Research ReportAltered gene expression in the emerging cerebellar primordium of Neurog1−/− mice

Expression of the basic helix-loop-helix (bHLH) transcription factor Neurogenin1 (Neurog1) coincides with the emergence of the cerebellum and Neurog1-expressing progenitors are fated to become Purkinje cells and later interneurons. However, the gene regulatory functions of Neurog1 in cerebellar development have not been characterized. We performed a genome-wide analysis of gene expression in the cerebellar primordium of E11.5 Neurog1 null (Neurog1−/−) mice to identify the Neurog1 transcriptome in the emerging cerebellum. This screen identified 117 genes differentially enriched in Neurog1−/− versus control sample sets with a high presence of gene sets enriched for functions in nervous system development. Hierarchical clustering revealed complete stratification of differentially expressed genes based on Neurog1 gene deletion status. In silico analysis of promoter regions identifies high probability Neurog1 regulatory (E-box) binding sites in 94 of the 117 differentially expressed genes and Pax6 binding motifs in 25 of these 94 promoters. Our data provide a framework for investigating Neurog1 transcriptional programs in early cerebellar development and suggest functional Neurog1-Pax6 cross-talk in the activation of downstream targets.

Research highlights► Genome-wide analysis of gene expression in the emerging cerebellum of E11.5 Neurog1 null (Neurog1−/−) mice identifies 117 genes differentially enriched in Neurog1−/− versus control sample sets. ► In silico analysis of transcriptional binding sites identifies high probability Neurog1 regulatory (E-box) sites in the promoters of 94 of the 117 differentially expressed genes. ► Combined analysis of promoter regions for potential co-transcriptional targets identified regulatory binding motifs for Pax6 in 25 of these 94 genes suggesting Neurog1-Pax6 cross-talk in the emerging cerebellum.