Epidermal cell fusion promotes the transition from an embryonic to a larval transcriptome in C. elegans

Cell fusion is a fundamental process in the development of many multicellular organisms but its precise role in gene regulation and differentiation remains largely unknown. The Caenorhabditis elegans epidermis, which is comprised of multiple syncytial cells in the adult, represents a powerful model for studying cell fusion in the context of animal development. The largest of these epidermal syncytia, hyp7, integrates 139 individual nuclei through processive cell fusion mediated by the fusogenic protein EFF-1. To explore the role of cell fusion on developmental progression and associated gene expression changes, we conducted transcriptomic analyses of eff-1 fusion-defective C. elegans mutants. Our RNAseq findings showed widespread transcriptomic changes including the enrichment of epidermal genes and molecular pathways involved in epidermal function during development. Single-molecule fluorescence in situ hybridization further validated the observed altered expression of mRNA transcripts. Moreover, bioinformatic analysis suggests that fusion may play a key role in promoting developmental progression within the epidermis. Our results underscore the significance of cell-cell fusion in shaping transcriptional programs during development. Summary Statementeff-1 meditated cell fusion drives transcriptomic progression from an embryonic to larval state in the C. elegans epidermis, without which developmental progression is delayed.