Marsh Eric D, Minarcik Jennifer, Campbell Kenneth, Brooks-Kayal Amy R, Golden Jeffrey A
Division of Neurology, Children's Hospital of Philadelphia and the University of Pennsylvania, Philadelphia 19130, USA.
Dev Neurobiol. 2008 Mar;68(4):434-45. doi: 10.1002/dneu.20602.
Cortical interneuron dysfunction has been implicated in multiple human disorders including forms of epilepsy, mental retardation, and autism. Although significant advances have been made, understanding the biologic basis of these disorders will require a level of anatomic, molecular, and genetic detail of interneuron development that currently does not exist. To further delineate the pathways modulating interneuron development we performed fluorescent activated cell sorting (FACs) on genetically engineered mouse embryos that selectively express green fluorescent protein (GFP) in developing interneurons followed by whole genome microarray expression profiling on the isolated cells. Bioinformatics analysis revealed expression of both predicted and unexpected genes in developing cortical interneurons. Two unanticipated pathways discovered to be up regulated prior to interneurons differentiating in the cortex were ion channels/neurotransmitters and synaptic/vesicular related genes. A significant association of neurological disease related genes to the population of developing interneurons was found. These results have defined new and potentially important data on gene expression changes during the development of cortical interneurons. In addition, these data can be mined to uncover numerous novel genes involved in the generation of interneurons and may suggest genes/pathways potentially involved in a number of human neurological disorders.
皮质中间神经元功能障碍与多种人类疾病有关，包括癫痫、智力迟钝和自闭症等形式。尽管已经取得了重大进展，但要了解这些疾病的生物学基础，还需要目前尚不存在的中间神经元发育的解剖学、分子和遗传学细节水平。为了进一步描绘调节中间神经元发育的途径，我们对基因工程小鼠胚胎进行了荧光激活细胞分选（FACs），这些胚胎在发育中的中间神经元中选择性表达绿色荧光蛋白（GFP），然后对分离出的细胞进行全基因组微阵列表达谱分析。生物信息学分析揭示了发育中的皮质中间神经元中预测基因和意外基因的表达情况。在皮质中间神经元分化之前发现上调的两条意外途径是离子通道/神经递质和突触/囊泡相关基因。发现神经疾病相关基因与发育中的中间神经元群体有显著关联。这些结果定义了关于皮质中间神经元发育过程中基因表达变化的新的且可能重要的数据。此外，这些数据可以挖掘以发现参与中间神经元生成的众多新基因，并可能提示可能参与多种人类神经疾病的基因/途径。
