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Nature. 2019 Jan;565(7739):356-360. doi: 10.1038/s41586-018-0847-y. Epub 2019 Jan 9.

Subcellular transcriptomes and proteomes of developing axon projections in the cerebral cortex.

Author information

1
Department of Stem Cell and Regenerative Biology, Center for Brain Science, and Harvard Stem Cell Institute, Harvard University, Cambridge, MA, USA. apoulopoulos@som.umaryland.edu.
2
Department of Pharmacology and Program in Neuroscience, University of Maryland School of Medicine, Baltimore, MD, USA. apoulopoulos@som.umaryland.edu.
3
Department of Stem Cell and Regenerative Biology, Center for Brain Science, and Harvard Stem Cell Institute, Harvard University, Cambridge, MA, USA.
4
Bioinformatics core, Harvard T. H. Chan School of Public Health, Harvard University, Boston, MA, USA.
5
Department of Stem Cell and Regenerative Biology, Center for Brain Science, and Harvard Stem Cell Institute, Harvard University, Cambridge, MA, USA. jeffrey_macklis@harvard.edu.

Abstract

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 selection1. 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 mTOR2, together with mRNAs that contain mTOR-dependent motifs3,4. 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.

PMID:
30626971
PMCID:
PMC6484835
DOI:
10.1038/s41586-018-0847-y
[Indexed for MEDLINE]
Free PMC Article

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