Document Detail

Transposon mutagenesis with coat color genotyping identifies an essential role for Skor2 in sonic hedgehog signaling and cerebellum development.
MedLine Citation:
PMID:  21937600     Owner:  NLM     Status:  MEDLINE    
Correct development of the cerebellum requires coordinated sonic hedgehog (Shh) signaling from Purkinje to granule cells. How Shh expression is regulated in Purkinje cells is poorly understood. Using a novel tyrosinase minigene-tagged Sleeping Beauty transposon-mediated mutagenesis, which allows for coat color-based genotyping, we created mice in which the Ski/Sno family transcriptional co-repressor 2 (Skor2) gene is deleted. Loss of Skor2 leads to defective Purkinje cell development, a severe reduction of granule cell proliferation and a malformed cerebellum. Skor2 is specifically expressed in Purkinje cells in the brain, where it is required for proper expression of Shh. Skor2 overexpression suppresses BMP signaling in an HDAC-dependent manner and stimulates Shh promoter activity, suggesting that Skor2 represses BMP signaling to activate Shh expression. Our study identifies an essential function for Skor2 as a novel transcriptional regulator in Purkinje cells that acts upstream of Shh during cerebellum development.
Baiping Wang; Wilbur Harrison; Paul A Overbeek; Hui Zheng
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural    
Journal Detail:
Title:  Development (Cambridge, England)     Volume:  138     ISSN:  1477-9129     ISO Abbreviation:  Development     Publication Date:  2011 Oct 
Date Detail:
Created Date:  2011-09-22     Completed Date:  2011-11-28     Revised Date:  2013-06-27    
Medline Journal Info:
Nlm Unique ID:  8701744     Medline TA:  Development     Country:  England    
Other Details:
Languages:  eng     Pagination:  4487-97     Citation Subset:  IM    
Huffington Center on Aging, Baylor College of Medicine, Houston, TX 77030, USA.
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MeSH Terms
Bone Morphogenetic Proteins / metabolism
Cell Differentiation
Cerebellum / abnormalities,  growth & development*,  metabolism*
Gene Expression Regulation, Developmental
Hair Color / genetics
Hedgehog Proteins / genetics*,  metabolism*
Histone Deacetylases / metabolism
Mice, Knockout
Mice, Transgenic
Monophenol Monooxygenase / genetics
Mutagenesis, Insertional
Proto-Oncogene Proteins / deficiency,  genetics*,  metabolism*
Purkinje Cells / cytology,  metabolism
Repressor Proteins / deficiency,  genetics*,  metabolism*
Signal Transduction
Transforming Growth Factor beta / metabolism
Transposases / genetics
Grant Support
Reg. No./Substance:
0/Bone Morphogenetic Proteins; 0/Corl2 protein, mouse; 0/Hedgehog Proteins; 0/Proto-Oncogene Proteins; 0/Repressor Proteins; 0/Shh protein, mouse; 0/Skil protein, mouse; 0/Transforming Growth Factor beta; EC Monooxygenase; EC 2.7.7.-/Transposases; EC 2.7.7.-/sleeping beauty transposase, human; EC Deacetylases

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

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