At some point in your life you were made up of just two cells – the egg and the sperm from your parents. It was during embryonic development, in the womb, that you took the form resembling the person you are now. And it was during this period that your brain, arguably the most complex known structure in the universe and one that defines you, has developed. It might not feel like a great feat to you now, but your genetic machinery had to work extremely hard to make sure everything goes according to plan in building your brain. Many people are not so lucky: when their brain growth is disturbed during development, they live with devastating conditions. Two common conditions resulting from derailed brain growth are microcephaly and brain cancer; the former is a result of decreased brain growth, and the latter a consequence of growth getting out of control.
In my research, I try to understand how growth is regulated in one part of the brain called the cerebellum. This brain structure is located at the back of your head, towards the base of the skull. The cerebellum has historically been considered as the main fine motor movement control centre, but has recently been heavily implicated in human cognitive diseases, especially in autism. However, the most fatal human disorder affecting the cerebellum is medulloblastoma – a devastating childhood cancer that develops due to dysregulated growth of a single cell type.
Granule cells of the cerebellum are the most numerous cell type in the human brain. They account for more than half of all brain cells. It is therefore extremely important that regulation of their division and maturation is highly controlled. We know a lot about their development already but many questions remain about these cells decide to stop multiplying and become mature and therefore non-cancerous.
One way of trying to understand a biological process is to look at its evolutionary path. We can study existing animals to see how they differ in their developmental mechanisms and, knowing their evolutionary histories and how they relate to each other, we can understand better why and how differences evolved. In cerebellar development a major difference between amniotes (reptiles, birds and mammals) and anamniotes (fish and amphibians) is that, in the former, granule cells form a distinctive and transient proliferative layer on top of the developing cerebellum whilst in the latter they never form such a layer, instead migrating away from their birthplace as mature neurons. We have studied two organisms to get a closer look at this process – the frog and the chicken. Using this approach we have identified a new genetic mechanism that seems to control granule cell proliferation.
The metamorphic frog, surprisingly to us, does form a secondary layer of granule cells in a similar way to the chicken. However, these granule cells never divide in this layer, contrary to the bird. We looked at the genes involved in this process and found that, in the frog, two genes are present in granule cells at the same time, whereas in the chick there is a long delay between when these genes are switched on. This delay, we think, is responsible for allowing granule cells time to divide. When we forced the chick granule cells to have both genes switched on at the same time, like in the frog, we completely stopped their ability to divide. We therefore understand a little bit better how granule cells are able to multiply and therefore, how to stop that ability. We hope that this, and similar research, will help us control human brain growth abnormalities in the future.
About the Author
Michalina Hanzel is a PhD student in the department of Developmental Neurobiology at King’s College London, funded by the MRC. Her interests lie in brain development, specifically how brain cells make decisions to divide or mature. Her studies have taken her all over the world, from Rockefeller University in New York City to the Japanese island of Okinawa, allowing her to combine her two passions – biological research and travel. She loves discussing science, recently co-organising a seminar series NEUReka! to bring the most engaging neuroscientists to London students. In her spare time she enjoys cooking, travelling and philosophical discussions.