PUBLICATION

ndrg4 is required for normal myocyte proliferation during early cardiac development in zebrafish

Authors

Qu, X., Jia, H., Garrity, D.M., Tompkins, K., Batts, L., Appel, B., Zhong, T.P., and Baldwin, H.S.

ID

ZDB-PUB-080415-16

Date

2008

Source

Developmental Biology 317(2): 486-496 (Journal)

Registered Authors

Garrity, Deborah, Zhong, Tao P.

Keywords

Zebrafish, ndrg4, Cardiogenesis, Myocardium, tbx5, tbx20

MeSH Terms

Heart/embryology
Phenotype*
Bone Morphogenetic Proteins/metabolism
Bone Morphogenetic Protein 4
Zebrafish Proteins/genetics
Zebrafish Proteins/metabolism*
Myocytes, Cardiac/metabolism
Myocytes, Cardiac/physiology*
Nerve Tissue Proteins/genetics
Nerve Tissue Proteins/metabolism*
Oligonucleotides/genetics
Mutation/genetics
Animals
Cell Proliferation
Zebrafish/embryology*
Versicans/metabolism
Muscle Proteins/genetics
Muscle Proteins/metabolism*
T-Box Domain Proteins/metabolism
Cloning, Molecular
In Situ Hybridization

(all 21)

PubMed

18407257 Full text @ Dev. Biol.

Abstract

NDRG4 is a novel member of the NDRG family (N-myc downstream-regulated gene). The roles of NDRG4 in development have not previously been evaluated. We show that, during zebrafish embryonic development, ndrg4 is expressed exclusively in the embryonic heart, the central nervous system (CNS) and the sensory system. Ndrg4 knockdown in zebrafish embryos causes a marked reduction in proliferative myocytes and results in hypoplastic hearts. This growth defect is associated with cardiac phenotypes in morphogenesis and function, including abnormal heart looping, inefficient circulation and weak contractility. We reveal that ndrg4 is required for restricting the expression of versican and bmp4 to the developing atrioventricular canal. This constellation of ndrg4 cardiac defects phenocopies those seen in mutant hearts of heartstrings (hst), the tbx5 loss-of-function mutants in zebrafish. We further show that ndrg4 expression is significantly decreased in hearts with reduced tbx5 activities. Conversely, increased expression of tbx5 that is due to tbx20 knockdown leads to an increase in ndrg4 expression. Together, our studies reveal an essential role of ndrg4 in regulating proliferation and growth of cardiomyocytes, suggesting that ndrg4 may function downstream of tbx5 during heart development and growth.

Genes / Markers

Figures

Show all Figures

Expression

Gene	Fish	Conditions	Stage	Anatomy	Assay	Figure
bmp4	WT	control	Long-pec	atrioventricular canal	ISH	Fig. 8
bmp4	WT + MO2-ndrg4	standard conditions	Long-pec	atrioventricular canal	ISH	Fig. 8
bmp4	WT + MO2-ndrg4	standard conditions	Long-pec	cardiac ventricle	ISH	Fig. 8
DsRed2	f2Tg	control	Long-pec	atrium	IFL	Fig. 6
DsRed2	f2Tg	control	Long-pec	cardiac muscle cell	IFL	Fig. 6
DsRed2	f2Tg	control	Long-pec	cardiac ventricle	IFL	Fig. 6
DsRed2	f2Tg + MO2-ndrg4	standard conditions	Long-pec	atrium	IFL	Fig. 6
DsRed2	f2Tg + MO2-ndrg4	standard conditions	Long-pec	cardiac muscle cell	IFL	Fig. 6
DsRed2	f2Tg + MO2-ndrg4	standard conditions	Long-pec	cardiac ventricle	IFL	Fig. 6
GFP	f1Tg	standard conditions	Long-pec to Protruding-mouth	atrium	IFL	Fig. 5

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Phenotype

Fish	Conditions	Stage	Phenotype	Figure
WT + MO1-tbx5a	standard conditions	Prim-15	heart development disrupted, abnormal	Fig. 9
WT + MO1-tbx5a	standard conditions	Prim-15	heart morphology, abnormal	Fig. 9
WT + MO1-tbx5a	standard conditions	Long-pec	heart development disrupted, abnormal	Fig. 9
WT + MO1-tbx5a	standard conditions	Long-pec	heart morphology, abnormal	Fig. 9
WT + MO2-ndrg4	standard conditions	Prim-5 to Prim-15	heart tube morphology, normal	text only
WT + MO2-ndrg4	standard conditions	Prim-25	heart development disrupted, abnormal	text only
WT + MO2-ndrg4	standard conditions	Prim-25	heart tube morphology, abnormal	text only
WT + MO2-ndrg4	standard conditions	Long-pec	atrioventricular canal cardiac muscle cell mislocalised, abnormal	Fig. 8
WT + MO2-ndrg4	standard conditions	Long-pec	atrium dilated, abnormal	Fig. 4
WT + MO2-ndrg4	standard conditions	Long-pec	blood circulation disrupted, abnormal	Fig. 4

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Mutations / Transgenics

Allele	Construct	Type	Affected Genomic Region
f1Tg	Tg(myl7:GFP)	Transgenic Insertion
f2Tg	Tg(-5.1myl7:DsRed2-NLS)	Transgenic Insertion
m21		Point Mutation	tbx5a

Human Disease / Model

Sequence Targeting Reagents

Target	Reagent	Reagent Type
ndrg4	MO1-ndrg4	MRPHLNO
ndrg4	MO2-ndrg4	MRPHLNO
tbx5a	MO1-tbx5a	MRPHLNO
tbx20	MO1-tbx20	MRPHLNO

Fish

Fish
f1Tg
f1Tg + MO2-ndrg4
f2Tg
f2Tg + MO2-ndrg4
tbx5a^m21/m21
WT
WT + MO1-tbx5a
WT + MO1-tbx20
WT + MO2-ndrg4

Antibodies

Orthology

Gene	Orthology
ndrg4

Engineered Foreign Genes

Marker	Marker Type	Name
DsRed2	EFG	DsRed2
GFP	EFG	GFP

Mapping

Qu et al., 2008 ZDB-PUB-080415-16 PMID:18407257

ndrg4 is required for normal myocyte proliferation during early cardiac development in zebrafish

Qu et al., 2008

ZDB-PUB-080415-16
PMID:18407257