1). In contrast, development time was minimized at intermediate P:C ratios, around 1:2. Next, we subjected larvae to two-choice tests to determine how they regulated their protein and carbohydrate intake in relation to these life history traits. Our results show that larvae targeted their consumption to P:C ratios that minimized development time. Finally, we examined whether adult females also chose to lay their eggs in the P:C ratios that minimized developmental time. Using a three-choice assay, we found that adult females preferentially laid their eggs in food P:C ratios that were suboptimal for all larval life history traits. Our results demonstrate that D. melanogaster larvae make foraging decisions that trade-off developmental time with body size, ovariole number, and survival. In addition, adult females make oviposition decisions that do not appear to benefit the larvae. We propose that these decisions may reflect the living nature of the larval nutritional environment in rotting fruit. These studies illustrate the interaction between the nutritional environment, life history traits, and foraging choices in D. melanogaster, and lend insight into the ecology of their foraging decisions.
Publisher: Cold Spring Harbor Laboratory
Date: 06-02-2020
DOI: 10.1101/2020.02.05.935098
Abstract: Blood cells, known as hemocytes in invertebrates, play important and conserved roles in immunity, wound healing and tissue remodelling. The control of hemocyte number is therefore critical to ensure these functions are not compromised, and studies using Drosophila are proving useful for understanding how this occurs. Recently, the well characterised embryonic patterning gene, torso-like ( tsl ), was identified as being required both for normal hemocyte number and for providing immunity against certain pathogens. Here, we report that Tsl is required specifically during the larval phase of hematopoiesis, and that the reduced hemocyte number found in tsl mutant larvae is likely the result of a reduced larval growth rate and compromised insulin signalling. Consistent with this, we find that impairing insulin-mediated growth, either by nutrient deprivation or genetically, results in fewer hemocytes. This is likely the result of impaired insulin-like signalling in the hemocytes themselves since modulation of Insulin-like Receptor (InR) activity specifically in hemocytes causes concomitant changes to their population size in developing larvae. Taken together, our work reveals the strong relationship that exists between body size and hemocyte number, and suggests that insulin-like signalling contributes to, but is not solely responsible for, keeping these tightly aligned during larval development.
Publisher: eLife Sciences Publications, Ltd
Date: 14-12-2020
Publisher: The Royal Society
Date: 12-2022
DOI: 10.1098/RSOB.220319
Abstract: Dietary interventions that restrict protein intake have repeatedly been shown to offer beneficial health outcomes to the consumer. Benefits such as increased stress tolerance can be observed when in idual amino acids are restricted, thus mimicking dietary protein restriction. Here, we sought to further understand the relationship between dietary amino acids and stress tolerance using Drosophila melanogaster . Using a chemically defined medium for Drosophila , we found that transiently restricting adult flies of a single essential amino acid generally protects against a lethal dose of the naturally occurring insecticide, nicotine. This protection varied with the identity of the focal amino acid and depended on the duration and intensity of its restriction. To understand the molecular basis of these effects, we modified the signalling of two cellular sensors of amino acids, GCN2 and mTORC1, in combination with amino acid restriction. We found that GCN2 was necessary for diets to protect against nicotine, whereas the suppression of mTORC1 was sufficient to induce nicotine resistance. This finding implies that amino acid restriction acts via amino acid signalling to cross-protect against seemingly unrelated stressors. Altogether, our study offers new insights into the physiological responses to restriction of in idual amino acids that confer stress tolerance.
Publisher: Proceedings of the National Academy of Sciences
Date: 28-04-2014
Abstract: Understanding how organisms regulate their body size is a fundamental problem in biology. Body size regulation involves the careful integration of mechanisms that control growth rate with those that control growth duration. In insects, developmental hormones such as juvenile hormone and ecdysone regulate developmental transitions and growth duration. The conserved insulin-signaling pathway regulates growth rates. Our studies reveal an intimate link between the three, whereby juvenile hormone controls body size by regulating ecdysone synthesis, which in turn modifies insulin signaling. In vertebrates, hormones such as androgens and estrogens interact with insulin signaling to influence tumor growth. By studying the developmental context of hormone interactions, our data reveal fundamental features of body size regulation that have important consequences for understanding cancer growth.
Publisher: Oxford University Press (OUP)
Date: 07-2020
Abstract: Blood cells, known as hemocytes in invertebrates, play important and conserved roles in immunity, wound healing and tissue remodelling. The control of hemocyte number is therefore critical to ensure these functions are not compromised, and studies using Drosophila melanogaster are proving useful for understanding how this occurs. Recently, the embryonic patterning gene, torso-like (tsl), was identified as being required both for normal hemocyte development and for providing immunity against certain pathogens. Here, we report that Tsl is required specifically during the larval phase of hematopoiesis, and that tsl mutant larvae likely have reduced hemocyte numbers due to a reduced larval growth rate and compromised insulin signaling. Consistent with this, we find that impairing insulin-mediated growth, either by nutrient deprivation or genetically, results in fewer hemocytes. This is likely the result of impaired insulin-like signaling in the hemocytes themselves, since modulation of Insulin-like Receptor (InR) activity specifically in hemocytes causes concomitant changes to their population size in developing larvae. Taken together, our work reveals the strong relationship that exists between body size and hemocyte number, and suggests that insulin-like signaling contributes to, but is not solely responsible for, keeping these tightly aligned during larval development.
