Linked Life Data

12397114

Source:http://linkedlifedata.com/resource/pubmed/id/12397114

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
21
pubmed:dateCreated
2002-10-24
pubmed:abstractText
The molecular genetic mechanisms of cartilage construction are incompletely understood. Zebrafish embryos homozygous for jellyfish (jef) mutations show craniofacial defects and lack cartilage elements of the neurocranium, pharyngeal arches, and pectoral girdle similar to humans with campomelic dysplasia. We show that two alleles of jef contain mutations in sox9a, one of two zebrafish orthologs of the human transcription factor SOX9. A mutation induced by ethyl nitrosourea changed a conserved nucleotide at a splice junction and severely reduced splicing of sox9a transcript. A retrovirus insertion into sox9a disrupted its DNA-binding domain. Inhibiting splicing of the sox9a transcript in wild-type embryos with splice site-directed morpholino antisense oligonucleotides produced a phenotype like jef mutant larvae, and caused sox9a transcript to accumulate in the nucleus; this accumulation can serve as an assay for the efficacy of a morpholino independent of phenotype. RNase-protection assays showed that in morpholino-injected animals, the percent of splicing inhibition decreased from 80% at 28 hours post fertilization to 45% by 4 days. Homozygous mutant embryos had greatly reduced quantities of col2a1 message, the major collagen of cartilage. Analysis of dlx2 expression showed that neural crest specification and migration was normal in jef (sox9a) embryos. Confocal images of living embryos stained with BODIPY-ceramide revealed at single-cell resolution the formation of precartilage condensations in mutant embryos. Besides the lack of overt cartilage differentiation, pharyngeal arch condensations in jef (sox9a) mutants lacked three specific morphogenetic behaviors: the stacking of chondrocytes into orderly arrays, the individuation of pharyngeal cartilage organs and the proper shaping of individual cartilages. Despite the severe reduction of cartilages, analysis of titin expression showed normal muscle patterning in jef (sox9a) mutants. Likewise, calcein labeling revealed that early bone formation was largely unaffected in jef (sox9a) mutants. These studies show that jef (sox9a) is essential for both morphogenesis of condensations and overt cartilage differentiation.
pubmed:grant
pubmed:commentsCorrections
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
0950-1991
pubmed:author
pubmed:issnType
Print
pubmed:volume
129
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
5065-79
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed-meshheading:12397114-Alleles, pubmed-meshheading:12397114-Animals, pubmed-meshheading:12397114-Base Sequence, pubmed-meshheading:12397114-Bone Development, pubmed-meshheading:12397114-Cartilage, pubmed-meshheading:12397114-Chondrogenesis, pubmed-meshheading:12397114-DNA, Complementary, pubmed-meshheading:12397114-Disease Models, Animal, pubmed-meshheading:12397114-Gene Duplication, pubmed-meshheading:12397114-Gene Expression Regulation, Developmental, pubmed-meshheading:12397114-High Mobility Group Proteins, pubmed-meshheading:12397114-Humans, pubmed-meshheading:12397114-Muscles, pubmed-meshheading:12397114-Mutation, pubmed-meshheading:12397114-Oligodeoxyribonucleotides, Antisense, pubmed-meshheading:12397114-Osteochondrodysplasias, pubmed-meshheading:12397114-Pharynx, pubmed-meshheading:12397114-RNA Splicing, pubmed-meshheading:12397114-SOX9 Transcription Factor, pubmed-meshheading:12397114-Transcription Factors, pubmed-meshheading:12397114-Zebrafish
pubmed:year
2002
pubmed:articleTitle
A zebrafish sox9 gene required for cartilage morphogenesis.
pubmed:affiliation
Institute of Neuroscience, University of Oregon, Eugene 97403, USA.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, U.S. Gov't, P.H.S., Research Support, U.S. Gov't, Non-P.H.S., Research Support, Non-U.S. Gov't