Dual functional activity of semaphorin 3B is required for positioning the anterior commissure.
Chemorepulsion by semaphorins plays a critical role during the development of neuronal projections. Although semaphorin-induced chemoattraction has been reported in vitro, the contribution of this activity to axon pathfinding is still unclear. Using genetic and culture models, we provide evidence that both attraction and repulsion by Sema3B, a secreted semaphorin, are critical for the positioning of a major brain commissural projection, the anterior commissure (AC). NrCAM, an immunoglobulin superfamily adhesion molecule of the L1 subfamily, associates with neuropilin-2 and is a component of a receptor complex for Sema3B and Sema3F. Finally, we show that activation of the FAK/Src signaling cascade distinguishes Sema3B-mediated attractive from repulsive axonal responses of neurons forming the AC, revealing a mechanism underlying the dual activity of this guidance cue.
Falk
Julien
J
NMDA, UMR CNRS 6156, Institut de Biologie du Dèveloppement de Marseille, Parc Scientifique de Luminy, 13288 Marseille cedex 9, France.
Julien
Falk
F
Bechara
Ahmad
A
Fiore
Roberto
R
Nawabi
Homaira
H
Zhou
Heather
H
Hoyo-Becerra
Carolina
C
Bozon
Muriel
M
Rougon
Geneviève
G
Grumet
Martin
M
Püschel
Andreas W
AW
Sanes
Joshua R
JR
Castellani
Valérie
V
D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D000367:Age Factors; D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D001369:Axons / Q000378:metabolism; D015152:Blotting, Northern / Q000379:methods; D015153:Blotting, Western / Q000379:methods; D015815:Cell Adhesion Molecules / Q000378:metabolism; D002449:Cell Aggregation / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D002522:Chlorocebus aethiops; D003001:Cloning, Molecular / Q000379:methods; D018920:Coculture Techniques / Q000379:methods; D004791:Enzyme Inhibitors / Q000494:pharmacology; D051417:Focal Adhesion Kinase 1 / Q000378:metabolism; D020439:Growth Cones / Q000502:physiology; D007150:Immunohistochemistry / Q000379:methods; D047468:Immunoprecipitation / Q000379:methods; D017403:In Situ Hybridization / Q000379:methods; D007211:Indoles / Q000494:pharmacology; D051379:Mice; D018345:Mice, Knockout; D009474:Neurons / Q000378:metabolism*; D039943:Neuropilin-2 / Q000378:metabolism; D009833:Olfactory Pathways / Q000254:growth & development / Q000378:metabolism; D011485:Protein Binding / Q000502:physiology; D012333:RNA, Messenger / Q000096:biosynthesis; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D039961:Semaphorins / Q000172:deficiency / Q000502:physiology*; D012686:Septal Nuclei / Q000166:cytology* / Q000254:growth & development / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D013449:Sulfonamides / Q000494:pharmacology; D014162:Transfection / Q000379:methods; D019061:src-Family Kinases / Q000502:physiology
D048868:Adaptor Proteins, Signal Transducing; D015815:Cell Adhesion Molecules; D004791:Enzyme Inhibitors; C491468:Fyb protein, mouse; D007211:Indoles; D039943:Neuropilin-2; C491151:Nrcam protein, mouse; D012333:RNA, Messenger; C416927:SU 6656; D039961:Semaphorins; D013449:Sulfonamides; D051417:Focal Adhesion Kinase 1; C496051:Ptk2 protein, mouse; D019061:src-Family Kinases