Human Brain 'Organoids' Offer New Insight Into Rare Developmental Disease
Study implicates neural stem cell defects in smooth brain syndrome
Research led by scientists at UC San Francisco and Case Western Reserve University School of Medicine has used brain “organoids” — tiny 3-D models of human organs that scientists grow in a dish to study disease — to identify root causes of Miller-Dieker Syndrome (MDS), a rare genetic disorder that causes fatal brain malformations. MDS is caused by a deletion of a section of human chromosome 17 containing genes important for neural development. The result is a brain whose outer layer, the neocortex, which is normally folded and furrowed to fit more brain into a limited skull, instead has a smooth appearance (lissencephaly) and is often smaller than normal (microcephaly). The disease is accompanied by severe seizures and intellectual disabilities, and few infants born with MDS survive beyond childhood. In the new study, the research team transformed skin cells from MDS patients and normal adults into neural stem cells, which they placed in a 3-D culture system to grow organoid models of the human neocortex with and without the genetic defect that causes MDS.
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