期刊
FRONTIERS IN NEURAL CIRCUITS
卷 7, 期 -, 页码 -出版社
FRONTIERS RESEARCH FOUNDATION
DOI: 10.3389/fncir.2013.00202
关键词
axon; branching; neurotrophin; synapse; endocytosis; thalamus; neocortex; development
资金
- Japanese Ministry of Education, Culture, Sports, Science, and Technology [23115102]
- Japan Society for the Promotion of Sciences to Nobuhiko Yamamoto [20300110, 23300118]
- Wellcome Trust
- Swedish Research Council [3050, 2862]
- Knut and Alice Wallenberg Foundation
- Carl and Axel Molin i Motala minne-foundation
- Grants-in-Aid for Scientific Research [20300110, 23300118] Funding Source: KAKEN
- Medical Research Council [MC_U105178794] Funding Source: researchfish
- MRC [MC_U105178794] Funding Source: UKRI
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.
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