14-P019 Netrin1 in forebrain development

Netrin1 is a member of a family of secreted molecules implicated in axon guidance, neuronal migration and apoptosis during development of central nervous system (CNS). Netrin1 signals in CNS through a group of transmembrane receptors belonging to the DCC (deleted in colorectal cancer) and C. elegans Unc5-related families. Netrin1 mutant mice die usually at birth with several CNS defects, but heterozygous mice are normal. We made Netrin1 expression analysis in developing and postnatal mouse brain. Netrin1 was strongly expressed in the proliferative ventricular zone (VZ) in embryonic brain and in the developmentally related ependymal layer of the postnatal brain. Isolated Netrin1 positive neurospheres from VZ/ependymal layer expressed several neural stem cell markers, were able to self-renew and differentiated into neurons, astrocytes and oligodendrocytes. Netrin1 expressing cells were also apparent in the rostral migratory stream (RMS), along which newly born neuroblasts migrate from lateral ventricles to the olfactory bulb contributing a constant renewal of the peripheral olfactory system. Netrin1 –/– mice had a smaller olfactory bulbs and immunohistological analysis revealed that Netrin1 expressing cells form a heterogenous subset of precursor cells contributing both neural and glial populations in olfactory bulb.