Date of Award
Doctor of Philosophy (PhD)
Over the course of human development, the brain undergoes dramatic physical changes to achieve its final, convoluted shape. However, the forces underlying every cinch, bulge, and fold remain poorly understood. This doctoral research focuses on the mechanical processes responsible for early (embryonic) and late (preterm) brain development.
First, we examine early brain development in the chicken embryo, which is similar to human at these stages. Research has primarily focused on molecular signals to describe morphogenesis, but mechanical analysis can also provide important insights. Using a combination of experiments and finite element modeling, we find that actomyosin contraction is responsible for initial segmentation of the forebrain. By considering mechanical forces from the internal and external environment, we propose a role for mechanical feedback in maintaining these segments during subsequent inflation and bending. Next, we extend our analysis to division of right and left cerebral hemispheres. In this case, we discover that morphogen signals and mechanical feedback act synergistically to shape the hemispheres.
In human, cerebral hemispheres go on to form complex folds through a mechanical process that involves rapid expansion of the cortical surface. However, the spatiotemporal dynamics of cortical growth remain unknown in human. Here, we develop a novel strain energy minimization approach to measure regional growth in complex surfaces. By considering brain surfaces of preterm subjects, reconstructed from magnetic resonance imaging (MRI), this analysis reveals distinct patterns of cortical growth that evolve over the third trimester. This information provides a comprehensive view of cortical growth and folding, connecting what is known about patterns of development at the cellular and folding scales.
Abnormal brain morphogenesis can lead to serious structural defects and neurological disorders such as epilepsy and autism. By integrating mechanics, biology, and neuroimaging, we gain a more complete understanding of brain development. By studying physical changes from the simple, microscopic embryo to the macroscopic, folded cortex, we gain insight into relevant biological and physical mechanisms across developmental stages.
Larry A. Taber
Philip V. Bayly, Ruth J. Okamoto, Jin-Yu Shao, David C. Van Essen,