title: RNA-binding protein Vg1RBP regulates terminal arbor formation but not long-range axon navigation in the developing visual system.
abstract: Local synthesis of β-actin is required for attractive turning responses to guidance cues of growth cones in vitro but its functional role in axon guidance in vivo is poorly understood. The transport and translation of β-actin mRNA is regulated by the RNA-binding protein, Vg1RBP (zipcode-binding protein-1). To examine whether Vg1RBP plays a role in axon navigation in vivo, we disrupted Vg1RBP function in embryonic Xenopus laevis retinal ganglion cells by expressing a dominant-negative Vg1RBP and by antisense morpholino knockdown. We found that attractive turning to a netrin-1 gradient in vitro was abolished in Vg1RBP-deficient axons but, surprisingly, the long-range navigation from the retina to the optic tectum was unaffected. Within the tectum, however, the branching and complexity of axon terminals were significantly reduced. High-resolution time-lapse imaging of axon terminals in vivo revealed that Vg1RBP-GFP-positive granules accumulate locally in the axon shaft immediately preceding the emergence a filopodial-like protrusion. Comparative analysis of branch dynamics showed that Vg1RBP-deficient axons extend far fewer filopodial-like protrusions than control axons and indicate that Vg1RBP promotes filopodial formation, an essential step in branch initiation. Our findings show that Vg1RBP is required for terminal arborization but not long-range axon navigation and suggest that Vg1RBP-regulated mRNA translation promotes synaptic complexity.
authors.affiliation: Department of Physiology, Development, and Neuroscience, University of Cambridge, CB2 3DY, United Kingdom.
authors.forename: Adrianna
authors.initials: A
authors.lastname: Kalous
authors.forename: James I
authors.initials: JI
authors.lastname: Stake
authors.forename: Joel K
authors.initials: JK
authors.lastname: Yisraeli
authors.forename: Christine E
authors.initials: CE
authors.lastname: Holt
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D001369:Axons / Q000502:physiology*; D048708:Cell Growth Processes / Q000502:physiology; D002465:Cell Movement / Q000502:physiology; D020439:Growth Cones / Q000502:physiology; D066298:In Vitro Techniques; D009414:Nerve Growth Factors / Q000378:metabolism; D000075388:Netrin-1; D017729:Presynaptic Terminals / Q000502:physiology; D011554:Pseudopodia / Q000502:physiology; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D012165:Retinal Ganglion Cells / Q000502:physiology*; D013477:Superior Colliculi / Q000196:embryology / Q000502:physiology; D025521:Tumor Suppressor Proteins / Q000378:metabolism; D014795:Visual Pathways / Q000196:embryology / Q000502:physiology; D029867:Xenopus Proteins / Q000235:genetics / Q000378:metabolism*; D014982:Xenopus laevis
chemical_list: D000199:Actins; D009414:Nerve Growth Factors; D016601:RNA-Binding Proteins; D025521:Tumor Suppressor Proteins; D029867:Xenopus Proteins; D000075388:Netrin-1
keywords: RNA binding protein; axon branching; axon guidance