Dynamic Axonal Translation in Developing and Mature Visual Circuits

Shigeoka, Toshiaki; Jung, Hosung; Jung, Jane; Turner-Bridger, Benita; Ohk, Jiyeon; Lin, Julie Qiaojin; Amieux, Paul S.; Holt, Christine E.

doi:10.1016/j.cell.2016.05.029

Cited by 382 publications

(486 citation statements)

References 56 publications

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“…Indeed, axonal translation might be induced in some neurons only in response to specific physiological or pathological cues (4,61). In support of this idea, retinal ganglion cell axons harbour ribosome-associated mRNAs in the adult nervous system yet do not contain FXGs (5,14). Identification of specific RNA granules in other axonal populations promises to inform our understanding of mechanisms regulating translation in mature axons in the normal and diseased mammalian brain.…”

Section: Fxgs In the Adult Brainmentioning

confidence: 76%

“…One conceptually attractive solution to this challenge is the local translation of mRNAs in the axon. Translation in developing and regenerating axons is well documented (2,3), and recent evidence suggests that CNS axons in the mammalian brain may also utilize this mechanism (4,5). However the extent to which endogenous ribosomes, mRNA and translational regulators localize to adult brain axons that are integrated into mature circuitry is unknown (6,7).…”

Section: Introductionmentioning

confidence: 99%

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Axonal ribosomes and mRNAs associate with fragile X granules in adult rodent and human brains

et al. 2017

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Local mRNA translation in growing axons allows for rapid and precise regulation of protein expression in response to extrinsic stimuli. However, the role of local translation in mature CNS axons is unknown. Such a mechanism requires the presence of translational machinery and associated mRNAs in circuit-integrated brain axons. Here we use a combination of genetic, quantitative imaging and super-resolution microscopy approaches to show that mature axons in the mammalian brain contain ribosomes, the translational regulator FMRP and a subset of FMRP mRNA targets. This axonal translational machinery is associated with Fragile X granules (FXGs), which are restricted to axons in a stereotyped subset of brain circuits. FXGs and associated axonal translational machinery are present in hippocampus in humans as old as 57 years. This FXGassociated axonal translational machinery is present in adult rats, even when adult neurogenesis is blocked. In contrast, in mouse this machinery is only observed in juvenile hippocampal axons. This differential developmental expression was specific to the hippocampus, as both mice and rats exhibit FXGs in mature axons in the adult olfactory system. Experiments in Fmr1 null mice show that FMRP regulates axonal protein expression but is not required for axonal transport of ribosomes or its target mRNAs. Axonal translational machinery is thus a feature of adult CNS neurons. Regulation of this machinery by FMRP could support complex behaviours in humans throughout life.

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Section: Fxgs In the Adult Brainmentioning

confidence: 76%

Section: Introductionmentioning

confidence: 99%

Axonal ribosomes and mRNAs associate with fragile X granules in adult rodent and human brains

et al. 2017

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“…Axons of sensory, cortical, hippocampal, retinal ganglion, and motor neurons have been shown to contain complex mRNA populations by RNA-seq analyses of isolated axons (18,19,(46)(47)(48)(49)(50). Despite identifying thousands of axonal mRNAs, exceptionally few RBPs have been found to date in axons.…”

Section: Discussionmentioning

confidence: 99%

hnRNPs Interacting with mRNA Localization Motifs Define AxoNAl RNA Regulons

Lee

Oses-Prieto

Kawaguchi

et al. 2018

Molecular & Cellular Proteomics

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“…Because non-specifically bound mRNAs may be present in tissue without any epitopetagged ribosomes (e.g. Cre-negative RiboTag), Credependent RNA-seq reads can be chosen by unbiased statistical methods (Shigeoka et al 2016).…”

Section: Discussion and Future Directionsmentioning

confidence: 99%

Methods to analyze cell type-specific gene expression profiles from heterogeneous cell populations

Jung

2016

Animal Cells and Systems

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Recent technical progress in DNA and protein identification has made genome-wide survey of gene expression at tissue and animal levels a routine approach, such as microarray and RNA sequencing technologies to measure mRNA abundance and mass spectrometry to measure protein abundance. A key limitation in applying these genome-wide gene expression profiling methods at tissue and animal levels is that the contribution of a specific cell type to the total amount of measured gene expression cannot be determined. Here, we review currently available approaches to resolve this and discuss future directions of study to solve questions not addressable by state-ofthe-art techniques.ARTICLE HISTORY

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Dynamic Axonal Translation in Developing and Mature Visual Circuits

Cited by 382 publications

References 56 publications

Axonal ribosomes and mRNAs associate with fragile X granules in adult rodent and human brains

Axonal ribosomes and mRNAs associate with fragile X granules in adult rodent and human brains

hnRNPs Interacting with mRNA Localization Motifs Define AxoNAl RNA Regulons

Methods to analyze cell type-specific gene expression profiles from heterogeneous cell populations

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