does the road to aneuploidy pass through tetraploidy?
Caldwell et al. (2007) explored this further, finding that overexpression of the putative dominant-negative APC1-1450 leads to cytokinesis failure. They suggest that reduced MT contact with the cortex is the cause; consistent with this, they found a strong correlation between spindle rotation and failure to initiate a cytokinetic furrow (Fig. 4). The resulting tetraploidy could lead to aneuploidy after further divisions. One concern is that this occurred only after the overexpression of truncated APC1-1450 and was not reported in their earlier studies of APC knockdown (Green et al., 2005). Thus, it is possible that these effects are not strictly caused by APC loss of function. However, Kaplan’s laboratory did find elevated aneuploidy and tetraploidy in intestines of APCmin/+ mice, even in crypts that are presumably heterozygous mutant (Caldwell et al., 2007). Thus, they concluded that defects in astral MTs and altered spindle positioning caused by APC mutations result in cytokinesis fa
