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Despite the fact that metabolic studies played a prominent role in the early history of developmental biology research, the field of developmental metabolism was largely ignored following the advent of modern molecular biology. Metabolism, however, has recently re-emerged as a focal point of biomedical studies and, as a result, developmental biologists are once again exploring the chemical and energetic forces that shape growth, development and maturation. In May 2017, a diverse group of scientists assembled at the EMBO/EMBL Symposium 'Metabolism in Time and Space' to discuss how metabolism influences cellular and developmental processes. The speakers not only described how metabolic flux adapts to the energetic needs of a developing organism, but also emphasized that metabolism can directly regulate developmental progression. Overall, and as we review here, this interdisciplinary meeting provided a valuable forum to explore the interface between developmental biology and metabolism., Competing Interests: Competing interestsThe authors declare no competing or financial interests., (© 2017. Published by The Company of Biologists Ltd.)

The field of developmental metabolism is experiencing a technological revolution that is opening entirely new fields of inquiry. Advances in metabolomics, small-molecule sensors, single-cell RNA sequencing and computational modeling present new opportunities for exploring cell-specific and tissue-specific metabolic networks, interorgan metabolic communication, and gene-by-metabolite interactions in time and space. Together, these advances not only present a means by which developmental biologists can tackle questions that have challenged the field for centuries, but also present young scientists with opportunities to define new areas of inquiry. These emerging frontiers of developmental metabolism were at the center of a highly interactive 2023 EMBO workshop 'Developmental metabolism: flows of energy, matter, and information'. Here, we summarize key discussions from this forum, emphasizing modern developmental biology's challenges and opportunities. [ABSTRACT FROM AUTHOR]

Sustaining life requires efficient uptake of nutrients and conversion to useable forms. Almost everything about this process is dynamic. Nutrient availability fluctuates and changing environmental conditions impose new demands that can tip the metabolic equilibrium from biosynthesis and macromolecule storage to energy expenditure. At the same time, the organism itself changes, particularly during the rapid growth and differentiation in early development and also later in life as the adult ages. Here we review what has been learned from Drosophila melanogaster as an experimental model about the connections between external signals, signaling pathways, tissues and organs that allow animals to balance energy storage with expenditure in the face of change, both intrinsic and extrinsic. • Drosophila melanogaster is a powerful experimental system to study energy balance. • Communication between different organs/tissues is key for maintaining energy balance. • Nutritional requirements vary between different stages of organismal development. • Conserved signaling pathways link energy expenditure and storage to availability. [ABSTRACT FROM AUTHOR]

Developmental biologists have frequently pushed the frontiers of modern biomedical research. From the discovery and characterization of novel signal transduction pathways to exploring the molecular underpinnings of genetic inheritance, transcription, the cell cycle, cell death and stem cell biology, studies of metazoan development have historically opened new fields of study and consistently revealed previously unforeseen avenues of clinical therapies. From this perspective, it is not surprising that our community is now an integral part of the current renaissance in metabolic research. Amidst the global rise in metabolic syndrome, the discovery of novel signaling roles for metabolites, and the increasing links between altered metabolism and many human diseases, we as developmental biologists can contribute skills and expertise that are uniquely suited for investigating the mechanisms underpinning humanmetabolic health and disease. Here, we summarize the opportunities and challenges that our community faces, and discuss how developmental biologists canmake unique and valuable contributions to the field of metabolism and physiology. [ABSTRACT FROM AUTHOR]

Abstract: Recent research using Drosophila melanogaster has seen a resurgence in studies of metabolism and physiology. This review focuses on major methods used to conduct this work. These include protocols for dietary interventions, measurements of triglycerides, cholesterol, glucose, trehalose, and glycogen, stains for lipid detection, and the use of gas chromatography-mass spectrometry (GC-MS) to detect major polar metabolites. It is our hope that this will provide a useful framework for both new and current researchers in the field. [Copyright &y& Elsevier]

The ease of genetic manipulation in Drosophila melanogaster using the Gal4/UAS system has been beneficial in addressing key biological questions. Current modifications of this methodology to temporally induce transgene expression require temperature changes or exposure to exogenous compounds, both of which have been shown to have detrimental effects on physiological processes. The recently described auxin-inducible gene expression system (AGES) utilizes the plant hormone auxin to induce transgene expression and is proposed to be the least toxic compound for genetic manipulation, with no obvious effects on Drosophila development and survival in one wild-type strain. Here, we show that auxin delays larval development in another widely used fly strain, and that short- and long-term auxin exposure in adult Drosophila induces observable changes in physiology and feeding behavior. We further reveal a dosage response to adult survival upon auxin exposure, and that the recommended auxin concentration for AGES alters feeding activity. Furthermore, auxin-fed male and female flies exhibit a significant decrease in triglyceride levels and display altered transcription of fatty acid metabolism genes. Although fatty acid metabolism is disrupted, auxin does not significantly impact adult female fecundity or progeny survival, suggesting AGES may be an ideal methodology for studying limited biological processes. These results emphasize that experiments using temporal binary systems must be carefully designed and controlled to avoid confounding effects and misinterpretation of results. [ABSTRACT FROM AUTHOR]

