Dynamic Axonal Translation in Developing and Mature Visual Circuits.
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.
Department of Physiology, Development and Neuroscience, University of Cambridge, Downing Street, Cambridge CB2 3DY, UK.
Toshiaki
T
Shigeoka
Department of Anatomy, Brain Research Institute, and Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul 03722, Republic of Korea. Electronic address: hosungjung@yonsei.ac.kr.
Hosung
H
Jung
Department of Anatomy, Brain Research Institute, and Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul 03722, Republic of Korea.
Jane
J
Jung
Department of Physiology, Development and Neuroscience, University of Cambridge, Downing Street, Cambridge CB2 3DY, UK.
Benita
B
Turner-Bridger
Department of Anatomy, Brain Research Institute, and Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul 03722, Republic of Korea.
Jiyeon
J
Ohk
Department of Physiology, Development and Neuroscience, University of Cambridge, Downing Street, Cambridge CB2 3DY, UK.
Julie Qiaojin
JQ
Lin
Bastyr University Research Institute, Bastyr University, Kenmore, WA 98028, USA.
Paul S
PS
Amieux
Department of Physiology, Development and Neuroscience, University of Cambridge, Downing Street, Cambridge CB2 3DY, UK. Electronic address: ceh33@cam.ac.uk.
Christine E
CE
Holt
D017398:Alternative Splicing; D000818:Animals; D001369:Axons / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D051379:Mice; D014176:Protein Biosynthesis; D020543:Proteome / Q000032:analysis / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism; D012165:Retinal Ganglion Cells / Q000378:metabolism*; D012270:Ribosomes / Q000378:metabolism; D013477:Superior Colliculi / Q000378:metabolism; D009435:Synaptic Transmission
D020543:Proteome; D012333:RNA, Messenger