PUBLICATION

moz regulates Hox expression and pharyngeal segmental identity in zebrafish

Authors
Miller, C.T., Maves, L., and Kimmel, C.B.
ID
ZDB-PUB-040510-4
Date
2004
Source
Development (Cambridge, England)   131(10): 2443-2461 (Journal)
Registered Authors
Kimmel, Charles B., Maves, Lisa, Miller, Craig T.
Keywords
moz, Hox, hoxa2, Zebrafish, Cranial neural crest, Bapx1, Goosecoid, Homeosis, Pharynx
MeSH Terms
  • Pharynx/embryology*
  • Restriction Mapping
  • Morpholines/pharmacology
  • Histone Acetyltransferases/genetics*
  • Animals
  • Morphogenesis
  • Mutagenesis
  • Acetyltransferases/genetics*
  • Gene Expression Regulation, Developmental/genetics*
  • Genes, Homeobox/genetics
  • Body Patterning/genetics
  • Oligodeoxyribonucleotides/pharmacology
  • Recombinant Proteins/metabolism
  • Zebrafish Proteins/genetics*
  • Base Sequence
  • Homeodomain Proteins/genetics*
  • Zebrafish/embryology*
  • Zebrafish/genetics*
  • Cloning, Molecular
(all 19)
PubMed
15128673 Full text @ Development
Abstract
In vertebrate embryos, streams of cranial neural crest (CNC) cells migrate to form segmental pharyngeal arches and differentiate into segment-specific parts of the facial skeleton. To identify genes involved in specifying segmental identity in the vertebrate head, we screened for mutations affecting cartilage patterning in the zebrafish larval pharynx. We present the positional cloning and initial phenotypic characterization of a homeotic locus discovered in this screen. We show that a zebrafish ortholog of the human oncogenic histone acetyltransferase MOZ (monocytic leukemia zinc finger) is required for specifying segmental identity in the second through fourth pharyngeal arches. In moz mutant zebrafish, the second pharyngeal arch is dramatically transformed into a mirror-image duplicated jaw. This phenotype resembles a similar but stronger transformation than that seen in hox2 morpholino oligo (hox2-MO) injected animals. In addition, mild anterior homeotic transformations are seen in the third and fourth pharyngeal arches of moz mutants. moz is required for maintenance of most hox1-4 expression domains and this requirement probably at least partially accounts for the moz mutant homeotic phenotypes. Homeosis and defective Hox gene expression in moz mutants is rescued by inhibiting histone deacetylase activity with Trichostatin A. Although we find early patterning of the moz mutant hindbrain to be normal, we find a late defect in facial motoneuron migration in moz mutants. Pharyngeal musculature is transformed late, but not early, in moz mutants. We detect relatively minor defects in arch epithelia of moz mutants. Vital labeling of arch development reveals no detectable changes in CNC generation in moz mutants, but later prechondrogenic condensations are mispositioned and misshapen. Mirror-image hox2-dependent gene expression changes in postmigratory CNC prefigure the homeotic phenotype in moz mutants. Early second arch ventral expression of goosecoid (gsc) in moz mutants and in animals injected with hox2-MOs shifts from lateral to medial, mirroring the first arch pattern. bapx1, which is normally expressed in first arch postmigratory CNC prefiguring the jaw joint, is ectopically expressed in second arch CNC of moz mutants and hox2-MO injected animals. Reduction of bapx1 function in wild types causes loss of the jaw joint. Reduction of bapx1 function in moz mutants causes loss of both first and second arch joints, providing functional genetic evidence that bapx1 contributes to the moz-deficient homeotic pattern. Together, our results reveal an essential embryonic role and a crucial histone acetyltransferase activity for Moz in regulating Hox expression and segmental identity, and provide two early targets, bapx1 and gsc, of moz and hox2 signaling in the second pharyngeal arch.
Genes / Markers
Figures
Figure Gallery (10 images)
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Expression
Phenotype
Mutations / Transgenics
Allele Construct Type Affected Genomic Region
b719
    Small Deletion
    b963
      Point Mutation
      b999
        Point Mutation
        1 - 3 of 3
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        Human Disease / Model
        No data available
        Sequence Targeting Reagents
        Target Reagent Reagent Type
        hoxa2bMO1-hoxa2bMRPHLNO
        hoxb2aMO1-hoxb2aMRPHLNO
        kat6aMO1-kat6aMRPHLNO
        kat6aMO2-kat6aMRPHLNO
        kat6aMO3-kat6aMRPHLNO
        nkx3-2MO1-nkx3-2MRPHLNO
        1 - 6 of 6
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        Fish
        Antibodies
        No data available
        Orthology
        Gene Orthology
        kat6a
        1 - 1 of 1
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        Engineered Foreign Genes
        No data available
        Mapping
        Entity Type Entity Symbol Location
        ESTfc15g12Chr: 5 Details
        ESTfc32e05Chr: 5 Details
        GENEkat6aChr: 5 Details
        SSLPz6371Chr: 5 Details
        SSLPz7351Chr: 5 Details
        1 - 5 of 5
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