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Evolutionarily conserved transcriptional regulators control monoaminergic neuron development

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Item Type:Preprint
Title:Evolutionarily conserved transcriptional regulators control monoaminergic neuron development
Creators: Lewis, Clifton ORCID logoORCID: https://orcid.org/0000-0002-3077-8150, Goulty, Matthew ORCID logoORCID: https://orcid.org/0009-0001-5731-6722, Wroblewska, Aniela, Croxall, Nicola ORCID logoORCID: https://orcid.org/0009-0003-1061-6909, Onion, David ORCID logoORCID: https://orcid.org/0000-0002-4522-2307, Robinson, Sue, Zinzen, Robert P. ORCID logoORCID: https://orcid.org/0000-0002-8638-5102, Solana, Jordi ORCID logoORCID: https://orcid.org/0000-0002-6770-3929, Kyriacou, Charalambos P. ORCID logoORCID: https://orcid.org/0000-0003-4889-7606, Rosato, Ezio ORCID logoORCID: https://orcid.org/0000-0001-7297-4697 and Feuda, Roberto ORCID logoORCID: https://orcid.org/0000-0003-0857-1732
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.
Source:bioRxiv
Publisher:Cold Spring Harbor Laboratory Press
Article Number:2025.10.29.685200v2
Date:31 October 2025
Official Publication:https://doi.org/10.1101/2025.10.29.685200
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