Yiquan LuPhD Student

Imagine the human brain as a city, with the cortex as its city hall—the central hub where the most important decisions are made. This part of the brain plays a key role in our most complex thoughts and actions, and it has billions of interconnected brain cells – neurons. But how is this remarkable structure constructed with such high precision during pregnancy?

Just like a city’s buildings rely on architectural blueprints, cells in our body follow instructions encoded in our DNA and genes to perform functions and contribute to forming the cortex. Even though every cell in our body carries the same set of genes, they don’t all perform the same tasks.  For example, stem cells in the brain, which are mainly responsible for generating neuronal cells, activate only the genes necessary for their role while keeping unrelated genes inactive. This selective activation is regulated by a set of chemical tags on them known as histone modifications, which act like molecular switches to control when and where genes are turned on or off. 

To explore how genes’ selective activation is modulated in different cells during formation of the cortex, we collect and analyze donated human brain samples. Using a cutting-edge method called nanoCUT&Tag, which offers us a window into the cellular and molecular world, and capture high-resolution snapshots of these chemical tags in individual brain cells involved in cortex formation. Leveraging these large-scale data, our goal is to uncover the potential dynamic relationships between these chemical tags and their modulated genes during cortex formation. Moreover, we aim to identify abnormal patterns in these regulatory processes that may contribute to developmental disorders affecting the cortex.

In the end, this research could deepen our understanding of human brain development and may shed light on neurodevelopmental disorders such as autism and intellectual disorders, offering valuable insights for future diagnosis and treatment.