Resolving early embryonic metabolism in Drosophila through single-embryo metabolomics and transcriptomics.

Early embryonic development marks a shift from maternal factor reliance to zygotic control. Although transcriptional regulation during this period is well characterized, concurrent metabolic events remain largely unknown. Progress has been limited by technical challenges in analysing the small amounts of material and the rapid progression of development. Here, we present a high-resolution, single-embryo multi-omics dataset that captures transcriptional and metabolic dynamics during the first 3 h of Drosophila development. By profiling individual embryos, we uncover stage-specific transcriptional and metabolic programmes, including previously unrecognized transitions in nucleotides, amino acids and other metabolites. Integration of metabolites and transcript modules reveals a limited, selective functional coupling between metabolism and gene expression. This work reframes the maternal-to-zygotic transition as both a transcriptional and metabolic handoff and provides a valuable framework for studying metabolic regulation during development and beyond.