How different types of neurons in the cerebral cortex are formed

The human cerebral cortex consists of many cell types, each with its own unique function. How exactly these cells become specialized during development has long been of interest to neuroscientists. A new study by scientists at UCLA has identified entire networks of genes that coordinate this process.

The project began as a small analysis of existing data, but quickly grew into a large-scale study. Using single-cell transcriptomics techniques, the team combined dozens of databases on brain development into a single meta-atlas. This allowed them to track which groups of genes – called co-expression modules – are activated at specific times and control the formation of specific types of neurons.

“We found that these modules correspond to key stages in cell development and the formation of distinct neuronal subtypes,” explains senior project author Prof. Aparna Bhaduri. “For example, we identified genes responsible for the formation of deep cortical layers – and found that among them are those that have previously been linked to neurodevelopment and disorders, but their functions remained unknown.”

To test their findings, the scientists used a method of staining real brain tissue samples and used brain organoids – miniature 3D models of the brain grown from stem cells. The experiments confirmed: the modules they found do indeed influence the development of certain neurons.

This work not only lifts the veil on how the brain develops normally, but may also become the basis for future research into autism, developmental delays and other diseases. The meta-atlas created is already being used to study glioblastoma, the most aggressive form of brain cancer, and will further help pinpoint vulnerable links in neuronal development.

“Our data helps us not just ‘map’ the brain, but also understand the mechanisms and genes that govern its formation,” says first author Patricia Nano. “This is a resource that we hope will prove useful to scientists around the world.”