BioProject

The Notch pathway is a well conserved cell to cell communication mechanism that is normally involved in many developmental processes and when aberrantly activated it leads to diseases such as cancer. More...

The Notch pathway is a well conserved cell to cell communication mechanism that is normally involved in many developmental processes and when aberrantly activated it leads to diseases such as cancer. One such example is the neural stem cell tumours that arise from constitutive Notch activity in Drosophila neuroblasts from the larval Central Nervous System (CNS). To investigate how hyper-activation of Notch in larval neuroblasts leads to tumours, we mapped genome-widely the regions that are bound by Su(H) (the core Notch pathway transcription factor, known as CSL in mammals). We combined these results with the profiling of upregulated mRNAs in CNSs where Notch is hyper-activated for 24h vs control CNSs and identified 127 putative direct Notch targets in the hyperplastic CNSs. Included were genes associated with the neuroblast maintenance and self-renewal programme and genes coding for temporal transcription factors, which are involved in neuroblast progression and generation of progeny with specific identity over time. Thus, Notch induces neural stem cell tumors by promoting the expression of genes that contribute to stem cell identity and by reprogramming expression of temporal factors that regulate maturity. Overall design: Su(H) binding profile in Drosophila larval CNSs where Notch is constitutively active for 24 hours. In total there are 3 samples of Su(H) ChIP in Notch hyper-activated larval CNSs. Less...