Folding of Neural Tissue during In-Vitro Quasi Two-Dimensional Development


  Eyal Karzbrun  ,  Orly Reiner  
Department of Molecular Genetics, Weizmann Institute of Science

The brain is a highly complex structure with surface folds which begin to appear during early development. A physical understanding of the folding process is still lacking, due to the experimental challenges of studying three-dimensional embryos in real time. Here, we present an experimental system to study neuronal tissue development in-vitro from human stem cells, in a confined quasi two-dimensional geometry, which allows efficient nutrient exchange, long-term culturing and live-cell imaging. We observe the emergence of wrinkles on the tissue surface, during early development and before the appearance of neurons. The wrinkles exhibit a gaussian wavelength distribution and linear scaling with the tissue thickness, suggesting wavelength selection as a force balance between surface bending and bulk stretching. Our system can serve as a platform to study the effect of genetic mutations on neural development in-vitro.