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A High-Resolution Atlas of the Brain Predicts Lineage and Birth Order Underly Neuronal Identity.

Allen, A. M.; Neville, M. C.; Nojima, T.; Alejevski, F.; Agarwal, D.; Sims, D.; Goodwin, S. F.

2025-06-05 neuroscience
10.1101/2025.06.04.657818 bioRxiv
Show abstract

Gene expression shapes the nervous system at every biological level, from molecular and cellular processes defining neuronal identity and function to systems-level wiring and circuit dynamics underlying behaviour. Here, we generate the first high-resolution, single-cell transcriptomic atlas of the adult Drosophila melanogaster central brain by integrating multiple datasets, achieving an unprecedented tenfold coverage of every neuron in this complex tissue. We show that a neurons genetic identity overwhelmingly reflects its developmental origin, preserving a genetic address based on both lineage and birth order. We reveal foundational rules linking neurogenesis to transcriptional identity and provide a framework for systematically defining neuronal types. This atlas provides a powerful resource for mapping the cellular substrates of behaviour by integrating annotations of hemilineage, cell types/subtypes and molecular signatures of underlying physiological properties. It lays the groundwork for a long-sought bridge between developmental processes and the functional circuits that give rise to behaviour.

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