PUBLICATION

barx1 represses joints and promotes cartilage in the craniofacial skeleton

Authors
Nichols, J.T., Pan, L., Moens, C.B., and Kimmel, C.B.
ID
ZDB-PUB-130703-13
Date
2013
Source
Development (Cambridge, England)   140(13): 2765-2775 (Journal)
Registered Authors
Kimmel, Charles B., Moens, Cecilia, Nichols, James Tucker, Pan, Luyuan
Keywords
barx1, hand2, cartilage, joint, skeleton, zebrafish
MeSH Terms
  • Transcription Factors/genetics
  • Transcription Factors/metabolism*
  • Joints/embryology*
  • Joints/metabolism
  • Facial Bones/embryology
  • Facial Bones/metabolism*
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism*
  • Cartilage/embryology*
  • Cartilage/metabolism
  • Skull/embryology
  • Skull/metabolism*
  • Animals
  • Zebrafish/embryology*
  • Zebrafish/metabolism*
(all 15)
PubMed
23698351 Full text @ Development
Abstract

The evolution of joints, which afford skeletal mobility, was instrumental in vertebrate success. Here, we explore the molecular genetics and cell biology that govern jaw joint development. Genetic manipulation experiments in zebrafish demonstrate that functional loss, or gain, of the homeobox-containing gene barx1 produces gain, or loss, of joints, respectively. Ectopic joints in barx1 mutant animals are present in every pharyngeal segment, and are associated with disrupted attachment of bone, muscles and teeth. We find that ectopic joints develop at the expense of cartilage. Time-lapse experiments suggest that barx1 controls the skeletal precursor cell choice between differentiating into cartilage versus joint cells. We discovered that barx1 functions in this choice, in part, by regulating the transcription factor hand2. We further show that hand2 feeds back to negatively regulate barx1 expression. We consider the possibility that changes in barx1 function in early vertebrates were among the key innovations fostering the evolution of skeletal joints.

Genes / Markers
Marker Marker Type Name
barx1GENEBARX homeobox 1
chrdGENEchordin
furinaGENEfurin (paired basic amino acid cleaving enzyme) a
hand2GENEheart and neural crest derivatives expressed 2
myl7GENEmyosin, light chain 7, regulatory
nkx3-2GENENK3 homeobox 2
sox9aGENESRY-box transcription factor 9a
trps1GENEtrichorhinophalangeal syndrome I
1 - 8 of 8
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Figures
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Expression
Phenotype
Mutations / Transgenics
Allele Construct Type Affected Genomic Region
b1228TgTransgenic Insertion
    b1229TgTransgenic Insertion
      fh330
        Point Mutation
        fh331
          Point Mutation
          j1271aGtTransgenic Insertion
          s6
            Deficiency
            tg419
              Point Mutation
              vu234TgTransgenic Insertion
                y1TgTransgenic Insertion
                  zc81TgTransgenic Insertion
                  1 - 10 of 10
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                  Human Disease / Model
                  No data available
                  Sequence Targeting Reagents
                  No data available
                  Fish
                  Antibodies
                  Name Type Antigen Genes Isotypes Host Organism
                  Ab1-col2amonoclonal
                    IgG1Mouse
                    1 - 1 of 1
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                    Orthology
                    No data available
                    Engineered Foreign Genes
                    Marker Marker Type Name
                    CrimsonEFGCrimson
                    EGFPEFGEGFP
                    mRFPEFGmRFP
                    1 - 3 of 3
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                    Mapping
                    No data available