High resolution analysis of human cerebellar neurogenesis

人类小脑的先天缺陷很常见，人们对此知之甚少，并可能导致严重的认知障碍。 和运动障碍。尽管老鼠长期以来一直是人类大脑发育的模型，但我们最近 发现了人类和人类在组织发生和发育模式上的几个显著差异 小鼠小脑，包括在人类中存在的干细胞带，但在 老鼠。我们假设这些区域有助于人类体内细胞数量的总体增加 小脑，进而导致大小和叶状突起的显着增加。这些差异具有显著的 对人类小脑疾病发育发病机制的启示。这项研究旨在更好地 用组织学和转录组分析鉴定人小脑干细胞群体。我们会 首先进行彻底的免疫组织化学分析，以确定重要的发育事件 小脑室带。然后我们将表征一种新发现的 细胞类型在通常研究的动物模型中缺失。我们将进行严格的转录组分析 开发人类小脑以确定这些差异的分子驱动因素。这项研究利用了我们的 来自模式生物的大量小脑发育专业知识，具有独特的发育途径 人小脑组织。

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.