PUBLICATION

Analysis of zebrafish sidetracked mutants reveals a novel role for Plexin A3 in intraspinal motor axon guidance

Authors
Palaisa, K.A., and Granato, M.
ID
ZDB-PUB-070820-11
Date
2007
Source
Development (Cambridge, England)   134(18): 3251-3257 (Journal)
Registered Authors
Granato, Michael, Palaisa, Kelly
Keywords
none
MeSH Terms
  • Semaphorins/physiology
  • Receptors, Cell Surface/genetics
  • Receptors, Cell Surface/physiology*
  • Animals
  • Zebrafish/embryology*
  • Zebrafish/genetics
  • Axons/physiology*
  • Motor Neurons/cytology
  • Motor Neurons/physiology*
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/physiology*
  • Mutation
  • Growth Cones/physiology
  • Morphogenesis*/genetics
  • Spinal Cord/cytology
  • Spinal Cord/embryology*
(all 16)
PubMed
17699603 Full text @ Development
Abstract
One of the earliest guidance decisions for spinal cord motoneurons occurs when pools of motoneurons orient their growth cones towards a common, segmental exit point. In contrast to later events, remarkably little is known about the molecular mechanisms underlying intraspinal motor axon guidance. In zebrafish sidetracked (set) mutants, motor axons exit from the spinal cord at ectopic positions. By single-cell labeling and time-lapse analysis we show that motoneurons with cell bodies adjacent to the segmental exit point properly exit from the spinal cord, whereas those farther away display pathfinding errors. Misguided growth cones either orient away from the endogenous exit point, extend towards the endogenous exit point but bypass it or exit at non-segmental, ectopic locations. Furthermore, we show that sidetracked acts cell autonomously in motoneurons. Positional cloning reveals that sidetracked encodes Plexin A3, a semaphorin guidance receptor for repulsive guidance. Finally, we show that sidetracked (plexin A3) plays an additional role in motor axonal morphogenesis. Together, our data genetically identify the first guidance receptor required for intraspinal migration of pioneering motor axons and implicate the well-described semaphorin/plexin signaling pathway in this poorly understood process. We propose that axonal repulsion via Plexin A3 is a major driving force for intraspinal motor growth cone guidance.
Genes / Markers
Figures
Figure Gallery (4 images)
Show all Figures
Expression
Phenotype
Mutations / Transgenics
Allele Construct Type Affected Genomic Region
ml2TgTransgenic Insertion
    p13umal
      Point Mutation
      p55emcf
        Unknown
        1 - 3 of 3
        Show
        Human Disease / Model
        No data available
        Sequence Targeting Reagents
        No data available
        Fish
        Antibodies
        No data available
        Orthology
        No data available
        Engineered Foreign Genes
        Marker Marker Type Name
        GFPEFGGFP
        1 - 1 of 1
        Show
        Mapping