The human brain has a big job. It runs every system of the body, 24/7/365 and it does so better than any supercomputer on the planet. There is a great deal of research available on brain function, anatomy and all that can go wrong such as Alzheimer’s, traumatic brain injury and mental illnesses. It’s problematic however to research the living brain.
Medical ethics would never allow some experiments, and so there is still much we don’t know. Towards that end, researchers at the Weizmann Institute are creating mini-brains in the lab. Mini-brains, also known as organoids, start with stem cells and are cultured and grown into tiny versions of the human brain. This way, research that manipulates the development of the brain can be conducted on the organoids.
One of the critical parts of brain anatomy is the folding of cortical tissue. This occurs in utero and is usually complete by age two. The brain folding, a process known as “gyrification,” is necessary because neurons must transmit signals across the brain at ridiculously high rates of speed and the folds allow this process to happen, putting neurons that work together near each other via the folding. The team at the Weizmann Institute is looking at this process to learn more about a condition called lissencephaly, where a baby is born with no brain folds. Children born with lissencephaly have severe developmental disorders. Finding out what causes it is difficult, but the team hopes their research with organoids can shed light on the mechanism.
It’s a much more difficult process than tossing some cells into a petri dish and hoping a brain grows, however. Organoids often don’t vascularize, molecules within the mini-brains are hard to image, and their development is often haphazard. The team at Weizmann, led by Dr. Orly Reiner and Dr. Eyal Karzbrun approached the problem by developing a process where the organoid grows in a single direction and has a flat inner space. This shaping allows for better imaging and can be tracked. Dr. Reiner’s previous research into lissencephaly resulted in identifying the gene responsible for the disorder. The process used at the Institute is so efficient that in about two weeks, the organoids begin to wrinkle just as normal brain tissue does.
Since Dr. Reiner’s earlier research proved that a mutation in the LIS1 gene was responsible for the lack of brain folding, they were able to hone in on the molecular mechanism of the process by creating organoids that had the mutated LIS1 gene. Looking at the mini-brains this way they found those with the gene mutation created tissue that did not fold and was softer and “squishy.” The organoids were not only genetically different but were different structurally as well because of the mutation. Using atomic microscopy along with the earlier research on which gene was involved resulted in the team learning how the brain develops these crucial folds. Dr. Reiner summarized the work stating, “It’s not exactly a brain, but it is quite a good model for brain development. We now have a much better understanding of what makes a brain wrinkled or, in cases of those with one mutated gene, smooth.” Take a look at the video to learn more about this new finding. The research should go a long way towards understanding not only lissencephaly but other disorders like schizophrenia and epilepsy.