Pyruvate kinase (Pyk) is a rate-limiting enzyme that catalyzes the final metabolic reaction in glycolysis. The importance of this enzyme, however, extends far beyond ATP production, as Pyk is also known to regulate tissue growth, cell proliferation, and development. Studies of this enzyme in Drosophila melanogaster are complicated by the fact that the fly genome encodes 6 Pyk paralogs whose functions remain poorly defined. To address this issue, we used sequence distance and phylogenetic approaches to demonstrate that the gene Pyk encodes the enzyme most similar to the mammalian Pyk orthologs, while the other 5 Drosophila Pyk paralogs have significantly diverged from the canonical enzyme. Consistent with this observation, metabolomic studies of 2 different Pyk mutant strains revealed that larvae lacking Pyk exhibit a severe block in glycolysis, with a buildup of glycolytic intermediates upstream of pyruvate. However, our analysis also unexpectedly reveals that pyruvate levels are unchanged in Pyk mutants, indicating that larval metabolism maintains pyruvate pool size despite severe metabolic limitations. Consistent with our metabolomic findings, a complementary RNA-seq analysis revealed that genes involved in lipid metabolism and protease activity are elevated in Pyk mutants, again indicating that loss of this glycolytic enzyme induces compensatory changes in other aspects of metabolism. Overall, our study provides both insight into how Drosophila larval metabolism adapts to disruption of glycolytic metabolism as well as immediate clinical relevance, considering that Pyk deficiency is the most common congenital enzymatic defect in humans. [ABSTRACT FROM AUTHOR]

Metabolomic analysis provides a powerful new tool for studies of Drosophila physiology. This approach allows investigators to detect thousands of chemical compounds in a single sample, representing the combined contributions of gene expression, enzyme activity, and environmental context. Metabolomics has been used for a wide range of studies in Drosophila, often providing new insights into gene function and metabolic state that could not be obtained using any other approach. In this review, we survey the uses of metabolomic analysis since its entry into the field. We also cover the major methods used for metabolomic studies in Drosophila and highlight new directions for future research. [ABSTRACT FROM AUTHOR]

The metabolic enzymes that compose glycolysis, the citric acid cycle, and other pathways within central carbon metabolism have emerged as key regulators of animal development. These enzymes not only generate the energy and biosynthetic precursors required to support cell proliferation and differentiation, but also moonlight as regulators of transcription, translation, and signal transduction. Many of the genes associated with animal metabolism, however, have never been analyzed in a developmental context, thus highlighting how little is known about the intersection of metabolism and development. Here we address this deficiency by using the Drosophila TRiP RNAi collection to disrupt the expression of over 1,100 metabolism-associated genes within cells of the eye imaginal disc. Our screen not only confirmed previous observations that oxidative phosphorylation serves a critical role in the developing eye, but also implicated a host of other metabolic enzymes in the growth and differentiation of this organ. Notably, our analysis revealed a requirement for glutamine and glutamate metabolic processes in eye development, thereby revealing a role of these amino acids in promoting Drosophila tissue growth. Overall, our analysis highlights how the Drosophila eye can serve as a powerful tool for dissecting the relationship between development and metabolism. [ABSTRACT FROM AUTHOR]

The fruit fly Drosophila melanogaster has emerged as a powerful model for investigating the molecular mechanisms that regulate animal metabolism. However, a major limitation of these studies is that many metabolic assays are tedious, dedicated to analyzing a single molecule, and rely on indirect measurements. As a result, Drosophila geneticists commonly use candidate gene approaches, which, while important, bias studies toward known metabolic regulators. In an effort to expand the scope of Drosophila metabolic studies, we used the classic mutant lysine (lys) to demonstrate how a modern metabolomics approach can be used to conduct forward genetic studies. Using an inexpensive and well-established gas chromatography-mass spectrometry-based method, we genetically mapped and molecularly characterized lys by using free lysine levels as a phenotypic readout. Our efforts revealed that lys encodes the Drosophila homolog of Lysine Ketoglutarate Reductase/Saccharopine Dehydrogenase, which is required for the enzymatic degradation of lysine. Furthermore, this approach also allowed us to simultaneously survey a large swathe of intermediate metabolism, thus demonstrating that Drosophila lysine catabolism is complex and capable of influencing seemingly unrelated metabolic pathways. Overall, our study highlights how a combination of Drosophila forward genetics and metabolomics can be used for unbiased studies of animal metabolism, and demonstrates that a single enzymatic step is intricately connected to diverse aspects of metabolism. [ABSTRACT FROM AUTHOR]