NDLI: Heparan sulfate regulates intraretinal axon pathfinding by retinal ganglion cells.

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Heparan sulfate regulates intraretinal axon pathfinding by retinal ganglion cells.

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Heparan sulfate regulates intraretinal axon pathfinding by retinal ganglion cells.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Nakaishi-Fukuchi, Yuko Iwao, Keiichiro Takihara, Yuji Irie, Fumitoshi Ogata-Iwao, Minako Sato, Shigeru Furukawa, Takahisa Inatani, Masaru Yamaguchi, Yu Tanihara, Hidenobu
Description	Country affiliation: Japan Author Affiliation: Ogata-Iwao M ( Department of Ophthalmology and Visual Science, Kumamoto University Graduate School of Medical Sciences, Japan.)
Abstract	PURPOSE. Heparan sulfate (HS) is abundantly expressed in the developing neural retina; however, its role in the intraretinal axon guidance of retinal ganglion cells (RGCs) remains unclear. In this study, the authors examined whether HS was essential for the axon guidance of RGCs toward the optic nerve head. METHODS. The authors conditionally ablated the gene encoding the exostosin-1 (Ext1) enzyme, using the dickkopf homolog 3 (Dkk3)-Cre transgene, which disrupted HS expression in the mouse retina during directed pathfinding by RGC axons toward the optic nerve head. In situ hybridization, immunohistochemistry, DiI tracing, binding assay, and retinal explant assays were performed to evaluate the phenotypes of the mutants and the roles of HS in intraretinal axon guidance. RESULTS. Despite no gross abnormality in RGC distribution, the mutant RGC axons exhibited severe intraretinal guidance errors, including optic nerve hypoplasia, ectopic axon penetration through the full thickness of the neural retina and into the subretinal space, and disturbance of the centrifugal projection of RGC axons toward the optic nerve head. These abnormal phenotypes shared similarities with the RGC axon misguidance caused by mutations of genes encoding Netrin-1 and Slit-1/2. Explant assays revealed that the mutant RGCs exhibited disturbed Netrin-1-dependent axon outgrowth and Slit-2-dependent repulsion. CONCLUSIONS. The present study demonstrated that RGC axon projection toward the optic nerve head requires the expression of HS in the neural retina, suggesting that HS in the retina functions as an essential modulator of Netrin-1 and Slit-mediated intraretinal RGC axon guidance.
ISSN	01460404
e-ISSN	15525783
DOI	10.1167/iovs.11-7559
Journal	Investigative Opthalmology & Visual Science
Issue Number	9
Volume Number	52
Language	English
Publisher	Association for Research in Vision and Ophthalmology
Publisher Date	2011-08-22
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Axons Physiology Heparitin Sulfate Optic Disk Embryology Retina Retinal Ganglion Cells Animals Enzyme-linked Immunosorbent Assay Eye Abnormalities Physiopathology Fluorescent Antibody Technique, Indirect Immunoenzyme Techniques In Situ Hybridization Intercellular Signaling Peptides And Proteins Genetics Metabolism Mice Mice, Inbred C57bl Mice, Mutant Strains Mice, Transgenic N-acetylglucosaminyltransferases Nerve Growth Factors Nerve Tissue Proteins Neural Conduction Neuronal Plasticity Abnormalities Phenotype Polymerase Chain Reaction Tumor Suppressor Proteins Visual Pathways Discipline Ophthalmology
Content Type	Text
Resource Type	Article
Subject	Ophthalmology Sensory Systems Cellular and Molecular Neuroscience

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