PUBLICATION

Isl2b regulates anterior second heart field development in zebrafish

Authors

Witzel, H.R., Cheedipudi, S., Gao, R., Stainier, D.Y., Dobreva, G.D.

ID

ZDB-PUB-170121-4

Date

2017

Source

Scientific Reports 7: 41043 (Journal)

Registered Authors

Dobreva, Gergana, Stainier, Didier

Keywords

Differentiation, Morphogenesis

MeSH Terms

Transcription Factors/metabolism*
Heart/growth & development*
Zebrafish
Animals
Gene Expression Regulation, Developmental*
Myocardium/metabolism
LIM-Homeodomain Proteins/metabolism*

(all 7)

PubMed

28106108 Full text @ Sci. Rep.

Abstract

After initial formation, the heart tube grows by addition of second heart field progenitor cells to its poles. The transcription factor Isl1 is expressed in the entire second heart field in mouse, and Isl1-deficient mouse embryos show defects in arterial and venous pole development. The expression of Isl1 is conserved in zebrafish cardiac progenitors; however, Isl1 is required for cardiomyocyte differentiation only at the venous pole. Here we show that Isl1 homologues are expressed in specific patterns in the developing zebrafish heart and play distinct roles during cardiac morphogenesis. In zebrafish, isl2a mutants show defects in cardiac looping, whereas isl2b is required for arterial pole development. Moreover, Isl2b controls the expression of key cardiac transcription factors including mef2ca, mef2cb, hand2 and tbx20. The specific roles of individual Islet family members in the development of distinct regions of the zebrafish heart renders this system particularly well-suited for dissecting Islet-dependent gene regulatory networks controlling the behavior and function of second heart field progenitors in distinct steps of cardiac development.

Genes / Markers

Figures

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Expression

Gene	Fish	Conditions	Stage	Anatomy	Assay	Figure
EGFP	isl1a^sa29/sa29; s883Tg	standard conditions	20-25 somites	cardiac muscle cell	IHC	Fig. 1
EGFP	isl1a^sa29/sa29; s883Tg	standard conditions	Prim-5	cardiac muscle cell	IHC	Fig. 1
EGFP	isl1a^sa29/sa29; s883Tg	standard conditions	Long-pec	cardiac muscle cell	IHC	Fig. 1
EGFP	isl1a^sa29/sa29; s883Tg	standard conditions	Prim-5	cardiac muscle cell	IHC	Fig. 2
EGFP	isl1a^sa29/sa29; s883Tg + MO1-isl2a	standard conditions	Prim-5	cardiac muscle cell	IHC	Fig. 2
EGFP	isl1a^sa29/sa29; s883Tg + MO1-isl2a + MO2-isl2b	standard conditions	Prim-5	cardiac muscle cell	IHC	Fig. 2
EGFP	isl1a^sa29/sa29; s883Tg + MO2-isl2b	standard conditions	Prim-5	cardiac muscle cell	IHC	Fig. 2
EGFP	s843Tg + MO1-isl2a + MO2-isl2b	standard conditions	Prim-5	primitive heart tube endothelial cell	IHC	Fig. 2
EGFP	s883Tg	standard conditions	Prim-5	cardiac muscle cell	IHC	Fig. 2
EGFP	s883Tg	standard conditions	20-25 somites	cardiac muscle cell	IHC	Fig. 1

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Phenotype

Fish	Conditions	Stage	Phenotype	Figure
isl1a^sa29/sa29	standard conditions	Long-pec	heart myh6 expression decreased distribution, abnormal	Fig. 3
isl1a^sa29/sa29; s883Tg	standard conditions	20-25 somites	heart rudiment peripheral region ab2-isl labeling absent, abnormal	Fig. 1
isl1a^sa29/sa29; s883Tg	standard conditions	Prim-5	presumptive sinus venosus cardiac muscle cell ab2-isl labeling absent, abnormal	Fig. 2
isl1a^sa29/sa29; s883Tg	standard conditions	Long-pec	sinus venosus ab2-isl labeling absent, abnormal	Fig. 1
isl1a^sa29/sa29; s883Tg + MO1-isl2a	standard conditions	Prim-5	presumptive sinus venosus cardiac muscle cell ab2-isl labeling absent, abnormal	Fig. 2
isl1a^sa29/sa29; s883Tg + MO1-isl2a + MO2-isl2b	standard conditions	Prim-5	presumptive sinus venosus cardiac muscle cell ab2-isl labeling absent, abnormal	Fig. 2
isl1a^sa29/sa29; s883Tg + MO2-isl2b	standard conditions	Prim-5	presumptive sinus venosus cardiac muscle cell ab2-isl labeling absent, abnormal	Fig. 2
isl2a^uhm2/uhm2	standard conditions	Long-pec	heart morphology, normal	Fig. 3
isl2a^uhm2/uhm2	standard conditions	Protruding-mouth	cardiac ventricle position, abnormal	Fig. 3
isl2b^uhm1/uhm1	standard conditions	10-13 somites	anterior lateral plate mesoderm hand2 expression decreased amount, abnormal	Fig. 4

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Mutations / Transgenics

Allele	Construct	Type	Affected Genomic Region
f2Tg	Tg(-5.1myl7:DsRed2-NLS)	Transgenic Insertion
s843Tg	Tg(kdrl:EGFP)	Transgenic Insertion
s883Tg	Tg(myl7:EGFP-Hsa.HRAS)	Transgenic Insertion
sa29		Point Mutation	isl1a
uhm1		Small Deletion	isl2b
uhm2		Small Deletion	isl2a

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Human Disease / Model

Sequence Targeting Reagents

Target	Reagent	Reagent Type
isl2a	MO1-isl2a	MRPHLNO
isl2a	TALEN2-isl2a	TALEN
isl2b	MO2-isl2b	MRPHLNO
isl2b	TALEN1-isl2b	TALEN

Fish

Fish
isl1a^sa29/sa29
isl1a^sa29/sa29; s883Tg
isl1a^sa29/sa29; s883Tg + MO1-isl2a
isl1a^sa29/sa29; s883Tg + MO1-isl2a + MO2-isl2b
isl1a^sa29/sa29; s883Tg + MO2-isl2b
isl2a^uhm2/uhm2
isl2b^uhm1/uhm1
s843Tg
s843Tg + MO1-isl2a + MO2-isl2b
s883Tg

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Antibodies

Orthology

Engineered Foreign Genes

Marker	Marker Type	Name
DsRed2	EFG	DsRed2
EGFP	EFG	EGFP

Mapping

Witzel et al., 2017 ZDB-PUB-170121-4 PMID:28106108

Isl2b regulates anterior second heart field development in zebrafish

Witzel et al., 2017

ZDB-PUB-170121-4
PMID:28106108