Global analysis of gene regulation in the midline CNS

描述(申请人提供)：发育中的果蝇胚胎的专门中线前体产生特定的神经元组和GILA，是研究中枢神经系统发育和功能的极好的模型系统。利用现有的数据，我们的实验室已经构建了一个包含297个假定中线表达基因的数据库。由于大多数基因的确切表达模式尚不清楚，本建议的一个主要目标是使用高通量RNA原位杂交来定位这些基因在中枢神经系统中线发育过程中的表达模式。这一分析将提供(1)精炼的中线CNS分子图谱和(2)为中线CNS基因转录分析提供参考。为了确定这些基因中哪些与胶质发育有关，将使用RNA干扰和可用的遗传突变从功能上筛选中线胶质表达的基因以确定胶质表型。对于编码转录因子的胶质基因，将采用原位表达模式筛选和微阵列分析来确定突变遗传背景下的转录变化。这一分析将提供对中线中枢神经系统发育和调控中线胶质细胞发育和功能的转录途径的更清晰的理解。

DESCRIPTION (provided by applicant): Specialized midline precursors of the developing Drosophila embryo give rise to specific sets of neurons and gila, and serve as an excellent model system for the study of CNS development and function. Using available data, our lab has constructed a database of 297 putative midline-expressed genes. Since the exact expression patterns of a majority of these genes are unknown, a major goal of this proposal is to use high throughput RNA in situ hybridization to map the expression patterns of these genes during CNS midline development. This analysis will provide (1) a refined molecular map of the midline CNS and (2) serve as a reference for the analysis of midline CNS gene transcription. To determine which of these genes are involved in glial development, midline-glial-expressed genes will be functionally screened for glial phenotypes using RNA interference and available genetic mutants. For glial genes encoding transciption factors, in situ expression pattern screening and microarray analysis will be used to identify transcriptional changes in mutant genetic backgrounds. This analysis will provide a clearer understanding midline CNS development and the transcriptional pathways that regulate midline glial development and function.