PUBLICATION

Nr2f-dependent allocation of ventricular cardiomyocyte and pharyngeal muscle progenitors

Authors

Dohn, T.E., Ravisankar, P., Tirera, F.T., Martin, K.E., Gafranek, J.T., Duong, T.B., VanDyke, T.L., Touvron, M., Barske, L.A., Crump, J.G., Waxman, J.S.

ID

ZDB-PUB-190206-14

Date

2019

Source

PLoS Genetics 15: e1007962 (Journal)

Registered Authors

Barske, Lindsey, Crump, Gage DeKoeyer, Waxman, Joshua

Keywords

none

MeSH Terms

Transcription Factors/genetics
Transcription Factors/metabolism*
Signal Transduction
Animals, Genetically Modified
Mutation
Animals
Embryonic Stem Cells/cytology
Embryonic Stem Cells/metabolism
Pharyngeal Muscles/cytology
Pharyngeal Muscles/embryology
Pharyngeal Muscles/metabolism*
Cell Lineage/genetics
Myocytes, Cardiac/cytology
Myocytes, Cardiac/metabolism*
COUP Transcription Factor II/genetics
COUP Transcription Factor II/metabolism*
DNA-Binding Proteins/genetics
DNA-Binding Proteins/metabolism*
Heart Ventricles/cytology
Heart Ventricles/embryology
Heart Ventricles/metabolism
Promoter Regions, Genetic
Zebrafish/embryology
Zebrafish/genetics
Zebrafish/metabolism
Heart Defects, Congenital/embryology
Heart Defects, Congenital/genetics
Body Patterning/genetics
Zebrafish Proteins/genetics
Zebrafish Proteins/metabolism*
Humans
Models, Animal
Craniofacial Abnormalities/embryology
Craniofacial Abnormalities/genetics
Tretinoin/metabolism
Mesoderm/cytology
Mesoderm/embryology
Mesoderm/metabolism

(all 38)

PubMed

30721228 Full text @ PLoS Genet.

Abstract

Multiple syndromes share congenital heart and craniofacial muscle defects, indicating there is an intimate relationship between the adjacent cardiac and pharyngeal muscle (PM) progenitor fields. However, mechanisms that direct antagonistic lineage decisions of the cardiac and PM progenitors within the anterior mesoderm of vertebrates are not understood. Here, we identify that retinoic acid (RA) signaling directly promotes the expression of the transcription factor Nr2f1a within the anterior lateral plate mesoderm. Using zebrafish nr2f1a and nr2f2 mutants, we find that Nr2f1a and Nr2f2 have redundant requirements restricting ventricular cardiomyocyte (CM) number and promoting development of the posterior PMs. Cre-mediated genetic lineage tracing in nr2f1a; nr2f2 double mutants reveals that tcf21+ progenitor cells, which can give rise to ventricular CMs and PM, more frequently become ventricular CMs potentially at the expense of posterior PMs in nr2f1a; nr2f2 mutants. Our studies reveal insights into the molecular etiology that may underlie developmental syndromes that share heart, neck and facial defects as well as the phenotypic variability of congenital heart defects associated with NR2F mutations in humans.

Genes / Markers

Figures

Show all Figures

Expression

Fish	Conditions	Stage	Anatomy	Assay	Figure
nr2f1a^el512/el512	standard conditions	14-19 somites	neural crest	ISH	Fig. S8
nr2f1a^el512/el512; nr2f2^el506/el506	standard conditions	14-19 somites	neural crest	ISH	Fig. S8
nr2f1a^el512/el512; nr2f2^el506/+	standard conditions	14-19 somites	neural crest	ISH	Fig. S8
WT	standard conditions	14-19 somites	neural crest	ISH	Fig. S8
nr2f1a^el512/el512; la116Tg	standard conditions	Long-pec	pharyngeal arch	IHC	Fig. S6
nr2f1a^el512/el512; la116Tg	standard conditions	Long-pec	pharyngeal arch 1	IHC	Fig. S6
nr2f1a^el512/el512; la116Tg	standard conditions	Long-pec	pharyngeal arch 3	IHC	Fig. S6
nr2f1a^el512/el512; la116Tg	standard conditions	Long-pec	pharyngeal arch 4	IHC	Fig. S6
nr2f1a^el512/el512; la116Tg	standard conditions	Long-pec	pharyngeal arch 5	IHC	Fig. S6
nr2f1a^el512/el512; la116Tg	standard conditions	Long-pec	pharyngeal arch 6	IHC	Fig. S6

