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

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.
This work was supported by research grants from the Ministry of Education, Culture, Sports, Science & Technology (MEXT), Ministry of Health, Labor and Welfare (MHLW), Japan Society for the Promotion of Science (JSPS), Human Frontier Science Program (HFSP), Toray Science Foundation, Keio University Medical Science Fund, Inoue Foundation for Science, NOVARTIS Foundation (Japan) for the Promotion of Science, and Kowa Life Science Foundation. J.Y.W is supported by NIH (CA114197, CA107193) and James S. McDonnell Foundation. N.K. was an Inoue Fellow.