title: Regulation of thalamocortical axon branching by BDNF and synaptic vesicle cycling.
abstract: During development, axons form branches in response to extracellular molecules. Little is known about the underlying molecular mechanisms. Here, we investigate how neurotrophin-induced axon branching is related to synaptic vesicle cycling for thalamocortical axons. The exogenous application of brain-derived neurotrophic factor (BDNF) markedly increased axon branching in thalamocortical co-cultures, while removal of endogenous BDNF reduced branching. Over-expression of a C-terminal fragment of AP180 that inhibits clathrin-mediated endocytosis affected the laminar distribution and the number of branch points. A dominant-negative synaptotagmin mutant that selectively targets synaptic vesicle cycling, strongly suppressed axon branching. Moreover, axons expressing the mutant synaptotagmin were resistant to the branch-promoting effect of BDNF. These results suggest that synaptic vesicle cycling might regulate BDNF induced branching during the development of the axonal arbor.
authors.affiliation: Neuroscience Laboratories, Graduate School of Frontier Biosciences, Osaka University Suita, Osaka, Japan ; Division of Cell Biology, Department of Clinical and Experimental Medicine, Linköping University Linköping, Sweden.
authors.forename: Björn
authors.initials: B
authors.lastname: Granseth
authors.affiliation: Neuroscience Laboratories, Graduate School of Frontier Biosciences, Osaka University Suita, Osaka, Japan.
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Fukushima
authors.affiliation: Neuroscience Laboratories, Graduate School of Frontier Biosciences, Osaka University Suita, Osaka, Japan.
authors.forename: Noriuki
authors.initials: N
authors.lastname: Sugo
authors.affiliation: Sussex Neuroscience, School of Life Sciences, University of Sussex Brighton, UK.
authors.forename: Leon
authors.initials: L
authors.lastname: Lagnado
authors.affiliation: Neuroscience Laboratories, Graduate School of Frontier Biosciences, Osaka University Suita, Osaka, Japan.
authors.forename: Nobuhiko
authors.initials: N
authors.lastname: Yamamoto
mesh_terms: D000818:Animals; D001369:Axons / Q000187:drug effects / Q000378:metabolism*; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism* / Q000494:pharmacology; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism*; D004705:Endocytosis / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013572:Synaptic Vesicles / Q000187:drug effects / Q000378:metabolism*; D013788:Thalamus / Q000187:drug effects / Q000378:metabolism*
chemical_list: D019208:Brain-Derived Neurotrophic Factor
keywords: axon; branching; development; endocytosis; neocortex; neurotrophin; synapse; thalamus