Extracellular signals controlling neuroblast migration in the postnatal brain

Abstract

The most prominent example of long-distance migration in the postnatal brain is the rostral migratory stream (RMS) formed by neuroblasts originating in the subventricular zone (SVZ), one of the main neurogenic niches. Stem cell-derived neuroblasts leave the SVZ and migrate rostrally towards the olfactory bulb (OB), where they ultimately differentiate into inhibitory interneurons. This migration is essential for the proper integration of new neurons into the synaptic network and for the regulation of synaptic plasticity and olfactory memory. SVZ-derived postnatal neuroblasts undergo tangential migration independent of radial glia. They slide along each other in chains, which become progressively encased by an astrocytic tunnel throughout adulthood, while keeping in close contact with surrounding blood vessels. Once in the OB, neuroblasts switch to radial migration before differentiating. While the existence of an RMS is still controversial in the adult human brain, prominent migration of SVZ-derived neuroblasts towards the OB is observed in human infants, where it may play an important role in plasticity in a crucial period for the formation of synaptic networks. Moreover, SVZ neuroblasts are able to deviate from their migratory path to reach areas of injury and neurodegeneration. Identifying the extracellular factors and the intracellular mechanisms regulating neuroblast migration can therefore not only clarify a fundamental aspect of postnatal neurogenesis, but can also become relevant for therapeutic strategies exploiting the recruitment of endogenous stem cell-derived neural progenitors. This chapter presents an overview of the wide range of extracellular factors guiding neuroblast migration that have emerged over the last two decades.