期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 111, 期 42, 页码 15226-15231出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1402095111
关键词
development; neocortex; axon guidance; neuronal wiring
资金
- Ministry of Education, Culture, Sports, Science and Technology of Japan (MEXT) [23115102]
- MEXT [203001100, 20021018]
- Uehara Memorial Foundation
- Grants-in-Aid for Scientific Research [22115010, 20021018] Funding Source: KAKEN
Axon branching is remodeled by sensory-evoked and spontaneous neuronal activity. However, the underlying molecular mechanism is largely unknown. Here, we demonstrate that the netrin family member netrin-4 (NTN4) contributes to activity-dependent thalamocortical (TC) axon branching. In the postnatal developmental stages of rodents, ntn4 expression was abundant in and around the TC recipient layers of sensory cortices. Neuronal activity dramatically altered the ntn4 expression level in the cortex in vitro and in vivo. TC axon branching was promoted by exogenous NTN4 and suppressed by depletion of the endogenous protein. Moreover, unc-5 homolog B (Unc5B), which strongly bound to NTN4, was expressed in the sensory thalamus, and knockdown of Unc5B in thalamic cells markedly reduced TC axon branching. These results suggest that NTN4 acts as a positive regulator for TC axon branching through activity-dependent expression.
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