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Phenotype

Fish	Conditions	Stage	Phenotype	Figure
WT	chemical treatment by environment: cycloheximide	1-4 somites	lateral plate mesoderm nr2f1a expression increased distribution, abnormal	Fig. 1
WT	chemical treatment by environment: cycloheximide, chemical treatment by environment: retinoic acid	1-4 somites	lateral plate mesoderm nr2f1a expression increased amount, abnormal	Fig. 1
WT	chemical treatment by environment: cycloheximide, chemical treatment by environment: retinoic acid	1-4 somites	lateral plate mesoderm nr2f1a expression increased distribution, abnormal	Fig. 1
WT	chemical treatment by environment: cycloheximide, chemical treatment by environment: retinoic acid	1-4 somites	whole organism nr2f1a expression increased amount, abnormal	Fig. 1
WT	chemical treatment by environment: retinoic acid	1-4 somites	lateral plate mesoderm nr2f1a expression increased amount, abnormal	Fig. 1
WT	chemical treatment by environment: retinoic acid	1-4 somites	lateral plate mesoderm nr2f1a expression increased distribution, abnormal	Fig. 1
WT	chemical treatment by environment: retinoic acid	1-4 somites	whole organism nr2f1a expression increased amount, abnormal	Fig. 1
WT	chemical treatment by environment: retinoic acid	5-9 somites	anterior lateral plate mesoderm nr2f1a expression increased amount, abnormal	Fig. 1
WT	chemical treatment by environment: retinoic acid	5-9 somites	anterior lateral plate mesoderm nr2f1a expression increased distribution, abnormal	Fig. 1
WT	chemical treatment by environment: retinoic acid	10-13 somites	anterior lateral plate mesoderm nr2f2 expression increased distribution, abnormal	Fig. S2

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Mutations / Transgenics

Allele	Construct	Type	Affected Genomic Region
ci104Tg	Tg(hsp70l:EGFP-VP16-dnrarab,cryaa:DsRed)	Transgenic Insertion
el506		Small Deletion	nr2f2
el512		Small Deletion	nr2f1a
fb2Tg	Tg(myl7:LOXP-AmCyan-LOXP-ZsYellow)	Transgenic Insertion
fb5Tg	Tg(ubb:LOXP-AmCyan-LOXP-ZsYellow)	Transgenic Insertion
fb7Tg	TgBAC(-36nkx2.5:ZsYellow)	Transgenic Insertion
la116Tg	Tg(kdrl:GFP)	Transgenic Insertion
pd41Tg	TgBAC(tcf21:NLS-EGFP)	Transgenic Insertion
pd42Tg	TgBAC(cryaa:EGFP,tcf21:Cre-ERT2)	Transgenic Insertion
sd12Tg	Tg(myl7:h2az2a-mCherry)	Transgenic Insertion

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Human Disease / Model

Sequence Targeting Reagents

Fish

Fish
fb2Tg; pd42Tg
fb5Tg; pd42Tg
fb7Tg
nr2f1a^el512/el512
nr2f1a^el512/el512; fb2Tg; pd42Tg
nr2f1a^el512/el512; fb5Tg; pd42Tg
nr2f1a^el512/el512; la116Tg
nr2f1a^el512/el512; nr2f2^el506/el506
nr2f1a^el512/el512; nr2f2^el506/el506; fb2Tg; pd42Tg
nr2f1a^el512/el512; nr2f2^el506/el506; fb5Tg; pd42Tg

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Antibodies

Orthology

Engineered Foreign Genes

Marker	Marker Type	Name
AmCyan	EFG	AmCyan
Cre	EFG	Cre
DsRed	EFG	DsRed
EGFP	EFG	EGFP
GFP	EFG	GFP
mCherry	EFG	mCherry
ZsYellow	EFG	ZsYellow

Mapping

Dohn et al., 2019 ZDB-PUB-190206-14 PMID:30721228

Nr2f-dependent allocation of ventricular cardiomyocyte and pharyngeal muscle progenitors

Dohn et al., 2019

ZDB-PUB-190206-14
PMID:30721228