A tiny piece of genetic code significantly impacts brain cell connections, offering insights into neurological disorders and brain development.
Researchers at the Institute for Basic Science (IBS) discovered that a small segment of genetic code plays a crucial role in how brain cells connect and communicate. This finding could explain the origins of several neurological and psychiatric conditions, deepening our understanding of brain wiring.
The study, led by Director Kim Eunjoon at IBS, focused on the PTPδ protein, essential for synapse formation, the connections that allow brain cells to pass signals. While PTPδ has been linked to disorders like autism spectrum disorder (ASD) and ADHD, the researchers examined a tiny segment called mini-exon B.
Mini-exon B, only four amino acids long, is created through alternative splicing, where cells include or exclude genetic snippets to alter protein structure and function. Genetically engineered mice lacking mini-exon B had a low survival rate, highlighting its importance in early brain development.
Mice with one copy of the altered gene survived but showed anxiety-like behavior and reduced movement. Brain recordings revealed an imbalance in synaptic activity, a hallmark of neurodevelopmental and psychiatric disorders. The researchers found that mini-exon B is necessary for PTPδ to interact with another protein called IL1RAP, disrupting a critical pathway for forming excitatory synapses.
Director Eunjoon stated, "This study illustrates how even the tiniest genetic element can tip the balance of neural circuits." This discovery highlights the importance of studying not just genes themselves but also the tiny variations in how they're assembled.
This research is relevant given the growing evidence that disruptions in microexon splicing may underlie neuropsychiatric conditions. These insights could inform the development of therapies that target splicing regulation or restore normal synaptic balance in affected individuals, offering hope for treating brain disorders.