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

Autophagy is an evolutionarily conserved degradation and recycling process through which cells deliver cytoplasmic components such as toxic or defective proteins and organelles to lysosomes for clearance. 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. In parallel, we examined the autophagy-associated proteome within synaptosomes to better understand how autophagic proteins contribute to synaptic processes during critical stages of network formation. Together, these complementary approaches reveal new aspects of autophagy regulation during development and provide a foundation for identifying therapeutic targets for neurological disorders linked to impaired synaptic and cellular homeostasis.