Publisher: Elsevier BV
Date: 05-2022
Publisher: Oxford University Press (OUP)
Date: 28-12-2016
DOI: 10.1534/GENETICS.115.179960
Abstract: Animals from flies to humans adjust their development in response to environmental conditions through a series of developmental checkpoints, which alter the sensitivity of organs to environmental perturbation. Despite their importance, we know little about the molecular mechanisms through which this change in sensitivity occurs. Here we identify two phases of sensitivity to larval nutrition that contribute to plasticity in ovariole number, an important determinant of fecundity, in Drosophila melanogaster. These two phases of sensitivity are separated by the developmental checkpoint called “critical weight” poor nutrition has greater effects on ovariole number in larvae before critical weight than after. We find that this switch in sensitivity results from distinct developmental processes. In precritical weight larvae, poor nutrition delays the onset of terminal filament cell differentiation, the starting point for ovariole development, and strongly suppresses the rate of terminal filament addition and the rate of increase in ovary volume. Conversely, in postcritical weight larvae, poor nutrition affects only the rate of increase in ovary volume. Our results further indicate that two hormonal pathways, the insulin/insulin-like growth factor and the ecdysone-signaling pathways, modulate the timing and rates of all three developmental processes. The change in sensitivity in the ovary results from changes in the relative contribution of each pathway to the rates of terminal filament addition and increase in ovary volume before and after critical weight. Our work deepens our understanding of how hormones act to modify the sensitivity of organs to environmental conditions, thereby affecting their plasticity.
Publisher: Elsevier BV
Date: 02-2016
DOI: 10.1016/J.COIS.2016.02.010
Abstract: The relationship between organ and body size, known as morphological allometry, has fascinated biologists for over a century because changes in allometry generate the vast ersity of organism shapes. Nevertheless, progress has been limited in understanding the genetic mechanisms that regulate allometries and how these mechanisms evolve. This is perhaps because allometry is measured at the population level, however adult organ and body size depends on genetic background and the developmental environment of in iduals. Recent findings have enhanced our understanding of how insects regulate their organ and body sizes in response to environmental conditions, particularly nutritional availability. We argue that merging these developmental insights with a population genetics approach will provide a powerful system for understanding the evolution of allometry.
Publisher: The Royal Society
Date: 09-2022
DOI: 10.1098/RSOB.220037
Abstract: Organ growth is tightly regulated across environmental conditions to generate an appropriate final size. While the size of some organs is free to vary, others need to maintain constant size to function properly. This poses a unique problem: how is robust final size achieved when environmental conditions alter key processes that regulate organ size throughout the body, such as growth rate and growth duration? While we know that brain growth is ‘spared’ from the effects of the environment from humans to fruit flies, we do not understand how this process alters growth dynamics across brain compartments. Here, we explore how this robustness in brain size is achieved by examining differences in growth patterns between the larval body, the brain and a brain compartment—the mushroom bodies—in Drosophila melanogaster across both thermal and nutritional conditions. We identify key differences in patterns of growth between the whole brain and mushroom bodies that are likely to underlie robustness of final organ shape. Further, we show that these differences produce distinct brain shapes across environments.
Publisher: Springer Science and Business Media LLC
Date: 22-07-2015
DOI: 10.1038/SREP12383
Abstract: 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.
Publisher: Annual Reviews
Date: 07-01-2021
DOI: 10.1146/ANNUREV-ENTO-041620-083838
Abstract: All organisms are exposed to changes in their environment throughout their life cycle. When confronted with these changes, they adjust their development and physiology to ensure that they can produce the functional structures necessary for survival and reproduction. While some traits are remarkably invariant, or robust, across environmental conditions, others show high degrees of variation, known as plasticity. Generally, developmental processes that establish cell identity are thought to be robust to environmental perturbation, while those relating to body and organ growth show greater degrees of plasticity. However, ex les of plastic patterning and robust organ growth demonstrate that this is not a hard-and-fast rule.In this review, we explore how the developmental context and the gene regulatory mechanisms underlying trait formation determine the impacts of the environment on development in insects. Furthermore, we outline future issues that need to be resolved to understand how the structure of signaling networks defines whether a trait displays plasticity or robustness.
Publisher: Elsevier BV
Date: 11-2021
Publisher: Cold Spring Harbor Laboratory
Date: 10-11-2021
DOI: 10.1101/2021.11.08.467165
Abstract: Nutrition shapes a broad range of life history traits, ultimately impacting animal fitness. A key fitness-related trait, female fecundity is well known to change as a function of diet. In particular, the availability of dietary protein is one of the main drivers of egg production, and in the absence of essential amino acids egg laying declines. However, it is unclear whether all essential amino acids have the same impact on phenotypes like fecundity. Using a holidic diet, we fed adult female D. melanogaster diets that contain all necessary nutrients except one of the 10 essential amino acids and assessed the effects on egg production. For most essential amino acids, depleting a single amino acid induced as rapid a decline in egg production as when there were no amino acids in the diet. However, when either methionine or histidine were excluded from the diet, egg production declined more slowly. Next, we tested whether GCN2 and TOR were involved in this difference in response across amino acids. While mutations in GCN2 did not eliminate the differences in the rates of decline in egg laying among amino acid drop-out diets, we found that inhibiting TOR signalling caused egg laying to decline rapidly for all drop-out diets. TOR signalling does this by regulating the yolk-forming stages of egg chamber development. Our results suggest that amino acids differ in their ability to induce signalling via the TOR pathway. This is important because if phenotypes differ in sensitivity to in idual amino acids, this generates the potential for mismatches between the output of a pathway and the animal’s true nutritional status.
Publisher: eLife Sciences Publications, Ltd
Date: 23-02-2022
Publisher: Cold Spring Harbor Laboratory
Date: 08-03-2023
DOI: 10.1101/2023.03.07.531575
Abstract: Nutrition is an important determinant of an animal’s survival and fitness. Phenotypic plasticity allows a genotype to adjust life history traits to changes in its nutritional environment, and it varies among in iduals. The origin of this variation comes from differences in proximate mechanisms regulating trait expression. To understand how variation in plasticity is achieved, we made use of a Drosophila melanogaster isogenic panel to characterize nutritional plasticity for fecundity by feeding flies diets differing in their yeast content and counting the number of eggs produced. We then identified lines with the highest and lowest plastic responses to diet, and dissected the potential proximate mechanisms responsible for these differences in plasticity, including morphology, behaviour, and physiology. Our results suggest that variation in plasticity is not due to differences in ovariole number, but due to both increased food intake, and higher efficiency at converting food into eggs. Our results show that, in this population of D. melanogaster , variation in behaviour and physiology, but not morphology, underlies differences in plasticity for fecundity. Further, they set the stage for future studies aiming to understand how the proximate mechanisms that generate genetic variation in plasticity contribute to a population’s persistence when faced with environmental changes.
