PUBLICATION

The AP-1 transcription factor component Fosl2 potentiates the rate of myocardial differentiation from the zebrafish second heart field

Authors

Jahangiri, L., Sharpe, M., Novikov, N., González-Rosa, J.M., Borikova, A., Nevis, K., Paffett-Lugassy, N., Zhao, L., Adams, M., Guner-Ataman, B., Burns, C.E., Burns, C.G.

ID

ZDB-PUB-160107-8

Date

2016

Source

Development (Cambridge, England) 143: 113-22 (Journal)

Registered Authors

Burns (Erter), Caroline, Burns, Geoff, Paffett-Lugassy, Noelle, Zhao, Long

Keywords

AP-1, Cardiac development, Fosl2, Heart, Second heart field, Zebrafish

MeSH Terms

Zebrafish Proteins/genetics
Zebrafish Proteins/metabolism
Amino Acid Sequence
Heart/embryology*
Heart Defects, Congenital/genetics
Gene Knockout Techniques
Myocytes, Cardiac/cytology*
Gene Expression Regulation, Developmental
Myocardium/cytology
Transcription Factor AP-1/metabolism*
Animals
Cell Differentiation/physiology*
Cell Proliferation/genetics
Fos-Related Antigen-2/biosynthesis
Fos-Related Antigen-2/genetics
Fos-Related Antigen-2/metabolism*
Sequence Analysis, Protein
Animals, Genetically Modified
Zebrafish/embryology*

(all 19)

PubMed

26732840 Full text @ Development

Abstract

The vertebrate heart forms through successive phases of cardiomyocyte differentiation. Initially, cardiomyocytes derived from first heart field (FHF) progenitors assemble the linear heart tube. Thereafter, second heart field (SHF) progenitors differentiate into cardiomyocytes that are accreted to the poles of the heart tube over a well-defined developmental window. Although heart tube elongation deficiencies lead to life-threatening congenital heart defects, the variables controlling the initiation, rate and duration of myocardial accretion remain obscure. Here, we demonstrate that the AP-1 transcription factor, Fos-like antigen 2 (Fosl2), potentiates the rate of myocardial accretion from the zebrafish SHF. fosl2 mutants initiate accretion appropriately, but cardiomyocyte production is sluggish, resulting in a ventricular deficit coupled with an accumulation of SHF progenitors. Surprisingly, mutant embryos eventually correct the myocardial deficit by extending the accretion window. Overexpression of Fosl2 also compromises production of SHF-derived ventricular cardiomyocytes, a phenotype that is consistent with precocious depletion of the progenitor pool. Our data implicate Fosl2 in promoting the progenitor to cardiomyocyte transition and uncover the existence of regulatory mechanisms to ensure appropriate SHF-mediated cardiomyocyte contribution irrespective of embryonic stage.

Genes / Markers

Figures

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Expression

Gene	Fish	Conditions	Stage	Anatomy	Assay	Figure
DsRed2	f2Tg	standard conditions	Protruding-mouth	cardiac muscle cell nucleus	IFL	Fig. 4
DsRed2	f2Tg	standard conditions	Long-pec	cardiac muscle cell nucleus	IFL	Fig. 2
DsRed2	f2Tg	standard conditions	Prim-5	cardiac muscle cell nucleus	IFL	Fig. 2
DsRed2	f2Tg	standard conditions	Long-pec	cardiac muscle cell nucleus	IFL	Fig. 6
DsRed2	fosl2^fb15/fb15; f2Tg	standard conditions	Long-pec	cardiac muscle cell nucleus	IFL	Fig. 2
DsRed2	fosl2^fb15/fb15; f2Tg	standard conditions	Prim-5	cardiac muscle cell nucleus	IFL	Fig. 2
DsRed2	fosl2^fb15/fb15; f2Tg	standard conditions	Protruding-mouth	cardiac muscle cell nucleus	IFL	Fig. 4
DsRed2	fosl2^fb16/fb16; f2Tg	standard conditions	Long-pec	cardiac muscle cell nucleus	IFL	Fig. 2
DsRed2	fosl2^fb16/fb16; f2Tg	standard conditions	Prim-5	cardiac muscle cell nucleus	IFL	Fig. 2
fosl2	fosl2^fb15/fb15	standard conditions	Long-pec	whole organism	RTPCR	Fig. 1

1 - 10 of 49

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Phenotype

Fish	Conditions	Stage	Phenotype	Figure
WT + MO1-fosl2	standard conditions	Protruding-mouth	pericardium edematous, abnormal	Fig. 1
f1Tg + MO1-fosl2	standard conditions	Protruding-mouth	cardiac ventricle decreased size, abnormal	Fig. 1
fosl2^fb15/fb15	standard conditions	Prim-15	anatomical structure Ab1-fosl2 labeling absent, abnormal	Fig. 1
fosl2^fb15/fb15	standard conditions	Long-pec	bulbus arteriosus smooth muscle ab1-elnb labeling absent, abnormal	Fig. 2
fosl2^fb15/fb15	standard conditions	Long-pec	whole organism fosl2 expression decreased amount, abnormal	Fig. 1
fosl2^fb15/fb15; f1Tg	standard conditions	High-pec	cardiac ventricle decreased size, abnormal	Fig. 1
fosl2^fb15/fb15; f2Tg	standard conditions	Prim-5	cardiac muscle cell amount, normal	Fig. 2
fosl2^fb15/fb15; f2Tg	standard conditions	Long-pec	atrium cardiac muscle cell amount, normal	Fig. 2
fosl2^fb15/fb15; f2Tg	standard conditions	Long-pec	cardiac ventricle cardiac muscle cell decreased amount, abnormal	Fig. 2
fosl2^fb15/fb15; f2Tg	standard conditions	Protruding-mouth	atrium cardiac muscle cell amount, normal	Fig. 4

1 - 10 of 23

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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
fb2Tg	Tg(myl7:LOXP-AmCyan-LOXP-ZsYellow)	Transgenic Insertion
fb7Tg	TgBAC(-36nkx2.5:ZsYellow)	Transgenic Insertion
fb15		Small Deletion	fosl2
fb16		Small Deletion	fosl2
hsc4Tg	Tg(-0.8myl7:NLS-DsRedx)	Transgenic Insertion
hsc6Tg	Tg(myl7:NLS-KikGR)	Transgenic Insertion

1 - 8 of 8

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Human Disease / Model

Sequence Targeting Reagents

Target	Reagent	Reagent Type
fosl2	MO1-fosl2	MRPHLNO
fosl2	TALEN1-fosl2	TALEN

Fish

Fish
f1Tg
f1Tg; fb7Tg
f1Tg + MO1-fosl2
f2Tg
fosl2^fb15/fb15
fosl2^fb15/fb15; f1Tg
fosl2^fb15/fb15; f2Tg
fosl2^fb16/fb16
fosl2^fb16/fb16; f1Tg; fb7Tg
fosl2^fb16/fb16; f2Tg

Antibodies

Orthology

Gene	Orthology
fosl2

Engineered Foreign Genes

Marker	Marker Type	Name
AmCyan	EFG	AmCyan
DsRed2	EFG	DsRed2
GFP	EFG	GFP
KikGR	EFG	KikGR
ZsYellow	EFG	ZsYellow

Mapping

Jahangiri et al., 2016 ZDB-PUB-160107-8 PMID:26732840

The AP-1 transcription factor component Fosl2 potentiates the rate of myocardial differentiation from the zebrafish second heart field

Jahangiri et al., 2016

ZDB-PUB-160107-8
PMID:26732840