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Figuring out the ups and downsand sidewaysof neural development

One of the key controllers of neural development seems to depend on a simple cellular decision--whether to divide perpendicularly or in parallel to the embryonic structure called the neuroepithelium. Nevertheless, such orientation is critical, and understanding its machinery could help neuroscientists learn to control the division of adult neural stem cells to regenerate neural tissues.

Researchers know that during the earliest embryonic brain development, neural stem cells divide "symmetrically," producing identical immature progenitor cells that continue to proliferate. A bit later, however, when neural tissues need to begin to differentiate, the cells divide "asymmetrically," producing one proliferating progenitor and another that stops proliferating and differentiates into an adult neural cell. And during final brain development, the cells return to symmetric cell division, creating differentiated adult cells.

The two types of cell division seem to be governed by the orientation of the tiny bundles of fiber-like microtubules called spindles inside the dividing cell--whether the spindles are oriented parallel or perpendicular to the neuroepithelium. These spindles attach to the dividing chromosomes in the nucleus and drag the two copies apart, ensuring that each daughter cell has its fair share.

In an article in the November 23, 2005, issue of Neuron, Mihaela igman and colleagues have pinpointed a key regulator of spindle orientation in mammals. They drew on discoveries made in the fruit fly Drosophila, in which other researchers had found a gene called Inscuteable to be a central controller of spindle orientation. Analyzing genetic databases, igman and colleagues determined that versions of the Inscuteable gene could be found in higher animals, including mice, rats, and humans. Also, they found in their experiments, the mammalian version of Inscuteable (mInsc) appeared in regions of the cell and activated itself at times during cell divis
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Contact: Heidi Hardman
hhardman@cell.com
617-397-2879
Cell Press
22-Nov-2005


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