Publisher: Elsevier BV
Date: 04-2017
Publisher: Frontiers Media SA
Date: 2013
Publisher: Elsevier BV
Date: 08-2007
Publisher: Cold Spring Harbor Laboratory
Date: 17-12-2019
DOI: 10.1101/2019.12.16.878967
Abstract: As juvenile animals grow, their behaviour, physiology, and development need to be matched to environmental conditions to ensure they survive to adulthood. However, we know little about how behaviour and physiology are integrated with development to achieve this outcome. Neuropeptides are prime candidates for achieving this due to their well-known signalling functions in controlling many aspects of behaviour, physiology and development in response to environmental cues. In the growing Drosophila larva, while several neuropeptides have been shown to regulate feeding behaviour, and a handful to regulate growth, it is unclear if any of these play a global role in coordinating feeding behaviour with developmental programs. Here, we demonstrate that Neuropeptide F Receptor (NPFR), best studied as a conserved regulator of feeding behaviour from insects to mammals, also regulates development in Drosophila . Knocking down NPFR in the prothoracic gland, which produces the steroid hormone ecdysone, generates developmental delay and an extended feeding period, resulting in increased body size. We show that these effects are due to decreased ecdysone production, as these animals have reduced expression of ecdysone biosynthesis genes and lower ecdysone titres. Moreover, these phenotypes can be rescued by feeding larvae food supplemented with ecdysone. Further, we show that NPFR negatively regulates the insulin signalling pathway in the prothoracic gland to achieve these effects. Taken together, our data demonstrate that NPFR signalling plays a key role in regulating animal development and may thus play a global role in integrating feeding behaviour and development in Drosophila .
Publisher: Public Library of Science (PLoS)
Date: 19-06-2014
Publisher: Cold Spring Harbor Laboratory
Date: 14-08-2023
DOI: 10.1101/2023.08.10.552880
Abstract: Diet and health are strongly linked, though the strict changes in diet required to improve health outcomes are usually difficult to sustain. We sought to understand whether short term bouts of amino acid-specific modifications to the diet of Drosophila melanogaster could mimic the lifespan and stress resistance benefits of dietary restriction, without the requirement for drastic reductions in food intake. We found that flies fed diets lacking the essential amino acid isoleucine, but otherwise nutritionally complete, exhibited enhanced nicotine tolerance, indicating elevated detoxification capacity. The protection from isoleucine deprivation increased with the duration of exposure, up to a maximum at 7-day isoleucine deprivation for flies 2, 3, or 4 weeks of age, and a 5-day deprivation when flies were 5 weeks of age. Because of these beneficial effects on toxin resistance, we intermittently deprived flies of isoleucine during the first 6 weeks of adulthood and monitored the effect on lifespan. Lifespan was significantly extended when flies experienced short term isoleucine deprivation at 3 and 5 weeks of age, regardless of whether they were also deprived at 1 week. These results indicate that short-term bouts of isoleucine deprivation can extend lifespan and highlight its cumulative and time-dependent benefits. Interestingly, we found that isoleucine-deprived flies lost their protection against nicotine within three days of returning to fully fed conditions. Therefore, the mechanisms underlying lifespan extension may involve transient damage clearance during the bouts of isoleucine deprivation rather than sustained enhanced detoxification capacity. These data highlight a new time-restricted, nutritionally precise method to extend life in Drosophila melanogaster and point to a more manageable dietary method to combat ageing.
Publisher: The Royal Society
Date: 09-2017
DOI: 10.1098/RSOS.170375
Abstract: 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 in idual 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.
Publisher: eLife Sciences Publications, Ltd
Date: 09-03-2022
DOI: 10.7554/ELIFE.72666
Abstract: Animals develop in unpredictable, variable environments. In response to environmental change, some aspects of development adjust to generate plastic phenotypes. Other aspects of development, however, are buffered against environmental change to produce robust phenotypes. How organ development is coordinated to accommodate both plastic and robust developmental responses is poorly understood. Here, we demonstrate that the steroid hormone ecdysone coordinates both plasticity of organ size and robustness of organ pattern in the developing wings of the fruit fly Drosophila melanogaster . Using fed and starved larvae that lack prothoracic glands, which synthesize ecdysone, we show that nutrition regulates growth both via ecdysone and via an ecdysone-independent mechanism, while nutrition regulates patterning only via ecdysone. We then demonstrate that growth shows a graded response to ecdysone concentration, while patterning shows a threshold response. Collectively, these data support a model where nutritionally regulated ecdysone fluctuations confer plasticity by regulating disc growth in response to basal ecdysone levels and confer robustness by initiating patterning only once ecdysone peaks exceed a threshold concentration. This could represent a generalizable mechanism through which hormones coordinate plastic growth with robust patterning in the face of environmental change.
