title: Semaphorin 6B acts as a receptor in post-crossing commissural axon guidance.
abstract: Semaphorins are a large family of axon guidance molecules that are known primarily as ligands for plexins and neuropilins. Although class-6 semaphorins are transmembrane proteins, they have been implicated as ligands in different aspects of neural development, including neural crest cell migration, axon guidance and cerebellar development. However, the specific spatial and temporal expression of semaphorin 6B (Sema6B) in chick commissural neurons suggested a receptor role in axon guidance at the spinal cord midline. Indeed, in the absence of Sema6B, post-crossing commissural axons lacked an instructive signal directing them rostrally along the contralateral floorplate border, resulting in stalling at the exit site or even caudal turns. Truncated Sema6B lacking the intracellular domain was unable to rescue the loss-of-function phenotype, confirming a receptor function of Sema6B. In support of this, we demonstrate that Sema6B binds to floorplate-derived plexin A2 (PlxnA2) for navigation at the midline, whereas a cis-interaction between PlxnA2 and Sema6B on pre-crossing commissural axons may regulate the responsiveness of axons to floorplate-derived cues.
authors.affiliation: Institute of Molecular Life Sciences and Neuroscience Center Zurich, Winterthurerstrasse 190, Zurich 8057, Switzerland.
authors.forename: Irwin
authors.initials: I
authors.lastname: Andermatt
authors.affiliation: Institute of Molecular Life Sciences and Neuroscience Center Zurich, Winterthurerstrasse 190, Zurich 8057, Switzerland.
authors.forename: Nicole H
authors.initials: NH
authors.lastname: Wilson
authors.affiliation: Institute of Molecular Life Sciences and Neuroscience Center Zurich, Winterthurerstrasse 190, Zurich 8057, Switzerland.
authors.forename: Timothy
authors.initials: T
authors.lastname: Bergmann
authors.affiliation: Institute of Molecular Life Sciences and Neuroscience Center Zurich, Winterthurerstrasse 190, Zurich 8057, Switzerland.
authors.forename: Olivier
authors.initials: O
authors.lastname: Mauti
authors.affiliation: Institute of Molecular Life Sciences and Neuroscience Center Zurich, Winterthurerstrasse 190, Zurich 8057, Switzerland.
authors.forename: Matthias
authors.initials: M
authors.lastname: Gesemann
authors.affiliation: The Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, 725 N. Wolfe Street, Baltimore, MD 21205, USA.
authors.forename: Shanthini
authors.initials: S
authors.lastname: Sockanathan
authors.affiliation: Institute of Molecular Life Sciences and Neuroscience Center Zurich, Winterthurerstrasse 190, Zurich 8057, Switzerland esther.stoeckli@imls.uzh.ch.
authors.forename: Esther T
authors.initials: ET
authors.lastname: Stoeckli
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001369:Axons / Q000378:metabolism / Q000502:physiology*; D002465:Cell Movement / Q000502:physiology*; D002642:Chick Embryo; D007150:Immunohistochemistry; D008562:Membrane Glycoproteins / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D034622:RNA Interference; D039961:Semaphorins / Q000378:metabolism*; D013116:Spinal Cord / Q000166:cytology* / Q000196:embryology*
chemical_list: D008562:Membrane Glycoproteins; D009419:Nerve Tissue Proteins; D039961:Semaphorins
keywords: Chick; Cis-interaction; In ovo RNAi; PlexinA2; Spinal cord development