Combined Transcriptomic and Proteomic Profiling Uncovers Developmental Dynamics of Autophagy in the Cortex.

Unlike dividing cells, neurons depend on degradative pathways to prevent the buildup of cellular waste and to sustain nutrient and energy homeostasis. Emerging evidence indicates that autophagy is particularly critical during early development when neuronal circuits are being established, synaptic connections refined, and activity-dependent mechanisms sculpt overall network architecture.

Accordingly, loss of key autophagy-related genes in newly formed neurons disrupts differentiation, synaptic formation and neurotransmission. Despite these insights, the developmental regulation of autophagy genes remains poorly understood, and the composition of the autophagic machinery at synapses is still largely unresolved. To address this, we performed genome-wide transcriptomic analyses of the cortical brain region to characterize the maturation-dependent dynamics of autophagy–lysosomal genes.