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Lifelong maintenance of locomotion by embryonically active dopamine neurons

Padmanabhan, A.; Rahman, D.; Zhu, R.; Khorbtli, S.; Sathianathan, S.; Le Flohic, B.; Assanga Bisse, L.; Mollereau, B.; Huang, C.; Konstantinides, N.; Issa, A. R.

2025-12-02 neuroscience
10.64898/2025.11.28.691140 bioRxiv
Show abstract

Locomotor skills arise early in life and must be maintained throughout an animals lifespan, yet how this continuity is achieved despite major neural remodeling remains unclear. Using Drosophila, which undergoes complete metamorphosis, we show that dopamine neurons (DANs) are active during the embryonic stage and that this early activity is essential for locomotion across all developmental stages and adulthood. Through stage-specific behavioral assays, optogenetics, in vivo brain imaging, and fluorescent neuronal tracking, we identify a subset of ventral nervous system (VNS) DANs that modulate locomotor function throughout life. Transcriptomic analyses reveal that they maintain expression of developmental transcription factors. Knocking down these factors in post-mitotic VNS DANs impairs adult locomotion. These findings uncover a previously overlooked function for embryonic DANs and suggest that stable locomotion during nervous system maturation relies on persistent developmental regulator expression coupled with structural remodeling. HighlightsO_LILocomotor dopamine neurons (DANs) are already active in the Drosophila embryo C_LIO_LIDAN embryonic activity is essential for lifelong locomotor function C_LIO_LISelect embryo-born DANs undergo structural remodeling to maintain locomotion across developmental stages C_LIO_LIThese DANs remain functional by preserving their developmental identity and gene expression programs C_LI

Published in Cell Reports (predicted rank #2) · training set

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