PUBLICATION

In vivo evidence for transdifferentiation of peripheral neurons

Authors

Wright, M.A., Mo, W., Nicolson, T., and Ribera, A.B.

ID

ZDB-PUB-100806-23

Date

2010

Source

Development (Cambridge, England) 137(18): 3047-3056 (Journal)

Registered Authors

Mo, Weike, Nicolson, Teresa, Ribera, Angie, Wright, Melissa

Keywords

Dorsal root ganglia neurons, Transdifferentiation, Nav1.6, Zebrafish

MeSH Terms

Neurons/cytology*
Neurons/metabolism
Sodium Channels/deficiency
Sodium Channels/metabolism*
Cell Transdifferentiation
Cell Differentiation*
Ganglia, Spinal/cytology
Ganglia, Spinal/embryology
Ganglia, Spinal/metabolism
NAV1.6 Voltage-Gated Sodium Channel
Zebrafish Proteins/deficiency
Zebrafish Proteins/metabolism*
Gene Expression Regulation, Developmental
Zebrafish/growth & development*
Zebrafish/metabolism
Animals, Genetically Modified
Animals
Mutation
Tyrosine 3-Monooxygenase/metabolism
Cell Movement

(all 20)

PubMed

20685733 Full text @ Development

Abstract

It is commonly thought that differentiated neurons do not give rise to new cells, severely limiting the potential for regeneration and repair of the mature nervous system. However, we have identified cells in zebrafish larvae that first differentiate into dorsal root ganglia sensory neurons but later acquire a sympathetic neuron phenotype. These transdifferentiating neurons are present in wild-type zebrafish. However, they are increased in number in larvae that have a mutant voltage-gated sodium channel gene, scn8aa. Sodium channel knock-down promotes migration of differentiated sensory neurons away from the ganglia. Once in a new environment, sensory neurons transdifferentiate regardless of sodium channel expression. These findings reveal an unsuspected plasticity in differentiated neurons that points to new strategies for treatment of nervous system disease.

Genes / Markers

Figures

Show all Figures

Expression

Gene	Fish	Conditions	Stage	Qualifier	Anatomy	Assay	Figure
GFP	sb4Tg	control	Pec-fin to Protruding-mouth		dorsal root ganglion neuron	IHC	Fig. 2
GFP	sb4Tg	control	Day 4		dorsal root ganglion neuron neural crest derived	IHC	Fig. 1
GFP	sb4Tg	control	Protruding-mouth		dorsal root ganglion neuron neural crest derived	IHC	Fig. 1
GFP	sb4Tg	control	Pec-fin to Protruding-mouth		dorsal root ganglion	IHC	Fig. 2
GFP	sb4Tg + MO1-scn8aa	standard conditions	Pec-fin to Protruding-mouth		dorsal root ganglion neuron	IHC	Fig. 2
GFP	sb4Tg + MO1-scn8aa	standard conditions	Protruding-mouth		dorsal root ganglion neuron neural crest derived	IHC	Fig. 1
GFP	sb4Tg + MO1-scn8aa	standard conditions	Day 4		dorsal root ganglion neuron neural crest derived	IHC	Fig. 1
GFP	sb4Tg + MO1-scn8aa	standard conditions	Pec-fin to Protruding-mouth		dorsal root ganglion	IHC	Fig. 2
Kaede	rw0130aTg + MO1-scn8aa	standard conditions	Protruding-mouth to Days 7-13		dorsal root ganglion neuron	IFL	Fig. 3
th	scn8aa^{tW1752X/tW1752X}	control	Days 14-20	Not Detected	dorsal root ganglion neuron	IHC	Fig. 7

1 - 10 of 14

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Phenotype

Fish	Conditions	Stage	Phenotype	Figure
WT + MO1-scn8aa	standard conditions	Long-pec to Days 7-13	sensory perception of touch decreased magnitude, abnormal	Fig. 6
WT + MO1-scn8aa	standard conditions	Day 4 to Days 7-13	dorsal root ganglion axon collateral mislocalised laterally, abnormal	Fig. 4
WT + MO1-scn8aa	standard conditions	Day 4 to Days 7-13	dorsal root ganglion neuron mislocalised ventrally, abnormal	Fig. 4
WT + MO1-scn8aa	standard conditions	Day 4 to Days 7-13	dorsal root ganglion neuron mobile, abnormal	Fig. 4
WT + MO1-scn8aa	standard conditions	Day 4 to Days 7-13	neuron differentiation process quality, abnormal	Fig. 4
rw0130aTg + MO1-scn8aa	standard conditions	Protruding-mouth to Days 7-13	dorsal root ganglion neuron mislocalised ventrally, abnormal	Fig. 3
rw0130aTg + MO1-scn8aa	standard conditions	Protruding-mouth to Days 7-13	neuron migration process quality, abnormal	Fig. 3
sb4Tg + MO1-scn8aa	standard conditions	Pec-fin to Protruding-mouth	dorsal root ganglion neuron mislocalised ventrally, abnormal	Fig. 2
sb4Tg + MO1-scn8aa	standard conditions	Pec-fin to Protruding-mouth	neuron migration process quality, abnormal	Fig. 2
sb4Tg + MO1-scn8aa	standard conditions	Protruding-mouth	dorsal root ganglion neuron neural crest derived mislocalised ventrally, abnormal	Fig. 1

1 - 10 of 14

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Mutations / Transgenics

Allele	Construct	Type	Affected Genomic Region
hi1059Tg	Tg(nLacz-GTvirus)	Transgenic Insertion	neurog1
rw0130aTg	Tg(elavl3:Kaede)	Transgenic Insertion
sb4Tg	Tg(-3.4neurog1:GFP)	Transgenic Insertion
tW1752X		Point Mutation	scn8aa

1 - 4 of 4

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Human Disease / Model

Sequence Targeting Reagents

Target	Reagent	Reagent Type
scn8aa	MO1-scn8aa	MRPHLNO
scn8aa	MO4-scn8aa	MRPHLNO

Fish

Fish
neurog1^hi1059Tg/+ (AB)
rw0130aTg
rw0130aTg + MO1-scn8aa
sb4Tg
sb4Tg + MO1-scn8aa
scn8aa^{tW1752X/tW1752X}
WT
WT + MO1-scn8aa

Antibodies

Orthology

Engineered Foreign Genes

Marker	Marker Type	Name
GFP	EFG	GFP
Kaede	EFG	Kaede

Mapping

Entity Type	Entity Symbol	Location
Feature	tW1752X	Chr: 23 Details
GENE	scn8aa	Chr: 23 Details
SSLP	z14967	Chr: 23 Details
SSLP	z42693	Chr: 23 Details

Wright et al., 2010 ZDB-PUB-100806-23 PMID:20685733

In vivo evidence for transdifferentiation of peripheral neurons

Wright et al., 2010

ZDB-PUB-100806-23
PMID:20685733