Novel single-nucleus transcriptomics unravels developmental and functionally controlled principles of mammalian neuromuscular junctions.

Prof Ohno's team (Ohkawara et al. 2023, current issue) underscored the dynamic and functional features that co-shape the embryonic and early post-natal development of mammalian neuromuscular junctions (NMJs) using single-nucleus transcriptomics which provides specific insights into the activities of individually studied nuclei and their functional characteristics. Unlike other single-nucleus transcriptomics studies, which tend to be limited to single developmental time points, this article provides novel views of the complex developmental and regulatory dynamics and embryonic cell type origins underscoring the formation of functioning mammalian NMJs by combining this transcriptomic approach with interference tests in cultured C2C12 myotubes. This reveals intriguing novel links between the particular nicotinic acetylcholine receptor genes (nAChR) and regulator transcripts thereof and enables outlining the sequential development of functioning NMJs along embryogenesis and soon after delivery. Specifically, the timewise and cell type origins of the studied nuclei emerged as essential for NMJ neurogenesis and inter-cellular transfer of specific regulators has been indicated. Breaking the barriers between distinct research subdisciplines, this study opens new neurochemistry research directions that recombine developmental, regulatory, and functional transcriptomics in NMJ-including tissues. Moreover, these findings may facilitate tests of diverse pharmaceutical and therapeutic modulators of neuromuscular functioning in health and disease, assisting the translational research progress in treating devastating neuromuscular states such as in amyotrophic lateral sclerosis, myasthenia gravis or individuals poisoned occupationally or otherwise with anticholinesterase inhibitors.