Borghesani Paul R, Peyrin Jean Michel, Klein Robyn, Rubin Joshua, Carter Alexandre R, Schwartz Phillip M, Luster Andrew, Corfas Gabriel, Segal Rosalind A
Department of Pediatric Oncology, Dana-Farber Cancer Institute, 44 Binney Street, Boston, MA 02115, USA.
Development. 2002 Mar;129(6):1435-42. doi: 10.1242/dev.129.6.1435.
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).
在神经系统发育过程中，神经祖细胞在增殖区产生，然后退出细胞周期并从这些区域迁移离开。我们在此表明，在脑源性神经营养因子（Bdnf）基因敲除小鼠中，小脑颗粒细胞从其增殖区即外颗粒细胞层（EGL）迁出的过程受到损害。迁移受损的原因是脑源性神经营养因子（BDNF）直接且急性地刺激颗粒细胞迁移。纯化的Bdnf基因敲除颗粒细胞在沿胶质纤维迁移的起始阶段以及在博伊登室试验中均表现出缺陷。这种表型可通过外源性BDNF得以挽救。使用延时视频显微镜，我们发现BDNF具有急性促迁移作用，因为在添加后它能立即刺激单个颗粒细胞迁移。对迁移的刺激反映了BDNF的化学动力学和趋化作用。总体而言，这些数据表明BDNF对颗粒细胞具有直接的促迁移作用，并提供了一个促进从EGL向内颗粒细胞层（IGL）迁移的定向线索。
