Quantifying the Brain Developmental Trajectory of Autism-Associated Brain Overgrowth Using 3D Cellular Resolution Imaging
2019 Award: $39,069
Need/Problem: Alterations in brain development are associated with a variety of neuropsychiatric disorders, including autism spectrum disorder (ASD). Many studies demonstrate that mouse models re-capitulate a core human phenotype, brain overgrowth, associated with an increase in the neural progenitor pool and that this brain overgrowth shows a regionally specific pattern. However, we do not know the cell-types that are driving the effect. And due to the limited temporal resolution of previous immunohistochemistry, we do not know the full developmental trajectory of cell-types leading to brain overgrowth.
Grant Summary: We aim to develop high throughput computational tools for 3D light-sheet microscopy images to quantify the brain developmental trajectory of autism-associated brain overgrowth. The computational tools developed in this project will be used to study cortical development in the mouse brain, including how typical development is altered by an autism-associated genetic mutation.
Goals and Projected Outcomes: We expect that the tools developed in this proposal will be widely used in the field, as many mouse models of neuropsychiatric diseases exhibit pathology during neural development, but limited tools exist to comprehensively analyze these large datasets. We additionally hope to leverage the tools developed as part of this pilot award for further projects studying the differences in brain development among genetically diverse mice (collaborative cross) and genotyped human tissue samples.