title: BDNF stimulates migration of cerebellar granule cells.
abstract: 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).
authors.affiliation: Department of Pediatric Oncology, Dana-Farber Cancer Institute, 44 Binney Street, Boston, MA 02115, USA.
authors.forename: Paul R
authors.initials: PR
authors.lastname: Borghesani
authors.forename: Jean Michel
authors.initials: JM
authors.lastname: Peyrin
authors.forename: Robyn
authors.initials: R
authors.lastname: Klein
authors.forename: Joshua
authors.initials: J
authors.lastname: Rubin
authors.forename: Alexandre R
authors.initials: AR
authors.lastname: Carter
authors.forename: Phillip M
authors.initials: PM
authors.lastname: Schwartz
authors.forename: Andrew
authors.initials: A
authors.lastname: Luster
authors.forename: Gabriel
authors.initials: G
authors.lastname: Corfas
authors.forename: Rosalind A
authors.initials: RA
authors.lastname: Segal
mesh_terms: D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics* / Q000494:pharmacology; D002465:Cell Movement / Q000187:drug effects / Q000235:genetics*; D002531:Cerebellum / Q000166:cytology / Q000196:embryology / Q000502:physiology; D018507:Gene Expression Regulation, Developmental; D066298:In Vitro Techniques; D051379:Mice; D018345:Mice, Knockout; D018715:Microscopy, Video
chemical_list: D019208:Brain-Derived Neurotrophic Factor