Wednesday, 20 March 2019 14:49

Heterotopia model in the Petri dish Featured

Scientists at the Max Planck Institute for Psychiatry have used brain organoids to simulate the hereditary disease heterotopia. During brain development, cell migration disorders lead to node-like accumulations of grey matter outside the cerebral cortex.


As a result, the cerebral cortex is deformed and patients can suffer from epilepsy or mental retardation.

For their investigations, a team of scientists led by Dr. Silvia Cappello from the Department of Developmental Neurobiology of the Max Planck Institute for Psychiatry used connective tissue cells from skin biopsies of patients who had a mutation on the DCHS1 or FAT4 gene. The proteins produced by these genes normally form an important adhesion complex in migrating nerve cells. Adhesion is essential before a nerve cell migrates to its place of destination.

The cells were reprogrammed into induced pluripotent stem cells according to a specific procedure. From these iPS cells they developed nerve precursor cells and nerve cells (so-called brain organoids) were cultured.

The scientists observed that the patients' own cells inside the organoids differed in appearance and migration behaviour from those of healthy patients. In addition, they identified molecular signatures that are specific for these pathologically altered cells. These findings could represent valuable approaches and ideas for therapeutic options.

The scientists presented their model in the journal Nature Medicine:
Klaus, J., Kanton, S., Kyrousi, C., Ayo-Martin, A.C., Di Giaimo, R., Riesenberg, S., O'Neill, A.C., Camp, J.G., Tocco, C., Santel, M., Rusha, E., Drukker, M., Schroeder, M., Götz, M., Robertson, S.P., Treutlein, B. & Cappello, S. (2019). Altered neuronal migratory trajectories in human cerebral organoids derived from individuals with neuronal heterotopia. Nature medicine doi: 10.1038/s41591-019-0371-0.

Sources:
https://www.bionity.com/de/news/1160072/gehirnzellen-bilden-entwicklungsstoerung-im-labor-nach.html?pk_campaign=ca0264&WT.mc_id=ca0264
https://www.omim.org/entry/603057

More about heterotopia:
https://www.thieme-connect.com/products/ejournals/abstract/10.1055/s-0032-1322745