Document Detail


Retinal ganglion cell-derived sonic hedgehog signaling is required for optic disc and stalk neuroepithelial cell development.
MedLine Citation:
PMID:  12756179     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The development of optic stalk neuroepithelial cells depends on Hedgehog (Hh) signaling, yet the source(s) of Hh protein in the optic stalk is unknown. We provide genetic evidence that sonic hedgehog (Shh) from retinal ganglion cells (RGCs) promotes the development of optic disc and stalk neuroepithelial cells. We demonstrate that RGCs express Shh soon after differentiation, and cells at the optic disc in close proximity to the Shh-expressing RGCs upregulate Hh target genes, which suggests they are responding to RGC-derived Shh signaling. Conditional ablation of Shh in RGCs caused a complete loss of optic disc astrocyte precursor cells, resulting in defective axon guidance in the retina, as well as conversion of the neuroepithelial cells in the optic stalk to pigmented cells. We further show that Shh signaling modulates the size of the Pax2(+) astrocyte precursor cell population at the optic disc in vitro. Together, these data provide a novel insight into the source of Hh that promotes neuroepithelial cell development in the mammalian optic disc and stalk.
Authors:
Gabriel D Dakubo; Ya Ping Wang; Chantal Mazerolle; Katrina Campsall; Andrew P McMahon; Valerie A Wallace
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Development (Cambridge, England)     Volume:  130     ISSN:  0950-1991     ISO Abbreviation:  Development     Publication Date:  2003 Jul 
Date Detail:
Created Date:  2003-05-20     Completed Date:  2003-09-10     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  8701744     Medline TA:  Development     Country:  England    
Other Details:
Languages:  eng     Pagination:  2967-80     Citation Subset:  IM    
Affiliation:
Molecular Medicine Program, Ottawa Health Research Institute, 501 Smyth Road, Ottawa, ON K1H 8L6, Canada.
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MeSH Terms
Descriptor/Qualifier:
Animals
Astrocytes / cytology,  physiology
Biological Markers
Cell Differentiation / physiology
Cell Movement / physiology
Culture Techniques
Eye / embryology*,  growth & development
Gene Expression Regulation, Developmental
Hedgehog Proteins
In Situ Hybridization
Membrane Proteins / genetics,  metabolism
Mice
Mice, Transgenic
Morphogenesis / physiology*
Oncogene Proteins / genetics,  metabolism
Optic Nerve / cytology,  embryology,  growth & development,  pathology
Phenotype
Pigmentation / physiology
Receptors, Cell Surface
Retina / cytology,  physiology
Retinal Ganglion Cells / cytology,  metabolism*
Signal Transduction / physiology*
Trans-Activators / genetics,  metabolism*
Transcription Factors / genetics,  metabolism
Grant Support
ID/Acronym/Agency:
NS 33642/NS/NINDS NIH HHS
Chemical
Reg. No./Substance:
0/Biological Markers; 0/Gli protein; 0/Hedgehog Proteins; 0/Membrane Proteins; 0/Oncogene Proteins; 0/Receptors, Cell Surface; 0/Trans-Activators; 0/Transcription Factors; 0/patched receptors

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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