Publisher: Springer Science and Business Media LLC
Date: 07-06-2017
Publisher: Cold Spring Harbor Laboratory
Date: 21-08-2020
DOI: 10.1101/2020.08.21.260489
Abstract: Diet plays a significant role in maintaining lifelong health. In particular, lowering the dietary protein : carbohydrate ratio can improve lifespan. This has been interpreted as a direct effect of these macronutrients on physiology. Using Drosophila melanogaster , we show that the role of protein and carbohydrate on lifespan is indirect, acting by altering the partitioning of limiting amounts of dietary sterols between reproduction and lifespan. Shorter lifespans in flies fed on high protein : carbohydrate diets can be rescued by supplementing their food with cholesterol. Not only does this fundamentally alter the way we interpret the mechanisms of lifespan extension by dietary restriction, these data highlight the important principle that life histories can be affected by nutrient-dependent trade-offs that are indirect and independent of the nutrients (often macronutrients) that are the focus of study. This brings us closer to understanding the mechanistic basis of dietary restriction.
Publisher: Wiley
Date: 25-07-2013
DOI: 10.1002/WDEV.124
Publisher: Springer Science and Business Media LLC
Date: 28-03-2022
DOI: 10.1038/S41467-022-29183-X
Abstract: Carbohydrates, proteins and lipids are essential nutrients to all animals however, closely related species, populations, and in iduals can display dramatic variation in diet. Here we explore the variation in macronutrient tolerance in Drosophila melanogaster using the Drosophila genetic reference panel, a collection of ~200 strains derived from a single natural population. Our study demonstrates that D. melanogaster , often considered a “dietary generalist”, displays marked genetic variation in survival on different diets, notably on high-sugar diet. Our genetic analysis and functional validation identify several regulators of macronutrient tolerance, including CG10960/GLUT8 , Pkn and Eip75B . We also demonstrate a role for the JNK pathway in sugar tolerance and de novo lipogenesis. Finally, we report a role for tailles s, a conserved orphan nuclear hormone receptor, in regulating sugar metabolism via insulin-like peptide secretion and sugar-responsive CCHamide-2 expression. Our study provides support for the use of nutrigenomics in the development of personalized nutrition.
Publisher: Elsevier BV
Date: 10-2005
DOI: 10.1016/J.CUB.2005.09.017
Abstract: The timely onset of metamorphosis in holometabolous insects depends on their reaching the appropriate size known as critical weight. Once critical weight is reached, juvenile hormone (JH) titers decline, resulting in the release of prothoracicotropic hormone (PTTH) at the next photoperiod gate and thereby inducing metamorphosis. How in iduals determine when they have reached critical weight is unknown. We present evidence that in Drosophila, a component of the ring gland, the prothoracic gland (PG), assesses growth to determine when critical weight has been achieved. We used the GAL4/UAS system to suppress or enhance growth by overexpressing PTEN or Dp110, respectively, in various components of the ring gland. Suppression of the growth of the PG and CA, but not of the CA alone, produced larger-than-normal larvae and adults. Suppression of only PG growth resulted in nonviable larvae, but larvae with enlarged PGs produced significantly smaller larvae and adults. Rearing larvae with enlarged PGs under constant light enhanced these effects, suggesting a role for photoperiod-gated PTTH secretion. These larvae are smaller, in part as a result of their repressed growth rates, a phenotype that could be rescued through nutritional supplementation (yeast paste). Most importantly, larvae with enlarged PGs overestimated size so that they initiated metamorphosis before surpassing the minimal viable weight necessary to survive pupation. The PG acts as a size-assessing tissue by using insulin-dependent PG cell growth to determine when critical weight has been reached.
Publisher: MyJove Corporation
Date: 11-06-2020
DOI: 10.3791/61323
Publisher: Cold Spring Harbor Laboratory
Date: 06-06-2021
DOI: 10.1101/2021.06.04.447167
Abstract: Limiting calories or specific nutrients without malnutrition, otherwise known as dietary restriction (DR), has been shown to extend lifespan across a broad range of taxa. Our recent findings in Drosophila melanogaster show that supplementing flies on macronutrient-rich diets with additional cholesterol can extend lifespan to the same extent as DR. Macronutrient-rich diets drive high levels of egg production and in doing so deplete the mothers of somatic sterols that are essential for survival. Thus, DR may be beneficial for lifespan because it reduces egg production which in turn reduces the mother’s demand for sterols. If this is true, mothers must be prioritising their available sterols, whether from the diet or from their own bodies, to sustain high quality egg production. To test this, we measured the quality of eggs laid by mothers fed either cholesterol-sufficient or cholesterol-depleted diets. We found that even when the mother’s diet was completely devoid of cholesterol, high quality egg production persisted. Furthermore, we show that sterol-supplemented flies with long lives continue to lay high quality eggs that give rise to healthy offspring. Thus, in our assays, long life does not require a fecundity cost.
Publisher: Oxford University Press (OUP)
Date: 04-2018
DOI: 10.1534/GENETICS.117.300601
Abstract: In Drosophila, key developmental transitions are governed by the steroid hormone ecdysone. A number of neuropeptide-activated signaling pathways control ecdysone production in response to environmental signals, including the insulin signaling pathway, which regulates ecdysone production in response to nutrition. Here, we find that the Membrane Attack Complex/Perforin-like protein Torso-like, best characterized for its role in activating the Torso receptor tyrosine kinase in early embryo patterning, also regulates the insulin signaling pathway in Drosophila. We previously reported that the small body size and developmental delay phenotypes of torso-like null mutants resemble those observed when insulin signaling is reduced. Here we report that, in addition to growth defects, torso-like mutants also display metabolic and nutritional plasticity phenotypes characteristic of mutants with impaired insulin signaling. We further find that in the absence of torso-like, the expression of insulin-like peptides is increased, as is their accumulation in insulin-producing cells. Finally, we show that Torso-like is a component of the hemolymph and that it is required in the prothoracic gland to control developmental timing and body size. Taken together, our data suggest that the secretion of Torso-like from the prothoracic gland influences the activity of insulin signaling throughout the body in Drosophila.
