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 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.
Program in Neuroscience, University of Utah Medical Center, Salt Lake City, Utah, United States of America; Department of Neurobiology and Anatomy, University of Utah Medical Center, Salt Lake City, Utah, United States of America; Department of Ophthalmology/Visual Sciences, John A. Moran Center, University of Utah Medical Center, Salt Lake City, Utah, United States of America.
John A
JA
Gaynes
Department of Neurobiology and Anatomy, University of Utah Medical Center, Salt Lake City, Utah, United States of America.
Hideo
H
Otsuna
Department of Neurobiology and Anatomy, University of Utah Medical Center, Salt Lake City, Utah, United States of America; Max Planck Institute for Brain Research, Frankfurt am Main, Germany.
Douglas S
DS
Campbell
Sfida BioLogic, Inc., Salt Lake City, Utah, United States of America.
John P
JP
Manfredi
Program in Neuroscience, University of Utah Medical Center, Salt Lake City, Utah, United States of America; Department of Neurobiology and Anatomy, University of Utah Medical Center, Salt Lake City, Utah, United States of America; Department of Ophthalmology/Visual Sciences, John A. Moran Center, University of Utah Medical Center, Salt Lake City, Utah, United States of America.
Edward M
EM
Levine
Program in Neuroscience, University of Utah Medical Center, Salt Lake City, Utah, United States of America; Department of Neurobiology and Anatomy, University of Utah Medical Center, Salt Lake City, Utah, United States of America.
Chi-Bin
CB
Chien
D000199:Actins / Q000502:physiology; D000818:Animals; D001369:Axons / Q000502:physiology*; D055785:Gene Knockdown Techniques; D016601:RNA-Binding Proteins / Q000502:physiology*; D012165:Retinal Ganglion Cells / Q000502:physiology*; D015027:Zebrafish / Q000254:growth & development / Q000502:physiology; D029961:Zebrafish Proteins / Q000502:physiology*
D000199:Actins; C000607857:Igf2bp1 protein, zebrafish; D016601:RNA-Binding Proteins; D029961:Zebrafish Proteins