PUBLICATION

Clusters of neuronal neurofascin prefigure the position of a subset of nodes of Ranvier along individual central nervous system axons in vivo

Authors

Vagionitis, S., Auer, F., Xiao, Y., Almeida, R.G., Lyons, D.A., Czopka, T.

ID

ZDB-PUB-220217-6

Date

2022

Source

Cell Reports 38: 110366 (Journal)

Registered Authors

Almeida, Rafael, Auer, Franziska, Czopka, Tim, Lyons, David A., Vagionitis, Stavros, Xiao, Yan

Keywords

axon-oligodendrocyte interactions, central nervous system, myelination, node of Ranvier, zebrafish

MeSH Terms

Myelin Sheath/metabolism
Central Nervous System/metabolism*
Ranvier's Nodes/metabolism*
Animals
Axons/metabolism*
Mutation/genetics
Zebrafish/metabolism*
Genes, Reporter
Zebrafish Proteins/genetics
Zebrafish Proteins/metabolism*
Oligodendroglia/metabolism

(all 11)

PubMed

35172135 Full text @ Cell Rep.

Abstract

The spacing of nodes of Ranvier crucially affects conduction properties along myelinated axons. It is assumed that node position is primarily driven by growing myelin sheaths. Here, we reveal an additional mechanism of node positioning that is driven by the axon. Through longitudinal live imaging of node formation dynamics in the zebrafish central nervous system, we show that stable clusters of the cell adhesion molecule neurofascin a can accumulate at specific sites along axons prior to myelination. While some of these clusters are pushed into future node position by extending myelin sheaths, others are not and thus prefigure the position of where a mature node forms. Animals that lack full-length neurofascin a show increased internodal distances and less regular nodal spacing along single axons. Together, our data reveal the existence of an axonal mechanism to position nodes of Ranvier that does not depend on regulation by myelin sheath growth.

Genes / Markers

Figures

Show all Figures

Expression

Gene	Fish	Conditions	Stage	Anatomy	Assay	Figure
Cerulean	nfasca^{tum112/tum112}; tum101Tg/tum101Tg	standard conditions	Days 7-13	myelin accumulating cell anatomical axis	IFL	Figure 4
Cerulean	nfasca^{tum112/tum112}; tum101Tg/tum101Tg	standard conditions	Day 4 to Day 6	myelin accumulating cell	IFL	Figure 4
Cerulean	tum101Tg; ue601Tg	standard conditions	Days 7-13	myelin accumulating cell	IFL	Figure 1
mScarlet	tum111Tg; ue601Tg	standard conditions	Day 4	oligodendrocyte	IFL	Figure 2
YFP	tum101Tg; ue601Tg	standard conditions	Days 7-13	myelin accumulating cell	IFL	Figure 1
YFP	tum101Tg; ue601Tg	standard conditions	Day 5	neuron node of Ranvier	IFL	Figure 2
YFP	tum101Tg; ue601Tg	standard conditions	Days 7-13	neuron node of Ranvier	IFL	Figure 2
YFP	tum101Tg; ue601Tg	standard conditions	Days 7-13	neuron node of Ranvier	IFL	Figure 1
YFP	tum111Tg; ue601Tg	standard conditions	Day 4	neuron node of Ranvier	IFL	Figure 2

1 - 9 of 9

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Phenotype

Fish	Conditions	Stage	Phenotype	Figure
nfasca^{tum112/tum112}	standard conditions	Day 4 to Day 6	neuron node of Ranvier Ab2-nfasc labeling decreased amount, abnormal	Figure 4
nfasca^{tum112/tum112}; tum101Tg/tum101Tg	standard conditions	Days 7-13	myelin accumulating cell anatomical axis Cerulean expression spatial pattern, abnormal	Figure 4
nfasca^{tum112/tum112}; tum101Tg/tum101Tg	standard conditions	Days 7-13	myelinating Schwann cell regulation of myelination spatial distribution of a process, abnormal	Figure 4
tum101Tg; ue601Tg	standard conditions	Day 4 to Day 6	neuron node of Ranvier associated with myelin accumulating cell anatomical axis, normal	Figure 3
tum101Tg; ue601Tg	standard conditions	Day 4 to Day 6	neuron node of Ranvier in contact with myelin accumulating cell proximal/distal compartment boundary, normal	Figure 3
tum111Tg; ue601Tg	standard conditions	Day 4	oligodendrocyte in contact with neuron node of Ranvier, abnormal	Figure 2
tum111Tg; ue601Tg	standard conditions	Day 4	oligodendrocyte unfused from neuron node of Ranvier, normal	Figure 2
ue601Tg	standard conditions	Day 4 to Day 6	neuron node of Ranvier in contact with myelin accumulating cell proximal/distal compartment boundary, normal	Figure 3

1 - 8 of 8

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Mutations / Transgenics

Allele	Construct	Type	Affected Genomic Region
tum101Tg	Tg(mbpa:MA-Cerulean)	Transgenic Insertion
tum102Tg	Tg(mbpa:TagRFP-CAAX)	Transgenic Insertion
tum103Tg	Tg(mbpa:KillerRed)	Transgenic Insertion
tum111Tg	Tg(olig1:mScarlet-CAAX)	Transgenic Insertion
tum112		Small Deletion	nfasca
ue601Tg	Tg(cntn1b:cntn1b-KALTA4)	Transgenic Insertion

1 - 6 of 6

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Human Disease / Model

Sequence Targeting Reagents

Target	Reagent	Reagent Type
nfasca	CRISPR1-nfasca	CRISPR

Fish

Fish
nfasca^{tum112/tum112}
nfasca^{tum112/tum112}; tum101Tg/tum101Tg
tum101Tg; ue601Tg
tum111Tg; ue601Tg
ue601Tg

Antibodies

Name	Type	Antigen Genes	Isotypes	Host Organism
Ab2-nfasc	polyclonal		IgG1	Rabbit
Ab-3A10	monoclonal		IgG1	Mouse

Orthology

Engineered Foreign Genes

Marker	Marker Type	Name
mScarlet	EFG	mScarlet
Cerulean	EFG	Cerulean
KALTA4	EFG	KALTA4
KillerRed	EFG	KillerRed
TagRFP	EFG	TagRFP
YFP	EFG	YFP

Mapping

Vagionitis et al., 2022 ZDB-PUB-220217-6 PMID:35172135

Clusters of neuronal neurofascin prefigure the position of a subset of nodes of Ranvier along individual central nervous system axons in vivo

Vagionitis et al., 2022

ZDB-PUB-220217-6
PMID:35172135