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Neural stem cell study reveals mechanism that may play role in cancer
Date:9/5/2007

cellular end of the molecule, and adhesion.

Remarkably, says co-author Doris Wang, a student in the MD, PhD neuroscience program at UCSF and a member of the Kriegstein lab, we found that adhesion, alone, is necessary for the role of gap junctions during neuronal migration.

Further study revealed that the Cx43 and Cx26 molecular subunits interact with the neurons internal cytoskeleton to stabilize it on its path.

A series of time-lapse, live imaging studies of migrating neurons illuminated this phenomenon: The neurons start out with a branched leading process. Then one of the processes is stabilized and the neuron translocates its body into a swelling that forms in the stabilized leading process. When the levels of the gap junction protein are reduced, however, the neurons are no longer able to stabilize their leading processes and continue to send out multiple branches.

The revelation of the gap junctions role in neural migration is provocative, says Kriegstein, because the molecule is known to be involved in several disease processes, including the spread of cancers in the brain, skin and lung. Most brain tumors are made up of glial cells that spread throughout the brain by migrating along white matter pathways -- the network of neural fibers that connect neurons.

While roles for the gap junction channel in cancer have been demonstrated, Its possible, he says, that gap junctions are also using the cell adhesion function in these disease settings to support cell migration. If so, the mechanism could become a target for therapy.

The study also revealed another surprising phenomenon, says Kriegstein, the John G. Bowes Endowed Chair in Stem Cell and Tissue Biology. It has long been known that when neural stem cells divide they undergo a process of asymmetrical division, in which they produce one newborn neuron and one new neural stem cell. The understanding has been that the neurons then begin their migration along
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Contact: Jennifer OBrien
jobrien@pubaff.ucsf.edu
415-476-2557
University of California - San Francisco
Source:Eurekalert

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