INDUCING MAMMALIAN-LIKE CORTICAL FOLDING IN CHICK BRAINS

Cerebral cortex folding arises from interactions between biologically-driven tissue growth and mechanical instabilities, in part generated under physical constraints. In mammals, cortex folding occurs during embryonic and early postnatal development, making it difficult to disentangle the contributions from biological and physical mechanisms. Previous work from our lab identified genetic programs that specify the location of cortical folds. These may indirectly regulate the biophysical properties of tissue such as growth anisotropy, cortical thickness, stiffness, and developmental timing, altogether creating region-specific mechanical instabilities leading to folding. To assess whether any of these properties is sufficient for fold formation, we used the chick embryo as a tractable model in which mammalian-like folds do not occur naturally. By injecting Fibroblast Growth Factor 2 (FGF2, a robust promoter of neural stem cell proliferation) in the mesencephalic ventricular cavity of early chick embryos, we drove expansion and folding of the optic tectal cortex. FGF2 administration biased progenitors toward proliferation and reliably increased surface area and induced bona fide folds by embryonic day 12. Despite global tangential tissue expansion, folds emerged at specific conserved locations spanning the surface of the optic tectum. Our ongoing work pursues identifying the developmental events modified by FGF2 signaling and driving tissue folding, and how molecular/cellular events and mechanical constraints jointly shape brain folding.