Molecular control of neural progenitor migration. (360G-Wellcome-089236_Z_09_Z)

The subventricular zone (SVZ) is one of the largest sources of neural progenitor cells in the adult brain. These cells migrate from the SVZ following a very precise route, the rostral migratory stream (RMS), to reach the olfactory bulb. Importantly, the adult SVZ responds to insults by producing new progenitors that migrate to sites affected by neurodegenerative pathology or injury. However, still remarkably little is known about the molecular mechanisms controlling neural progenitor migration. Our aim is to identify and characterise regulators of neural progenitor migration. We have identified a set of candidate key molecules with a microarray screen performed by inhibiting neural stem cell migration. In addition, our preliminary data point to a role in neural progenitor migration for the cannabinoid system and for Ral GTPases, regulators of cell cytoskeleton and membrane traffic. The role of our candidate molecules will be tested in established in vitro migration assays using neur al stem cell lines and SVZ-derived neural progenitors nucleofected with targeting small interfering RNA, or expressing wild-type and mutant versions of proteins of interest. The most interesting candidates will then be functionally tested in vivo by lentiviral vector-mediated RNAi or overexpression in mouse SVZ-derived neuroblasts labelled with GFP.