title: Floor plate-derived neuropilin-2 functions as a secreted semaphorin sink to facilitate commissural axon midline crossing.
abstract: Commissural axon guidance depends on a myriad of cues expressed by intermediate targets. Secreted semaphorins signal through neuropilin-2/plexin-A1 receptor complexes on post-crossing commissural axons to mediate floor plate repulsion in the mouse spinal cord. Here, we show that neuropilin-2/plexin-A1 are also coexpressed on commissural axons prior to midline crossing and can mediate precrossing semaphorin-induced repulsion in vitro. How premature semaphorin-induced repulsion of precrossing axons is suppressed in vivo is not known. We discovered that a novel source of floor plate-derived, but not axon-derived, neuropilin-2 is required for precrossing axon pathfinding. Floor plate-specific deletion of neuropilin-2 significantly reduces the presence of precrossing axons in the ventral spinal cord, which can be rescued by inhibiting plexin-A1 signaling in vivo. Our results show that floor plate-derived neuropilin-2 is developmentally regulated, functioning as a molecular sink to sequester semaphorins, preventing premature repulsion of precrossing axons prior to subsequent down-regulation, and allowing for semaphorin-mediated repulsion of post-crossing axons.
authors.affiliation: Department of Biological Sciences, Rutgers University, Newark, New Jersey 07102, USA;
authors.forename: Berenice
authors.initials: B
authors.lastname: Hernandez-Enriquez
authors.affiliation: Laboratory of Brain Development and Repair, The Rockefeller University, New York, New York 10065, USA;
authors.forename: Zhuhao
authors.initials: Z
authors.lastname: Wu
authors.affiliation: Department of Biological Sciences, Rutgers University, Newark, New Jersey 07102, USA;
authors.forename: Edward
authors.initials: E
authors.lastname: Martinez
authors.affiliation: Laboratory of Brain Development and Repair, The Rockefeller University, New York, New York 10065, USA;
authors.forename: Olav
authors.initials: O
authors.lastname: Olsen
authors.affiliation: Amgen, Cambridge, Massachusetts 02141, USA;
authors.forename: Zaven
authors.initials: Z
authors.lastname: Kaprielian
authors.affiliation: Department of Biochemistry and Biophysics, University of North Carolina School of Medicine, Chapel Hill, North Carolina 27599, USA;
authors.forename: Patricia F
authors.initials: PF
authors.lastname: Maness
authors.affiliation: Division of Developmental Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio 45229, USA.
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Yoshida
authors.affiliation: Laboratory of Brain Development and Repair, The Rockefeller University, New York, New York 10065, USA;
authors.forename: Marc
authors.initials: M
authors.lastname: Tessier-Lavigne
authors.affiliation: Department of Biological Sciences, Rutgers University, Newark, New Jersey 07102, USA;
authors.forename: Tracy S
authors.initials: TS
authors.lastname: Tran
mesh_terms: D000818:Animals; D001369:Axons / Q000502:physiology*; D002478:Cells, Cultured; D066294:Commissural Interneurons / Q000166:cytology / Q000502:physiology*; D004622:Embryo, Mammalian; D017353:Gene Deletion; D018507:Gene Expression Regulation, Developmental; D051379:Mice; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D039943:Neuropilin-2 / Q000235:genetics / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism; D039961:Semaphorins / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D009419:Nerve Tissue Proteins; D039943:Neuropilin-2; C492114:Plxna1 protein, mouse; D011956:Receptors, Cell Surface; C526269:Sema3b protein, mouse; D039961:Semaphorins
keywords: explant cultures; neural development; pathfinding; semaphorin 3B; spinal cord