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Mental disabilities: a better understanding of the implicated genes

​Experiments in yeast to understand the causes of mental disability? As amazing as this may sound, researchers from the CEA-IRTSV have used this model to explain the molecular origin of certain defects in the human cortex. These results are published in the journal Nature Genetics.

Published on 5 December 2013

Thanks to progress in imaging, scientists understand more and more the anatomical abnormalities responsible for mental disabilities. Malformations of the cortex and impaired neuronal communication are particularly implicated. However, much remains to be accomplished in order to comprehend the origin of these disruptions. Biologists from the Institut Cochin have investigated a lead, the tubulin in neuronal cells (this protein constitutes microtubules present in the cytoskeleton of cells). This tubulin indeed proves to be mutated in patients with this condition. By what mechanisms does this mutation generate cortical malformations? To find out, researchers from the CEA-IRTSV reproduced the tubulin mutations present in sick people in the yeast Saccharomyces cerevisiae. The tubulin of this microorganism is in fact 75% identical to that of humans! Video-microscopy observations were then used to identify the effect of mutations on the cell cytoskeleton. The latter reorganizes completely with drastic changes in the number and length of microtubules, namely its constituent fibers. In addition, the magnitude of this reorganization appears to correlate with the severity of the disease in humans. This novel approach opens new perspectives to better understand the causes of mental disability and, ultimately, to find leads in early diagnosis.


Top: left, MRI radiological appearance of a normal brain. Right, a brain showing tubulin mutation. The cortical folds are thick, with an absence of grooves, and an anterior gyrus that is not very well marked. Bottom: microscopy of microtubules in yeast cells. Left, a normal cell. Right, cells in which the tubulin is mutated. Microtubules are more numerous and longer, and have lost their organization.

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