Cell
Volume 166, Issue 1, 30 June 2016, Pages 181-192
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Article
Dynamic Axonal Translation in Developing and Mature Visual Circuits

https://doi.org/10.1016/j.cell.2016.05.029Get rights and content
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Highlights

  • Dynamic translatome of retinal axons in vivo matches changing subcellular function

  • Adult CNS axons translate mRNAs for synaptic transmission and axon survival in vivo

  • Target mRNAs of key translation regulators show developmental co-regulation

  • Axon-specific sequence motifs link alternative splicing to axonal translation

Summary

Local mRNA translation mediates the adaptive responses of axons to extrinsic signals, but direct evidence that it occurs in mammalian CNS axons in vivo is scant. We developed an axon-TRAP-RiboTag approach in mouse that allows deep-sequencing analysis of ribosome-bound mRNAs in the retinal ganglion cell axons of the developing and adult retinotectal projection in vivo. The embryonic-to-postnatal axonal translatome comprises an evolving subset of enriched genes with axon-specific roles, suggesting distinct steps in axon wiring, such as elongation, pruning, and synaptogenesis. Adult axons, remarkably, have a complex translatome with strong links to axon survival, neurotransmission, and neurodegenerative disease. Translationally co-regulated mRNA subsets share common upstream regulators, and sequence elements generated by alternative splicing promote axonal mRNA translation. Our results indicate that intricate regulation of compartment-specific mRNA translation in mammalian CNS axons supports the formation and maintenance of neural circuits in vivo.

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