Global developmental gene expression and pathway analysis of normal brain development and mouse models of human neuronal migration defects

Proper cortical development relies on the balance of neuronal migration and proliferation. We investigated the gene expression differences of mouse knock-outs for Lissencephaly in humans. Our analysis suggests that gene expression and pathway analysis in mouse models of a similar disorder or within a common pathway can be used to define novel candidates for related human diseases. We investigated the developing brain of four mutants and wild-type mice using expression microarrays, bioinformatic analyses, and in vivo/in vitro experiments to address whether mutations in different members of the LIS1 neuronal migration complex lead to similar and/or distinct global gene expression alterations.正常大脑皮层发育依赖于神经元迁移（neuronal migration）与细胞增殖（proliferation）的动态平衡。本研究针对人类的无脑回畸形（Lissencephaly）相关基因，对其小鼠基因敲除模型（mouse knock-outs）的基因表达差异（gene expression differences）进行了探究。分析结果表明，针对此类相似疾病的小鼠模型或共同通路开展基因表达分析与通路分析，可为相关人类疾病鉴定出新型候选致病因子。我们借助基因表达微阵列（expression microarrays）、生物信息学分析（bioinformatic analyses）以及体内/体外实验（in vivo/in vitro experiments），对4株突变体小鼠（mutants）与野生型小鼠（wild-type mice）的发育中脑组织（developing brain）开展研究，以探究LIS1神经元迁移复合物（LIS1 neuronal migration complex）不同亚基的突变是否会引发相似或迥异的全局基因表达谱改变（global gene expression alterations）。