期刊
NATURE
卷 565, 期 7739, 页码 356-+出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/s41586-018-0847-y
关键词
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资金
- Harvard Center for Biological Imaging
- Paul G. Allen Frontiers Group
- Brain Research Foundation Scientific Innovations Award program
- NIH Pioneer Award [DP1 NS106665]
- Emily and Robert Pearlstein Fund
- Max and Anne Wien Professorship
- NIH [NS045523, NS075672, NS049553, NS041590, T32 AG000222]
- European Molecular Biology Organization Long Term Fellowship
- Human Frontier Science Program Long Term Fellowship
- Harvard NeuroDiscovery Center
- Harvard Stem Cell Institute
The development of neural circuits relies on axon projections establishing diverse, yet well-defined, connections between areas of the nervous system. Each projection is formed by growth cones-subcellular specializations at the tips of growing axons, encompassing sets of molecules that control projection-specific growth, guidance, and target selection(1). To investigate the set of molecules within native growth cones that form specific connections, here we developed growth cone sorting and subcellular RNA-proteome mapping, an approach that identifies and quantifies local transcriptomes and proteomes from labelled growth cones of single projections in vivo. Using this approach on the developing callosal projection of the mouse cerebral cortex, we mapped molecular enrichments in trans-hemispheric growth cones relative to their parent cell bodies, producing paired subcellular proteomes and transcriptomes from single neuron subtypes directly from the brain. These data provide generalizable proof-of-principle for this approach, and reveal molecular specializations of the growth cone, including accumulations of the growth-regulating kinase mTOR(2), together with mRNAs that contain mTOR-dependent motifs(3,4). These findings illuminate the relationships between subcellular distributions of RNA and protein in developing projection neurons, and provide a systems-level approach for the discovery of subtype- and stage-specific molecular substrates of circuit wiring, miswiring, and the potential for regeneration.
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