Publisher: The Company of Biologists
Date: 15-07-2009
DOI: 10.1242/DEV.032672
Abstract: In holometabolous insects, a species-specific size, known as critical weight, needs to be reached for metamorphosis to be initiated in the absence of further nutritional input. Previously, we found that reaching critical weight depends on the insulin-dependent growth of the prothoracic glands (PGs)in Drosophila larvae. Because the PGs produce the molting hormone ecdysone, we hypothesized that ecdysone signaling switches the larva to a nutrition-independent mode of development post-critical weight. Wing discs from pre-critical weight larvae [5 hours after third instar ecdysis (AL3E)]fed on sucrose alone showed suppressed Wingless (WG), Cut (CT) and Senseless(SENS) expression. Post-critical weight, a sucrose-only diet no longer suppressed the expression of these proteins. Feeding larvae that exhibit enhanced insulin signaling in their PGs at 5 hours AL3E on sucrose alone produced wing discs with precocious WG, CT and SENS expression. In addition,knocking down the Ecdysone receptor (EcR) selectively in the discs also promoted premature WG, CUT and SENS expression in the wing discs of sucrose-fed pre-critical weight larvae. EcR is involved in gene activation when ecdysone is present, and gene repression in its absence. Thus, knocking down EcR derepresses genes that are normally repressed by unliganded EcR,thereby allowing wing patterning to progress. In addition, knocking down EcR in the wing discs caused precocious expression of the ecdysone-responsive gene broad. These results suggest that post-critical weight, EcR signaling switches wing discs to a nutrition-independent mode of development via derepression.
Publisher: Cold Spring Harbor Laboratory
Date: 25-11-2022
DOI: 10.1101/2021.11.25.469978
Abstract: Animals regulate their diet in order to maximise the expression of fitness traits that often have different nutritional needs. These nutritional trade-offs have been experimentally uncovered using the Geometric framework for nutrition (GF). However, current analytical methods to measure such responses rely on either visual inspection or complex models applied to multidimensional performance landscapes, making these approaches subjective, or conceptually difficult, computationally expensive, and in some cases inaccurate. This limits our ability to understand how animal nutrition evolved to support life-histories within and between species. Here, we introduce a simple trigonometric model to measure nutritional trade-offs in multidimensional landscapes (‘Nutrigonometry’). Nutrigonometry is both conceptually and computationally easier than current approaches, as it harnesses the trigonometric relationships of right-angle triangles instead of vector calculations. Using landmark GF datasets, we first show how polynomial (Bayesian) regressions can be used for precise and accurate predictions of peaks and valleys in performance landscapes, irrespective of the underlying structure of the data (i.e., in idual food intakes vs fixed diet ratios). Using trigonometric relationships, we then identified the known nutritional trade-off between lifespan and reproductive rate both in terms of nutrient balance and concentration. Nutrigonometry enables a fast, reliable and reproducible quantification of nutritional trade-offs in multidimensional performance landscapes, thereby broadening the potential for future developments in comparative research on the evolution of animal nutrition.
Publisher: The Royal Society
Date: 02-2021
DOI: 10.1098/RSOB.200373
Abstract: In both mammals and insects, steroid hormones play a major role in directing the animal's progression through developmental stages. To maximize fitness outcomes, steroid hormone production is regulated by the environmental conditions experienced by the animal. In insects, the steroid hormone ecdysone mediates transitions between developmental stages and is regulated in response to environmental factors such as nutrition. These environmental signals are communicated to the ecdysone-producing gland via the action of neuropeptide and peptide hormone signalling pathways. While some of these pathways have been well characterized, there is evidence to suggest more signalling pathways than has previously been thought function to control ecdysone production, potentially in response to a greater range of environmental conditions. Here, we review the neuropeptide and peptide hormone signalling pathways known to regulate the production of ecdysone in the model genetic insect Drosophila melanogaster , as well as what is known regarding the environmental signals that trigger these pathways. Areas for future research are highlighted that can further contribute to our overall understanding of the complex orchestration of environmental, physiological and developmental cues that together produce a functioning adult organism.
Publisher: Frontiers Media SA
Date: 06-02-2019
Publisher: Elsevier BV
Date: 02-2019
DOI: 10.1016/J.COIS.2018.08.006
Abstract: Nutrition plays a central role in fecundity, regulating the onset of reproductive maturity, egg production, and the survival and health of offspring from insects to humans. Although decades of research have worked to uncover how nutrition mediates these effects, it has proven difficult to disentangle the relative role of nutrients as the raw material for egg and offspring development versus their role in stimulating endocrine cascades necessary to drive development. This has been further complicated by the fact that both nutrients and the signalling cascades they regulate interact in complex ways to control fecundity. Separating the two effects becomes important when trying to understand how fecundity is regulated, and in devising strategies to offset the negative effects of nutrition on reproductive health. In this review, we use the extensive literature on egg development in the fruit fly Drosophila melanogaster to explore how the nutrients from food provide the building blocks and stimulate signalling cascades necessary for making an egg.
Publisher: Wiley
Date: 2007
DOI: 10.1002/BIES.20552
Abstract: Size control depends on both the regulation of growth rate and the control over when to stop growing. Studies of Drosophila melanogaster have shown that insulin and Target of Rapamycin (TOR) pathways play principal roles in controlling nutrition-dependent growth rates. A TOR-mediated nutrient sensor in the fat body detects nutrient availability, and regulates insulin signaling in peripheral tissues, which in turn controls larval growth rates. After larvae initiate metamorphosis, growth stops. For growth to stop at the correct time, larvae need to surpass a critical weight. Recently, it was found that the insulin-dependent growth of the prothoracic gland is involved in assessing when critical weight has been reached. Furthermore, mutations in DHR4, a repressor of ecdysone signaling, reduce critical weight and adult size. Thus, the mechanisms that control growth rates converge on those assessing size to ensure that the larvae attain the appropriate size at metamorphosis.
