PUBLICATION

Unmyelinated sensory neurons use Neuregulin signals to promote myelination of interneurons in the CNS

Authors

Lysko, D.E., Talbot, W.S.

ID

ZDB-PUB-221118-4

Date

2022

Source

Cell Reports 41: 111669 (Journal)

Registered Authors

Talbot, William S.

Keywords

CP: Neuroscience, CRISPR, central nervous system, myelination, neuregulin1, oligodendrocyte, zebrafish

MeSH Terms

Animals
Central Nervous System*
Interneurons
Myelin Sheath/metabolism
Sensory Receptor Cells/physiology
Zebrafish*

(all 6)

PubMed

36384112 Full text @ Cell Rep.

Abstract

The signaling mechanisms neurons use to modulate myelination of circuits in the central nervous system (CNS) are only partly understood. Through analysis of isoform-specific neuregulin1 (nrg1) mutants in zebrafish, we demonstrate that nrg1 type II is an important regulator of myelination of two classes of spinal cord interneurons. Surprisingly, nrg1 type II expression is prominent in unmyelinated Rohon-Beard sensory neurons, whereas myelination of neighboring interneurons is reduced in nrg1 type II mutants. Cell-type-specific loss-of-function studies indicate that nrg1 type II is required in Rohon-Beard neurons to signal to other neurons, not oligodendrocytes, to modulate spinal cord myelination. Together, our data support a model in which unmyelinated neurons express Nrg1 type II proteins to regulate myelination of neighboring neurons, a mode of action that may coordinate the functions of unmyelinated and myelinated neurons in the CNS.

Genes / Markers

Marker	Marker Type	Name
erbb3b	GENE	erb-b2 receptor tyrosine kinase 3b
nrg1	GENE	neuregulin 1

Figures

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Expression

Gene	Fish	Conditions	Stage	Anatomy	Assay	Figure
GFP	nrg1^st150/st150; ue101Tg/ue101Tg; ue102Tg/ue102Tg	standard conditions	Protruding-mouth	spinal cord myelin sheath	IFL	Fig. 1
GFP	nrg1^st150/+; ue101Tg/ue101Tg; ue102Tg/ue102Tg	standard conditions	Protruding-mouth	spinal cord myelin sheath	IFL	Fig. 1
GFP	nrg1^st151/st151; ue101Tg/ue101Tg; ue102Tg/ue102Tg	standard conditions	Protruding-mouth	spinal cord myelin sheath	IFL	Fig. 1
GFP	nrg1^st152/st152; ue101Tg/ue101Tg; ue102Tg/ue102Tg	standard conditions	Protruding-mouth	spinal cord myelin sheath	IFL	Fig. 1
GFP	nrg1^st152/+; ue101Tg/ue101Tg; ue102Tg/ue102Tg	standard conditions	Protruding-mouth	spinal cord myelin sheath	IFL	Fig. 1
GFP	nrg1^st153/st153; ue101Tg/ue101Tg; ue102Tg/ue102Tg	standard conditions	Protruding-mouth	spinal cord myelin sheath	IFL	Fig. 1
GFP	ue101Tg/ue101Tg; ue102Tg/ue102Tg	standard conditions	Protruding-mouth	spinal cord myelin sheath	IFL	Fig. 1
nrg1	nrg1^st152/st152; st162Tg/st162Tg	standard conditions	Prim-5	notochord	ISH	Fig. 4
nrg1	nrg1^st152/st152; st162Tg/st162Tg	standard conditions	Prim-15	notochord	ISH	Fig. 4
nrg1	nrg1^st152/st152; st162Tg/st162Tg	standard conditions	Prim-15	Rohon-Beard neuron	ISH	Fig. 4

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Phenotype

Fish	Conditions	Stage	Phenotype	Figure
erbb3b^st48/st48	standard conditions	Day 5	oligodendrocyte myelin sheath decreased amount, abnormal	Fig. 2
erbb3b^st48/st48; ue101Tg/ue101Tg; ue102Tg/ue102Tg	standard conditions	Protruding-mouth	oligodendrocyte myelin sheath decreased amount, abnormal	Fig. 6
erbb3b^st48/st48; ue101Tg/ue101Tg; ue102Tg/ue102Tg	standard conditions	Protruding-mouth	Rohon-Beard neuron decreased amount, abnormal	Fig. 6
nrg1^st150/+	standard conditions	Day 5	oligodendrocyte myelin sheath normal amount, normal	Fig. 2
nrg1^st150/+; ue101Tg/ue101Tg; ue102Tg/ue102Tg	standard conditions	Protruding-mouth	spinal cord myelin sheath GFP expression decreased amount, abnormal	Fig. 1
nrg1^st150/st150	standard conditions	Day 5	oligodendrocyte myelin sheath decreased amount, abnormal	Fig. 2
nrg1^st150/st150; ue101Tg/ue101Tg; ue102Tg/ue102Tg	standard conditions	Protruding-mouth	spinal cord myelin sheath GFP expression decreased amount, abnormal	Fig. 1
nrg1^st152/+	standard conditions	Day 5	oligodendrocyte myelin sheath normal amount, normal	Fig. 2
nrg1^st152/+; ue101Tg/ue101Tg; ue102Tg/ue102Tg	standard conditions	Protruding-mouth	spinal cord myelin sheath GFP expression decreased amount, abnormal	Fig. 1
nrg1^st152/st152	standard conditions	Day 5	oligodendrocyte myelin sheath decreased amount, abnormal	Fig. 2

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Mutations / Transgenics

Allele	Construct	Type	Affected Genomic Region
st48		Point Mutation	erbb3b
st150		Indel	nrg1
st151		Indel	nrg1
st152		Small Deletion	nrg1
st153		Small Deletion	nrg1
st162Tg	Tg(-3.0nrg1:GFP-CAAX)	Transgenic Insertion
ue101Tg	Tg(cldnk:GAL4)	Transgenic Insertion
ue102Tg	Tg(14xUAS:MA-GFP)	Transgenic Insertion
zf148Tg	Tg(Xla.Tubb:DsRed)	Transgenic Insertion

1 - 9 of 9

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Human Disease / Model

Sequence Targeting Reagents

Target	Reagent	Reagent Type
nrg1	CRISPR6-nrg1	CRISPR
nrg1	CRISPR7-nrg1	CRISPR
nrg1	CRISPR8-nrg1	CRISPR

Fish

Antibodies

Orthology

Engineered Foreign Genes

Marker	Marker Type	Name
DsRed	EFG	DsRed
GAL4	EFG	GAL4
GFP	EFG	GFP

Mapping

Lysko et al., 2022 ZDB-PUB-221118-4 PMID:36384112

Unmyelinated sensory neurons use Neuregulin signals to promote myelination of interneurons in the CNS

Lysko et al., 2022

ZDB-PUB-221118-4
PMID:36384112