Many neurological conditions including autism, anorexia, epilepsy and schizophrenia are caused by the misfolding of the brain.
How the brain folds as a baby develops in the womb determines the brain function of the baby. Many conditions including premature births and fetal fetal growth restriction are also linked with brain folding and cognitive deficits.
In what may a major breakthrough in understanding the brain folding process, Australian and Swiss researchers have for the first time identified the genes linked with the development of the two types of brain folds — inward and outward — in the grey matter of the brain.
Using animal models that closely resemble human brain development, the study found differences in both genetic expression and neuron shape during the folding process.
Co-chief investigator Associate Professor Mary Tolcos said there were currently no therapies for the prevention or treatment of brain misfolding and no early test to detect problems before folding begins.
“We know folding happens in the second and third trimester of pregnancy and that all human brains fold along largely the same patterns,” said Tolcos, an Australian Research Council Future Fellow at RMIT.
“This suggests the process is heavily controlled by our genes but we’re only starting to understand how — it’s like having an intricately folded piece of origami that’s missing the instructions.
“Our study is a critical step towards fully understanding those genetic instructions, by pinpointing which genes are linked with fold development.
“The next step is to determine the precise role these genes play in the process, so we can work towards identifying potential therapeutic targets and develop interventions to prevent and fix misfolding in the brain.”
While the science of folding is still unclear, the latest evidence suggests grey matter in the developing brain expands faster than white matter, creating mechanical instability that leads to brain folding.
But the resulting “hill” and “valley” folds are not random — they follow a similar pattern in all folded brains of the same species.
The new study focused on sheep brains, which fold in the womb like the human brain.
Researchers investigated the genetic and microstructural differences in future grey matter, the cortical plate, in the parts of the brain just beneath the “hills” and “valleys.”
The areas were analysed at three points of development — when the brain was smooth, semi-folded and fully folded.
Postdoctoral researcher Dr Sebastian Quezada Rojas said it was the first study to look at the genetics of folding of the future grey matter, as the folding process develops over time.
“Understanding the changes in the cortical plate during brain folding is paramount since this region changes so dramatically during this process,” he said.