Journal
SCIENCE
Volume 344, Issue 6187, Pages 1020-1023Publisher
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/science.1252514
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Funding
- Funding Program for Next Generation World-Leading Researchers [LS021]
- Strategic Research Program for Brain Sciences (Development of Biomarker Candidates for Social Behavior)
- Comprehensive Brain Science Network
- Global Center of Excellence Program (Integrative Life Science Based on the Study of Biosignaling Mechanisms) from the Ministry of Education, Culture, Sports, Science and Technology of Japan
- [21220006]
- [25000015]
- [19100005]
- [24220007]
- [23650160]
- Grants-in-Aid for Scientific Research [221S0003, 25830004, 25000015, 25115010] Funding Source: KAKEN
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Neural circuits are shaped by elimination of early-formed redundant synapses during postnatal development. Retrograde signaling from postsynaptic cells regulates synapse elimination. In this work, we identified semaphorins, a family of versatile cell recognition molecules, as retrograde signals for elimination of redundant climbing fiber to Purkinje cell synapses in developing mouse cerebellum. Knockdown of Sema3A, a secreted semaphorin, in Purkinje cells or its receptor in climbing fibers accelerated synapse elimination during postnatal day 8 (P8) to P18. Conversely, knockdown of Sema7A, a membrane-anchored semaphorin, in Purkinje cells or either of its two receptors in climbing fibers impaired synapse elimination after P15. The effect of Sema7A involves signaling by metabotropic glutamate receptor 1, a canonical pathway for climbing fiber synapse elimination. These findings define how semaphorins retrogradely regulate multiple processes of synapse elimination.
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