Regulation of self-renewal and differentiation in the Drosophila CNS. (360G-Wellcome-092545_Z_10_Z)

The Drosophila nervous system is an excellent model system in which to analyse the molecular mechanisms controlling stem cell proliferation and differentiation, often at single cell resolution. We will use classical genetic and reverse genetic approaches, in combination with transcriptional profiling of small groups of stem cells and genome-wide DNA-binding analysis, to identify the molecular switches involved in the transition from symmetric to asymmetric division, and from self-renewal to diff erentiation. We will: 1) characterise the genetic switches that convert a symmetrically dividing neural stem cell into an asymmetrically dividing cell 2) identify the genetic networks leading from a neural stem cell to a differentiated neuron 2) test the role, in vivo, of key members of this network by targeted RNAi and screen for brain tumours (neuroblast overproliferation) or small brains (premature differentiation) 2) identify co-factors that modify the activity of the cell fate determi nant, Prospero, enabling it to repress stem cell genes and activate differentiation genes 4) identify the regulatory loops controlling the temporal progression of neurogenesis.