GONUTS has been updated to MW1.31 Most things seem to be working but be sure to report problems.

Have any questions? Please email us at ecoliwiki@gmail.com

PMID:20570969

From GONUTS
Jump to: navigation, search
Citation

Rice, DP, Connor, EC, Veltmaat, JM, Lana-Elola, E, Veistinen, L, Tanimoto, Y, Bellusci, S and Rice, R (2010) Gli3Xt-J/Xt-J mice exhibit lambdoid suture craniosynostosis which results from altered osteoprogenitor proliferation and differentiation. Hum. Mol. Genet. 19:3457-67

Abstract

Gli3 is a zinc-finger transcription factor whose activity is dependent on the level of hedgehog (Hh) ligand. Hh signaling has key roles during endochondral ossification; however, its role in intramembranous ossification is still unclear. In this study, we show that Gli3 performs a dual role in regulating both osteoprogenitor proliferation and osteoblast differentiation during intramembranous ossification. We discovered that Gli3Xt-J/Xt-J mice, which represent a Gli3-null allele, exhibit craniosynostosis of the lambdoid sutures and that this is accompanied by increased osteoprogenitor proliferation and differentiation. These cellular changes are preceded by ectopic expression of the Hh receptor Patched1 and reduced expression of the transcription factor Twist1 in the sutural mesenchyme. Twist1 is known to delay osteogenesis by binding to and inhibiting the transcription factor Runx2. We found that Runx2 expression in the lambdoid suture was altered in a pattern complimentary to that of Twist1. We therefore propose that loss of Gli3 results in a Twist1-, Runx2-dependent expansion of the sutural osteoprogenitor population as well as enhanced osteoblastic differentiation which results in a bony bridge forming between the parietal and interparietal bones. We show that FGF2 will induce Twist1, normalize osteoprogenitor proliferation and differentiation and rescue the lambdoid suture synostosis in Gli3Xt-J/Xt-J mice. Taken together, we define a novel role for Gli3 in osteoblast development; we describe the first mouse model of lambdoid suture craniosynostosis and show how craniosynostosis can be rescued in this model.

Links

PubMed PMC2916710 Online version:10.1093/hmg/ddq258

Keywords

Animals; Cell Differentiation; Cell Proliferation; Craniosynostoses/embryology; Craniosynostoses/genetics; Craniosynostoses/metabolism; Craniosynostoses/physiopathology; Disease Models, Animal; Female; Gene Expression Regulation, Developmental; Humans; Kruppel-Like Transcription Factors/genetics; Kruppel-Like Transcription Factors/metabolism; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Nerve Tissue Proteins/genetics; Nerve Tissue Proteins/metabolism; Osteoblasts/cytology; Osteoblasts/metabolism; Osteogenesis; Skull/abnormalities; Skull/cytology; Skull/embryology; Skull/metabolism; Stem Cells/cytology; Stem Cells/metabolism

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

MOUSE:FGF2

acts_upstream_of_or_within

GO:0008285: negative regulation of cell population proliferation

ECO:0000316: genetic interaction evidence used in manual assertion

MGI:MGI:95729

P

Seeded From UniProt

complete

MOUSE:FGF2

acts_upstream_of_or_within

GO:0045669: positive regulation of osteoblast differentiation

ECO:0000316: genetic interaction evidence used in manual assertion

MGI:MGI:95729

P

  • regulates_o_occurs_in:(EMAPA:18016)
  • regulates_o_results_in_acquisition_of_features_of:(CL:0000062)

Seeded From UniProt

complete

MOUSE:GLI3

acts_upstream_of_or_within

GO:0060367: sagittal suture morphogenesis

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:1856276

P

Seeded From UniProt

complete

MOUSE:GLI3

acts_upstream_of_or_within

GO:0060366: lambdoid suture morphogenesis

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:1856276

P

Seeded From UniProt

complete

MOUSE:GLI3

acts_upstream_of_or_within

GO:0060364: frontal suture morphogenesis

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:1856276

P

Seeded From UniProt

complete

MOUSE:GLI3

acts_upstream_of_or_within

GO:0060364: frontal suture morphogenesis

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:1856276

P

has_participant:(EMAPA:19198)

Seeded From UniProt

complete

MOUSE:GLI3

acts_upstream_of_or_within

GO:0060366: lambdoid suture morphogenesis

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:1856276

P

has_participant:(EMAPA:19227)

Seeded From UniProt

complete

MOUSE:GLI3

acts_upstream_of_or_within

GO:0060367: sagittal suture morphogenesis

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:1856276

P

has_participant:(EMAPA:19224)

