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Science. 2014 May 30;344(6187):1020-3. doi: 10.1126/science.1252514. Epub 2014 May 15.

Retrograde semaphorin signaling regulates synapse elimination in the developing mouse brain.

Author information

1
Department of Neurophysiology, Graduate School of Medicine, The University of Tokyo, Tokyo 113-0033, Japan.
2
Department of Anatomy, Hokkaido University Graduate School of Medicine, Sapporo 060-8638, Japan.
3
Laboratory of Animal Resources, Center for Disease Biology and Integrated Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo 113-0033, Japan.
4
Department of Neurophysiology, Gunma University Graduate School of Medicine, Maebashi, Gunma 371-8511, Japan.
5
Department of Neurophysiology, Graduate School of Medicine, The University of Tokyo, Tokyo 113-0033, Japan. mkano-tky@m.u-tokyo.ac.jp.

Abstract

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.

PMID:
24831527
DOI:
10.1126/science.1252514
[Indexed for MEDLINE]
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