FAN · Defining the functions of Elongator in adult brain neurogenesis

The olfactory bulb (OB) is one of the few structures in the adult forebrain in which there is a continuous supply of newborn neurons. Neuronal precursors are generated in the subventricular zone (SVZ) and follow an intricate migration path before reaching their final position in the OB.Familial dysautonomia is a neurodegenerative disorder that result from the impairment of Elongator activity. Elongator is a six unit complex assembled by its scaffold protein Elp1. The host laboratory has recently shown that the catalytic activity of this complex underlies radial migration and branching of cortical projection neurons by promoting the acetylation of α-tubulin.In the adult brain, the stem/neural progenitor express Elongator subunits and Elp1 level expression increases dramatically after treatment that promotes neurogenesis. The overall goal of the current project is to understand the functions of Elongator in adult brain neurogenesis.I propose:- To analyze the expression pattern of Elongator in adult SVZ.- To dissect the role of Elongator on neuroblasts migration within the rostral migratory stream (rostral migration) and the OB (radial migration).- To define the role of Elongator on interneuron differentiation in the OB.- To characterize new cytoplasmic targets of Elongator that promote adult neurogenesis.""