Document Detail

Purkinje cell phenotype restricts the distribution of unipolar brush cells.
MedLine Citation:
PMID:  19800947     Owner:  NLM     Status:  MEDLINE    
Cerebellar unipolar brush cells (UBCs) are glutamatergic interneurons of the granular layer. Previous studies have identified three distinct UBC subsets in the mouse cerebellar cortex: one expressing the calcium-binding protein calretinin (CR), a second expressing both the metabotropic glutamate receptor (mGluR)1alpha and phospholipase C(PLC)beta4, and a third expressing PLCbeta4 but not mGluR1alpha. We have investigated UBC topography in two strains of mutant mice: early B-cell factor 2 (Ebf2) null and scrambler. In Ebf2 null mice Purkinje cell topography is disrupted due to Purkinje cell death and ectopic gene expression. The topography of all three classes of UBCs is also abnormal: the CR(+) UBCs, which are normally aligned with zebrin II stripes, become homogeneously distributed; the numerical density of mGluRlalpha(+) UBCs is increased; and many PLCbeta4(+) UBCs are located ectopically. The UBC ectopia is not a cell-intrinsic action of the Ebf2 gene-analysis of the constitutive expression of a beta-galactoside reporter under the control of the Ebf2 promoter reveals no Ebf2 expression in UBCs at any stage of cerebellar development. In scrambler (Dab1(scm)), most Purkinje cells are ectopic but nevertheless have normal adult gene expression patterns. In scrambler, UBCs associate with specific ectopic Purkinje cell clusters. Finally, similar associations with specific Purkinje cell clusters are seen during normal cerebellar development. These data suggest that UBCs become regionally restricted during development through a non-cell-autonomous mechanism involving embryonic interactions with different Purkinje cell subtypes.
S-H Chung; R V Sillitoe; L Croci; A Badaloni; G Consalez; R Hawkes
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2009-10-02
Journal Detail:
Title:  Neuroscience     Volume:  164     ISSN:  1873-7544     ISO Abbreviation:  Neuroscience     Publication Date:  2009 Dec 
Date Detail:
Created Date:  2009-11-16     Completed Date:  2010-02-19     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  7605074     Medline TA:  Neuroscience     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1496-508     Citation Subset:  IM    
Department of Cell Biology & Anatomy, Hotchkiss Brain Institute and Genes and Development Research Group, Faculty of Medicine, University of Calgary, Calgary, AB T2N 4N1, Canada.
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MeSH Terms
Basic Helix-Loop-Helix Transcription Factors / genetics
Calcium-Binding Protein, Vitamin D-Dependent / metabolism
Cell Death
Cell Polarity
Cerebellum / cytology*,  embryology,  metabolism
Interneurons / cytology*
Mice, Knockout
Nerve Tissue Proteins / genetics,  metabolism
Purkinje Cells / cytology*,  metabolism
Receptors, Metabotropic Glutamate / metabolism
Grant Support
//Canadian Institutes of Health Research
Reg. No./Substance:
0/Basic Helix-Loop-Helix Transcription Factors; 0/Calcium-Binding Protein, Vitamin D-Dependent; 0/Dab1 protein, mouse; 0/Ebf2 protein, mouse; 0/Nerve Tissue Proteins; 0/Receptors, Metabotropic Glutamate; 0/calretinin; 0/metabotropic glutamate receptor type 1; 0/zebrin II

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