Key factor in brain development revealed, offers insight into disorder

“Just like a pulley, dynein draws the microtubules through it and that, in turn, rotates the spindle,” suggests Wynshaw-Boris.

Loss of Lis1, results in reduced and weakened microtubules and an inability of the mitotic spindle to rotate the microtubules properly in the apical-basal axis.

Of note, while loss of Lis1 is catastrophic in neuroepithelial stem cells, it is not so in radial glial progenitor cells. The reason is not entirely clear, says Wynshaw-Boris, but the scientists hypothesize that neuroepithelial stem cells require a greater tightness of control of the plane of cell division. In support of this notion, while neuroepithelial stem cells appear to always divide symmetrically, radial glial progenitor cells often divide asymmetrically to produce one daughter cell (radial glial progenitor cell) and one newborn nerve cell.

“The study sheds some light on the differences in the regulation of symmetric and asymmetric divisions in neuroepithelial stem cells and radial glial progenitor cells,” says Wynshaw-Boris.

More broadly, he says, the findings suggest that neural migration birth defects, such as lissencephaly, may be caused by defects in other processes, as well, including proliferation, division and, in this case stem cell division. “It gives insight,” he says, “into these rare diseases and what’s important for normal brain development.”

The co-first authors of the study were Jessica Yingling and Yong Ha Youn. Other co-authors of the study were Dawn Darling, Kazuhito Toyo-oka, Tiziano Pramparo and Shinji Hirosune.

The study was funded by the National Institutes of Health and National Science Foundation.

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Related links:

Wynshaw-Boris lab: http://www.ucsf.edu/bms/faculty/wynshawboris.html