Transcriptional Profiling Reveals the Transcription Factor Networks Regulating the Survival of Striatal Neurons

The striatum is structurally highly diverse and its organ functionality critically depends on a normal embryonic development. Although several studies on the gene functional changes that occur during striatal development, a system-wide analysis of the underlying molecular changes is lacking. Here, we present a comprehensive temporal transcriptome atlas of the mouse striatum at multiple developmental stages. Quantitative analysis of 15443 gene products allows us to explore the trajectory of striatal development and identify the correlation between the striatal development and Huntington9s disease (HD). More importantly, we provided the global landscape of 277 transcription factor (TF) networks based on co-expression analysis and machine learning. Furthermore, we identified the hub TFs Six3 and Meis2 which are involved in regulating the apoptosis of striatal neurons. Finally, using conditional knockout (CKO) mice and RNA-Seq data, we verified that Six3 and Meis2 indeed regulated neuronal apoptosis and inferred their downstream targets in the striatum