Dr. Yunsik Kang studies how the nervous system develops. The nervous system is the body’s communication network between the brain, spinal cord and nerves. It controls everything you do, from breathing and moving to thinking and feeling. The brain, spinal cord and nerves work together to send messages between different parts of the body and the brain.

Yunsik and his team are on a quest to learn how certain cells in the nervous system work together to build, sculpt and remodel neural connections during development to produce the perfectly sculpted product – the mature brain. To learn about this important process, Yunsik and his team study the developing nervous system in fruit flies (scientific name Drosophila melanogaster) during a phase called ‘metamorphosis’ during which the nervous system is undergoing massive changes. They hope to uncover the molecular mechanisms of neuronal remodeling during development to better understand how it works when functioning properly. They will then use this information to better understand what goes wrong and how certain defects in this process could be linked to neurodevelopmental disorders such as autism and schizophrenia.

Dr. Yunsik Kang and the Freeman research team published a pre-print science article in the journal of BioRxiv in November 2023 titled, ‘Tweek-dependent formation of ER-PM contact sites enables astrocyte phagocytic function and remodeling of neurons.’

To gain a better understanding of the research in this article, please read the easy-to-understand summary below.

Tweek-dependent formation of ER-PM contact sites enables astrocyte phagocytic function and remodeling of neurons

Did you know that during development our nervous system’s start out with an overabundance of brain cells, called neurons, and neuronal connections? It’s true! During nervous system development, just like an artist creating a sculpture, excess brain cells and connections must be carved away to create the brain. This process of ‘sculpting’ the brain during development is called neuronal remodeling and it can lead to a lot of cellular waste from the parts of the brain that are carved away during development.

Through studying the developing nervous system of fruit flies (Drosophila) during the transformation from larva to adult in fruit flies, Yunsik found that a brain cell called an astrocyte takes on the ability to consume broken down nerve connections and cellular debris. You can think of the astrocyte as the cell that cleans up all the fragments that are removed or carved away during the sculpting process. They also found a protein called Tweek that becomes more active in astrocytes during this process. Tweek is essential for these cells to efficiently clear the waste. It seems that Tweek works by helping to connect two parts of the cell, the endoplasmic reticulum (ER) and the plasma membrane (PM), which is critical to the process. Without Tweek, this connection is disrupted, leading to problems. Similar issues happen in humans with mutations in the human version of Tweek, which is linked to Alkuraya-Kucinskas syndrome, a severe neurodevelopmental disorder. Tweek seems to play a vital role in maintaining important cell connections and ensuring astrocytes can effectively clean up neuronal waste during neuronal development. This type of research could be used to better understand what goes wrong in neurodevelopmental disorders, such as autism and schizophrenia, and provide opportunities for developing effective therapies in the future.