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

current study, however, the team made the unexpected finding that gap junctions also play a crucial role in neuronal migration and that they function in a previously unrecognized way. Rather than functioning as a conduit through which molecular signals move, the two fused hemi-channels serve as a form of adhesion between the migrating neurons and the neural stem cell fibers.

Cell adhesion is a common mechanism, but its function had not been detected previously in gap junctions.

The discovery that gap junctions were involved in migration in any capacity was a surprise. Elias had been investigating whether the molecule functioned as a channel to regulate cell proliferation within embryonic neural stem cells of the developing rat brain, building on preliminary findings from the Kriegstein lab 15 years ago.

As part of one study, she had reduced the levels of gap junctions in the neural stem cells. To our surprise, she says, the newborn neurons that the stem cells produced piled up on one another and failed to migrate into the cortex.

To establish the role that gap junctions might play in neuronal migration, the team focused on the activity of the molecules subunits, known as connexons, in a series of studies in the developing rat brain. They honed in on two of these proteins Cx26 and Cx43 because they determined that they were expressed at high levels in migrating neurons and along radial fibers and that they were, in fact, highly localized in regions of the neurons that were in contact with radial fibers.

In a notable finding, says Elias, blocking the activity of either subunit significantly impaired migration to the neocortex, as seen in a striking cellular redistribution pattern of the neurons.

To determine the mechanism by which the gap junctions were functioning, the team selectively blocked three plausible mechanisms: the well-known channel function, a form of cellular signaling that relies on the intra
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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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