PUBLICATION

The proteasome subunit psmb1 is essential for craniofacial cartilage maturation and morphogenesis

Authors
Miller, B.M., Goessling, W.
ID
ZDB-PUB-240823-2
Date
2024
Source
JCI insight   9(16): (Journal)
Registered Authors
Goessling, Wolfram
Keywords
Cartilage, Development, Embryonic development
Datasets
GEO:GSE243072
MeSH Terms
  • Zebrafish Proteins*/genetics
  • Zebrafish Proteins*/metabolism
  • Chondrocytes*/metabolism
  • Gene Expression Regulation, Developmental
  • Cartilage*/embryology
  • Cartilage*/metabolism
  • Craniofacial Abnormalities/genetics
  • Craniofacial Abnormalities/pathology
  • Animals
  • Mutation
  • Chondrogenesis/genetics
  • Proteasome Endopeptidase Complex*/genetics
  • Proteasome Endopeptidase Complex*/metabolism
  • Morphogenesis*/genetics
  • Zebrafish*/genetics
  • Tendons/abnormalities
  • Tendons/embryology
  • Tendons/metabolism
  • Tendons/pathology
  • Cell Differentiation/genetics
(all 20)
PubMed
39171526 Full text @ JCI Insight
Abstract
Craniofacial dysmorphisms are among the most common birth defects. Proteasome mutations frequently result in craniofacial dysmorphisms, including lower jaw malformations; however, the underlying mechanisms are unknown. Here, we used a zebrafish proteasome subunit β 1 (psmb1) mutant to define the cellular mechanisms underlying proteasome mutation-induced craniofacial dysmorphisms. psmb1 mutants exhibited a flattened ceratohyal and smaller Meckel's and palatoquadrate cartilages. Ceratohyal flattening was a result of failed chondrocyte convergent extension, accompanied by reduced numbers of chondrocytes in the lower jaw due to defects in chondrocyte differentiation. Morphogenesis of craniofacial muscles and tendons was similarly perturbed. psmb1 mutants lacked the hyohyal muscles, and craniofacial tendons were shortened and disorganized. We additionally identified a critical period for proteasome function in craniofacial development, specifically during chondrocyte and muscle differentiation. psmb1 overexpression in sox10+ cells of mutant embryos rescued both cartilage and tendon phenotypes but induced only a partial rescue of the muscle phenotype, indicating that psmb1 was required in both tissue-autonomous and nonautonomous fashions during craniofacial development. Overall, our work demonstrates that psmb1 is required for craniofacial cartilage, tendon, and muscle differentiation and morphogenesis.
Genes / Markers
Figures
Figure Gallery (6 images)
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Expression
Gene Antibody Fish Conditions Stage Qualifier Anatomy Assay Figure
acta1aABstandard conditionsProtruding-mouthRTPCR
acta1apsmb1hi2939Tg/hi2939Tgstandard conditionsProtruding-mouthRTPCR
col10a1aABstandard conditionsProtruding-mouthRTPCR
col10a1apsmb1hi2939Tg/hi2939Tgstandard conditionsProtruding-mouthRTPCR
col11a2ABstandard conditionsProtruding-mouthRTPCR
col11a2psmb1hi2939Tg/hi2939Tgstandard conditionsProtruding-mouthRTPCR
col2a1aABstandard conditionsProtruding-mouthRTPCR
col2a1apsmb1hi2939Tg/hi2939Tgstandard conditionsProtruding-mouthRTPCR
matn1ABstandard conditionsProtruding-mouthRTPCR
matn1psmb1hi2939Tg/hi2939Tgstandard conditionsProtruding-mouthRTPCR
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Phenotype
Fish Conditions Stage Phenotype Figure
psmb1hi2939Tg/hi2939Tgstandard conditionsLong-pec
psmb1hi2939Tg/hi2939Tgstandard conditionsLong-pec
psmb1hi2939Tg/hi2939Tgstandard conditionsPec-fin
psmb1hi2939Tg/hi2939Tgstandard conditionsPec-fin
psmb1hi2939Tg/hi2939Tgstandard conditionsPec-fin
psmb1hi2939Tg/hi2939Tgstandard conditionsPec-fin
psmb1hi2939Tg/hi2939Tgstandard conditionsPec-fin
psmb1hi2939Tg/hi2939Tgstandard conditionsProtruding-mouth
psmb1hi2939Tg/hi2939Tgstandard conditionsProtruding-mouth
psmb1hi2939Tg/hi2939Tgstandard conditionsProtruding-mouth
1 - 10 of 67
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Mutations / Transgenics
Allele Construct Type Affected Genomic Region
cz3327TgTransgenic Insertion
    fb301TgTransgenic Insertion
      hi2939TgTransgenic Insertion
      s854TgTransgenic Insertion
        twu5TgTransgenic Insertion
          y1TgTransgenic Insertion
            zf393TgTransgenic Insertion
              zf4006TgTransgenic Insertion
                1 - 8 of 8
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                Human Disease / Model
                No data available
                Sequence Targeting Reagents
                No data available
                Fish
                Fish
                AB
                psmb1hi2939Tg/hi2939Tg
                psmb1hi2939Tg/hi2939Tg; s854Tg
                psmb1hi2939Tg/hi2939Tg; y1Tg
                psmb1hi2939Tg/hi2939Tg; zf393Tg
                psmb1hi2939Tg/hi2939Tg; zf393Tg; zf4006Tg
                psmb1hi2939Tg/hi2939Tg; zf4006Tg
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                Antibodies
                Name Type Antigen Genes Isotypes Host Organism
                Ab1-col2amonoclonal
                  		IgG1Mouse
                  Ab2-sox9apolyclonal
                    		IgGRabbit
                    Ab-A4.1025monoclonal
                      		IgG2aMouse
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                      Orthology
                      No data available
                      Engineered Foreign Genes
                      Marker Marker Type Name
                      CeruleanEFGCerulean
                      EGFPEFGEGFP
                      GFPEFGGFP
                      KaedeEFGKaede
                      mCherryEFGmCherry
                      1 - 5 of 5
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                      Mapping
                      No data available
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                      Citation
                      Miller, B.M., Goessling, W. (2024) The proteasome subunit psmb1 is essential for craniofacial cartilage maturation and morphogenesis. JCI insight. 9(16):.