Publisher: Public Library of Science (PLoS)
Date: 29-02-2016
Publisher: Frontiers Media SA
Date: 16-02-2022
DOI: 10.3389/FCELL.2022.822685
Abstract: Nutrition shapes a broad range of life-history traits, ultimately impacting animal fitness. A key fitness-related trait, female fecundity is well known to change as a function of diet. In particular, the availability of dietary protein is one of the main drivers of egg production, and in the absence of essential amino acids egg laying declines. However, it is unclear whether all essential amino acids have the same impact on phenotypes like fecundity. Using a holidic diet, we fed adult female Drosophila melanogaster diets that contained all necessary nutrients except one of the 10 essential amino acids and assessed the effects on egg production. For most essential amino acids, depleting a single amino acid induced as rapid a decline in egg production as when there were no amino acids in the diet. However, when either methionine or histidine were excluded from the diet, egg production declined more slowly. Next, we tested whether GCN2 and TOR mediated this difference in response across amino acids. While mutations in GCN2 did not eliminate the differences in the rates of decline in egg laying among amino acid drop-out diets, we found that inhibiting TOR signalling caused egg laying to decline rapidly for all drop-out diets. TOR signalling does this by regulating the yolk-forming stages of egg chamber development. Our results suggest that amino acids differ in their ability to induce signalling via the TOR pathway. This is important because if phenotypes differ in sensitivity to in idual amino acids, this generates the potential for mismatches between the output of a pathway and the animal’s true nutritional status.
Publisher: Cold Spring Harbor Laboratory
Date: 29-03-2020
DOI: 10.1101/2020.03.26.010538
Abstract: Diet composition, especially the relative abundance of key macronutrients, is well known to affect animal wellbeing by changing reproductive output, metabolism and length of life. However, less attention has been paid to the ways the quality of these nutrients modify these macronutrient interactions. Nutritional Geometry can be used to model the effects of multiple dietary components on life-history traits and to compare these responses when diet quality is varied. Previous studies have shown that dietary protein quality can be increased for egg production in Drosophila melanogaster by matching the dietary amino acid proportions to the balance of amino acids used by the sum of proteins in the fly’s in silico translated exome. Here, we show that dietary protein quality dramatically alters the effect of protein quantity on female reproduction across a broad range of diets varying in both protein and carbohydrate concentrations. These data show that when sources of ingredients vary, their relative value to the consumer can vastly differ and yield very different physiological outcomes. Such variations could be particularly important for meta analyses that look to draw generalisable conclusions from erse studies.
Publisher: Elsevier BV
Date: 2022
Publisher: Public Library of Science (PLoS)
Date: 13-02-2023
DOI: 10.1371/JOURNAL.PGEN.1010635
Abstract: Dietary nutrient composition is essential for shaping important fitness traits and behaviours. Many organisms are protein limited, and for Drosophila melanogaster this limitation manifests at the level of the single most limiting essential Amino Acid (AA) in the diet. The identity of this AA and its effects on female fecundity is readily predictable by a procedure called exome matching in which the sum of AAs encoded by a consumer’s exome is used to predict the relative proportion of AAs required in its diet. However, the exome matching calculation does not weight AA contributions to the overall profile by protein size or expression. Here, we update the exome matching calculation to include these weightings. Surprisingly, although nearly half of the transcriptome is differentially expressed when comparing male and female flies, we found that creating transcriptome-weighted exome matched diets for each sex did not enhance their fecundity over that supported by exome matching alone. These data indicate that while organisms may require different amounts of dietary protein across conditions, the relative proportion of the constituent AAs remains constant. Interestingly, we also found that exome matched AA profiles are generally conserved across taxa and that the composition of these profiles might be explained by energetic and elemental limitations on microbial AA synthesis. Thus, it appears that ecological constraints amongst autotrophs shape the relative proportion of AAs that are available across trophic levels and that this constrains biomass composition.
Publisher: Cold Spring Harbor Laboratory
Date: 16-12-2020
DOI: 10.1101/2020.12.16.423141
Abstract: Animals develop in unpredictable, variable environments. In response to environmental change some aspects of development adjust to generate plastic phenotypes. Other aspects of development, however, are buffered against environmental change to produce robust phenotypes. How organ development is coordinated to accommodate both plastic and robust developmental responses is poorly understood. Here, we demonstrate that the steroid hormone ecdysone coordinates both plasticity of organ size and robustness of organ pattern in the developing wings of the fruit fly Drosophila melanogaster . Using fed and starved larvae that lack prothoracic glands, which synthesise ecdysone, we show that nutrition regulates growth both via ecdysone and via an ecdysone-independent mechanism, while nutrition regulates patterning only via ecdysone. We then demonstrate that growth shows a graded response to ecdysone concentration, while patterning shows a threshold response. Collectively, these data support a model where nutritionally-regulated ecdysone fluctuations confer plasticity by regulating disc growth in response to basal ecdysone levels, and confers robustness by initiating patterning only once ecdysone peaks exceeds a threshold concentration. This could represent a generalizable mechanism through which hormones coordinate plastic growth with robust patterning in the face of environmental change.
