All cells rely on a complex set of metabolic processes to generate energy and produce the building blocks for cellular membranes and macromolecules. In addition to these fundamental functions for metabolic pathways, it has become increasingly clear – particularly from work in the cancer field – that metabolites can have instructive roles on cell behaviour via effects on gene expression and signalling. Development is another obvious context in which cells may also use metabolic cues, alongside genetic regulation, to rapidly integrate spatial information and signals that occur during key developmental processes, such as patterning, cell fate determination and morphogenesis. However, the extent to which nutrients and metabolites play instructive roles during development and regeneration is only beginning to be uncovered.
In this Special Issue, we highlight this exciting and rapidly developing field through a set of research and review-type articles that examine the relationship between metabolic and developmental processes in a diverse range of systems across both plant and animal kingdoms. Moreover, these research articles also demonstrate the diversity of metabolic pathways involved in development. One-carbon metabolism, which produces units for methylation, nucleotide and amino acid biosynthesis, is implicated in controlling neurogenic transitions in the mouse neocortex (Saha et al., 2023), development of the neuroepithelia in the Drosophila optic lobe (Silva et al., 2023) and intestinal development and homeostasis in mice (Li et al., 2023). Amino acids themselves can have important signalling functions: L-proline exhibits growth factor-like properties that induce mouse embryonic stem cell differentiation (Glover et al., 2023) and glutamine protects spermatogonial stem cells from reactive oxygen species generated through mitochondrial oxidative metabolism (Miyazaki et al., 2023). In addition to amino acids, the importance of carbohydrate metabolism is shown through the response of the plant root meristem to sugar signalling (Olatunji et al., 2023) and the role of sugar and starch metabolism in wheat grain development (Xu et al., 2023). Dietary sugar also plays a role in determining Drosophila fertility, independent of its adipogenic effects (Dutra Nunes and Drummond-Barbosa, 2023). Further experiments in Drosophila reveal additional functions of lipid metabolism and storage: lipid droplets are spatially sorted within the embryo (Kilwein et al., 2023) and lipid droplet cargo release is dynamically regulated for developmental processes (Giedt et al., 2023). Finally, the developmental roles of iron metabolism, required for heme biosynthesis, are also highlighted. Heme deficiency in zebrafish red blood cells is detrimental to haematopoietic stem/progenitor cell survival (Lv and Liu, 2023), while iron deficiency in the gestational mouse affects interneuron subtype specification in the neocortex (Rudy et al., 2023).
In the review-type articles, Ferenc and Ikmi provide an overview of the nutritional control of development in different species (Ferenc and Ikmi, 2023) and Tu and colleagues describe specific roles of nutrients, such as vitamins, in mammalian development, differentiation and disease (Tu et al., 2023). In addition, Zhao and colleagues survey the dynamic metabolic changes that occur during early mammalian development to meet context-specific requirements, such as global epigenetic modifications during zygotic genome activation (Zhao et al., 2023). In a similar vein, Mahmoud illustrates how metabolic transitions are necessary to adapt to changing environments, animal development and tissue regeneration (Mahmoud, 2023). Furthermore, Vanderwall and Gendron summarise how mechanisms that sense metabolic states regulate growth and development in plants (Vanderwall and Gendron, 2023). Tippetts and colleagues discuss how metabolites function in animal developmental signalling and diapause, both as substrates for ligand modifications and as signalling cues themselves (Tippetts et al., 2023). Finally, Suzawa and Bland provide a concise overview of how a key metabolic signal, insulin, functions within a whole organism (Suzawa and Bland, 2023), and Kramer and colleagues discuss placental metabolic communication that influences maternal and fetal growth and development (Kramer et al., 2023).
Together, these articles illustrate the power of developmental systems in linking metabolic, genetic and signalling programmes, and demonstrate some of the many ways in which dynamic metabolic activity can influence developmental processes. As the field continues to grow, we look forward to opportunities to uncover how metabolism interacts with other cues, such as mechanical feedback.
We hope this issue piques your interest and that you will continue to consider the diverse functions of metabolism in the context of developmental biology. We also hope that you will submit your next article in this growing field to Development.
