Axons from different circuits and cell types are intermingled, and isolation techniques that lack genetic targeting likely mask neuronal class specific features. Axonal compartments, such as axon growth cones, are typically isolated by tissue dissociation and sorting techniques, resulting in substantial losses of axon components ( Chauhan et al., 2020 Poulopoulos et al., 2019). Mapping axonal proteomes from specific neurons directly in the vertebrate brain remains extremely challenging. The postnatal proteome of developing axons remains largely unknown for any neuronal type. Therefore, it is important that measurements of the microdomain proteomes also contain cell-type specific information. In addition, neuronal cell types are characterized by distinct patterns of gene expression ( Saunders et al., 2018 Zeisel et al., 2018), implying biodiversity of their somatic, dendritic, and axonal proteomes. Thus, proteomic rather than transcriptomic techniques are necessary to capture the functional state of axons this is especially important for axon guidance signaling that is highly regulated by post translational modifications such as protein phosphorylation ( Costa-Mattioli et al., 2009). Although axons contain machinery for local protein synthesis ( Hafner et al., 2019), a large fraction of the neuroproteome is synthesized in the soma and trafficked throughout the cell, as evidenced by generally greater abundance of transcripts in the soma, compared to neurites ( Glock et al., 2021). Developing axons require local protein synthesis and dynamics to coordinate axon outgrowth and growth cone collapse ( Lin and Holt, 2007). During the embryonic and early postnatal stages, axons rapidly grow and navigate to target regions across the brain ( Winnubst et al., 2019). While these subcellular domains are maintained and regulated by both local and distal cues, local proteome regulation is particularly important for fine-tuning neural connectivity during circuit development and in the context of plasticity ( Gonzalez-Lozano et al., 2016 Poulopoulos et al., 2019 Schanzenbächer et al., 2018). Neurons are morphologically diverse cells that compartmentalize cellular signaling and information processing in cell bodies, dendrites, and axons, enabling spatiotemporal control over synaptic transmission.
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