INN researchers engineer self-folding human brain tissues that recreate the earliest stages of brain development

A new lab-grown model reveals how genetic mutations disrupt early brain formation, offering fresh insight into developmental disorders.

Understanding how the brain forms during its earliest stages has long been out of reach for scientists. This understanding is especially important in the presence of genetic mutations that cause abnormalities in brain structure. A team led by INN researcher Dr. Lisa Julian, Assistant Professor at SFU’s Department of Molecular Biology and Biochemistry, has now developed a method to model this elusive process using human stem cells. These findings were recently published in Cell Reports Methods.

By combining 3D bioprinting and strategies to coax these stem cells into brain tissues, Dr. Julian’s team has created tiny, self-organizing “neural tube” tissues that mimic the earliest stages of human brain formation. Strikingly, these tissues behave much like the developing human brain. When the team introduced genetic mutations that cause brain malformations, which lead to severe epilepsy, psychiatric and intellectual disabilities, the tissues developed abnormally with an increase in the number of bends and folds. Cortical folding is a unique feature in large mammals but has rarely been reproduced in lab-grown brain models. By studying this effect, Dr. Julian and her team have identified a key gene, TSC2, and a related signaling pathway, mTORC1, that help guide how the brain shapes itself in its earliest stages.