In lab, IL-17A triggers early folding in human fetal cortex

Under the microscope, a folded piece of developing human cortex sits outside the body, kept alive in a controlled, nutrient-rich environment. At the University of Aberdeen, researchers led by Dr. Daniel Berg and Dr. Eunchai Kang used these 3D cerebroids to test how an inflammatory signal associated with maternal immune activation might affect the fetal brain.

The experiment focused on IL-17A, an inflammatory signaling protein. The team used human fetal tissue from the dorsolateral prefrontal cortex, collected following the elective termination of pregnancy, and compared cerebroids exposed to IL-17A with untreated tissue. The signal caused the developing cortex to fold prematurely, while also increasing cortical thickness and accelerating the production and maturation of neurons.

The model was designed to address a weakness in brain organoids, simplified organs grown from stem cells. Organoids are widely used in neuroscience, but they do not reliably reproduce the full biological complexity of human organs. Cerebroids preserve more of the typical structure, cellular diversity and organization found in the developing human cortex, giving researchers a closer look at how tissue itself responds.

The researchers combined microscopy and cell labeling with RNA sequencing and proteomics to trace the response. They found that IL-17A acted directly on neural stem cells and that sustained activation of the NF-κB signaling pathway appeared to drive the changes. Blocking that pathway reversed many of the effects, pointing to a mechanism that can now be tested in further studies rather than a finished explanation.

So, concretely, the cerebroid system gives brain researchers a human tissue model for examining how inflammatory signals may alter early cortical development. It does not show that maternal inflammation causes neurodevelopmental conditions: the findings are laboratory results, and the biological pathways still need investigation in cerebroids, organoids and animal models. Berg's team plans to build cerebroids from other developing brain regions and study responses from immune cells, blood vessels and specialized neural stem cells.