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Mammalian axonal development begins in embryonic stages and continues postnatally. After birth, axonal proteomic landscape changes rapidly, coordinated by transcription, protein turnover, and post-translational modifications. Comprehensive profiling of axonal proteomes across neurodevelopment is limited, with most studies lacking cell-type and neural circuit specificity, resulting in substantial information loss. We create a Cre-dependent APEX2 reporter mouse line and map cell-type-specific proteome of corticostriatal projections across postnatal development. We synthesize analysis frameworks to define temporal patterns of axonal proteome and phosphoproteome, identifying co-regulated proteins and phosphorylations associated with genetic risk for human brain disorders. We discover proline-directed kinases as major developmental regulators. APEX2 transgenic reporter proximity labeling offers flexible strategies for subcellular proteomics with cell type specificity in early neurodevelopment, a critical period for neuropsychiatric disease.more » « less
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Werbin, Zoey R.; Heidari, Leila; Buckley, Sarabeth; Brochu, Paige; Butler, Lindsey J.; Connolly, Catherine; Houttuijn Bloemendaal, Lucila; McCabe, Tempest D.; Miller, Tara K.; Hutyra, Lucy R. (, PLOS ONE)Ustaoglu, Eda (Ed.)
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