Document Detail

Ventral midbrain glia express region-specific transcription factors and regulate dopaminergic neurogenesis through Wnt-5a secretion.
MedLine Citation:
PMID:  16243537     Owner:  NLM     Status:  MEDLINE    
Glial cells have been classically described as supporting cells for neurons. Recently, additional roles during neural development have begun to emerge. Here, we report that ventral midbrain glia, including astrocytes and radial glia, are the source of signals required by neural precursors to acquire a dopaminergic phenotype. We found that ventral midbrain glia, but not cortical glia, secrete high levels of the glycolipoprotein Wnt-5a, express region-specific transcription factors such as Pax-2, En-1 and Otx-2 and increase the differentiation of cortical or ventral midbrain Nurr1 precursors into tyrosine hydroxylase-positive neurons. Moreover, blocking experiments using a Wnt-5a blocking antibody indicated that the effects of ventral midbrain glia on Nurr1-positive neural precursors are partially mediated by Wnt-5a. Thus, our results identify Wnt-5a as an important component of the dopaminergic inductive activity of the ventral midbrain glia.
Gonçalo Castelo-Branco; Kyle M Sousa; Vitezslav Bryja; Luisa Pinto; Joseph Wagner; Ernest Arenas
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2005-10-21
Journal Detail:
Title:  Molecular and cellular neurosciences     Volume:  31     ISSN:  1044-7431     ISO Abbreviation:  Mol. Cell. Neurosci.     Publication Date:  2006 Feb 
Date Detail:
Created Date:  2006-02-13     Completed Date:  2006-06-13     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  9100095     Medline TA:  Mol Cell Neurosci     Country:  United States    
Other Details:
Languages:  eng     Pagination:  251-62     Citation Subset:  IM    
Laboratory of Molecular Neurobiology, Department of Medical Biochemistry and Biophysics, Karolinska Institute, Scheeles vag 1, A1, plan 2, 17177 Stockholm, Sweden.
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MeSH Terms
Antibodies / metabolism
Cell Differentiation
Cells, Cultured
Cerebral Cortex / cytology,  metabolism
Coculture Techniques
DNA-Binding Proteins / metabolism
Dopamine / biosynthesis*
Mesencephalon / anatomy & histology,  cytology*,  metabolism
Neuroglia / cytology,  metabolism*
Nuclear Receptor Subfamily 4, Group A, Member 2
Rats, Sprague-Dawley
Signal Transduction / physiology
Transcription Factors / genetics,  metabolism*
Wnt Proteins / genetics,  secretion*
Reg. No./Substance:
0/Antibodies; 0/DNA-Binding Proteins; 0/Nr4a2 protein, rat; 0/Nuclear Receptor Subfamily 4, Group A, Member 2; 0/Transcription Factors; 0/Wnt Proteins; 0/Wnt5a protein, rat

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