目的 鉴定与肠神经系统发育以及先天性巨结肠（HSCR）发生相关的转录因子。方法 运用ChEA3数据库 对调控HSCR易感基因表达的转录因子进行预测以及富集分析，使用GeneMANIA在线工具构建转录因子与靶基因的蛋 白-蛋白相互作用网络图，探讨其可能调控的分子通路，以Human Protein Atlas数据库对转录因子进行蛋白表达定位，探 究其在神经系统和结肠的表达情况。采用实时荧光定量PCR方法，验证相关转录因子在30例HSCR患儿的狭窄段和扩张 段肠管标本中的表达差异。结果 用ChEA 3数据库对已报道的119个HSCR易感基因的转录因子预测及富集分析发现， FOXP2可以靶向作用于其中46个基因。在GeneMANIA数据库中分析显示FOXP2可能调控多个HSCR易感基因的表达， 与Hedgehog通路的GLI 3共表达，与PTCH1存在遗传相互作用。Human Protein Atlas数据库分析显示，FOXP2蛋白在脑神 经元细胞和结肠组织中高表达。30例HSCR患儿中位年龄为1岁，其中男23例、女7例，荧光定量PCR结果显示，FOXP 2 的mRNA表达量在病变组织较临近正常组织下降，差异有统计学意义（t= 5.819，P

Objective To explore the transcription factors involved in the development of the enteric nervous system and the pathogenesis of Hirschsprung disease (HSCR). Methods The ChEA 3 database was used to do analysis of prediction and enrichment of the target transcription factors that regulate the expression of HSCR susceptibility genes. The GeneMANIA online tool was utilized to construct a protein-protein interaction network diagram between transcription factors and target genes for exploration of their possible regulatory molecular pathways. Human Protein Atlas database was used to locate the protein expression of transcription factors and explores their expression in the nervous system and colon. Quantitative real-time polymerase chain reaction (qRT-PCR) analysis was performed to verify the expression differences of related transcription factors in the stenotic and dilated bowel specimens of 30 children with HSCR. Results The ChEA 3 database was used to analyze prediction and enrichment of the transcription factors of 119 reported HSCR susceptibility genes, and it was found that FOXP2 can target 46 of them. Analysis in the GeneMANIA database shows that FOXP2 may regulate the expression of multiple HSCR susceptibility genes, co-expression with GLI 3 of the Hedgehog pathway, and genetic interaction with PTCH 1 . Human protein Atlas database analysis shows that FOXP 2 protein is highly expressed in brain neuronal cells and colon tissues. The median age of 30 children ( 23 boys and 7 girls) with HSCR was 1 year. The qRT-PCR results showed that the expression of FOXP2 mRNA in pathological tissues was lower than that in adjacent normal tissues, and the difference was statistically significant (t= 5 . 82 , P< 0 . 0001 ). Conclusions FOXP2 may influence the development of intestinal nerve cells through the regulation of Hedgehog signaling pathway, and thus contribute to the pathogenesis of HSCR.