Publisher: Elsevier BV
Date: 02-2021
Publisher: Wiley
Date: 10-08-2020
DOI: 10.1111/EVO.14065
Publisher: The Company of Biologists
Date: 04-2010
DOI: 10.1242/DEV.037218
Abstract: To elucidate the role of juvenile hormone (JH) in metamorphosis of Drosophila melanogaster, the corpora allata cells, which produce JH, were killed using the cell death gene grim. These allatectomized (CAX) larvae were smaller at pupariation and died at head eversion. They showed premature ecdysone receptor B1 (EcR-B1) in the photoreceptors and in the optic lobe, downregulation of proliferation in the optic lobe, and separation of R7 from R8 in the medulla during the prepupal period. All of these effects of allatectomy were reversed by feeding third instar larvae on a diet containing the JH mimic (JHM) pyriproxifen or by application of JH III or JHM at the onset of wandering. Eye and optic lobe development in the Methoprene-tolerant (Met)-null mutant mimicked that of CAX prepupae, but the mutant formed viable adults, which had marked abnormalities in the organization of their optic lobe neuropils. Feeding Met27 larvae on the JHM diet did not rescue the premature EcR-B1 expression or the downregulation of proliferation but did partially rescue the premature separation of R7, suggesting that other pathways besides Met might be involved in mediating the response to JH. Selective expression of Met RNAi in the photoreceptors caused their premature expression of EcR-B1 and the separation of R7 and R8, but driving Met RNAi in lamina neurons led only to the precocious appearance of EcR-B1 in the lamina. Thus, the lack of JH and its receptor Met causes a heterochronic shift in the development of the visual system that is likely to result from some cells ‘misinterpreting’ the ecdysteroid peaks that drive metamorphosis.
Publisher: The Royal Society
Date: 06-05-2008
Abstract: The regulation of static allometry is a fundamental developmental process, yet little is understood of the mechanisms that ensure organs scale correctly across a range of body sizes. Recent studies have revealed the physiological and genetic mechanisms that control nutritional variation in the final body and organ size in holometabolous insects. The implications these mechanisms have for the regulation of static allometry is, however, unknown. Here, we formulate a mathematical description of the nutritional control of body and organ size in Drosophila melanogaster and use it to explore how the developmental regulators of size influence static allometry. The model suggests that the slope of nutritional static allometries, the ‘allometric coefficient’, is controlled by the relative sensitivity of an organ's growth rate to changes in nutrition, and the relative duration of development when nutrition affects an organ's final size. The model also predicts that, in order to maintain correct scaling, sensitivity to changes in nutrition varies among organs, and within organs through time. We present experimental data that support these predictions. By revealing how specific physiological and genetic regulators of size influence allometry, the model serves to identify developmental processes upon which evolution may act to alter scaling relationships.
Publisher: eLife Sciences Publications, Ltd
Date: 25-11-2014
DOI: 10.7554/ELIFE.03091
Abstract: Despite their fundamental importance for body size regulation, the mechanisms that stop growth are poorly understood. In Drosophila melanogaster, growth ceases in response to a peak of the molting hormone ecdysone that coincides with a nutrition-dependent checkpoint, critical weight. Previous studies indicate that insulin/insulin-like growth factor signaling (IIS)/Target of Rapamycin (TOR) signaling in the prothoracic glands (PGs) regulates ecdysone biosynthesis and critical weight. Here we elucidate a mechanism through which this occurs. We show that Forkhead Box class O (FoxO), a negative regulator of IIS/TOR, directly interacts with Ultraspiracle (Usp), part of the ecdysone receptor. While overexpressing FoxO in the PGs delays ecdysone biosynthesis and critical weight, disrupting FoxO–Usp binding reduces these delays. Further, feeding ecdysone to larvae eliminates the effects of critical weight. Thus, nutrition controls ecdysone biosynthesis partially via FoxO–Usp prior to critical weight, ensuring that growth only stops once larvae have achieved a target nutritional status.
Publisher: Elsevier BV
Date: 02-2005
Publisher: Cold Spring Harbor Laboratory
Date: 19-12-2019
DOI: 10.1101/2019.12.18.880708
Abstract: Adult body size is determined by the quality and quantity of nutrients available to animals. In insects, nutrition affects adult size primarily during the nymphal or larval stages. However, measures of adult size like body weight are likely to also change with adult nutrition. In this study, we sought to the roles of nutrition throughout the life cycle on adult body weight and the size of two appendages, the wing and the femur, in the fruit fly Drosophila melanogaster . We manipulated nutrition in two ways: by varying the protein to carbohydrate content of the diet, called macronutrient restriction, and by changing the caloric density of the diet, termed caloric restriction. We employed a fully factorial design to manipulate both the larval and adult diets for both diet types. We found that manipulating the larval diet had greater impacts on all measures of adult size. Further, macronutrient restriction was more detrimental to adult size than caloric restriction. For adult body weight, a rich adult diet mitigated the negative effects of poor larval nutrition for both types of diets. In contrast, small wing and femur size caused by poor larval diet could not be increased with the adult diet. Taken together, these results suggest that appendage size is fixed by the larval diet, while those related to body composition remain sensitive to adult diet. Further, our studies provide a foundation for understanding how the nutritional environment of juveniles affects how adults respond to diet.
Publisher: Wiley
Date: 05-09-2020
Publisher: Frontiers Media SA
Date: 2012
Publisher: Public Library of Science (PLoS)
Date: 19-06-2014
Publisher: University of Chicago Press
Date: 05-2023
DOI: 10.1086/723599
Publisher: Springer Science and Business Media LLC
Date: 06-03-2019
Publisher: Elsevier BV
Date: 12-2017
DOI: 10.1016/J.GDE.2017.08.001
Abstract: The rise in obesity in human populations has reinvigorated research focused on how nutrition impacts life history traits, including body size, lifespan, reproductive success, stress resistance and propensity for disease. Studies have ranged in their approach from identifying the molecular machinery responding to changes in nutrient levels, to understanding the hormonal changes that occur in response to diet, to mapping the response of differing life history traits over complex dietary landscapes. Connecting insights across these approaches presents significant challenges primarily because we lack information about how signalling pathways respond to dietary complexity. Here, we offer our perspective on how to integrate insights from the cellular to the whole organism to understand the regulation of life history traits.
