Researchers used brain cell cultures derived from reprogrammed skin cells of patients with lissencephaly, a rare inherited brain disorder characterized by severe developmental delay and a smooth rather than folded brain surface structure, to identify the developmental defect in the brain cells harboring the genetic mutation that causes the disease.
The researchers found the patient-derived brain cells carrying the mutation matured more slowly and had problems with mobility, which impairs their ability to reach the correct brain site. This study provides novel insights into the disease mechanism, which is potentially important for developing therapeutic strategies for lissencephaly.
Animal models with the genetic mutation do not mimic the human disease, and donor tissue is scarce due to the rarity of the disease. Thus, this cellular model of lissenchephaly derived from patients increases the opportunity to study and find human-relevant insights about mechanisms of the disease and brain development in general. This technique can be adapted to study other human genetic diseases of the brain.
Shahsavani M, Pronk R, Falk F, et al. An in vitro model of lissencephaly: expanding the role of DCX during neurogenesis. Mol Psychiatry. Published online September 19, 2017. doi: 10.1038/mp.2017.175.