Mini-Brains Grown in Lab to Study DISC1 Mutations

Researchers from Brigham and Women’s Hospital are creating new technologies for gene-editing tools and mini-brains to better understand the effects of DISC1 mutations in cerebaral organoids.

The reason for this study is due to major mental illnesses such as schizophrenia, depression, bipolar disorder and many more which share a common genetic link in the brain. Previous studies have shown that people affected from these illnesses share a mutation in the gene DISC1. There are already existing studies about how DISC1 mutations alter the brain, but just in animal models. To show this development in the human brain is much more difficult, so researchers had to find the right tools.

Thanks to advancements in engineering human stem cells researchers are now enabled to grow mini-brains in labs and insert mutations into those cells. Those so called “mini-brains” can be very helpful for modelling brain development, not only the two-dimensional, but also three-dimensional structure and function of the cells.

The researchers were using a specific tool called CRISPR-Cas9 to compare mini-brains grown from stem cells with and without this specific DISC1 mutation. The result was, that mini-brains with the DISC1 mutation showed structural disruptions. More specifically, the fluid-filled spaces in the mutated brains were more numerous and smaller, which means that although the cells are present, they are not in their expected location.

Additionally, DISC1-mutant mini-brains showed increased signalling in the WNT pathway. The WNT pathway is important for patterning organs, especially when it comes to bipolar disorders. So, researchers added an inhibitor of the WNT pathway to the growing DISC1-mutant mini-brains and had been able to rescue those. Conclusion of this study is that the WNT pathway may be responsible for the observed structural disruption in the brains with a DISC1 mutation, and could be a potential target pathway for future therapies.

References:

  • Science Daily 04/2018). 3-D human ‘mini brains’ shed new light for major mental illnesses https://www.sciencedaily.com/releases/2018/04/18041914150.htm. Accessed on: 12/05/2018
  • Bulletin. Mini Brains Shed Light on Mutations Tied to Mental Illnesses. https://bwhbulletin.org/2018/05/04/mini-brains-shed-light-on-mutation-tied-to-mental-illnesses/ Accessed on: 12/05/2018