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Vol. 9, Issue 8, 2173-2184, August 1998
Department of Physiology, University of Massachusetts Medical
School, Worcester, Massachusetts 01655
While astral microtubules are believed to be primarily responsible
for the stimulation of cytokinesis in Echinoderm
embryos, it has been suggested that a signal emanating from the
chromosomal region and mediated by the interzonal microtubules
stimulates cytokinesis in cultured mammalian cells. To test this
hypothesis, we examined cytokinesis in normal rat kidney cells treated
with an inhibitor of topoisomerase II,
(+)-1,2-bis(3,5-dioxopiperaz-inyl-1-yl)propane, which prevents the
separation of sister chromatids and the formation of a spindle
interzone. The majority of treated cells showed various degrees of
abnormality in cytokinesis. Furrows frequently deviated from the
equatorial plane, twisting daughter cells into irregular shapes. Some
cells developed furrows in regions outside the equator or far away from
the spindle. In addition, F-actin and myosin II accumulated at the
lateral ingressing margins but did not form a continuous band along the
equator as in control cells. Imaging of microinjected 5- (and 6-)
carboxymtetramethylrhodamine-tubulin revealed that a unique set of
microtubules projected out from the chromosomal vicinity upon anaphase
onset. These microtubules emanated toward the lateral cortex, where
they delineated sites of microtubule bundle formation, cortical
ingression, and F-actin and myosin II accumulation. As centrosome
integrity and astral microtubules appeared unperturbed by
(+)-1,2-bis(3,5-dioxopiperaz-inyl-1-yl)propane treatment, the present
observations cannot be easily explained by the conventional model
involving astral microtubules. We suggest that in cultured epithelial
cells the organization of the chromosomes dictates the organization of
midzone microtubules, which in turn determines and maintains the
cleavage activity.
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