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Evolutionarily conserved transcriptional regulators control monoaminergic neuron development

2025/10/29 by Clifton Lewis, Matthew Goulty, Aniela Wroblewska +8 · 1 voice
Biochemistry, Genetics and Molecular Biology · #Developmental Biology and Gene Regulation #Single-cell and spatial transcriptomics #Zebrafish Biomedical Research Applications

paper · pdf · doi:10.1101/2025.10.29.685200

Abstract

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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