Exploring the Role of CUL9 in Cortical Structure and Neuronal Morphology

Cullin-9 (CUL9) is a member of the Cullin ubiquitin ligase family strongly expressed in the brain. Recently, the Deshmukh Lab has identified behavioral deficits including anxiety, hyperactivity, and social defects in Cul9 knockout mice. The association of Cul9 genetic variants with schizophrenia suggests that CUL9 plays an important role in the brain. However, CUL9’s specific function remains virtually unknown. This study sought to explore the physiological role of CUL9 in the brain by investigating the impact of Cul9 loss on cortical and neuronal morphology. Confocal images of brain sections from wild type and Cul9 knockout mice were stained for various cortical markers and analyzed for differences in cortical layer size. Results showed lateral ventricle enlargement in Cul9 knockout consistent with abnormalities identified in schizophrenia patients. To examine the morphology of cortical projection neurons in vivo, wild type and Cul9 knockout mice were crossed with Thy1-YFP mice and three-dimensional confocal images of these neurons were reconstructed and quantified. Interestingly, cortical excitatory neurons from Cul9 knockout brains displayed decreased dendritic complexity compared to their wild type counterparts. These results suggest that CUL9 influences neuronal arborization. Interestingly, this trend parallels the results of previous studies associating reduced dendritic complexity with schizophrenia and opens avenues to further understanding how CUL9 may affect normal brain function.Bachelor of Scienc