Non-SMC condensin I complex proteins control chromosome segregation and survival of proliferating cells in the zebrafish neural retina.
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.
Seipold
Sabine
S
Max Delbrück Center (MDC) for Molecular Medicine, Berlin, Germany. sabine3000@gmail.com
Priller
Florian C
FC
Goldsmith
Paul
P
Harris
William A
WA
Baier
Herwig
H
Abdelilah-Seyfried
Salim
S
D000251:Adenosine Triphosphatases / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D017209:Apoptosis / Q000235:genetics / Q000502:physiology; D049109:Cell Proliferation; D020090:Chromosome Segregation / Q000235:genetics / Q000502:physiology*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D046912:Multiprotein Complexes / Q000235:genetics / Q000378:metabolism*; D012160:Retina / Q000166:cytology* / Q000378:metabolism*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D015027:Zebrafish; D029961:Zebrafish Proteins / Q000235:genetics / Q000378:metabolism*
D004268:DNA-Binding Proteins; D046912:Multiprotein Complexes; D016159:Tumor Suppressor Protein p53; D029961:Zebrafish Proteins; C108312:condensin complexes; D000251:Adenosine Triphosphatases