Seeded From UniProt

complete

MOUSE:GLI3

acts_upstream_of_or_within

GO:0045669: positive regulation of osteoblast differentiation

ECO:0000316: genetic interaction evidence used in manual assertion

MGI:MGI:95516

P

  • regulates_o_occurs_in:(EMAPA:18016)
  • regulates_o_results_in_acquisition_of_features_of:(CL:0000062)

Seeded From UniProt

complete

MOUSE:GLI3

acts_upstream_of_or_within

GO:0045669: positive regulation of osteoblast differentiation

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:1856276

P

  • regulates_o_occurs_in:(EMAPA:18016)
  • regulates_o_results_in_acquisition_of_features_of:(CL:0000062)

Seeded From UniProt

complete

MOUSE:GLI3

acts_upstream_of_or_within

GO:0008285: negative regulation of cell population proliferation

ECO:0000316: genetic interaction evidence used in manual assertion

MGI:MGI:95516

P

Seeded From UniProt

complete

MOUSE:GLI3

acts_upstream_of_or_within

GO:0008285: negative regulation of cell population proliferation

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:1856276

P

Seeded From UniProt

complete


See also

References

See Help:References for how to manage references in GONUTS.

Navigation menu

Internal error - GONUTS

GONUTS has been updated to MW1.31 Most things seem to be working but be sure to report problems.

Have any questions? Please email us at ecoliwiki@gmail.com

Internal error

Jump to: navigation, search

[3e0832ea882d6371f31931d9] /wiki/index.php/PMID:20570969 Error from line 252 of /usr/local/github/wiki-extensions/wiki-extensions-hulab/AnnotationLinks/AnnotationLinks.php: Call to a member function getIdentifier() on null

Backtrace:

#0 /usr/local/github/wiki-extensions/wiki-extensions-hulab/AnnotationLinks/AnnotationLinks.php(70): AnnotationLinks::getQuickGOannotations(string, array)
#1 /var/www/html/go/wiki/includes/parser/Parser.php(3888): AnnotationLinks::renderAnnotations(NULL, array, Parser, PPFrame_DOM)
#2 /var/www/html/go/wiki/includes/parser/Preprocessor_DOM.php(1362): Parser->extensionSubstitution(array, PPFrame_DOM)
#3 /var/www/html/go/wiki/includes/parser/Parser.php(2942): PPFrame_DOM->expand(DOMElement, integer)
#4 /var/www/html/go/wiki/includes/parser/Parser.php(1293): Parser->replaceVariables(string)
#5 /var/www/html/go/wiki/includes/parser/Parser.php(443): Parser->internalParse(string)
#6 /var/www/html/go/wiki/includes/content/WikitextContent.php(323): Parser->parse(string, Title, ParserOptions, boolean, boolean, integer)
#7 /var/www/html/go/wiki/includes/content/AbstractContent.php(516): WikitextContent->fillParserOutput(Title, integer, ParserOptions, boolean, ParserOutput)
#8 /var/www/html/go/wiki/includes/jobqueue/jobs/RefreshLinksJob.php(231): AbstractContent->getParserOutput(Title, integer, ParserOptions, boolean)
#9 /var/www/html/go/wiki/includes/jobqueue/jobs/RefreshLinksJob.php(126): RefreshLinksJob->runForTitle(Title)
#10 /var/www/html/go/wiki/includes/jobqueue/JobRunner.php(296): RefreshLinksJob->run()
#11 /var/www/html/go/wiki/includes/jobqueue/JobRunner.php(193): JobRunner->executeJob(RefreshLinksJob, Wikimedia\Rdbms\LBFactorySimple, BufferingStatsdDataFactory, integer)
#12 /var/www/html/go/wiki/includes/MediaWiki.php(1002): JobRunner->run(array)
#13 /var/www/html/go/wiki/includes/MediaWiki.php(988): MediaWiki->triggerSyncJobs(integer, MediaWiki\Logger\LegacyLogger)
#14 /var/www/html/go/wiki/includes/MediaWiki.php(912): MediaWiki->triggerJobs()
#15 /var/www/html/go/wiki/includes/MediaWiki.php(727): MediaWiki->restInPeace(string, boolean)
#16 /var/www/html/go/wiki/includes/MediaWiki.php(750): MediaWiki->{closure}()
#17 /var/www/html/go/wiki/includes/MediaWiki.php(557): MediaWiki->doPostOutputShutdown(string)
#18 /var/www/html/go/wiki/index.php(42): MediaWiki->run()
#19 {main}

Navigation menu