New Neurons Clear the Path of Astrocytic Processes for Their Rapid Migration in the Adult Brain

Abstract

SUMMARY In the long-range neuronal migration of adult mammals, young neurons travel from the subventricular zone to the olfactory bulb, a long journey (millimeters to centimeters, depending on the species). How can these neurons migrate through the dense meshwork of neuronal and glial processes of the adult brain parenchyma? Previous studies indicate that young neurons achieve this by migrating in chains through astrocytic tunnels. Here, we report that young migrating neurons actively control the formation and maintenance of their own migration route. New neurons secrete the diffusible protein Slit1, whose receptor, Robo, is expressed on astrocytes. We show that the Slit-Robo pathway is required for morphologic and organizational changes in astrocytes that result in the formation and maintenance of the astrocytic tunnels. Through this neuron-glia interaction, the new neurons regulate the formation of the astrocytic meshwork that is needed to enable their rapid and directional migration in adult brain.

Identification and characterization of neuroblasts in the subventricular zone and rostral migratory stream of the adult human brain

“…In contrast to previous studies [33], we also found no evidence of Dcx+/Tuj1+ or Dcx+ cells in the adult human OB. Recent work has shown that neuroblasts clear the path of glial processes for their migration in the RMS of the adult mouse brain [34]. Given that neuroblasts actively control the formation and maintenance of their own migratory route [34], it is difficult to imagine that such a small number of neuroblasts can successfully establish a long and complex migratory route from the SVZ to the OB.…”

“…Recent work has shown that neuroblasts clear the path of glial processes for their migration in the RMS of the adult mouse brain [34]. Given that neuroblasts actively control the formation and maintenance of their own migratory route [34], it is difficult to imagine that such a small number of neuroblasts can successfully establish a long and complex migratory route from the SVZ to the OB. Thus, it is likely that migration from the adult human SVZ to the OB is an impossible mission for neuroblasts.…”

Speed control for neuronal migration in the postnatal brain by Gmip-mediated local inactivation of RhoA

“…Brains were fixed by transcardiac perfusion with 4% paraformaldehyde in 0.1 M phosphate buffer, postfixed overnight in the same fixative, and 60-mm-thick floating coronal or sagittal sections were prepared using a vibratome (VT1200S, Leica, Heidelberg, Germany) as reported previously 15,54 . For immunostaining, the sections were incubated for 1 h in blocking solution (10% donkey serum and 0.2% Triton X-100 in PBS), overnight at 4°C with the primary antibodies, and for 2 h at room temperature with Alexa Fluor-conjugated secondary antibodies (Invitrogen, Carlsbad, CA).…”

“…During this process, new neurons generated in the ventricular-subventricular zone (V-SVZ) of the lateral walls of the lateral ventricles migrate over a long distance along a pathway called the rostral migratory stream (RMS) towards the OB [9][10][11][12][13] . As they migrate, the neurons move along complex mesh-like routes through astrocyte tunnels by forming elongated cell aggregates called 'chains' 14,15 , and within the aggregates these neurons also move over and past one another 16 . Once in the OB, the neurons migrate radially to their final position in the appropriate layer, where they differentiate into one of the two types of local olfactory interneurons: granule cells (GCs) or periglomerular cells (PGCs) 10,17 .…”

Roles of Planar Cell Polarity Signaling in Maturation of Neuronal Precursor Cells in the Postnatal Mouse Olfactory Bulb

“…S4--S6), suggesting that this pathway's function in NPC migration into the OB is cell-autonomous. On the other hand, NPC migration in the SVZ-RMS-OB path is known to be regulated by the surrounding cells, including ependymal cells, astrocytes, and blood vessels [54][55][56][57]. Since Dvl2 and Vangl2 are expressed broadly in this region (Supporting Information Fig.…”