The RNA Binding Protein Igf2bp1 Is Required for Zebrafish RGC Axon Outgrowth In Vivo

Attractive growth cone turning requires Igf2bp1-dependent local translation of β-actin mRNA in response to external cues in vitro. While in vivo studies have shown that Igf2bp1 is required for cell migration and axon terminal branching, a requirement for Igf2bp1 function during axon outgrowth has no...

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Bibliographic Details
Published in:PloS one 2015-09, Vol.10 (9), p.e0134751-e0134751
Main Authors: Gaynes, John A, Otsuna, Hideo, Campbell, Douglas S, Manfredi, John P, Levine, Edward M, Chien, Chi-Bin
Format: Article
Language:English
Subjects:
3' Untranslated regions
Actin
Actins - physiology
Animals
Axon guidance
Axonogenesis
Axons
Axons - physiology
Binding proteins
Brain-derived neurotrophic factor
Cell migration
Cell survival
Cones
Cues
Danio rerio
Fluorescence
Gene Knockdown Techniques
Genetic aspects
Growth cones
In vivo methods and tests
Kinases
mRNA
Neurosciences
Optic tract
Physiological aspects
Proteins
Retina
Retinal ganglion cells
Retinal Ganglion Cells - physiology
Ribonucleic acid
RNA
RNA-binding protein
RNA-Binding Proteins - physiology
Rodents
Superior colliculus
Translation
Xenopus laevis
Zebrafish
Zebrafish - growth & development
Zebrafish - physiology
Zebrafish Proteins - physiology
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Summary:Attractive growth cone turning requires Igf2bp1-dependent local translation of β-actin mRNA in response to external cues in vitro. While in vivo studies have shown that Igf2bp1 is required for cell migration and axon terminal branching, a requirement for Igf2bp1 function during axon outgrowth has not been demonstrated. Using a timelapse assay in the zebrafish retinotectal system, we demonstrate that the β-actin 3'UTR is sufficient to target local translation of the photoconvertible fluorescent protein Kaede in growth cones of pathfinding retinal ganglion cells (RGCs) in vivo. Igf2bp1 knockdown reduced RGC axonal outgrowth and tectal coverage and retinal cell survival. RGC-specific expression of a phosphomimetic Igf2bp1 reduced the density of axonal projections in the optic tract while sparing RGCs, demonstrating for the first time that Igf2bp1 is required during axon outgrowth in vivo. Therefore, regulation of local translation mediated by Igf2bp proteins may be required at all stages of axon development.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0134751