Brain folding: an important feature of complex brains

Brain folding emerges at the same time when regional differences appear and interregional connections develop. The striking correspondance between the patterns of brain folding and the functional organization of the brain has puzzled generations of neuroscientists

  • Brain macroscale
  • Microscale
  • Unsolved questions

Since the discovery that brain folding does not occur because of limited cranial volume, there have been two separate approaches to study brain folding: one focused on cellular and molecular processes, and the other one on tissue mechanics.

In collaboration, our international team set out to combine expertise in both fields to uncover the causes and consequences of brain folding. How does the interaction between molecular processes and tissue mechanics shape brain folding, and how does brain folding shape them?

Cellular and molecular processes

Gene expression & stem cell proliferation

In the perspective of life sciences, brain folding arises from heterogeneous patterns of gene expression and stem cell proliferation. The Borrell Lab is a leading expert in this field, and you can find more details on their website.

Molecular regulation of neurogenesis

Heterogeneous gene expression also leads to distinct patterns of neurogenesis and neuronal migration. Laurent Nguyen is a leader in this field and you can discover their research on the website.

Tissue mechanical processes

Local cellular forces & mechanosensitivity

In the perspective of life sciences, brain folding arises from patterns of mechanical forces in the developing brain. The impact of a nerve cell's local mechanical environment such as tissue stiffness on cell growth and axonal guidance has been shown by Kristian Franze, leading expert in the field.

Global impact of mechanical forces

Tissue growth can also trigger mechanical instabilities at a global level of the entire brain which constrain and guide developmental and evolutionary processes as demonstrated in biomechanical models of brain development pioneered by Roberto Toro.

Holistic understanding of the processes that operate during development and underlie brain folding

None of the current models is sufficient to understand the mechanisms underlying brain folding. With the joint expertise across our labs, bringing together these complementary research fields and approaches, we should be able to build a holistic view on the processes underlying brain folding.

Victor Borrell

The Borrell Lab has a long track record in research on cortical folding. Using cutting edge molecular biology tools, we have identified a new cell type critical for cortex folding and gene expression patterns that map cortical folds.

Laurent Nguyen

Laurent Nguyen investigates mechanisms of cerebral cortex development, focusing on neural migration and cell interactions. He has demonstrated that neuronal migration shapes cortical morphogenesis.

Kristian Franze

Kristian Franze is one of the pioneers in the field of experimental neural mechanics. His lab provided the first evidence for the regulation of brain development by local tissue stiffness and cellular forces.

Roberto Toro

Roberto Toro studies the relationship between brain geometry and brain organisation, including brain connectivity. His team has pioneered the development of biomechanical models of brain development showing how homogeneous growth can produce folding that looks similar to the folds in a real brain.

In collaboration, we will analyze cortical development at the tissue, cell, and gene levels across three model systems with different levels of brain folding.

We will integrate the data we obtain on tissue mechanics, molecular and cellular processes into a computational model of the mechanisms of brain folding.

We will test the consequences of brain folding on neural circuits and animal behaviour.

Alltogether, we will uncover the mechanisms of brain folding and its impact on brain connectivity, generate an integrated web atlas of multiple features of the developing brain in ferret and mouse, and generate an application to simulate brain folding.

  • CSIC
  • Cambridge
  • Liege
  • pasteur