Cerebral Cortex Advance Access published online on July 18, 2007
Cerebral Cortex, doi:10.1093/cercor/bhm114
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Pax6–/– Mice Have a Cell Nonautonomous Defect in Nonradial Interneuron Migration
1 Neuroscience Program, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA, 2 Department of Pathology, Abramson Research Center, Children's Hospital of Philadelphia, Room 516h, 34th and Civic Center Boulevard, Philadelphia, PA 19104, USA, 3 Department of Pathology, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA
Address correspondence to email: goldenj{at}mail.med.upenn.edu.
The mammalian neocortex comprises two major neuronal subtypes; interneurons derived from the ganglionic eminence (GE) and projection neurons from the cortical ventricular zone (VZ). These separate origins necessitate distinct pathways of migration. Using mouse genetics and embryonic forebrain slice culture assays, we sought to identify substrates and/or guidance molecules for nonradial cell migration (NRCM). Mice carrying a mutation in Pax6 (Sey–/–), a paired domain transcription factor, are reported to have increased numbers of cortical inhibitory interneurons, suggesting that Pax6 could induce inhibitors of interneuron development or alternatively play a repressive role in guiding NRCM and/or specifying interneurons. Unexpectedly, we found a cell nonautonomous reduction in the distance Sey–/– neurons migrated, reflecting a disorganized migration, with frequent changes in direction. In contrast, no difference in the number of nonradially migrating GE cells was observed in Sey–/– mice. Our data indicate that the increased numbers of interneurons observed in Sey–/– do not result from an increased rate or number of nonradially migrating cells; instead, loss of Pax6 results in the ectopic specification of interneurons in the cortical VZ. Further, our data indicate that the known axonal disorganization in Sey–/– mice contributes to the observed reduced distance of NRCM.
Key Words: GABAergic interneuron neuronal specification nonradial migration patterning Small eye