Polarized Signaling Endosomes Coordinate BDNF-Induced Chemotaxis of Cerebellar Precursors

• DOI: 10.1016/j.neuron.2007.05.030
• Publication Date: 2007-07-06T11:02:57Z
• Authors: Pengcheng Zhou; Marimelia Porcion...; Mariecel Pilapil; Yicheng Chen; Yoojin Choi; Kimberley F. Tolias; Jay B. Bikoff; Elizabeth J. Hong; Michael E. Greenberg; Rosalind A. Segal
• Keywords: rac1 GTP-Binding Protein; 570; Neuroscience(all); 610; Endosomes; Cytoplasmic Granules; MOLNEURO; Mice; Phosphatidylinositol 3-Kinases; 03 medical and health sciences; Cell Movement; Cerebellum; Animals; Receptor, trkB; cdc42 GTP-Binding Protein; Mice, Knockout; 0303 health sciences; Brain-Derived Neurotrophic Factor; Chemotaxis; Stem Cells; Lentivirus; Neuropeptides; Endocytosis; rac GTP-Binding Proteins; SIGNALING; CELLBIO; rhoA GTP-Binding Protein; Signal Transduction

During development, neural precursors migrate in response to positional cues such as growth factor gradients. However, the mechanisms that enable precursors to sense and respond to such gradients are poorly understood. Here we show that cerebellar granule cell precursors (GCPs) migrate along a gradient of brain-derived neurotrophic factor (BDNF), and we demonstrate that vesicle trafficking is critical for this chemotactic process. Activation of TrkB, the BDNF receptor, stimulates GCPs to secrete BDNF, thereby amplifying the ambient gradient. The BDNF gradient stimulates endocytosis of TrkB and associated signaling molecules, causing asymmetric accumulation of signaling endosomes at the subcellular location where BDNF concentration is maximal. Thus, regulated BDNF exocytosis and TrkB endocytosis enable precursors to polarize and migrate in a directed fashion along a shallow BDNF gradient.