Pax6-/- mice have a cell nonautonomous defect in nonradial interneuron migration.
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.
Gopal
Pallavi P
PP
Neuroscience Program, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.
Golden
Jeffrey A
JA
D000818:Animals; D001369:Axons / Q000473:pathology; D002465:Cell Movement; D005124:Eye Abnormalities; D005136:Eye Proteins / Q000235:genetics*; D005260:Female; D018507:Gene Expression Regulation, Developmental; D018398:Homeodomain Proteins / Q000235:genetics*; D007395:Interneurons / Q000473:pathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D019579:Neocortex / Q000002:abnormalities* / Q000473:pathology*; D009433:Neural Inhibition; D000071841:PAX6 Transcription Factor; D051761:Paired Box Transcription Factors / Q000235:genetics*; D011247:Pregnancy; D012097:Repressor Proteins / Q000235:genetics*; D005680:gamma-Aminobutyric Acid / Q000502:physiology
D005136:Eye Proteins; D018398:Homeodomain Proteins; D000071841:PAX6 Transcription Factor; D051761:Paired Box Transcription Factors; C000605732:Pax6 protein, mouse; D012097:Repressor Proteins; D005680:gamma-Aminobutyric Acid