Researchers map brain development at the protein level in unprecedented detail

Researchers at the University of Virginia have created the first comprehensive protein-level atlas of brain development, providing unprecedented insight into how the brain forms and potential implications for understanding neurological disorders. The study, published in Nature Neuroscience, analyzed over 24 million individual cells from mouse brains, revealing detailed molecular pathways that guide brain development from early embryonic stages through early postnatal development.

The research team, led by Professors Christopher Deppmann and Eli Zunder, used an innovative technique called mass cytometry to track 40 different proteins across various brain regions and developmental stages. The approach provided a more detailed view of cellular function than previous studies that primarily examined RNA.

"While RNA studies have given us important insights, proteins are the actual workforce of cells," explained Deppmann, a professor in the College and Graduate School of Arts & Sciences’ Department of Biology. "By studying proteins directly, we can better understand how cells are functioning and communicating during brain development."

According to Deppman, the study’s key findings includes the discovery of two distinct developmental pathways for oligodendrocytes, cells that insulate nerve fibers in the brain. The study also offers new insights into how different brain cell types emerge and mature over time, detailed mapping of protein patterns across four major brain regions during development, and evidence of early microglial activity (brain immune cells) during development. These insights could inform future research into a wide range of neurological disorders like autism, Alzheimer’s and schizophrenia.

The study establishes mass cytometry as a powerful tool for studying brain development, potentially opening new avenues for research into neurological conditions. "This atlas provides a foundation for understanding what might go wrong in various neurological disorders," said Zunder, an assistant professor of biomedical engineering with UVA’s School of Engineering and Applied Science. "By knowing how proteins normally guide brain development, we can better identify what changes in disease conditions."

The research was supported by the National Institute of Neurological Disorders and Stroke and represents a collaboration across multiple departments at UVA.