How to grow a brain in a test-tube!

By Sue Surkes

Weizmann Institute’s study of brain wrinkling opens way for future research into disorders such as microcephaly, epilepsy and schizophrenia

An Israeli research team has discovered a way to grow a miniature version of the human brain that undergoes wrinkling in a similar way to a real brain, paving the way for scientists to better understand a congenital defect.

Roughly one in 30,000 babies are born with smooth brains. They go on to suffer from severe developmental difficulties and a relatively low life expectancy.

That led the Institute’s Dr. Eyal Karzbrun to develop a new approach to growing organoids — simplified, miniature versions of bodily organs produced in test tubes

In order to allow for high-quality optical imaging and microscope tracking of wrinkle development, Karzbrun managed to use embryonic stem cells to grow a “mini-brain” that was round and flat with a thin space in the middle.

By the second week of the tiny organoid’s growth and development, the team was able to observe wrinkles beginning to appear and then to deepen. Karzbrun said, “This is the first time that folding has been observed in organoids, apparently due to the architecture of our system,” he said.

The findings were reported in Nature Physics.

Screenshot from time-lapse images showing development of a brain organoid that incorporates the gene mutation causing smooth brain syndrome.

The research team then grew a mini-brain incorporating a gene carried by babies with smooth brain syndrome that the institute’s Prof. Orly Reiner had identified in 1993.

The organoids with the mutated gene grew to the same proportions as the others, but developed few folds. The ones they did develop were very different in shape from the normal wrinkles.

Using atomic force microscopy, which yields a high level of resolution on extremely tiny surfaces, they found physical and biological differences between the cells in the two little “brains,” discovering, for example, that the normal brain cells were about twice as stiff as the soft, mutated ones.

“We now have a much better understanding of what makes a brain wrinkled or, in cases of those with one mutated gene, smooth,” Reiner said.

The researchers plan to continue developing their approach, in the belief that it could open new possibilities for understanding developmental disorders such as microcephaly, epilepsy and schizophrenia.