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Publication : Multiple roles for slits in the control of cell migration in the rostral migratory stream.

First Author  Nguyen-Ba-Charvet KT Year  2004
Journal  J Neurosci Volume  24
Issue  6 Pages  1497-506
PubMed ID  14960623 Mgi Jnum  J:90079
Mgi Id  MGI:3042495 Doi  10.1523/JNEUROSCI.4729-03.2004
Citation  Nguyen-Ba-Charvet KT, et al. (2004) Multiple roles for slits in the control of cell migration in the rostral migratory stream. J Neurosci 24(6):1497-506
abstractText  The subventricular zone (SVZ) contains undifferentiated cells, which proliferate and generate olfactory bulb (OB) interneurons. Throughout life, these cells leave the SVZ and migrate along the rostral migratory stream (RMS) to the OB where they differentiate. In vitro, the septum and the choroid plexus (CP) secrete repulsive factors that could orient the migration of OB precursors. Slit1 and Slit2, two known chemorepellents for developing axons, can mimic this effect. We show here that the Slit receptors Robo2 and Robo3/Rig-1 are expressed in the SVZ and the RMS and that Slit1 and Slit2 are still present in the adult septum. Using Slit1/2-deficient mice, we found that Slit1 and Slit2 are responsible for both the septum and the CP repulsive activity in vitro. In adult mice lacking Slit1, small chains of SVZ-derived cells migrate caudally into the corpus callosum, supporting a role for Slits in orienting the migration of SVZ cells. Surprisingly, in adult mice, Slit1 was also expressed by type A and type C cells in the SVZ and RMS, suggesting that Slit1 could act cell autonomously. This hypothesis was tested using cultures of SVZ explants or isolated neurospheres from Slit1-/- or Slit1+/- mice. In both types of cultures, the migration of SVZ cells was altered in the absence of Slit1. This suggests that the regulation of the migration of OB precursors by Slit proteins is complex and not limited to repulsion.
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