Folding of the tectal cortex by local remodeling of neural differentiation

The folding pattern of the brain cortex is a precisely regulated process, but the mechanism involved during development remains unclear. A proposed theory predicts that the initiation of cortical folding depends, at least partly, on nonuniform distribution of neuronal differentiation and neurite growth. We tested this theory experimentally, by remodeling the normal pattern of neuronal cell differentiation within the embryonic optic tectum. Multiple foci of activated fibroblast growth factor signaling were created in the tectal cortex to locally change the neural differentiation and axonal growth patterns. At these foci, tectal cells remained undifferentiated and their radial and tangential migration was suppressed. These local changes in the neuronal cell differentiation resulted in a conversion of the tectal cortex from smoothly extended into precociously folded. The results provide in vivo experimental evidence that microscopic changes in the neuronal cell differentiation pattern can induce or remodel the folding pattern of the brain cortex.