| Sonic hedgehog has a dual effect on the growth of retinal ganglion axons depending on its concentration. | |
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MedLine Citation:
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PMID: 15800198 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The stereotypical projection of retinal ganglion cell (RGC) axons to the optic disc has served as a good model system for studying axon guidance. By both in vitro and in vivo experiments, we show that a secreted molecule, Sonic hedgehog (Shh), may play a critical role in the process. It is expressed in a dynamic pattern in the ganglion cell layer with a relatively higher expression in the center of the retina. Through gel culture and stripe assays, we show that Shh has a dual effect on RGC axonal growth, acting as a positive factor at low concentrations and a negative factor at high concentrations. Results from time-lapse video microscopic and stripe assay experiments further suggest that the effects of Shh on axons are not likely attributable to indirect transcriptional regulation by Shh. Overexpression of Shh protein or inhibition of Shh function inside the retina resulted in a complete loss of centrally directed projection of RGC axons, suggesting that precise regulation of Shh level inside the retina is critical for the projection of RGC axons to the optic disc. |
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Authors:
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Adrianne Kolpak; Jinhua Zhang; Zheng-Zheng Bao |
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Publication Detail:
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Type: Comparative Study; In Vitro; Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S. |
Journal Detail:
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Title: The Journal of neuroscience : the official journal of the Society for Neuroscience Volume: 25 ISSN: 1529-2401 ISO Abbreviation: J. Neurosci. Publication Date: 2005 Mar |
Date Detail:
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Created Date: 2005-03-31 Completed Date: 2006-03-23 Revised Date: 2011-09-26 |
Medline Journal Info:
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Nlm Unique ID: 8102140 Medline TA: J Neurosci Country: United States |
Other Details:
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Languages: eng Pagination: 3432-41 Citation Subset: IM |
Affiliation:
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Department of Medicine and Cell Biology, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Age Factors Animals Axons / drug effects, physiology* Cells, Cultured Chick Embryo Coculture Techniques / methods Dose-Response Relationship, Drug Drug Interactions Fluorescent Antibody Technique / methods Gene Expression Regulation, Developmental / physiology Green Fluorescent Proteins / metabolism Growth Cones / drug effects, physiology Hedgehog Proteins In Situ Hybridization / methods Neural Inhibition / drug effects, physiology Optic Disk / cytology, metabolism Organ Culture Techniques / methods RNA, Messenger / metabolism Recombinant Proteins / metabolism Retina / cytology*, metabolism Retinal Ganglion Cells / cytology*, drug effects Time Factors Trans-Activators / genetics, physiology* Veratrum Alkaloids / pharmacology |
| Grant Support | |
ID/Acronym/Agency:
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R01 EY014980-02/EY/NEI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Hedgehog Proteins; 0/RNA, Messenger; 0/Recombinant Proteins; 0/Trans-Activators; 0/Veratrum Alkaloids; 0/rCAS protein, recombinant; 147336-22-9/Green Fluorescent Proteins; 4449-51-8/cyclopamine |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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