Regulation of life or death fate in Drosophila neural stem cells. Richa Arya, Ying Tan, Hsiao-Yu Huang, Francisca Rodriguez, Tatavik Keshishyan, Megumu Yamada-Mabuchi, Kristin White. CBRC, MGH/HARVARD, CHARLESTOWN, MA.

   Whether to survive or die is a critical decision cells make during development. Although the canonical apoptotic pathways are well characterized, very little is known about how these pathways are activated only in doomed cells. Apoptosis is a major process that shapes the developing nervous system in many animals. Our lab is studying how the spatial and temporal regulation of developmental apoptosis takes place in the Drosophila neural stem cells or neuroblasts(NBs). We found that the apoptotic activators reaper (rpr) , grim, and sickle (skl) are required for the normal death of NBs in the abdominal region of the ventral nerve cord. We have genetically identified a 25kb NB specific cis-regulatory region (NBRR) for rpr, grim, and skl that is necessary for the elimination of these cells. Based on evolutionary conservation and available ChIP data, we selected a 5kb portion of this region to generate GFP-reporter flies (NBRR1-GFP). NBRR1-GFP is expressed in a subset of abdominal NBs in the late embryo, in cells that also express rpr and grim. This strongly supports the idea that this region includes cis-regulatory sequences for the regulation of rpr and grim in doomed NBs. To identify the upstream regulators that could directly and/or indirectly regulate the NBRR, we performed an open ended RNAi screen for transcriptional regulators that are required for the apoptosis of embryonic abdominal NBs. We have identified a number of candidates. Based on GO function these candidates fall in various functional categories from CNS development to chromatin remodelling. In the study we have described the apoptotic genes and the regulatory region necessary for NB apoptosis. Currently we are asking how various upstream regulators identified in our screen are involved in initiating the death of specific cells during development.