High resolution analysis of human cerebellar neurogenesis

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Human birth defects of the cerebellum are common, poorly understood and can cause significant cognitive and motor disabilities. Although the mouse has long been a model for human brain development, we recently discovered several significant differences in histogenesis and developmental patterns between the human and mouse cerebellum, including the presence of stem cell zones that are present in human but absent in the mouse. We hypothesize that these zones contribute to the overall increase in cell number within the human cerebellum which in turn causes a significant increase in size and foliation. These differences have significant implications for the developmental pathogenesis of human cerebellar disorders. This study aims to better characterize human cerebellar stem cell populations using histological and transcriptome analysis. We will begin by carrying out a thorough immunohistochemical analysis to identify important developmental events in the cerebellar ventricular zone. We will then characterize the morphology and distribution of a newly identified cell type absent in commonly studied animal models. We will perform rigorous transcriptome analyses of the developing human cerebellum to define the molecular drivers of these differences. This study leverages our substantial cerebellar developmental expertise from model organisms with unique access to developing human cerebellar tissue.