Metabolism and Development
It has long been known that metabolic demands evolve during different stages of mammalian embryogenesis, and that metabolic anomalies (e.g. nutritional deficiencies in the mother) can interfere with organogenesis. We want to decode the relationships between particular metabolic activities and particular developmental events, and IEMs provide a valuable starting point to this challenge. Because IEMs are monogenic disorders, all aspects of these diseases arise from mutation of a single node in the metabolic network. Some IEMs cause defects in organogenesis, indicating that particular metabolic activities are required for specific aspects of development. We are interested in malformations and defects in lineage commitment that arise downstream of human IEM mutations. As a system to study these mutations in mice, we developed an approach to observe metabolic activities across time and location during mid-gestation in utero (see figure, Solmonson et al, Nature 2022). This has allowed us to detect evolving, tissue-specific patterns of nutrient utilization in the developing embryo, and to pinpoint how IEMs perturb these patterns.
