As the brain develops, proliferating cells organize into structures, differentiate, migrate, extrude long processes and connect with other cells. These biological processes produce mechanical forces that shape cellular dynamics and organ patterning. A major unanswered question in developmental biology is how the mechanical forces produced during development are detected and transduced by cells to impact the biochemical and genetic programs of development. New biophysical approaches are required to answer this question.
We aim to uncover the mechanical dynamics underlying human neural development by generating new molecular, imaging and bioengineering tools. We will measure and manipulate mechanical forces at different timepoints of human brain organoid formation. These studies will provide quantitative and mechanistic insights on the role of mechanical forces during development, and demonstrate how development fails when they are disrupted.
Defective brain development can lead to devastating neurodevelopmental disorders. The proposed work will greatly enhance our knowledge of how mechanical cues shape the fetal brain ? and how these processes can go awry. This will help us understand how the normal brain develops, and suggest new strategies for how to prevent and treat neurodevelopmental disorders.