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Development 129, 3147-3160 (2002)
© 2002 The Company of Biologists Limited

Control of cortical interneuron migration by neurotrophins and PI3-kinase signaling

Franck Polleux1, Kristin L. Whitford2, Paul A. Dijkhuizen2, Tania Vitalis3 and Anirvan Ghosh2,*

1 INSERM U.371, 18 avenue Doyen Lépine, 69675 Bron, France
2 Department of Neuroscience, Johns Hopkins University School of Medicine, 725 N Wolfe St, Baltimore, MD 21205, USA
3 Department of Biomedical Sciences, University of Edinburgh, Hugh Robson Building, Georges Square, Edinburgh EH8 9XD, UK

*Author for correspondence (e-mail: aghosh{at}jhmi.edu)

Accepted 22 March 2002

During telencephalic development, cells from the medial ganglionic eminence (MGE) are thought to migrate to the neocortex to give rise to a majority of cortical GABAergic interneurons. By combining time-lapse video-microscopy, immunofluorescence and pharmacological perturbations in a new in vitro migration assay, we find that MGE-derived cells migrate through the entire extent of the cortex and into the CA fields of the hippocampus, but avoid the dentate gyrus. Migrating neurons initially travel within the marginal zone and intermediate zone, and can enter the cortical plate from either location. Tangential migration is strongly stimulated by BDNF and NT4 and attenuated by the Trk-family inhibitor, K252a, suggesting that migration is regulated by TrkB signaling. Furthermore, TrkB-null mice show a significant decrease in the number of calbindin-positive neurons migrating tangentially in the embryonic cortex. BDNF and NT4 cause rapid activation of PI3-kinase in MGE cells, and inhibition of PI3-kinase (but not of MAP kinase or PLC{gamma}) dramatically attenuates tangential migration. These observations suggest that TrkB signaling, via PI3-kinase activation, plays an important role in controlling interneuron migration in the developing cerebral cortex.

Key words: Neurotrophins, Mouse, CNS/migration, Interneuron




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