PUBLICATION

Non-SMC condensin I complex proteins control chromosome segregation and survival of proliferating cells in the zebrafish neural retina

Authors
Seipold, S., Priller, F.C., Goldsmith, P., Harris, W.A., Baier, H., and Abdelilah-Seyfried, S.
ID
ZDB-PUB-090716-9
Date
2009
Source
BMC Developmental Biology   9: 40 (Journal)
Registered Authors
Abdelilah-Seyfried, Salim, Baier, Herwig, Harris, William A.
Keywords
none
MeSH Terms
  • Immunohistochemistry
  • Chromosome Segregation/genetics
  • Chromosome Segregation/physiology*
  • Adenosine Triphosphatases/genetics
  • Adenosine Triphosphatases/metabolism*
  • Animals
  • In Situ Hybridization
  • Zebrafish
  • Cell Proliferation
  • Tumor Suppressor Protein p53/metabolism
  • Multiprotein Complexes/genetics
  • Multiprotein Complexes/metabolism*
  • DNA-Binding Proteins/genetics
  • DNA-Binding Proteins/metabolism*
  • Apoptosis/genetics
  • Apoptosis/physiology
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism*
  • Retina/cytology*
  • Retina/metabolism*
(all 20)
PubMed
19586528 Full text @ BMC Dev. Biol.
Abstract
BACKGROUND: The condensation of chromosomes and correct sister chromatid segregation during cell division is an essential feature of all proliferative cells. Structural maintenance of chromosomes (SMC) and non-SMC proteins form the condensin I complex and regulate chromosome condensation and segregation during mitosis. However, due to the lack of appropriate mutants, the function of the condensin I complex during vertebrate development has not been described. RESULTS: Here, we report the positional cloning and detailed characterization of retinal phenotypes of a zebrafish mutation at the cap-g locus. High resolution live imaging reveals that the progression of mitosis between prometa- to telophase is delayed and that sister chromatid segregation is impaired upon loss of CAP-G. CAP-G associates with chromosomes between prometa- and telophase of the cell cycle. Loss of the interaction partners CAP-H and CAP-D2 causes cytoplasmic mislocalization of CAP-G throughout mitosis. DNA content analysis reveals increased genomic imbalances upon loss of non-SMC condensin I subunits. Within the retina, loss of condensin I function causes increased rates of apoptosis among cells within the proliferative ciliary marginal zone (CMZ) whereas postmitotic retinal cells are viable. Inhibition of p53-mediated apoptosis partially rescues cell numbers in cap-g mutant retinae and allows normal layering of retinal cell types without alleviating their aberrant nuclear sizes. CONCLUSIONS: Our findings indicate that the condensin I complex is particularly important within rapidly amplifying progenitor cell populations to ensure faithful chromosome segregation. In contrast, differentiation of postmitotic retinal cells is not impaired upon polyploidization.
Genes / Markers
Figures
Figure Gallery (8 images)
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Expression
Phenotype
Mutations / Transgenics
Allele Construct Type Affected Genomic Region
kca6TgTransgenic Insertion
    kca66TgTransgenic Insertion
      s105
        Point Mutation
        1 - 3 of 3
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        Human Disease / Model
        No data available
        Sequence Targeting Reagents
        Target Reagent Reagent Type
        ncapd2MO1-ncapd2MRPHLNO
        ncapgMO1-ncapgMRPHLNO
        ncaphMO1-ncaphMRPHLNO
        tp53MO4-tp53MRPHLNO
        1 - 4 of 4
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        Fish
        Antibodies
        Name Type Antigen Genes Isotypes Host Organism
        zn-5monoclonalIgG1Mouse
        zpr-1monoclonalIgG1Mouse
        1 - 2 of 2
        Show
        Orthology
        Gene Orthology
        ncapg
        1 - 1 of 1
        Show
        Engineered Foreign Genes
        Marker Marker Type Name
        GFPEFGGFP
        1 - 1 of 1
        Show
        Mapping
        No data available