Editors' ChoiceNeurobiology

Make Me a Path

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Science Signaling  03 Aug 2010:
Vol. 3, Issue 133, pp. ec237
DOI: 10.1126/scisignal.3133ec237

In adult mammals, newly generated neurons, which arise in a specific region of the brain called the subventricular zone (SVZ), may have to migrate long distances to their sites of maturation and synapse formation. One example is the neurons of the olfactory bulb, which are generated continuously and migrate through the rostral migratory stream (RMS) within tubular structures formed by astrocytes. The Slit family of secreted factors regulates neuronal migration through binding receptors of the Robo family. Kaneko et al. provide evidence from analysis of slit1-deficient mice (S1–/–) that migrating immature olfactory neurons secrete Slit1, which is detected by Robo receptors on the glia to instruct the formation of the glial tube through which the neurons then migrate. The brains of slit1-deficient mice exhibited altered morphology of the RMS, with the proximal part thickened and the distal part thinned compared to the brains of wild-type animals. Analysis of proliferation (BrdU staining) and apoptosis (caspase cleavage) indicated that lack of Slit1 did not affect these processes. Analysis of the migration of labeled neurons in brain slices or in vivo revealed that the S1–/– mice exhibited slower migration (slices), with fewer reaching the olfactory bulb (in vivo). Although the young neurons formed their typical migrating chain structure, the astrocytic processes of the glial tubes that form this migration pathway were disorganized in the Slit1-deficient mouse brains. Staining of brain sections revealed that Robo2 was abundant in the astrocytes that formed the glial tubes of this olfactory neuron pathway and was less abundant in the young neurons. Robo3 was also detected in both the neurons and the astrocytes. In an in vitro assay, primary astrocytes from the SVZ and RMS were repelled from gels containing cells transfected to express Slit, and this repulsion was reduced if the astrocytes were transfected with a dominant-negative form of Robo or if Robo2 or Robo3 were knocked down. In culture, SVZ neurons from S1–/– mice migrated more slowly when plated on astrocytes, and these neurons induced the formation of astrocytic furrows around the neurons with lower frequency than did SVZ neurons from wild-type mice. Similar phenotypes were observed when wild-type neurons were plated on astrocytes expressing the dominant-negative Robo. Thus, Slit released from the immature neurons appears to instruct the Robo-positive astrocytes to form the glial tube to facilitate proper migration.

N. Kaneko, O. Marin, M. Koike, Y. Hirota, Y. Uchiyama, J. Y. Wu, Q. Lu, M. Tessier-Lavigne, A. Alvarez-Buylla, H. Okano, J. L. R. Rubenstein, K. Sawamoto, New neurons clear the path of astrocytic processes for their rapid migration in the adult brain. Neuron 67, 213–223 (2010). [PubMed]

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