Evolutionarily conserved transcriptional regulators control monoaminergic neuron development

Lewis, C.; Goulty, M.; Wroblewska, A.; Croxall, N.; Onion, D.; Robinson, S.; Zinzen, R. P.; Solana, J.; Kyriacou, C. P.; Rosato, E.; Feuda, R.

doi:10.1101/2025.10.29.685200

bioRxiv · 10.1101/2025.10.29.685200

Evolutionarily conserved transcriptional regulators control monoaminergic neuron development

Lewis, C.·Goulty, M.·Wroblewska, A.·Croxall, N.·Onion, D.·Robinson, S.·Zinzen, R. P.·Solana, J.·Kyriacou, C. P.·Rosato, E.·Feuda, R.

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Abstract

To what extent conserved developmental programs specify homologous cell types is a central question in biology. Here, we address this by focusing on reconstructing monoaminergic neuron development in Drosophila melanogaster embryo using time- resolved single-cell genomics, spatial transcript mapping with hybridisation chain reaction, and targeted metabolomics. We uncover a regulatory landscape in which specific transcription factors are activated before biosynthetic enzymes, establishing a prospective temporal architecture for monoaminergic fate specification. Comparative analyses of developmental single-cell atlases from zebrafish and sea urchin indicate that components of this machinery are conserved across [~]550 million years of bilaterian evolution with orthologous transcription factors showing similar temporal dynamics. Together, these findings point to a putatively conserved regulatory core that interfaces with other context-dependent transcription factors; this interplay accommodates monoaminergic multifunction and subtype diversity across distinct neuroanatomies.

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Lewis, C., Goulty, M., Wroblewska, A., Croxall, N., Onion, D., Robinson, S., Zinzen, R. P., Solana, J., Kyriacou, C. P., Rosato, E., Feuda, R.. 2025-10-29. Evolutionarily conserved transcriptional regulators control monoaminergic neuron development. https://doi.org/10.1101/2025.10.29.685200

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