PUBLICATION

Fgf4 is required for left-right patterning of visceral organs in zebrafish

Authors

Yamauchi, H., Miyakawa, N., Miyake, A., and Itoh, N.

ID

ZDB-PUB-090616-6

Date

2009

Source

Developmental Biology 332(1): 177-185 (Journal)

Registered Authors

Itoh, Nobuyuki, Miyake, Ayumi

Keywords

Fgf, Fgf4, Asymmetry, Left–right, Patterning, Liver, Pancreas, Heart, Zebrafish, Kupffer's vesicle

MeSH Terms

Animals
Body Patterning*
Cilia/metabolism
Embryo, Nonmammalian/cytology
Embryo, Nonmammalian/metabolism
Fibroblast Growth Factors/metabolism*
Gene Expression Regulation, Developmental
Gene Knockdown Techniques
Heart/embryology
Left-Right Determination Factors
Liver/embryology
Liver/metabolism
Mesoderm/metabolism
Notochord/metabolism
Pancreas/embryology
Pancreas/metabolism
Viscera/embryology*
Viscera/metabolism
Zebrafish/embryology*
Zebrafish/genetics
Zebrafish Proteins/metabolism*

(all 21)

PubMed

19481538 Full text @ Dev. Biol.

Abstract

Fgf signaling plays essential roles in many developmental events. To investigate the roles of Fgf4 signaling in zebrafish development, we generated Fgf4 knockdown embryos by injection with Fgf4 antisense morpholino oligonucleotides. Randomized LR patterning of visceral organs including the liver, pancreas, and heart was observed in the knockdown embryos. Prominent expression of Fgf4 was observed in the posterior notochord and Kupffer's vesicle region in the early stages of segmentation. Lefty1, lefty2, southpaw, and pitx2 are known to play crucial roles in LR patterning of visceral organs. Fgf4 was essential for the expression of lefty1, which is necessary for the asymmetric expression of southpaw and pitx2 in the lateral plate mesoderm, in the posterior notochord, and the expression of lefty2 and lefty1 in the left cardiac field. Fgf8 is also known to be crucial for the formation of Kupffer's vesicle, which is needed for the LR patterning of visceral organs. In contrast, Fgf4 was required for the formation of cilia in Kupffer's vesicle, indicating that the role of Fgf4 in the LR patterning is quite distinct from that of Fgf8. The present findings indicate that Fgf4 plays a unique role in the LR patterning of visceral organs in zebrafish.

Genes / Markers

Marker	Marker Type	Name
cp	GENE	ceruloplasmin
dnah9	GENE	dynein, axonemal, heavy chain 9
eef1a1l1	GENE	eukaryotic translation elongation factor 1 alpha 1, like 1
fgf19	GENE	fibroblast growth factor 19
fgf4	GENE	fibroblast growth factor 4
fgf8a	GENE	fibroblast growth factor 8a
foxa3	GENE	forkhead box A3
lft1	GENE	lefty1
lft2	GENE	lefty2
myl7	GENE	myosin, light chain 7, regulatory

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Figures

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Expression

Gene	Fish	Conditions	Stage	Qualifier	Anatomy	Assay	Figure
cp	WT	standard conditions	Long-pec		liver	ISH	Fig. 2
cp	WT + MO3-fgf4	standard conditions	Long-pec		liver	ISH	Fig. 2
dnah9	WT	standard conditions	Bud		forerunner cell group	ISH	Fig. 4
dnah9	WT	standard conditions	5-9 somites		Kupffer's vesicle	ISH	Fig. 3
fgf19	WT	standard conditions	1-cell to 5-9 somites	Not Detected	whole organism	RTPCR	Fig. 3
fgf4	WT	standard conditions	Long-pec		fin bud	ISH	Fig. 3
fgf4	WT	standard conditions	5-9 somites		Kupffer's vesicle	ISH	Fig. 3
fgf4	WT	standard conditions	5-9 somites		Kupffer's vesicle	ISH	Fig. 6
fgf4	WT	standard conditions	Long-pec		midbrain hindbrain boundary	ISH	Fig. 3
fgf4	WT	standard conditions	Prim-5		midbrain hindbrain boundary	ISH	Fig. 3

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Phenotype

Fish	Conditions	Stage	Phenotype	Figure
WT + MO2-fgf4	standard conditions	Long-pec	determination of heart left/right asymmetry disrupted, abnormal	Fig. 2
WT + MO2-fgf4	standard conditions	Long-pec	heart mislocalised, abnormal	Fig. 2
WT + MO2-fgf4	standard conditions	Pec-fin	determination of liver left/right asymmetry disrupted, abnormal	Fig. 2
WT + MO2-fgf4	standard conditions	Pec-fin	determination of pancreatic left/right asymmetry disrupted, abnormal	Fig. 2
WT + MO2-fgf4	standard conditions	Pec-fin	liver mislocalised, abnormal	Fig. 2
WT + MO2-fgf4	standard conditions	Pec-fin	pancreas mislocalised, abnormal	Fig. 2
WT + MO3-fgf4	standard conditions	5-9 somites	Kupffer's vesicle motile cilium decreased length, abnormal	Fig. 4
WT + MO3-fgf4	standard conditions	20-25 somites	determination of heart left/right asymmetry disrupted, abnormal	Fig. 5
WT + MO3-fgf4	standard conditions	20-25 somites	heart development disrupted, abnormal	Fig. 5
WT + MO3-fgf4	standard conditions	Long-pec	determination of heart left/right asymmetry disrupted, abnormal	Fig. 2

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Mutations / Transgenics

Human Disease / Model

Sequence Targeting Reagents

Target	Reagent	Reagent Type
fgf4	MO2-fgf4	MRPHLNO
fgf4	MO3-fgf4	MRPHLNO
fgf8a	MO3-fgf8a	MRPHLNO

Fish

Fish
WT
WT + MO2-fgf4
WT + MO3-fgf4
WT + MO3-fgf4 + MO3-fgf8a
WT + MO3-fgf8a

Antibodies

Orthology

Engineered Foreign Genes

Mapping

Yamauchi et al., 2009 ZDB-PUB-090616-6 PMID:19481538

Fgf4 is required for left-right patterning of visceral organs in zebrafish

Yamauchi et al., 2009

ZDB-PUB-090616-6
PMID:19481538