Publisher: Informa UK Limited
Date: 20-10-2014
DOI: 10.4161/CIB.29240
Publisher: eLife Sciences Publications, Ltd
Date: 07-10-2021
Publisher: Springer Science and Business Media LLC
Date: 23-10-2020
DOI: 10.1186/S40850-020-00063-5
Abstract: Organisms show an incredibly erse array of body and organ shapes that are both unique to their taxon and important for adapting to their environment. Achieving these specific shapes involves coordinating the many processes that transform single cells into complex organs, and regulating their growth so that they can function within a fully-formed body. Conceptually, body and organ shape can be separated in two categories, although in practice these categories need not be mutually exclusive. Body shape results from the extent to which organs, or parts of organs, grow relative to each other. The patterns of relative organ size are characterized using allometry. Organ shape, on the other hand, is defined as the geometric features of an organ’s component parts excluding its size. Characterization of organ shape is frequently described by the relative position of homologous features, known as landmarks, distributed throughout the organ. These descriptions fall into the domain of geometric morphometrics. In this review, we discuss the methods of characterizing body and organ shape, the developmental programs thought to underlie each, highlight when and how the mechanisms regulating body and organ shape might overlap, and provide our perspective on future avenues of research.
Publisher: Cold Spring Harbor Laboratory
Date: 09-2020
DOI: 10.1101/2020.09.01.277046
Abstract: Organ growth is tightly regulated across environmental conditions to generate appropriate final size. While the size of some organs is free to vary, others need to maintain constant size to function properly. This poses a unique problem: how is robust final size achieved when environmental conditions can alter some major growth processes? While we know that brain growth is “spared” from the effects of the environment from humans to fruit flies, we do not understand how this process alters growth dynamics across brain compartments. Here, we explore how this robustness in brain size is achieved by examining differences in growth patterns between the larval body, the brain, and a brain compartment – the mushroom bodies – in Drosophila melanogaster across both thermal and nutritional conditions. We identify key differences in patterns of growth between the whole brain and mushroom bodies that are likely to underlie robustness of final organ shape. Further, we show that these differences produce distinct brain shapes across environments. A long-standing question in Biology has been how fully functional multicellular organisms with highly specialized organs are generated, given that organs initiate growth at different times across development. Although the genetic mechanisms that underlie growth has been studied extensively, we are yet to understand how growth pattern of organs produces distinct final shapes across changing environmental conditions. We use the Drosophila brain, to reveal that key differences in growth dynamics are likely to underlie robustness of final organ shape and are tuned by nutrition and temperature. Further deepening our knowledge of how final organ shape is maintained across environmental conditions.
Publisher: Elsevier BV
Date: 2023
Publisher: The Company of Biologists
Date: 07-2017
DOI: 10.1242/JEB.156646
Abstract: Mapping brain function to brain structure is a fundamental task for neuroscience. For such an endeavour, the Drosophila larva is simple enough to be tractable, yet complex enough to be interesting. It features about 10,000 neurons and is capable of various taxes, kineses and Pavlovian conditioning. All its neurons are currently being mapped into a light-microscopical atlas, and Gal4 strains are being generated to experimentally access neurons one at a time. In addition, an electron microscopic reconstruction of its nervous system seems within reach. Notably, this electron microscope-based connectome is being drafted for a stage 1 larva – because stage 1 larvae are much smaller than stage 3 larvae. However, most behaviour analyses have been performed for stage 3 larvae because their larger size makes them easier to handle and observe. It is therefore warranted to either redo the electron microscopic reconstruction for a stage 3 larva or to survey the behavioural faculties of stage 1 larvae. We provide the latter. In a community-based approach we called the Ol1mpiad, we probed stage 1 Drosophila larvae for free locomotion, feeding, responsiveness to substrate vibration, gentle and nociceptive touch, burrowing, olfactory preference and thermotaxis, light avoidance, gustatory choice of various tastants plus odour–taste associative learning, as well as light/dark–electric shock associative learning. Quantitatively, stage 1 larvae show lower scores in most tasks, arguably because of their smaller size and lower speed. Qualitatively, however, stage 1 larvae perform strikingly similar to stage 3 larvae in almost all cases. These results bolster confidence in mapping brain structure and behaviour across developmental stages.
Publisher: Frontiers Media SA
Date: 03-02-2015
Publisher: Elsevier BV
Date: 07-2007
DOI: 10.1016/J.YMGME.2007.02.003
Abstract: Calreticulin (CRT) is a Ca(2+)-binding protein of the endoplasmic reticulum essential for cardiac development. For further investigation of the functional mechanism of calreticulin, we generated transgenic mice with spatiotemporal overexpression of calreticulin using a cre-loxP system. To elucidate the role of the protein in cardiogenesis, we adopted Nkx2.5-cre mice for heart specific overexpression. The overexpression of calreticulin was associated with arrhythmia, chamber dilation and sudden death, as observed in 6- to 10-week-old mice. Furthermore, transgenic mice displayed marked edema at 7-weeks of age. RT-PCR analysis revealed that the expression of hyperpolerization-activated cyclic nucleotide-gated channel1 (HCN1), an essential component for cardiac pace maker activity, had receded in the heart of transgenic mice. In addition, the protein level of connexin40 (Cx40), connexin43 (Cx43), components of gap junction, and myocyte-enhancer factor (MEF) 2C, a cardiac-specific transcriptional factor, were reduced in the transgenic mice hearts. These findings suggest that calreticulin affects cardiac arrhythmia with disruption of cardiac signaling, such as the HCN family members, and with low levels of Cx40 and Cx43. Overepression of calreticulin also leads to a decreased protein level of MEF2C and this may cause changes in cardiac structure. Our findings support calreticulin being critical for normal heart function and structure. These mice are a useful model for the study of endoplasmic reticulum proteins, such as calreticulin, in various tissues.
Location: United States of America
Location: United Kingdom of Great Britain and Northern Ireland
Start Date: 07-2017
End Date: 12-2021
Amount: $736,828.00
Funder: Australian Research Council
View Funded ActivityStart Date: 2016
End Date: 06-2021
Amount: $379,400.00
Funder: Australian Research Council
View Funded Activity