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

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Expression

Phenotype

Fish	Conditions	Stage	Phenotype	Figure
plxna3^{p55emcf/p55emcf}	standard conditions	Prim-5	MiP motor neuron axon mislocalised, abnormal	Fig. 1
plxna3^{p55emcf/p55emcf}	standard conditions	Prim-5	motor neuron axon guidance disrupted, abnormal	Fig. 1
plxna3^{p55emcf/p55emcf}	standard conditions	Prim-5	RoP motor neuron axon mislocalised, abnormal	Fig. 1
plxna3^{p55emcf/p55emcf}	standard conditions	Long-pec	CaP motoneuron axon increased branchiness, abnormal	Fig. 2
plxna3^{p55emcf/p55emcf}	standard conditions	Long-pec	MiP motor neuron axon increased branchiness, abnormal	Fig. 2
plxna3^{p55emcf/p55emcf}	standard conditions	Long-pec	motor neuron axon guidance disrupted, abnormal	Fig. 2
plxna3^{p55emcf/p55emcf}	standard conditions	Long-pec	RoP motor neuron axon increased branchiness, abnormal	Fig. 2

1 - 7 of 7

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Mutations / Transgenics

Allele	Construct	Type	Affected Genomic Region
ml2Tg	Tg(mnx1:GFP)	Transgenic Insertion
p13umal		Point Mutation	plxna3
p55emcf		Unknown	plxna3

Human Disease / Model

Sequence Targeting Reagents

Fish

Fish
ml2Tg
plxna3^{p13umal/p13umal}
plxna3^{p55emcf/p55emcf}
WT

Antibodies

Orthology

Engineered Foreign Genes

Marker	Marker Type	Name
GFP	EFG	GFP

Mapping

Palaisa et al., 2007 ZDB-PUB-070820-11 PMID:17699603

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

Palaisa et al., 2007

ZDB-PUB-070820-11
PMID:17699603