Dual Function of NRP1 in Axon Guidance and Subcellular Target Recognition in Cerebellum.
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.
Department of Neurobiology, Institut de Génomique Fonctionnelle, CNRS, UMR5203, 34090 Montpellier, France; INSERM, U1191, 34094 Montpellier, France; Université de Montpellier, 34090 Montpellier, France; Department of Basic Neurosciences, University of Geneva Medical School, CH-1211 Geneva 4, Switzerland.
Ludovic
L
Telley
Department of Neurobiology, Institut de Génomique Fonctionnelle, CNRS, UMR5203, 34090 Montpellier, France; INSERM, U1191, 34094 Montpellier, France; Université de Montpellier, 34090 Montpellier, France; Department of Basic Neurosciences, University of Geneva Medical School, CH-1211 Geneva 4, Switzerland.
Christelle
C
Cadilhac
Department of Neurobiology, Institut de Génomique Fonctionnelle, CNRS, UMR5203, 34090 Montpellier, France; INSERM, U1191, 34094 Montpellier, France; Université de Montpellier, 34090 Montpellier, France; Department of Physiology Development and Neuroscience, University of Cambridge, Anatomy Building, Downing Street, Cambridge CB2 3DY, UK.
Jean-Michel
JM
Cioni
Department of Neurobiology, Institut de Génomique Fonctionnelle, CNRS, UMR5203, 34090 Montpellier, France; INSERM, U1191, 34094 Montpellier, France; Université de Montpellier, 34090 Montpellier, France.
Veronique
V
Saywell
Department of Neurobiology, Institut de Génomique Fonctionnelle, CNRS, UMR5203, 34090 Montpellier, France; INSERM, U1191, 34094 Montpellier, France; Université de Montpellier, 34090 Montpellier, France.
Céline
C
Jahannault-Talignani
Institute of Developmental Genetics, Helmholtz Zentrum München-German Research Center for Environmental Health, 85764 Neuherberg, Germany.
Rosa E
RE
Huettl
Aix-Marseille Université, CNRS, CRN2M-UMR7286, 13284 Marseille, France.
Catherine
C
Sarrailh-Faivre
Department of Basic Neurosciences, University of Geneva Medical School, CH-1211 Geneva 4, Switzerland; Department of Mental Health and Psychiatry, University of Geneva Medical School, CH-1211 Geneva 4, Switzerland.
Alexandre
A
Dayer
Institute of Developmental Genetics, Helmholtz Zentrum München-German Research Center for Environmental Health, 85764 Neuherberg, Germany.
Andrea B
AB
Huber
Department of Neurobiology, Institut de Génomique Fonctionnelle, CNRS, UMR5203, 34090 Montpellier, France; INSERM, U1191, 34094 Montpellier, France; Université de Montpellier, 34090 Montpellier, France. Electronic address: fabrice.ango@igf.cnrs.fr.
Fabrice
F
Ango
D000818:Animals; D000071437:Axon Guidance / Q000502:physiology*; D016466:CHO Cells; D015815:Cell Adhesion Molecules / Q000378:metabolism; D002531:Cerebellum / Q000166:cytology* / Q000254:growth & development*; D018920:Coculture Techniques; D003412:Cricetulus; D059330:GABAergic Neurons / Q000502:physiology*; D006801:Humans; D009414:Nerve Growth Factors / Q000378:metabolism; D055495:Neurogenesis / Q000502:physiology; D039942:Neuropilin-1 / Q000502:physiology*; D011689:Purkinje Cells / Q000502:physiology; D040121:Semaphorin-3A / Q000502:physiology; D013569:Synapses / Q000502:physiology
D015815:Cell Adhesion Molecules; D009414:Nerve Growth Factors; C504593:Nfasc protein, mouse; D040121:Semaphorin-3A; D039942:Neuropilin-1