Loss of Drosophila borealin causes polyploidy, delayed apoptosis and abnormal tissue development.
The chromosomal passenger complex (CPC) is a key regulator of mitosis in many organisms, including yeast and mammals. Its components co-localise at the equator of the mitotic spindle and function interdependently to control multiple mitotic events such as assembly and stability of bipolar spindles, and faithful chromosome segregation into daughter cells. Here, we report the first detailed characterisation of a CPC mutation in Drosophila, using a loss-of-function allele of borealin (borr). Like its mammalian counterpart, Borr colocalises with the CPC components Aurora B kinase and Incenp in mitotic Drosophila cells, and is required for their localisation to the mitotic spindle. borr mutant cells show multiple mitotic defects that are consistent with loss of CPC function. These include a drastic reduction of histone H3 phosphorylation at serine 10 (a target of Aurora B kinase), a pronounced attenuation at prometaphase and multipolar spindles. Our evidence suggests that borr mutant cells undergo multiple consecutive abnormal mitoses, producing large cells with giant nuclei and high ploidy that eventually apoptose. The delayed apoptosis of borr mutant cells in the developing wing disc appears to cause non-autonomous repair responses in the neighbouring wild-type epithelium that involve Wingless signalling, which ultimately perturb the tissue architecture of adult flies. Unexpectedly, during late larval development, cells survive loss of borr and develop giant bristles that may reflect their high degree of ploidy.
Hanson
Kirsten K
KK
MRC Laboratory of Molecular Biology, Cambridge CB2 2QH, UK.
Kelley
Ann C
AC
Bienz
Mariann
M
D000818:Animals; D017209:Apoptosis; D018797:Cell Cycle Proteins / Q000235:genetics* / Q000378:metabolism / Q000502:physiology; D048429:Cell Size; D004330:Drosophila / Q000235:genetics*; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D004625:Embryo, Nonmammalian / Q000737:chemistry / Q000166:cytology / Q000648:ultrastructure; D004848:Epithelium / Q000502:physiology; D006657:Histones / Q000378:metabolism; D008938:Mitosis; D046912:Multiprotein Complexes / Q000172:deficiency / Q000235:genetics; D009154:Mutation; D010766:Phosphorylation; D011123:Polyploidy; D008941:Spindle Apparatus / Q000378:metabolism; D014921:Wings, Animal / Q000166:cytology / Q000254:growth & development
C490157:CDCA8 protein, human; D018797:Cell Cycle Proteins; D029721:Drosophila Proteins; D006657:Histones; D046912:Multiprotein Complexes