THE ROLE OF STRESS RESPONSE SIGNALING PATHWAYS THAT GOVERN DENDRITE PRUNING IN DROSOPHILA SENSORY NEURONS

Abstract

Neuronal pruning is a crucial developmental step of the nervous system to remove unnecessary dendrites or axons. The evolutionarily conserved Nrf2-Keap1 pathway is a key antioxidant response pathway that protects cells or organisms against devastating effects of oxidative stress. Here, I demonstrate a cell-autonomous role of the Nrf2-Keap1pathway in governing dendrite pruning in Drosophila sensory neurons. Importantly, Nrf2-Keap1 signaling is activated downstream of the steroid hormone ecdysone via nuclear translocation of CncC(Drosophila homolog of Nrf2). Interestingly, Nrf2-Keap1 signaling regulates dendrite pruning independently of its canonical antioxidant response pathway, but instead through proteasomal degradation. Next, I show that the metabolic regulator AMP-activated protein kinase (AMPK) activates Nrf2-Keap1 pathway via inhibition of the insulin pathway to promote dendrite pruning.