PUBLICATION

Loss of embryonic neural crest derived cardiomyocytes causes adult onset hypertrophic cardiomyopathy in zebrafish

Authors

Abdul-Wajid, S., Demarest, B.L., Yost, H.J.

ID

ZDB-PUB-181106-6

Date

2018

Source

Nature communications 9: 4603 (Journal)

Registered Authors

Demarest, Bradley, Yost, H. Joseph

Keywords

none

MeSH Terms

Mutation/genetics
Receptors, Notch/metabolism
Jagged-2 Protein/metabolism
Zebrafish Proteins/metabolism
Neural Crest/embryology*
Neural Crest/pathology*
Embryo, Nonmammalian/pathology*
Zebrafish/embryology*
Heart Failure/embryology
Heart Failure/pathology
Heart/embryology
Body Patterning
Animals
Myocytes, Cardiac/metabolism
Myocytes, Cardiac/pathology*
Cardiomegaly/embryology*
Cardiomyopathies/embryology*

(all 17)

PubMed

30389937 Full text @ Nat. Commun.

Abstract

Neural crest cells migrate to the embryonic heart and transform into a small number of cardiomyocytes, but their functions in the developing and adult heart are unknown. Here, we show that neural crest derived cardiomyocytes (NC-Cms) in the zebrafish ventricle express Notch ligand jag2b, are adjacent to Notch responding cells, and persist throughout life. Genetic ablation of NC-Cms during embryogenesis results in diminished jag2b, altered Notch signaling and aberrant trabeculation patterns, but is not detrimental to early heart function or survival to adulthood. However, embryonic NC-Cm ablation results in adult fish that show severe hypertrophic cardiomyopathy (HCM), altered cardiomyocyte size, diminished adult heart capacity and heart failure in cardiac stress tests. Adult jag2b mutants have similar cardiomyopathy. Thus, we identify a cardiomyocyte population and genetic pathway that are required to prevent adult onset HCM and provide a zebrafish model of adult-onset HCM and heart failure.

Genes / Markers

Figures

Show all Figures

Expression

Gene	Fish	Conditions	Stage	Anatomy	Assay	Figure
EGFP	co26Tg; um14Tg (AB)	standard conditions	Protruding-mouth	heart	IFL	Fig. 3
EGFP	zy62Tg; zy70Tg (AB)	standard conditions	Protruding-mouth	cardiac muscle cell	IFL	Fig. 1
EGFP	zy62Tg; zy70Tg (AB)	standard conditions	Long-pec	cardiac muscle cell	IFL	Fig. 1
EGFP	zy62Tg; zy70Tg (AB)	standard conditions	Day 4	cardiac muscle cell	IFL	Fig. 1
EGFP	zy62Tg; zy70Tg (AB)	standard conditions	Day 6	cardiac muscle cell	IFL	Fig. 1
EGFP	zy62Tg; zy70Tg (AB)	standard conditions	Days 14-20	cardiac muscle cell	IFL	Fig. 1
EGFP	zy62Tg; zy70Tg (AB)	standard conditions	Prim-5	cardiac muscle cell	IFL	Fig. 1
EGFP	zy62Tg; zy70Tg (AB)	standard conditions	Prim-15	cardiac muscle cell	IFL	Fig. 1
jag2b	co26Tg; um14Tg (AB)	standard conditions	Protruding-mouth	cardiac muscle cell	ISH	Fig. 2
jag2b	zy62Tg; zy70Tg (AB)	control	Day 4	heart	RTPCR	Fig. 3

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Phenotype

Fish	Conditions	Stage	Phenotype	Figure
co26Tg; um14Tg (AB)	chemical treatment: metronidazole	Day 5	trabecular layer of ventricle TagRFP expression decreased amount, abnormal	Fig. 2
jag2b^hu3425/+ (AB)	chemical treatment: metronidazole	Adult	ventricular myocardium hypertrophic, abnormal	Fig. 5
jag2b^{hu3425/hu3425} (AB)	chemical treatment: metronidazole	Adult	trabecular layer of ventricle increased amount, abnormal	Fig. 5
jag2b^{hu3425/hu3425} (AB)	chemical treatment: metronidazole	Adult	ventricular myocardium hypertrophic, abnormal	Fig. 5
zy62Tg (AB)	chemical treatment: metronidazole	Day 5	cardiac muscle cell normal amount, normal	Fig. 2
zy62Tg; zy70Tg (AB)	control	Day 5	cardiac muscle cell normal amount, normal	Fig. 2
zy62Tg; zy70Tg (AB)	chemical treatment: metronidazole	Day 4	heart jag2b expression decreased amount, abnormal	Fig. 3
zy62Tg; zy70Tg (AB)	chemical treatment: metronidazole	Day 5	cardiac muscle cell decreased amount, abnormal	Fig. 2
zy62Tg; zy70Tg (AB)	chemical treatment: metronidazole	Day 5	trabecular layer of ventricle spatial pattern, abnormal	Fig. 2
zy62Tg; zy70Tg (AB)	chemical treatment: metronidazole	Adult	cardiac muscle cell increased size, abnormal	Fig. 4

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Mutations / Transgenics

Allele	Construct	Type	Affected Genomic Region
co26Tg	Tg(sox10:TagRFP)	Transgenic Insertion
cz1701Tg	Tg(-3.5ubb:LOXP-EGFP-LOXP-mCherry)	Transgenic Insertion
hu3425		Point Mutation	jag2b
um14Tg	Tg(EPV.Tp1-Mmu.Hbb:EGFP)	Transgenic Insertion
zy62Tg	Tg(myl7:LOXP-EGFP-LOXP-TagRFP-2A-NTR)	Transgenic Insertion
zy70Tg	Tg(sox10:Cre,cryaa:DsRed)	Transgenic Insertion

1 - 6 of 6

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Human Disease / Model

Human Disease	Fish	Conditions	Evidence
hypertrophic cardiomyopathy	zy62Tg; zy70Tg (AB)	chemical treatment: metronidazole	TAS
hypertrophic cardiomyopathy	jag2b^{hu3425/hu3425} (AB)	chemical treatment: metronidazole	TAS
hypertrophic cardiomyopathy	jag2b^hu3425/+ (AB)	chemical treatment: metronidazole	TAS

1 - 3 of 3

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Sequence Targeting Reagents

Fish

Fish
co26Tg; um14Tg (AB)
jag2b^{hu3425/hu3425} (AB)
jag2b^hu3425/+ (AB)
zy62Tg (AB)
zy62Tg; zy70Tg (AB)

Antibodies

Orthology

Engineered Foreign Genes

Marker	Marker Type	Name
Cre	EFG	Cre
DsRed	EFG	DsRed
EGFP	EFG	EGFP
mCherry	EFG	mCherry
NTR	EFG	NTR
TagRFP	EFG	TagRFP

Mapping

Abdul-Wajid et al., 2018 ZDB-PUB-181106-6 PMID:30389937

Loss of embryonic neural crest derived cardiomyocytes causes adult onset hypertrophic cardiomyopathy in zebrafish

Abdul-Wajid et al., 2018

ZDB-PUB-181106-6
PMID:30389937