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Development 129, 1435-1442 (2002)
© 2002 The Company of Biologists Limited

BDNF stimulates migration of cerebellar granule cells

Paul R. Borghesani1,3,*, Jean Michel Peyrin2,*, Robyn Klein4,*, Joshua Rubin1, Alexandre R. Carter1,3, Phillip M. Schwartz1, Andrew Luster4, Gabriel Corfas2,{dagger} and Rosalind A. Segal1,3,5,{ddagger}

1 Department of Pediatric Oncology, Dana-Farber Cancer Institute, 44 Binney Street, Boston, MA 02115, USA
2 Division of Neuroscience, The Children’s Hospital, Boston, MA 02115, USA
3 Department of Neurobiology, Harvard Medical School, Boston, MA 02115, USA
4 Center for Immunology and Inflammatory Diseases, Massachusetts General Hospital, Charlestown, MA 02129, USA
* The first three authors contributed equally
{dagger} The last two authors contributed equally

{ddagger}Author for correspondence (e-mail: Rosalind_segal{at}dfci.harvard.edu)

Accepted 17 December 2001

During development of the nervous system, neural progenitors arise in proliferative zones, then exit the cell cycle and migrate away from these zones. Here we show that migration of cerebellar granule cells out of their proliferative zone, the external granule cell layer (EGL), is impaired in Bdnf–/– mice. The reason for impaired migration is that BDNF directly and acutely stimulates granule cell migration. Purified Bdnf–/– granule cells show defects in initiation of migration along glial fibers and in Boyden chamber assays. This phenotype can be rescued by exogenous BDNF. Using time-lapse video microscopy we find that BDNF is acutely motogenic as it stimulates migration of individual granule cells immediately after addition. The stimulation of migration reflects both a chemokinetic and chemotactic effect of BDNF. Collectively, these data demonstrate that BDNF is directly motogenic for granule cells and provides a directional cue promoting migration from the EGL to the internal granule cell layer (IGL).

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Key words: BDNF, Granule cells, Cell migration, CNS, Mouse




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© The Company of Biologists Ltd 2002