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
-
- Axons/physiology*
- Motor Neurons/cytology
- Motor Neurons/physiology*
- Receptors, Cell Surface/genetics
- Receptors, Cell Surface/physiology*
- Spinal Cord/cytology
- Spinal Cord/embryology*
- Zebrafish Proteins/genetics
- Zebrafish Proteins/physiology*
- Growth Cones/physiology
- Mutation
- Animals
- Morphogenesis*/genetics
- Zebrafish/embryology*
- Zebrafish/genetics
- Semaphorins/physiology
- PubMed
- 17699603 Full text @ Development
Citation
Palaisa, K.A., and Granato, M. (2007) Analysis of zebrafish sidetracked mutants reveals a novel role for Plexin A3 in intraspinal motor axon guidance. Development (Cambridge, England). 134(18):3251-3257.
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
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping