Subcellular transcriptomes and proteomes of developing axon projections in the cerebral cortex
PublisherNature Publishing Group
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AbstractThe 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.
SponsorsThis work was supported by grants to J.D.M. from the Paul G. Allen Frontiers Group, Brain Research Foundation Scientific Innovations Award program
NIH Pioneer Award DP1 NS106665, Emily and Robert Pearlstein Fund, and the Max and Anne Wien Professorship
with additional infrastructure support from NIH grants NS045523, NS075672, NS049553, and NS041590.
Identifier to cite or link to this itemhttps://www.scopus.com/inward/record.uri?eid=2-s2.0-85060132690&doi=10.1038%2fs41586-018-0847-y&partnerID=40&md5=7a9eed5a430bc42cf96fcc44161407e3; http://hdl.handle.net/10713/10520
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