Spatiotemporal proteomic and transcriptomic landscape of DAT+ dopaminergic neurons development and function.

Dopaminergic (DA) neurons expressing the dopamine transporter (DAT) play vital roles in physiology and the regulation of mental and neurological disorders. This study investigates spatiotemporal proteomic and transcriptomic changes in DAT+ DA neurons from key brain regions-the nucleus accumbens (NAc), substantia nigra (SNc), and ventral tegmental area (VTA)-at postnatal milestones: day 7 (P7), day 30 (P30), and day 60 (P60). Using advanced multi-omics techniques, including ultrasensitive trace sample proteomics and SMART-seq2, we reveal distinct molecular profiles within DA neuron populations, reflecting their developmental progression and functional roles. Immunofluorescence mapping validates these findings and underscores the dynamic molecular architecture of DA neurons. Aldh1a1 expression, a key enzyme for retinoic acid production, progressively increases over time, reflecting its involvement in neuronal development and specialized functions. This study provides valuable insights into the development and function of DAT+ DA neurons.