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A flip of the mitotic spindle has disastrous consequences for epithelial cells
Date:7/21/2013

division began, the mitotic spindle (which faithfully distributes chromosomes into each daughter cell) invariably oriented itself parallel to the apical surface of the epithelium.

In other words, if you pointed a tiny camera in your gut toward dividing epithelial cells of its lining, you would "see" the mitotic spindle looking like a symmetrical web, exactly like it did in your high school biology textbook.

To determine why its orientation was non-random, the group did an equivalent experiment. Using high resolution fluorescence imaging to look inside dividing cells in developing wing discs, they observed that the two poles of the spindle were always near the septate junctions, specific regions of close molecular contact between neighboring cells. Two junction components, proteins called Discs Large and Scribble, were juxtaposed to the spindle, suggesting they might act as cues to orient it.

The seemingly odd names given to these factors decades ago reflect what biologists saw in fly mutants lacking each protein. In flies without Discs Large, the imaginal discs are massively overgrown, while fly embryos lacking Scribble resemble a chaotic scribble reminiscent of a tumor. Gibson reasoned that the reported tumor-suppressive activity of these proteins might be linked to a role in keeping the mitotic spindle in line.

So his group genetically deleted Scribble, Discs Large and a host of other factors in wing disc cells and watched what happened when cells divided, an effort aided by a customized microscope built by the Stowers Microscopy Center. What they saw was dramatic: Scribble deletion caused the mitotic spindle to flip over at a random angle, as did deletion of Discs Large. Next, by directly perturbing the spindle, the researchers video-captured the process by which cells with misoriented spindles began to peel away, or delaminate, from the epithelium.

"I did not expect that spindle orientation defects could be suffici
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Contact: Gina Kirchweger
gxk@stowers.org
816-806-1036
Stowers Institute for Medical Research
Source:Eurekalert

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