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Dual function of NRP1 in axon guidance and subcellular target recognition in cerebellum.
Neuron 91, 1276-1291 (2016)
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DOI
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Subcellular target recognition in the CNS is the culmination of a multiple-step program including axon guidance, target recognition, and synaptogenesis. In cerebellum, basket cells (BCs) innervate the soma and axon initial segment (AIS) of Purkinje cells (PCs) to form the pinceau synapse, but the underlying mechanisms remain incompletely understood. Here, we demonstrate that neuropilin-1 (NRP1), a Semaphorin receptor expressed in BCs, controls both axonal guidance and subcellular target recognition. We show that loss of Semaphorin 3A function or specific deletion of NRP1 in BCs alters the stereotyped organization of BC axon and impairs pinceau synapse formation. Further, we identified NRP1 as a trans-synaptic binding partner of the cell adhesion molecule neurofascin-186 (NF186) expressed in the PC AIS during pinceau synapse formation. These findings identify a dual function of NRP1 in both axon guidance and subcellular target recognition in the construction of GABAergic circuitry.
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Publication type
Article: Journal article
Document type
Scientific Article
Keywords
Cell-adhesion Molecule; Initial Segment; Synaptic Connections; Semaphorin 3a; Neurofascin; L1; Interneurons; Gene; Neuropilin-1; Inhibition
ISSN (print) / ISBN
0896-6273
e-ISSN
1097-4199
Journal
Neuron
Quellenangaben
Volume: 91,
Issue: 6,
Pages: 1276-1291
Publisher
Cell Press
Publishing Place
Cambridge, Mass.
Non-patent literature
Publications
Reviewing status
Peer reviewed
Institute(s)
Institute of Developmental Genetics (IDG)