[rael-science] Live Imaging Puts New Light on Stem Cell Division

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Live Imaging Puts New Light on Stem Cell Division
http://www.sciencedaily.com/releases/2010/09/100901132147.htm

ScienceDaily (Sep. 1, 2010) — A long-held assumption about
asymmetrical division of stem cells has cracked. Researchers at the
University of Oregon report that the mitotic spindle does not act
alone -- that cortical proteins help to position a cleavage furrow in
the right location.

Their discovery, described in the Sept. 2 issue of the journal Nature,
provides a new window on how stem cells divide to produce two unequal
daughter cells: one that lives on as a new stem cell and other,
smaller cell, that adopts a new function, in this case as a neuron.

A three-member team focused on Drosophila (fruit flies) neural stem
cells known as neuroblasts, long known for dividing asymmetrically.
What is learned in these flies often applies to many other mitotic
(dividing) cells in other organisms such as mammals, including humans.

"This addresses a fundamental question in cell biology, namely how a
cell knows where to place a cleavage furrow and thus divide in a
symmetrical or asymmetrical fashion," said Clemens Cabernard, a
postdoctoral fellow in the lab of Chris Doe, a Howard Hughes Medical
Institute investigator in the UO Institute of Molecular Biology and
director of the UO Institute of Neuroscience. Also on the team was
Kenneth E. Prehoda, a UO biochemist and member of the Institute of
Molecular Biology.

What the UO team found is that neuroblasts have two distinct dividing
pathways that appear to work redundantly: one that is polarity induced
and one that is spindle induced, Cabernard said.

Theories on cleavage furrow positioning during cell division have
centered on the mitotic spindle, a network of fibers called
microtubules.

One idea is that microtubules from spindle poles reach to the cortex,
which delivers a positive or negative signal to determine the position
of the cleavage ring. Another idea is that microtubule fibers from the
center of the spindle reach out to the cortex resulting in the
assembly of a cleavage ring (a complex consisting of several proteins,
one of which is called myosin). A third model involves both. It was
thought that asymmetrically dividing cells, such as drosophila
neuroblasts, generate an asymmetric spindle and can position the
cleavage ring in an asymmetric position, as opposed to symmetrically
dividing cells that construct a symmetric spindle.

"We found a new mechanism in which a cleavage furrow can be placed at
an asymmetric position," Cabernard said. "First, by way of a couple of
experiments, we ruled out that the cleavage furrow is solely dependent
on the position and symmetry/asymmetry of the mitotic spindle."

First researchers used mutants that lack astral microtubules, the
microtubule fibers reaching out from the spindle poles towards the
cortex and watched with live imaging what happens to the cleavage
furrow. A cleavage furrow still occurred in an asymmetric position.
This has been seen before but not using the same markers, Cabernard
said.

Next, researchers removed the entire spindle from the picture with
targeted drugs. Usually cells stop dividing in this condition, but a
genetic trick allows these cells to initiate cell division despite the
lack of a mitotic spindle. Surprisingly, researchers found, the
proteins involved in constructing a cleavage furrow became localized
in an asymmetric fashion and positioned a cleavage furrow in an
asymmetric position -- pretty much like in wild-type neuroblasts.
"Although cell division could not be completed, the dividing point was
correctly marked," Cabernard said. "This told us that there must be a
mechanism independent of the spindle."

In a third set of experiments, the research team rotated the mitotic
spindle of neuroblasts using genetic mutants and thus changed the
position of any spindle-derived signal. Interestingly, the team found
that two cleavage furrows now formed, but only one coincided with the
new position of the mitotic spindle, strongly supporting the
hypothesis that a spindle independent signal also is used. Further
experiments revealed that a cortical protein, required for proper
neural stem cell divisions in mice and humans, is necessary for the
asymmetric positioning of the cleavage furrow.

One of the marker proteins watched closely in the experiments was
myosin. When a cell starts the division process, Cabernard said, the
spindle is symmetrical but the myosin markers segregated toward the
basal side -- and is localized in an asymmetric fashion -- which
becomes smaller and transforms into a neuron upon cell division.

Although this research addresses a basic question in cell biology, the
findings have important implications. Asymmetric cell division in fly
or human stem cells is important to generate a number of
differentiating cells while retaining a stem cell as a back up copy.

Previous work by Cabernard and Doe showed that if drosophila
neuroblasts divide in a symmetric manner, which doesn't normally
happen, two neuroblasts are generated. Thus, the researchers said, it
is crucial for a stem cell to know where to place a cleavage furrow to
produce all the required neurons. Similar results have been observed
in neural stem cells in mice.

The National Institutes of Health, American Heart Association, Swiss
National Science Foundation and Howard Hughes Medical Institute
supported the research.

Story Source:

The above story is reprinted (with editorial adaptations by
ScienceDaily staff) from materials provided by University of Oregon.


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"Ethics" is simply a last-gasp attempt by deist conservatives and
orthodox dogmatics to keep humanity in ignorance and obscurantism,
through the well tried fermentation of fear, the fear of science and
new technologies.

There is nothing glorious about what our ancestors call history,
it is simply a succession of mistakes, intolerances and violations.

On the contrary, let us embrace Science and the new technologies
unfettered, for it is these which will liberate mankind from the
myth of god, and free us from our age old fears, from disease,
death and the sweat of labour.

Rael
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