Gating of Sema3E/PlexinD1 signaling by neuropilin-1 switches axonal repulsion to attraction during brain development.
The establishment of functional neural circuits requires the guidance of axons in response to the actions of secreted and cell-surface molecules such as the semaphorins. Semaphorin 3E and its receptor PlexinD1 are expressed in the brain, but their functions are unknown. Here, we show that Sema3E/PlexinD1 signaling plays an important role in initial development of descending axon tracts in the forebrain. Early errors in axonal projections are reflected in behavioral deficits in Sema3E null mutant mice. Two distinct signaling mechanisms can be distinguished downstream of Sema3E. On corticofugal and striatonigral neurons expressing PlexinD1 but not Neuropilin-1, Sema3E acts as a repellent. In contrast, on subiculo-mammillary neurons coexpressing PlexinD1 and Neuropilin-1, Sema3E acts as an attractant. The extracellular domain of Neuropilin-1 is sufficient to convert repulsive signaling by PlexinD1 to attraction. Our data therefore reveal a "gating" function of neuropilins in semaphorin-plexin signaling during the assembly of forebrain neuronal circuits.
Developmental Biology Institute of Marseille Luminy, CNRS UMR 6216, University of Mediterranee, Case 907, Parc Scientifique de Luminy, 13288 Marseille cedex 09, France.
Sophie
S
Chauvet
Samia
S
Cohen
Yutaka
Y
Yoshida
Lylia
L
Fekrane
Jean
J
Livet
Odile
O
Gayet
Louis
L
Segu
Marie-Christine
MC
Buhot
Thomas M
TM
Jessell
Christopher E
CE
Henderson
Fanny
F
Mann
D000818:Animals; D001007:Anxiety / Q000235:genetics / Q000523:psychology; D001369:Axons / Q000378:metabolism / Q000502:physiology*; D001519:Behavior / Q000502:physiology; D015153:Blotting, Western; D001921:Brain / Q000166:cytology* / Q000254:growth & development*; D002478:Cells, Cultured; D018920:Coculture Techniques; D003598:Cytoskeletal Proteins; D006023:Glycoproteins / Q000096:biosynthesis / Q000502:physiology*; D007150:Immunohistochemistry; D047468:Immunoprecipitation; D017403:In Situ Hybridization; D047908:Intracellular Signaling Peptides and Proteins; D008297:Male; D008562:Membrane Glycoproteins / Q000096:biosynthesis / Q000502:physiology*; D008565:Membrane Proteins / Q000096:biosynthesis / Q000502:physiology*; D008569:Memory Disorders / Q000235:genetics / Q000523:psychology; D051379:Mice; D018345:Mice, Knockout; D009419:Nerve Tissue Proteins / Q000096:biosynthesis / Q000502:physiology*; D009434:Neural Pathways / Q000254:growth & development / Q000502:physiology; D039942:Neuropilin-1 / Q000096:biosynthesis / Q000502:physiology*; D039961:Semaphorins; D015398:Signal Transduction / Q000502:physiology*
D003598:Cytoskeletal Proteins; D006023:Glycoproteins; D047908:Intracellular Signaling Peptides and Proteins; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; C473552:Plxnd1 protein, mouse; C111150:Sema3e protein, mouse; D039961:Semaphorins; D039942:Neuropilin-1