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Another Step in Understanding Microcephaly

Errors in the formation of neurons can lead to neurodevelopmental disorders such as microcephaly, an abnormally small brain. Prof. Clemens Cabernard’s team at the Biozentrum, University of Basel, has examined a protein that is involved in the development of microcephaly. As the scientists report in “Cell Reports”, this protein plays an important role in the cell division of neural stem cells and fulfills two very different tasks.

28 January 2016

The human brain consists of some 200 billion nerve cells. These develop from very few neural stem cells, which are the key to healthy brain development. Errors in stem cell division, caused by genetic defects, can lead to malformations such as microcephaly. The clinical picture is characterized by a reduced brain volume and mental retardation.

So far twelve genes and their proteins are known to be associated with the development of microcephaly. In neural stem cells of the fruit fly Drosophila melanogaster, so-called neuroblasts, the researchers led by Prof. Clemens Cabernard from the Biozentrum of the University of Basel have now investigated more closely one of these proteins, named Wdr62. It turned out that Wdr62 plays an important role in asymmetrical cell division as well as in brain development.

Neural stem cells divide asymmetrically

stem cells
Centrosome (magenta) that organizes an array of microtubules (cyan) in a Drosophila neural stem cell. © Biozentrum, University of Basel

The neuroblasts, like all stem cells, have the exceptional ability to divide asymmetrically. This gives rise to two daughter cells with different properties. While one retains stem cell character, the second becomes a precursor cell, which differentiates into a nerve cell. Asymmetric cell division is determined by the positioning of the two different centrosomes. These two poles are anchored to the mitotic spindle, consisting of microtubules and define the division axis of the cell.

Protein Wdr62 important for asymmetry of centrosomes

The team of Cabernard reports that the protein Wdr62 stabilizes the microtubuli and thus supports the formation of asymmetric centrosomes. “The lack of Wdr62 in Drosophila neuroblasts clearly shows its importance”, says Cabernard. “Because this leads to defective centrosomes causing errors in their positioning and segregation and consequently compromises the orientation of the spindle apparatus in the dividing cell.”

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